Impact of Orientation on the Vitamin D Weighted Exposure of a Human in an Urban Environment

PubMed Central

Schrempf, Michael; Thuns, Nadine; Lange, Kezia

2017-01-01

The vitamin D3-weighted UV exposure of a human with vertical posture was calculated for urban locations to investigate the impact of orientation and obstructions on the exposure. Human exposure was calculated by using the 3D geometry of a human and integrating the radiance, i.e., the radiant energy from the direct solar beam and the diffuse sky radiation from different incident and azimuth angles. Obstructions of the sky are derived from hemispherical images, which are recorded by a digital camera with a fisheye lens. Due to the low reflectivity of most surfaces in the UV range, the radiance from obstructed sky regions was neglected. For spring equinox (21 March), the exposure of a human model with winter clothing in an environment where obstructions cover 40% of the sky varies by up to 25%, depending on the orientation of the human model to the sun. The calculation of the accumulated vitamin D3-weighted exposure of a human with winter clothing walking during lunch break shows that human exposure is reduced by the obstruction of buildings and vegetation by 40%. PMID:28813022

Habitat Management to Reduce Human Exposure to Trypanosoma cruzi and Western Conenose Bugs (Triatoma protracta).

PubMed

Shender, Lisa; Niemela, Michael; Conrad, Patricia; Goldstein, Tracey; Mazet, Jonna

2016-09-01

Chagas disease, which manifests as cardiomyopathy and severe gastrointestinal dysfunction, is caused by Trypanosoma cruzi, a vector-borne parasite. In California, the vector Triatoma protracta frequently colonizes woodrat (Neotoma spp.) lodges, but may also invade nearby residences, feeding upon humans and creating the dual risk of bite-induced anaphylaxis and T. cruzi transmission. Our research aimed to assess T. cruzi presence in woodrats in a previously unstudied northern California area, statistically evaluate woodrat microhabitat use with respect to vegetation parameters, and provide guidance for habitat modifications to mitigate public health risks associated with Tr. protracta exposure. Blood samples from big-eared woodrats (N. macrotis) trapped on rural private properties yielded a T. cruzi prevalence of 14.3%. Microhabitat analyses suggest that modifying vegetation to reduce understory density within a 40 meter radius of human residences might minimize woodrat lodge construction within this buffer area, potentially decreasing human exposure to Tr. protracta.

Sun Exposure and Its Effects on Human Health: Mechanisms through Which Sun Exposure Could Reduce the Risk of Developing Obesity and Cardiometabolic Dysfunction

PubMed Central

Fleury, Naomi; Geldenhuys, Sian; Gorman, Shelley

2016-01-01

Obesity is a significant burden on global healthcare due to its high prevalence and associations with chronic health conditions. In our animal studies, ongoing exposure to low dose ultraviolet radiation (UVR, found in sunlight) reduced weight gain and the development of signs of cardiometabolic dysfunction in mice fed a high fat diet. These observations suggest that regular exposure to safe levels of sunlight could be an effective means of reducing the burden of obesity. However, there is limited knowledge around the nature of associations between sun exposure and the development of obesity and cardiometabolic dysfunction, and we do not know if sun exposure (independent of outdoor activity) affects the metabolic processes that determine obesity in humans. In addition, excessive sun exposure has strong associations with a number of negative health consequences such as skin cancer. This means it is very important to “get the balance right” to ensure that we receive benefits without increasing harm. In this review, we detail the evidence around the cardiometabolic protective effects of UVR and suggest mechanistic pathways through which UVR could be beneficial. PMID:27727191

Human quarantine: Toward reducing infectious pressure on chimpanzees at the Taï Chimpanzee Project, Côte d'Ivoire.

PubMed

Grützmacher, Kim; Keil, Verena; Leinert, Vera; Leguillon, Floraine; Henlin, Arthur; Couacy-Hymann, Emmanuel; Köndgen, Sophie; Lang, Alexander; Deschner, Tobias; Wittig, Roman M; Leendertz, Fabian H

2018-01-01

Due to their genetic relatedness, great apes are highly susceptible to common human respiratory pathogens. Although most respiratory pathogens, such as human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), rarely cause severe disease in healthy human adults, they are associated with considerable morbidity and mortality in wild great apes habituated to humans for research or tourism. To prevent pathogen transmission, most great ape projects have established a set of hygiene measures ranging from keeping a specific distance, to the use of surgical masks and establishment of quarantines. This study investigates the incidence of respiratory symptoms and human respiratory viruses in humans at a human-great ape interface, the Taï Chimpanzee Project (TCP) in Côte d'Ivoire, and consequently, the effectiveness of a 5-day quarantine designed to reduce the risk of potential exposure to human respiratory pathogens. To assess the impact of quarantine as a preventative measure, we monitored the quarantine process and tested 262 throat swabs for respiratory viruses, collected during quarantine over a period of 1 year. Although only 1 subject tested positive for a respiratory virus (HRSV), 17 subjects developed symptoms of infection while in quarantine and were subsequently kept from approaching the chimpanzees, preventing potential exposure in 18 cases. Our results suggest that quarantine-in combination with monitoring for symptoms-is effective in reducing the risk of potential pathogen exposure. This research contributes to our understanding of how endangered great apes can be protected from human-borne infectious disease. © 2017 Wiley Periodicals, Inc.

Management concerns about known and potential impacts of lead use in shooting and in fishing activities

USGS Publications Warehouse

Goddard, C.I.; Leonard, N.J.; Stang, D.L.; Wingate, P.J.; Rattner, B.A.; Franson, J.C.; Sheffield, S.R.

2008-01-01

We present a summary of the technical review, jointly requested by the American Fisheries Society and The Wildlife Society, addressing the hazards to wildlife resulting from lead objects or fragments introduced into aquatic and terrestrial environments from the use of ammunition and fishing tackle. Impacts from lead are well documented in humans, as well as in terrestrial and aquatic organisms. Concern about impacts from lead ammunition and fishing tackle has resulted in the development of non-lead alternatives, educational campaigns, and regulations to restrict their use. This article discusses the general biological impacts of lead exposure from fishing and shooting activities to fish, wildlife, and humans; summarizes existing and proposed regulations to reduce lead exposure to biota; reviews alternatives to lead materials that are currently available for fishing; and outlines options for further actions to reduce wildlife and human exposure to lead from fishing activities.

EXPOSURE RECONSTRUCTION FOR REDUCING UNCERTAINTY IN RISK ASSESSMENT: EXAMPLE USING MTBE BIOMARKERS AND SIMPLE PHARMACOKINETIC MODEL

EPA Science Inventory

Adverse health risks from environmental agents are generally related to average (long term) exposures. We used results from a series of controlled human exposure tests and classical first order rate kinetics calculations to estimate how well spot measurements of methyl tertiary ...

Determination of Important Nuclear Fragmentation Processes for Human Space Radiation Protection

NASA Technical Reports Server (NTRS)

Lin, Zi-Wei

2007-01-01

We present a semi-analytical method to determine which partial cross sections of nuclear fragmentations most affect the shielded dose equivalent due to exposure to galactic cosmic rays. The cross sections thus determined will require more theoretical and/or experimental studies in order for us to better predict, reduce and mitigate the radiation exposure in human space explorations.

Heavy metals in drinking water: Occurrences, implications, and future needs in developing countries.

PubMed

Chowdhury, Shakhawat; Mazumder, M A Jafar; Al-Attas, Omar; Husain, Tahir

2016-11-01

Heavy metals in drinking water pose a threat to human health. Populations are exposed to heavy metals primarily through water consumption, but few heavy metals can bioaccumulate in the human body (e.g., in lipids and the gastrointestinal system) and may induce cancer and other risks. To date, few thousand publications have reported various aspects of heavy metals in drinking water, including the types and quantities of metals in drinking water, their sources, factors affecting their concentrations at exposure points, human exposure, potential risks, and their removal from drinking water. Many developing countries are faced with the challenge of reducing human exposure to heavy metals, mainly due to their limited economic capacities to use advanced technologies for heavy metal removal. This paper aims to review the state of research on heavy metals in drinking water in developing countries; understand their types and variability, sources, exposure, possible health effects, and removal; and analyze the factors contributing to heavy metals in drinking water. This study identifies the current challenges in developing countries, and future research needs to reduce the levels of heavy metals in drinking water. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensors and Apps for Community-Based Atmospheric Monitoring

EPA Science Inventory

Recent advances in both sensors and wireless communication provide opportunities for improved exposure assessment and increasing community involvement in reducing levels of human exposure to airborne contaminants. These new technologies can enhance data collection to answer scien...

Ultraviolet radiation, vitamin D and the development of obesity, metabolic syndrome and type-2 diabetes.

PubMed

Gorman, Shelley; Lucas, Robyn M; Allen-Hall, Aidan; Fleury, Naomi; Feelisch, Martin

2017-03-16

Obesity is increasing in prevalence in many countries around the world. Its causes have been traditionally ascribed to a model where energy intake exceeds energy consumption. Reduced energy output in the form of exercise is associated with less sun exposure as many of these activities occur outdoors. This review explores the potential for ultraviolet radiation (UVR), derived from sun exposure, to affect the development of obesity and two of its metabolic co-morbidities, type-2 diabetes and metabolic syndrome. We here discuss the potential benefits (or otherwise) of exposure to UVR based on evidence from pre-clinical, human epidemiological and clinical studies and explore and compare the potential role of UVR-induced mediators, including vitamin D and nitric oxide. Overall, emerging findings suggest a protective role for UVR and sun exposure in reducing the development of obesity and cardiometabolic dysfunction, but more epidemiological and clinical research is required that focuses on measuring the direct associations and effects of exposure to UVR in humans.

Assessing human health risks from pesticide use in conventional and innovative cropping systems with the BROWSE model.

PubMed

Lammoglia, Sabine-Karen; Kennedy, Marc C; Barriuso, Enrique; Alletto, Lionel; Justes, Eric; Munier-Jolain, Nicolas; Mamy, Laure

2017-08-01

Reducing the risks and impacts of pesticide use on human health and on the environment is one of the objectives of the European Commission Directive 2009/128/EC in the quest for a sustainable use of pesticides. This Directive, developed through European national plans such as Ecophyto plan in France, promotes the introduction of innovative cropping systems relying, for example, on integrated pest management. Risk assessment for human health of the overall pesticide use in these innovative systems is required before the introduction of those systems to avoid that an innovation becomes a new problem. The objectives of this work were to assess and to compare (1) the human exposure to pesticides used in conventional and innovative cropping systems designed to reduce pesticide needs, and (2) the corresponding risks for human health. Humans (operator and residents) exposure to pesticides and risks for human health were assessed for each pesticide with the BROWSE model. Then, a method was proposed to represent the overall risk due to all pesticides used in one system. This study considers 3 conventional and 9 associated innovative cropping systems, and 116 plant protection products containing 89 different active substances (i.e. pesticides). The modelling results obtained with BROWSE showed that innovative cropping systems such as low input or no herbicide systems would reduce the risk for human health in comparison to the corresponding conventional cropping systems. On the contrary, BROWSE showed that conservation tillage system would lead to unacceptable risks in the conditions of our study, because of a high number of pesticide applications, and especially of some herbicides. For residents, the dermal absorption was the main exposure route while ingestion was found to be negligible. For operators, inhalation was also a predominant route of exposure. In general, human exposure to pesticides and human health risks were found to be correlated to the treatment frequency index TFI (number of registered doses of pesticides used per hectare for one copping season), confirming the relationship between the reduction of pesticide use and the reduction of risks. Assessment with the BROWSE model helped to identify cropping systems with decreased risks from pesticides for human health and to propose some improvements to the cropping systems by identifying the pesticides that led to unacceptable risks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cadmium: Simulation of environmental control strategies to reduce exposure

NASA Astrophysics Data System (ADS)

Yost, K. J.; Miles, L. J.; Greenkorn, R. A.

1981-07-01

The effects of selected environmental control strategies on human dietary and respiratory exposure to environmental cadmium (Cd) have been simulated. For each control strategy, mean Cd dietary and respiratory exposures are presented for a twenty-year simulation period. Human exposures related to cadmium are associated with both process waste disposal and product disposal. Dietary exposure is by far the dominant mechanism for Cd intake. Dietary exposure related to aqueous discharges is primarily a result of municipal sludge landspreading, whereas that associated with emissions to the atmosphere derives mainly from the deposition on cropland of airborne particulates from product incineration. Only relatively small dietary exposure reductions are possible through restrictions on any single Cd use. Combinations of waste management and environmental control measures promise greater reductions in dietary and respiratory exposure than those achievable through use restrictions.

Use of a human skin in vitro model to investigate the influence of 'every-day' clothing and skin surface decontamination on the percutaneous penetration of organophosphates.

PubMed

Moore, C A; Wilkinson, S C; Blain, P G; Dunn, M; Aust, G A; Williams, F M

2014-08-17

Organophosphates (OPs) are widely used in agriculture. Many studies have investigated the capability of personal protective equipment (PPE) to reduce chemical exposure; however, investigations into the protective effect of 'every-day' clothing are rare. The purpose of this study was to investigate the protective effect of 'every-day' clothing against dermal exposure and to measure early decontamination of skin following exposure to chlorpyrifos and dichlorvos. Using human skin in vitro, absorption of (14)C-labelled chlorpyrifos (500 ng/cm(2)), was shown to be significantly reduced when applied to clothed skin (cotton shirt), regardless of application vehicle (isopropanol (IPA) or propylene glycol (PG)). The majority of applied dose was retained within the clothing after 4 h exposure. Significant reduction in absorption of chlorpyrifos (in PG) was seen through clothed skin when supplemented with skin decontamination at 4 h, compared with clothed skin decontaminated after 24 h, however, this was not observed with IPA. Absorption of dichlorvos (5 μg/cm(2)) was greater through unclothed skin than chlorpyrifos for all vehicles (IPA, isopropyl myristate (IPM) and PG). Significant reduction in absorption was observed when decontaminating clothed skin at 30 min, compared with decontamination at 24 h (post-exposure) for all vehicles. indicate that 'every-day' clothing is effective at reducing exposure to chemicals in contact with skin. Washing the skin surface immediately following removal of exposed clothing can further reduce exposure, depending on the properties of the chemical and vehicle applied. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Heat, Human Performance, and Occupational Health: A Key Issue for the Assessment of Global Climate Change Impacts.

PubMed

Kjellstrom, Tord; Briggs, David; Freyberg, Chris; Lemke, Bruno; Otto, Matthias; Hyatt, Olivia

2016-01-01

Ambient heat exposure is a well-known health hazard, which reduces human performance and work capacity at heat levels already common in tropical and subtropical areas. Various health problems have been reported. Increasing heat exposure during the hottest seasons of each year is a key feature of global climate change. Heat exhaustion and reduced human performance are often overlooked in climate change health impact analysis. Later this century, many among the four billion people who live in hot areas worldwide will experience significantly reduced work capacity owing to climate change. In some areas, 30-40% of annual daylight hours will become too hot for work to be carried out. The social and economic impacts will be considerable, with global gross domestic product (GDP) losses greater than 20% by 2100. The analysis to date is piecemeal. More analysis of climate change-related occupational health impact assessments is greatly needed.

A Preliminary Assessment of the Benefits of Reducing Formaldehyde Exposures (1984)

EPA Pesticide Factsheets

The report reviews a variety of regulatory responses that EPA might consider in developing regulatory strategies for controlling human exposures under the Toxic Substance Control Act and previewed issues that may arise in a regulatory impact analysis.

Toxicity of cadmium and its health risks from leafy vegetable consumption.

PubMed

Huang, Yingying; He, Chuntao; Shen, Chuang; Guo, Jingjie; Mubeen, Samavia; Yuan, Jiangang; Yang, Zhongyi

2017-04-19

Cadmium (Cd) is a highly toxic heavy metal and has spread widely in the environment in recent decades. This review summarizes current knowledge about Cd contamination of leafy vegetables, its toxicity, exposure, health risks, and approaches to reducing its toxicity in humans. Leafy vegetable consumption has been identified as a dominant exposure pathway of Cd in the human body. An overview of Cd pollution in leafy vegetables as well as the main sources of Cd is given. Notable estimated daily intakes and health risks of Cd exposure through vegetable consumption for humans are revealed in occupational exposure areas and even in some reference areas. Vegetable consumption is one of the most significant sources of exposure to Cd, particularly in occupational exposure regions. Therefore, numerous approaches have been developed to minimize the accumulation of Cd in leafy vegetables, among which the breeding of Cd pollution-safe cultivars is one of the most effective tools. Furthermore, dietary supplements from leafy vegetables perform positive roles in alleviating Cd toxicity in humans with regard to the effects of essential mineral elements, vitamins and phytochemicals taken into the human body via leafy vegetable consumption.

Inhibition of fried meat-induced rectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt

EPA Science Inventory

Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 sub...

Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers

PubMed Central

2014-01-01

Background Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects. Methods Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells. Results The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells. Conclusions A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions. PMID:24621126

Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

PubMed Central

Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

2012-01-01

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pocar, Paola, E-mail: paola.pocar@unimi.it; Fianda

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring.more » In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP reduced oocyte and blastocyst developmental competence up to F3. • DEHP altered expression levels for key genes in ovary and blastocysts up to F4. • DEHP's adverse effects were observed at doses relevant for human exposure.« less

Fetal Liver Bisphenol A Concentrations and Biotransformation Gene Expression Reveal Variable Exposure and Altered Capacity for Metabolism in Humans

PubMed Central

Nahar, Muna S.; Liao, Chunyang; Kannan, Kurunthachalam; Dolinoy, Dana C.

2013-01-01

Widespread exposure to the endocrine active compound, bisphenol A (BPA), is well documented in humans. A growing body of literature suggests adverse health outcomes associated with varying ranges of exposure to BPA. In the current study, we measured the internal dose of free BPA and conjugated BPA and evaluated gene expression of bio-transformation enzymes specific for BPA metabolism in 50 first- and second-trimester human fetal liver samples. Both free BPA and conjugated BPA concentrations varied widely, with free BPA exhibiting three times higher concentrations than conjugated BPA concentrations. As compared to gender-matched adult liver controls, UDP-glucuronyltransferase, sulfotransferase, and steroid sulfatase genes exhibited reduced expression whereas β-glucuronidase mRNA expression remained unchanged in the fetal tissues. This study provides evidence that there is considerable exposure to BPA during human pregnancy and that the capacity for BPA metabolism is altered in the human fetal liver. PMID:23208979

ANALYTICAL METHODS FOR ASSESSING THE MAGNITUDE OF HUMAN INGESTION OF RECREATIONAL WATER DURING SWIMMING ACTIVITY

EPA Science Inventory

The EPA's Beaches Environmental Assessment, Closure, and Health (BEACH) Program is a multi-year, multifaceted strategy for reducing human exposure to certain risks from infectious pathogenic organisms associated with human behavior, and activities related to hygienic practices, o...

A Review of the Diagnosis and Treatment of Ochratoxin A Inhalational Exposure Associated with Human Illness and Kidney Disease including Focal Segmental Glomerulosclerosis

PubMed Central

Hope, Janette H.; Hope, Bradley E.

2012-01-01

Ochratoxin A (OTA) exposure via ingestion and inhalation has been described in the literature to cause kidney disease in both animals and humans. This paper reviews Ochratoxin A and its relationship to human health and kidney disease with a focus on a possible association with focal segmental glomerulosclerosis (FSGS) in humans. Prevention and treatment strategies for OTA-induced illness are also discussed, including cholestyramine, a bile-acid-binding resin used as a sequestrant to reduce the enterohepatic recirculation of OTA. PMID:22253638

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes

PubMed Central

Smith, Laura E.; Prendergast, Andrew J.; Turner, Paul C.; Humphrey, Jean H.; Stoltzfus, Rebecca J.

2017-01-01

Pregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight. PMID:28500823

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes.

PubMed

Smith, Laura E; Prendergast, Andrew J; Turner, Paul C; Humphrey, Jean H; Stoltzfus, Rebecca J

2017-04-01

AbstractPregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight.

Spectral properties of plant leaves pertaining to urban landscape design of broad-spectrum solar ultraviolet radiation reduction

NASA Astrophysics Data System (ADS)

Yoshimura, Haruka; Zhu, Hui; Wu, Yunying; Ma, Ruijun

2010-03-01

Human exposure to harmful ultraviolet (UV) radiation has important public health implications. Actual human exposure to solar UV radiation depends on ambient UV irradiance, and the latter is influenced by ground reflection. In urban areas with higher reflectivity, UV exposure occurs routinely. To discover the solar UV radiation regulation mechanism of vegetation, the spectral reflectance and transmittance of plant leaves were measured with a spectrophotometer. Typically, higher plants have low leaf reflectance (around 5%) and essentially zero transmittance throughout the UV region regardless of plant species and seasonal change. Accordingly, incident UV radiation decreases to 5% by being reflected and is reduced to zero by passing through a leaf. Therefore, stratified structures of vegetation are working as another terminator of UV rays, protecting whole terrestrial ecosystems, while vegetation at waterfronts contributes to protect aquatic ecosystems. It is possible to protect the human population from harmful UV radiation by urban landscape design of tree shade and the botanical environment. Even thin but uniformly distributed canopy is effective in attenuating UV radiation. To intercept diffuse radiation, UV screening by vertical structures such as hedges should be considered. Reflectivity of vegetation is around 2%, as foliage surfaces reduce incident UV radiation via reflection, while also eliminating it by transmittance. Accordingly, vegetation reduces incident UV radiation to around 2% by reflection. Vegetation influence on ambient UV radiation is broad-spectrum throughout the UV region. Only trees provide cool UV protective shade. Urban landscapes aimed at abating urban heat islands integrated with a reduction of human UV over-exposure would contribute to mitigation of climate change.

Birth weight, head circumference, and prenatal exposure to acrylamide from maternal diet: the European prospective mother-child study (NewGeneris).

PubMed

Pedersen, Marie; von Stedingk, Hans; Botsivali, Maria; Agramunt, Silvia; Alexander, Jan; Brunborg, Gunnar; Chatzi, Leda; Fleming, Sarah; Fthenou, Eleni; Granum, Berit; Gutzkow, Kristine B; Hardie, Laura J; Knudsen, Lisbeth E; Kyrtopoulos, Soterios A; Mendez, Michelle A; Merlo, Domenico F; Nielsen, Jeanette K; Rydberg, Per; Segerbäck, Dan; Sunyer, Jordi; Wright, John; Törnqvist, Margareta; Kleinjans, Jos C; Kogevinas, Manolis

2012-12-01

Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother-child study. Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006-2010. Maternal diet was estimated through food-frequency questionnaires. Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was -132 g (95% CI: -207, -56); the corresponding difference for head circumference was -0.33 cm (95% CI: -0.61, -0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.

Relative bioavailability of arsenic contaminated soils in a mouse model

EPA Science Inventory

Exposure to As contaminated soils compels extensive soil cleanups so that human health risks are minimized. In order to improve exposure estimates and potentially reduce remediation costs, determination of the bioavailability of As in soils is needed. The objective of this study ...

Roadside vegetation barrier designs to mitigate near-road air pollution impacts

EPA Science Inventory

With increasing evidence that exposures to air pollution near large roadways increases risks of a number of adverse human health effects, identifying methods to reduce these exposures has become a public health priority. Roadside vegetation barriers have shown the potential to re...

Radiation Shielding Optimization on Mars

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Mertens, Chris J.; Blattnig, Steve R.

2013-01-01

Future space missions to Mars will require radiation shielding to be optimized for deep space transit and an extended stay on the surface. In deep space, increased shielding levels and material optimization will reduce the exposure from most solar particle events (SPE) but are less effective at shielding against galactic cosmic rays (GCR). On the surface, the shielding provided by the Martian atmosphere greatly reduces the exposure from most SPE, and long-term GCR exposure is a primary concern. Previous work has shown that in deep space, additional shielding of common materials such as aluminum or polyethylene does not significantly reduce the GCR exposure. In this work, it is shown that on the Martian surface, almost any amount of aluminum shielding increases exposure levels for humans. The increased exposure levels are attributed to neutron production in the shield and Martian regolith as well as the electromagnetic cascade induced in the Martian atmosphere. This result is significant for optimization of vehicle and shield designs intended for the surface of Mars.

Human whole body cold adaptation.

PubMed

Daanen, Hein A M; Van Marken Lichtenbelt, Wouter D

2016-01-01

Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced vasodilation in fingers and toes compared to Caucasians and Inuit. About 40,000 y after humans left Africa, natives in cold terrestrial areas seems to have developed not only behavioral adaptations, but also physiological adaptations to cold. Dedicated studies show that repeated whole body exposure of individual volunteers, mainly Caucasians, to severe cold results in reduced cold sensation but no major physiological changes. Repeated cold water immersion seems to slightly reduce metabolic heat production, while repeated exposure to milder cold conditions shows some increase in metabolic heat production, in particular non-shivering thermogenesis. In conclusion, human cold adaptation in the form of increased metabolism and insulation seems to have occurred during recent evolution in populations, but cannot be developed during a lifetime in cold conditions as encountered in temperate and arctic regions. Therefore, we mainly depend on our behavioral skills to live in and survive the cold.

Human whole body cold adaptation

PubMed Central

Daanen, Hein A.M.; Van Marken Lichtenbelt, Wouter D.

2016-01-01

ABSTRACT Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced vasodilation in fingers and toes compared to Caucasians and Inuit. About 40,000 y after humans left Africa, natives in cold terrestrial areas seems to have developed not only behavioral adaptations, but also physiological adaptations to cold. Dedicated studies show that repeated whole body exposure of individual volunteers, mainly Caucasians, to severe cold results in reduced cold sensation but no major physiological changes. Repeated cold water immersion seems to slightly reduce metabolic heat production, while repeated exposure to milder cold conditions shows some increase in metabolic heat production, in particular non-shivering thermogenesis. In conclusion, human cold adaptation in the form of increased metabolism and insulation seems to have occurred during recent evolution in populations, but cannot be developed during a lifetime in cold conditions as encountered in temperate and arctic regions. Therefore, we mainly depend on our behavioral skills to live in and survive the cold. PMID:27227100

PERFLUORINATED COMPOUNDS: EMERGING POPs WITH POTENTIAL IMMUNOTOXICITY

PubMed Central

Corsini, Emanuela; Luebke, Robert W.; Germolec, Dori R.; DeWitt, Jamie C.

2015-01-01

Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, and surfactants. They possess a strong carbon-fluorine bond, which leads to their environmental persistence. There is evidence from both epidemiology and laboratory studies that PFCs may be immunotoxic, affecting both cell-mediated and humoral immunity. Reported effects of PFCs include decreased spleen and thymus weights and cellularity, reduced antibody production, reduced survival after influenza infection, and altered cytokine production. Immunosuppression is a critical effect associated with exposure to PFCs, as it has been reported to reduce antibody responses to vaccination in children. Mounting evidence suggests that immunotoxicity in experimental animals can occur at serum concentrations below, within, or just above the reported range for highly exposed humans and wildlife. Considering bioaccumulation and exposure to multiple PFCs, the risk of immunotoxicity for humans and wildlife cannot be discounted. This review will discuss current and recently published work exploring the immunomodulatory effects of PFCs in experimental animals and humans. PMID:24503008

Applications of nanoporous cyclodextrin polymers to prevent exposure to mycotoxins

USDA-ARS?s Scientific Manuscript database

As a continued effort to maintain a safe food supply, new strategies and technologies are developed in order to reduce human and animal exposure to contaminants. Agricultural commodities are occasionally contaminated by certain species of fungi that produce mycotoxins at levels that are health risks...

The role of the location of personal exposimeters on the human body in their use for assessing exposure to the electromagnetic field in the radiofrequency range 98-2450 MHz and compliance analysis: evaluation by virtual measurements.

PubMed

Gryz, Krzysztof; Zradziński, Patryk; Karpowicz, Jolanta

2015-01-01

The use of radiofrequency (98-2450 MHz range) personal exposimeters to measure the electric field (E-field) in far-field exposure conditions was modelled numerically using human body model Gustav and finite integration technique software. Calculations with 256 models of exposure scenarios show that the human body has a significant influence on the results of measurements using a single body-worn exposimeter in various locations near the body ((from -96 to +133)%, measurement errors with respect to the unperturbed E-field value). When an exposure assessment involves the exposure limitations provided for the strength of an unperturbed E-field. To improve the application of exposimeters in compliance tests, such discrepancies in the results of measurements by a body-worn exposimeter may be compensated by using of a correction factor applied to the measurement results or alternatively to the exposure limit values. The location of a single exposimeter on the waist to the back side of the human body or on the front of the chest reduces the range of exposure assessments uncertainty (covering various exposure conditions). However, still the uncertainty of exposure assessments using a single exposimeter remains significantly higher than the assessment of the unperturbed E-field using spot measurements.

The Role of the Location of Personal Exposimeters on the Human Body in Their Use for Assessing Exposure to the Electromagnetic Field in the Radiofrequency Range 98–2450 MHz and Compliance Analysis: Evaluation by Virtual Measurements

PubMed Central

Zradziński, Patryk

2015-01-01

The use of radiofrequency (98–2450 MHz range) personal exposimeters to measure the electric field (E-field) in far-field exposure conditions was modelled numerically using human body model Gustav and finite integration technique software. Calculations with 256 models of exposure scenarios show that the human body has a significant influence on the results of measurements using a single body-worn exposimeter in various locations near the body ((from −96 to +133)%, measurement errors with respect to the unperturbed E-field value). When an exposure assessment involves the exposure limitations provided for the strength of an unperturbed E-field. To improve the application of exposimeters in compliance tests, such discrepancies in the results of measurements by a body-worn exposimeter may be compensated by using of a correction factor applied to the measurement results or alternatively to the exposure limit values. The location of a single exposimeter on the waist to the back side of the human body or on the front of the chest reduces the range of exposure assessments uncertainty (covering various exposure conditions). However, still the uncertainty of exposure assessments using a single exposimeter remains significantly higher than the assessment of the unperturbed E-field using spot measurements. PMID:25879021

Nuclear Fragmentation Processes Relevant for Human Space Radiation Protection

NASA Technical Reports Server (NTRS)

Lin, Zi-Wei

2007-01-01

Space radiation from cosmic ray particles is one of the main challenges for human space explorations such-as a moon base or a trip to Mars. Models have been developed in order to predict the radiation exposure to astronauts and to evaluate the effectiveness of different shielding materials, and a key ingredient in these models is the physics of nuclear fragmentations. We have developed a semi-analytical method to determine which partial cross sections of nuclear fragmentations most affect the radiation dose behind shielding materials due to exposure to galactic cosmic rays. The cross sections thus determined will require more theoretical and/or experimental studies in order for us to better predict, reduce and mitigate the radiation exposure in human space explorations.

Zoonoses of rabbits and rodents.

PubMed

Hill, William Allen; Brown, Julie Paige

2011-09-01

Millions of households in the US own rabbits or rodents, including hamsters, guinea pigs, and gerbils. Activities such as hunting and camping also involve human interactions with wild rabbits and rodents. In many environments, feral rabbits and rodents live in close proximity to humans, domesticated animals, and other wildlife. Education of rodent and rabbit owners and individuals with occupational or recreational exposures to these species is paramount to reduce the prevalence of zoonoses associated with rabbit and rodent exposure.

DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker.

PubMed

Daudee, Rotem; Gonen, Rafi; German, Uzi; Orion, Itzhak; Alfassi, Zeev B; Priel, Esther

2018-06-01

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60 Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.

Heat-mediated reduction of apoptosis in UVB-damaged keratinocytes in vitro and in human skin ex vivo.

PubMed

Calapre, Leslie; Gray, Elin S; Kurdykowski, Sandrine; David, Anthony; Hart, Prue; Descargues, Pascal; Ziman, Mel

2016-05-26

UV radiation induces significant DNA damage in keratinocytes and is a known risk factor for skin carcinogenesis. However, it has been reported previously that repeated and simultaneous exposure to UV and heat stress increases the rate of cutaneous tumour formation in mice. Since constant exposure to high temperatures and UV are often experienced in the environment, the effects of exposure to UV and heat needs to be clearly addressed in human epidermal cells. In this study, we determined the effects of repeated UVB exposure 1 kJ/m(2) followed by heat (39 °C) to human keratinocytes. Normal human ex vivo skin models and primary keratinocytes (NHEK) were exposed once a day to UVB and/or heat stress for four consecutive days. Cells were then assessed for changes in proliferation, apoptosis and gene expression at 2 days post-exposure, to determine the cumulative and persistent effects of UV and/or heat in skin keratinocytes. Using ex vivo skin models and primary keratinocytes in vitro, we showed that UVB plus heat treated keratinocytes exhibit persistent DNA damage, as observed with UVB alone. However, we found that apoptosis was significantly reduced in UVB plus heat treated samples. Immunohistochemical and whole genome transcription analysis showed that multiple UVB plus heat exposures induced inactivation of the p53-mediated stress response. Furthermore, we demonstrated that repeated exposure to UV plus heat induced SIRT1 expression and a decrease in acetylated p53 in keratinocytes, which is consistent with the significant downregulation of p53-regulated pro-apoptotic and DNA damage repair genes in these cells. Our results suggest that UVB-induced p53-mediated cell cycle arrest and apoptosis are reduced in the presence of heat stress, leading to increased survival of DNA damaged cells. Thus, exposure to UVB and heat stress may act synergistically to allow survival of damaged cells, which could have implications for initiation skin carcinogenesis.

Killing of Campylobacter on contaminated plastic and wooden cutting boards by glycerol monocaprate (monocaprin).

PubMed

Thormar, H; Hilmarsson, H

2010-09-01

Contamination in the kitchen with foodborne bacteria is a risk factor in human exposure to these pathogens, an important route being transfer of bacteria from contaminated cutting boards and other surfaces to humans. The aim of this study was to test microbicidal emulsions of glycerol monocaprate (monocaprin) against Campylobacter on contaminated cutting boards. Plastic and wooden cutting boards, soiled with meat juice heavily contaminated with Campylobacter, were treated for 2 min with emulsions of monocaprin (MC) made in water or in buffer at low pH. Viable Campylobacter counts were reduced below the detectable level on plastic board surfaces after treatment with MC emulsions with or without 1.25% washing-up liquids (WUL). The counts were also greatly reduced on wooden boards (P < 0.05). Monocaprin emulsions and mixtures of MC emulsions and WUL may be useful as sanitizers/disinfectants in kitchens and in other food preparing and processing facilities. Cleaning with MC emulsions with or without WUL may reduce the risk of human exposure to Campylobacter.

Report: Progress Made, but Improvements Needed at CTS of Asheville Superfund Site in North Carolina to Advance Cleanup Pace and Reduce Potential Exposure

EPA Pesticide Factsheets

Report #16-P-0296, August 31, 2016. EPA Region 4 can accelerate the cleanup and completeness of work, and improve public communications, to better control human exposure to unsafe industrial contamination at the CTS site.

BIOSENSORS RESEARCH FOR DEVELOPMENT OF INNOVATIVE MONITORING TECHNIQUES THAT SUPPORT EXPOSURE ASSESSMENT RELATED TO THE SUPERFUND PROGRAM

EPA Science Inventory

One of the approaches for reducing uncertainties in the assessment of human exposure is to better characterize the hazardous wastes that contaminate our environment. A significant limitation to this approach, however, is that sampling and laboratory analysis of contaminated envi...

Accountability: Evaluating the Impact of Regulatory Policies on Air Quality, Human Health, and the Environment

EPA Science Inventory

This presentation discusses "accountability"; e.g., do emission-control regulations really reduce exposure to pollutants and improve human health? In this presentation, we provide examples of how to examine this and related questions.

Arsenic accumulation in rice: Consequences of rice genotypes and management practices to reduce human health risk.

PubMed

Islam, Shofiqul; Rahman, Mohammad Mahmudur; Islam, M R; Naidu, Ravi

2016-11-01

Rice is an essential staple food and feeds over half of the world's population. Consumption of rice has increased from limited intake in Western countries some 50years ago to major dietary intake now. Rice consumption represents a major route for inorganic arsenic (As) exposure in many countries, especially for people with a large proportion of rice in their daily diet as much as 60%. Rice plants are more efficient in assimilating As into its grains than other cereal crops and the accumulation may also adversely affect the quality of rice and their nutrition. Rice is generally grown as a lowland crop in flooded soils under reducing conditions. Under these conditions the bioavailability of As is greatly enhanced leading to excessive As bioaccumulation compared to that under oxidizing upland conditions. Inorganic As species are carcinogenic to humans and even at low levels in the diet pose a considerable risk to humans. There is a substantial genetic variation among the rice genotypes in grain-As accumulation as well as speciation. Identifying the extent of genetic variation in grain-As concentration and speciation of As compounds are crucial to determining the rice varieties which accumulate low inorganic As. Varietal selection, irrigation water management, use of fertilizer and soil amendments, cooking practices etc. play a vital role in reducing As exposure from rice grains. In the meantime assessing the bioavailability of As from rice is crucial to understanding human health exposure and reducing the risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

PubMed

Calderon-Gierszal, Esther L; Prins, Gail S

2015-01-01

Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA) can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC) into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother–Child Study (NewGeneris)

PubMed Central

Pedersen, Marie; von Stedingk, Hans; Botsivali, Maria; Agramunt, Silvia; Alexander, Jan; Brunborg, Gunnar; Chatzi, Leda; Fleming, Sarah; Fthenou, Eleni; Granum, Berit; Gutzkow, Kristine B.; Hardie, Laura J.; Knudsen, Lisbeth E.; Kyrtopoulos, Soterios A.; Mendez, Michelle A.; Merlo, Domenico F.; Nielsen, Jeanette K.; Rydberg, Per; Segerbäck, Dan; Sunyer, Jordi; Wright, John; Törnqvist, Margareta; Kleinjans, Jos C.

2012-01-01

Background: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. Objectives: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother–child study. Methods: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006–2010. Maternal diet was estimated through food-frequency questionnaires. Results: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was –132 g (95% CI: –207, –56); the corresponding difference for head circumference was –0.33 cm (95% CI: –0.61, –0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. Conclusions: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women. PMID:23092936

RNA interference in a maize pathogen reduces toxin production

USDA-ARS?s Scientific Manuscript database

The fungus Fusarium verticillioides can produce fumonisin mycotoxins in ears under certain environmental conditions. Because fumonisins are unhealthy for humans and livestock, control strategies with nominal risk to the environment are needed to reduce fumonisin exposure. Host-induced gene silencing...

Biological monitoring to determine worker dose in a butadiene processing plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bechtold, W.E.; Hayes, R.B.

1995-12-01

Butadiene (BD) is a reactive gas used extensively in the rubber industry and is also found in combustion products. Although BD is genotoxic and acts as an animal carcinogen, the evidence for carcinogenicity in humans is limited. Extrapolation from animal studies on BD carcinogenicity to risk in humans has been controversial because of uncertainties regarding relative biologic exposure and related effects in humans vs. experimental animals. To reduce this uncertainty, a study was designed to characterize exposure to BD at a polymer production facility and to relate this exposure to mutational and cytogenetic effects. Biological monitoring was used to bettermore » assess the internal dose of BD received by the workers. Measurement of 1,2-dihydroxy-4-(N-acetylcysteinyl) butane (M1) in urine served as the biomarker in this study. M1 has been shown to correlate with area monitoring in previous studies. Most studies that relate exposure to a toxic chemical with its biological effects rely on exposure concentration as the dose metric; however, exposure concentration may or may not reflect the actual internal dose of the chemical.« less

Mastication as a Stress-Coping Behavior

PubMed Central

Iinuma, Mitsuo

2015-01-01

Exposure to chronic stress induces various physical and mental effects that may ultimately lead to disease. Stress-related disease has become a global health problem. Mastication (chewing) is an effective behavior for coping with stress, likely due to the alterations chewing causes in the activity of the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Mastication under stressful conditions attenuates stress-induced increases in plasma corticosterone and catecholamines, as well as the expression of stress-related substances, such as neurotrophic factors and nitric oxide. Further, chewing reduces stress-induced changes in central nervous system morphology, especially in the hippocampus and hypothalamus. In rodents, chewing or biting on wooden sticks during exposure to various stressors reduces stress-induced gastric ulcer formation and attenuates spatial cognitive dysfunction, anxiety-like behavior, and bone loss. In humans, some studies demonstrate that chewing gum during exposure to stress decreases plasma and salivary cortisol levels and reduces mental stress, although other studies report no such effect. Here, we discuss the neuronal mechanisms that underline the interactions between masticatory function and stress-coping behaviors in animals and humans. PMID:26090453

Current status of Mycobacterium avium subspecies paratuberculosis infection in animals & humans in India: What needs to be done?

PubMed

Singh, Ajay Vir; Chauhan, Devendra Singh; Singh, Shoor Vir; Kumar, Vijay; Singh, Abhinendra; Yadav, Anjali; Yadav, Virendra Singh

2016-11-01

Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as a major health problem for domestic livestock and human beings. Reduced per animal productivity of domestic livestock seriously impacts the economics of dairy farming globally. High to very high bioload of MAP in domestic livestock and also in the human population has been reported from north India. Presence of live MAP bacilli in commercial supplies of raw and pasteurized milk and milk products indicates its public health significance. MAP is not inactivated during pasteurization, therefore, entering into human food chain daily. Recovery of MAP from patients with inflammatory bowel disease or Crohn's disease and animal healthcare workers suffering with chronic gastrointestinal problems indicate a close association of MAP with a number of chronic and other diseases affecting human health. Higher bioload of MAP in the animals increases the risk of exposure to the human population with MAP. This review summarizes the current status of MAP infection in animals as well as in human beings and also highlights the prospects of effective management and control of disease in animals to reduce the risk of exposure to human population.

Reducing Blood-borne Exposure in Interventional Radiology: What the IR Should Know

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tso, David K.; Athreya, Sriharsha, E-mail: sathreya@stjoes.ca

2013-08-01

Interventional radiologists are at risk of exposure to blood-borne pathogens in their day-to-day practice. Percutaneous exposure from unsafe sharps handling, mucocutaneous exposure from body fluid splashes, and glove perforation from excessive wear can expose the radiologist to potentially infectious material. The increasing prevalence of blood-borne pathogens, including hepatitis B and C, and human immunodeficiency virus, puts nurses, residents, fellows, and interventional radiologists at risk for occupational exposure. This review outlines suggestions to establish a culture of safety in the interventional suite.

Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.

PubMed

Kee, Kehkooi; Flores, Martha; Cedars, Marcelle I; Reijo Pera, Renee A

2010-09-01

Historically, effects of environmental toxicants on human development have been deduced via epidemiological studies because direct experimental analysis has not been possible. However, in recent years, the derivation of human pluripotent stem cells has provided a potential experimental system to directly probe human development. Here, we used human embryonic stem cells (hESCs) to study the effect of environmental toxicants on human germ cell development, with a focus on differentiation of the founding population of primordial germ cells (PGCs), which will go on to form the oocytes of the adult. We demonstrate that human PGC numbers are specifically reduced by exposure to polycyclic aromatic hydrocarbons (PAHs), a group of toxicants common in air pollutants released from gasoline combustion or tobacco smoke. Further, we demonstrate that the adverse effects of PAH exposure are mediated through the aromatic hydrocarbon receptor (AHR) and BAX pathway. This study demonstrates the utility of hESCs as a model system for direct examination of the molecular and genetic pathways of environmental toxicants on human germ cell development.

Human exposures to immobilising agents: results of an online survey.

PubMed

Haymerle, A; Fahlman, A; Walzer, C

2010-08-28

Cases of human exposure to veterinary injectable anaesthetics were reviewed following a literature search and completion of an online questionnaire in an attempt to provide an objective approach to the problem. The modified Glasgow Coma Scale was used to rank cases according to their severity. From the cases examined, results showed that intoxication with potent opioids, such as etorphine, carfentanil and thiafentanil, need to be treated with antagonists such as naloxone, nalmefene or naltrexone, and not with antagonists with agonistic properties, such as diprenorphine. With regard to the alpha(2)-agonists xylazine, detomidine, medetomidine and romifidine, no antagonist is currently accredited for human use. Atipamezole, a specific alpha(2)-antagonist, is widely used in veterinary medicine and has been used experimentally to reverse dexmetomidine in a study in human medicine. The high concentrations of alpha(2)-agonists being used in zoo and wildlife medicine warrant the accreditation of atipamezole for use in cases of human exposure. Knowledge and availability of the appropriate antagonist are essential in cases of human intoxication with injectable anaesthetics. Preventive measures, such as wearing gloves and eye protection, need to be used more regularly to reduce the risk of exposure.

Comparison of human exposure pathways in an urban brownfield: reduced risk from paving roads.

PubMed

James, Kyle; Farrell, Richard E; Siciliano, Steven D

2012-10-01

Risk assessments often do not quantify the risk associated with soil inhalation. This pathway generally makes a negligible contribution to the cumulative risk, because soil ingestion is typically the dominant exposure pathway. Conditions in northern or rural centers in Canada characterized by large areas of exposed soil, including unpaved roads, favor the resuspension of soil particles, making soil inhalation a relevant risk pathway. The authors determined and compared human exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from soil ingestion and inhalation and analyzed the carcinogenic and noncarcinogenic risks before and after roads were paved in a northern community. To determine the inhalation exposure, three size fractions of airborne particulate matter were collected (total suspended particulates [TSP], particulate matter with an aerodynamic diameter less than 10 µm [PM10], and particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) before and after roads were paved. Road paving reduced the concentration of many airborne contaminants by 25 to 75%, thus reducing risk. For example, before paving, the carcinogenic risk associated with inhalation of Cr was 3.4 excess cancers per 100,000 people exposed, whereas after paving, this risk was reduced to 1.6 in 100,000. Paving roads reduced the concentrations of total suspended particulates (TSP; p < 0.1) and PM10 (p < 0.05) but not PM25. Consequently, the ingestion of inhaled soil particles was substantially reduced. The authors conclude that resuspended soil is likely an important source of risk for many northern communities and that paving roads is an effective method of reducing risk from the inhalation of soil particles. Copyright © 2012 SETAC.

Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

NASA Technical Reports Server (NTRS)

Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

1998-01-01

Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

Increased beta-adrenergic responsiveness induced by 14 days exposure to simulated microgravity

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Polet, J. L.; Engelke, K. A.; Hoffler, G. W.; Lane, L. D.; Blomqvist, C. G.

1995-01-01

Increased sensitivity of end-organ responses to neuroendocrine stimuli as a result of prolonged exposure to the relative inactivity of microgravity has recently been hypothesized. This notion is based on the inverse relationship between circulating norepinephrine and beta-adrenoreceptor sensitivity. The beta-adrenoreceptor activity is reduced in individuals who have elevated plasma norepinephrine as a result of regular exposure to upright posture and physical exercise. In contrast, adrenoreceptor hypersensitivity has been reported in patients with dysautonomias in which circulating catecholamines are absent or reduced. Taken together, these studies and the observation that circulating plasma norepinephrine has been reduced during spaceflight and in groundbased simulations of microgravity prompt the suggestion that adrenoreceptor hypersensitivity may be a consequence of the adaptation to spaceflight. We conducted an experiment designed to measure cardiovascular responses to adrenoreceptor agonists in human subjects before and after prolonged exposure to 6 deg head-down tilt (HDT) to test the hypothesis that adaptation to microgravity increases adrenoreceptor responsiveness, and that this adaptation is associated with reduced levels of circulating norepinephrine.

Ventricular transcriptional data provide mechanistic insights into diesel exhaust induced attenuation of cardiac contractile response and blood pressure

EPA Science Inventory

Human exposures to near road ambient particulate matter and its major component, diesel exhaust (DE), have been associated with cardiovascular impairments however the mechanisms and the role of hypertension are not well understood. We have shown that DE exposure reduces blood pre...

Development of a Sampler for Total Aerosol Deposition in the Human Respiratory Tract

PubMed Central

Koehler, Kirsten A.; Clark, Phillip; Volckens, John

2009-01-01

Studies that seek to associate reduced human health with exposure to occupational and environmental aerosols are often hampered by limitations in the exposure assessment process. One limitation involves the measured exposure metric itself. Current methods for personal exposure assessment are designed to estimate the aspiration of aerosol into the human body. Since a large proportion of inhaled aerosol is subsequently exhaled, a portion of the aspirated aerosol will not contribute to the dose. This leads to variable exposure misclassification (for heterogenous exposures) and increased uncertainty in health effect associations. Alternatively, a metric for respiratory deposition would provide a more physiologically relevant estimate of risk. To address this challenge, we have developed a method to estimate the deposition of aerosol in the human respiratory tract using a sampler engineered from polyurethane foam. Using a semi-empirical model based on inertial, gravitational, and diffusional particle deposition, a foam was engineered to mimic aerosol total deposition in the human respiratory tract. The sampler is comprised of commercially available foam with fiber diameter = 49.5 μm (equivalent to industry standard 100 PPI foam) of 8 cm thickness operating at a face velocity of 1.3 m s−1. Additionally, the foam sampler yields a relatively low-pressure drop, independent of aerosol loading, providing uniform particle collection efficiency over time. PMID:19638392

Quantitative risk assessment of human campylobacteriosis associated with thermophilic Campylobacter species in chickens.

PubMed

Rosenquist, Hanne; Nielsen, Niels L; Sommer, Helle M; Nørrung, Birgit; Christensen, Bjarke B

2003-05-25

A quantitative risk assessment comprising the elements hazard identification, hazard characterization, exposure assessment, and risk characterization has been prepared to assess the effect of different mitigation strategies on the number of human cases in Denmark associated with thermophilic Campylobacter spp. in chickens. To estimate the human exposure to Campylobacter from a chicken meal and the number of human cases associated with this exposure, a mathematical risk model was developed. The model details the spread and transfer of Campylobacter in chickens from slaughter to consumption and the relationship between ingested dose and the probability of developing campylobacteriosis. Human exposure was estimated in two successive mathematical modules. Module 1 addresses changes in prevalence and numbers of Campylobacter on chicken carcasses throughout the processing steps of a slaughterhouse. Module 2 covers the transfer of Campylobacter during food handling in private kitchens. The age and sex of consumers were included in this module to introduce variable hygiene levels during food preparation and variable sizes and compositions of meals. Finally, the outcome of the exposure assessment modules was integrated with a Beta-Poisson dose-response model to provide a risk estimate. Simulations designed to predict the effect of different mitigation strategies showed that the incidence of campylobacteriosis associated with consumption of chicken meals could be reduced 30 times by introducing a 2 log reduction of the number of Campylobacter on the chicken carcasses. To obtain a similar reduction of the incidence, the flock prevalence should be reduced approximately 30 times or the kitchen hygiene improved approximately 30 times. Cross-contamination from positive to negative flocks during slaughter had almost no effect on the human Campylobacter incidence, which indicates that implementation of logistic slaughter will only have a minor influence on the risk. Finally, the simulations showed that people in the age of 18-29 years had the highest risk of developing campylobacteriosis.

Thermoelectric technique to precisely control hyperthermic exposures of human whole blood.

PubMed

DuBose, D A; Langevin, R C; Morehouse, D H

1996-12-01

The need in military research to avoid exposing humans to harsh environments and reduce animal use requires the development of in vitro models for the study of hyperthermic injury. A thermoelectric module (TEM) system was employed to heat human whole blood (HWB) in a manner similar to that experienced by heat-stroked rats. This system precisely and accurately replicated mild, moderate, and extreme heat-stress exposures. Temperature changes could be monitored without the introduction of a test sample thermistor, which reduced contamination problems. HWB with hematocrits of 45 or 50% had similar heating curves, indicating that the system compensated for differences in sample character. The unit's size permitted its containment within a standard carbon dioxide incubator to further control sample environment. These results indicate that the TEM system can precisely control temperature change in this heat stress in vitro model employing HWB. Information obtained from such a model could contribute to military preparedness.

Multimedia models of human exposure to industrial emissions through food products: Identifying the critical pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKone, T.E.; Maddalena, R.L.; Dowdy, D.L.

1995-12-31

The magnitude of potential human exposure through foods can be and has been assessed through food-product samples. Reducing these exposures requires that measuring not only the exposure media (food) concentrations but also defining the processes that link various contaminant sources to food. The authors present here a general approach for quantifying human exposure to contaminants in home-grown foods using four factors-ambient environmental concentrations in air and soil; bioconcentration factors between air, soil, leaves, and roots; translocations from leaves and roots to edible-plant parts; and human activity patterns associated with consumption of home-grown food products. The authors combined these factors inmore » a general model and used sensitivity analyses to assess the important contributions to the imprecision of exposure estimates. Despite large uncertainties about human activities, they found the major source of uncertainty (variance) in exposure estimates is attributable to imprecision in quantifying bioconcentration. This is especially evident for persistent and fat-soluble compounds--such as PCBs, PAHs, dioxins, and furans. The evaluation of analytical and theoretical methods used to characterize bioconcentration factors reveals that molecular connectivity indices (MCIs) based on molecular structure are better predictors of bioconcentration in plants than are the solubility factors currently in use. The authors describe ongoing laboratory experiments in exposure chambers with garden foods such as leafy vegetables and root crops. They then assess the ability of these methods to better define chemical mass transfers among the components of the home-garden system-air, soil-organic phases, soil solution, plant roots, and plant leaves.« less

Biological and statistical approaches to predicting human lung cancer risk from silica.

PubMed

Kuempel, E D; Tran, C L; Bailer, A J; Porter, D W; Hubbs, A F; Castranova, V

2001-01-01

Chronic inflammation is a key step in the pathogenesis of particle-elicited fibrosis and lung cancer in rats, and possibly in humans. In this study, we compute the excess risk estimates for lung cancer in humans with occupational exposure to crystalline silica, using both rat and human data, and using both a threshold approach and linear models. From a toxicokinetic/dynamic model fit to lung burden and pulmonary response data from a subchronic inhalation study in rats, we estimated the minimum critical quartz lung burden (Mcrit) associated with reduced pulmonary clearance and increased neutrophilic inflammation. A chronic study in rats was also used to predict the human excess risk of lung cancer at various quartz burdens, including mean Mcrit (0.39 mg/g lung). We used a human kinetic lung model to link the equivalent lung burdens to external exposures in humans. We then computed the excess risk of lung cancer at these external exposures, using data of workers exposed to respirable crystalline silica and using Poisson regression and lifetable analyses. Finally, we compared the lung cancer excess risks estimated from male rat and human data. We found that the rat-based linear model estimates were approximately three times higher than those based on human data (e.g., 2.8% in rats vs. 0.9-1% in humans, at mean Mcrit lung burden or associated mean working lifetime exposure of 0.036 mg/m3). Accounting for variability and uncertainty resulted in 100-1000 times lower estimates of human critical lung burden and airborne exposure. This study illustrates that assumptions about the relevant biological mechanism, animal model, and statistical approach can all influence the magnitude of lung cancer risk estimates in humans exposed to crystalline silica.

Biological Response to SPE Exposures

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F. A.; Kim, M.; Shinn, J. L.; Jones, T. D.; Chang, C. K.

2004-01-01

It has long been recognized that a single solar particle event (SPE) can produce, over a short period of time, exposures on the order of LD50 for humans under normal physiological conditions. It is further recognized that recovery from injury over the period of exposure would greatly increase the chances of survival (dose rate effects) although such effects were left unquantified. In the present report we use the bioresponse model derived from a broad range of animal and human exposure data for evaluation of troop readiness in tactical nuclear warfare to evaluate the biological risk posed by the solar event of 4 August 1972. The astronaut blood forming organ (BFO) exposure in deep space would have been 2.2 Sv (1.6 Gy) in a space suit, 1.8 Sv (1.3 Gy) in an aluminum pressure vessel, and 0.7 Sv (0.5 Gy) in an equipment room compared to an X-ray mortality threshold of 1.5 Gy (assuming high dose rate). We find BFO dose rate effectiveness factors for this SPE on the order of 3 to 4, greatly reducing the mortality risks for this event. There is an approximate 3 percent chance that an even larger event may occur for which exposures could be 2-4 times higher. Assured survival of the astronaut requires added shelter shielding and a warning system for this event. The required mass of the shelter shield can be greatly reduced by using hydrogenous materials such as polymers, water, food, and other biological materials in its construction. Limitations of the current bioresponse model arise from the exposures taking place in the microgravity environment wherein the immune system is already challenged and the effective mortality threshold may be reduced by a factor of two. Such microgravity effects could greatly affect astronaut risks.

Physiological response of cardiac tissue to bisphenol a: alterations in ventricular pressure and contractility

PubMed Central

Brooks, Daina; Chandra, Akhil; Jaimes, Rafael; Sarvazyan, Narine; Kay, Matthew

2015-01-01

Biomonitoring studies have indicated that humans are routinely exposed to bisphenol A (BPA), a chemical that is commonly used in the production of polycarbonate plastics and epoxy resins. Epidemiological studies have shown that BPA exposure in humans is associated with cardiovascular disease; however, the direct effects of BPA on cardiac physiology are largely unknown. Previously, we have shown that BPA exposure slows atrioventricular electrical conduction, decreases epicardial conduction velocity, and prolongs action potential duration in excised rat hearts. In the present study, we tested if BPA exposure also adversely affects cardiac contractile performance. We examined the impact of BPA exposure level, sex, and pacing rate on cardiac contractile function in excised rat hearts. Hearts were retrogradely perfused at constant pressure and exposed to 10−9-10−4 M BPA. Left ventricular developed pressure and contractility were measured during sinus rhythm and during pacing (5, 6.5, and 9 Hz). Ca2+ transients were imaged from whole hearts and from neonatal rat cardiomyocyte layers. During sinus rhythm in female hearts, BPA exposure decreased left ventricular developed pressure and inotropy in a dose-dependent manner. The reduced contractile performance was exacerbated at higher pacing rates. BPA-induced effects on contractile performance were also observed in male hearts, albeit to a lesser extent. Exposure to BPA altered Ca2+ handling within whole hearts (reduced diastolic and systolic Ca2+ transient potentiation) and neonatal cardiomyocytes (reduced Ca2+ transient amplitude and prolonged Ca2+ transient release time). In conclusion, BPA exposure significantly impaired cardiac performance in a dose-dependent manner, having a major negative impact upon electrical conduction, intracellular Ca2+ handing, and ventricular contractility. PMID:25980024

Effects of sublethal exposure to boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta.

PubMed

Ali, Arshad; Xue, Rui-De; Barnard, Donald R

2006-09-01

Effects of sublethal exposure to 0.1% boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta were studied in the laboratory. Survival of males as well as females was significantly reduced when exposed to the bait, compared to control adults. The host-seeking and bloodfeeding activities in the baited females decreased, but the mean duration of blood engorgement (probing to voluntary withdrawal of proboscis) was not significantly different between the baited and control females. The landing and biting rates (human forearm) were significantly reduced in the baited females compared to nonbaited controls. Fecundity and fertility (based on number of laid eggs per female and percentage egg hatch, respectively) in the baited females were significantly reduced, and ovarian development was retarded. Sublethal exposure to sugar-based boric acid bait has the potential to reduce adult populations of St. albopicta.

Issues on human acceleration tolerance after long-duration space flights

NASA Technical Reports Server (NTRS)

Kumar, K. Vasantha; Norfleet, William T.

1992-01-01

This report reviewed the literature on human tolerance to acceleration at 1 G and changes in tolerance after exposure to hypogravic fields. It was found that human tolerance decreased after exposure to hypokinetic and hypogravic fields, but the magnitude of such reduction ranged from 0 to 30 percent for plateau G forces and 30 to 70 percent for time tolerance on sustained G forces. A logistic regression model of the probability of individuals with 25 percent reduction in +Gz tolerance after 1 to 41 days of hypogravic exposures was constructed. The estimated values from the model showed a good correlation with the observed data. A brief review of the need for in-flight centrifuge during long-duration missions was also presented. Review of the available data showed that the use of countermeasures (such as anti-G suits, periodic acceleration, and exercise) reduced the decrement in acceleration tolerance after long-duration space flights. Areas of further research include quantification of the effect of countermeasures on tolerance, and methods to augment tolerance during and after exposures to hypogravic fields. Such data are essential for planning long-duration human missions.

Pulmonary effects of exposure to fine fibreglass: irregular opacities and small airways obstruction.

PubMed Central

Kilburn, K H; Powers, D; Warshaw, R H

1992-01-01

OBJECTIVE--Man made mineral fibres imitate asbestos and produce tumours of the pleura in animals. To answer the question, Does prolonged exposure to fibreglass adversely affect pulmonary function or produce radiographic abnormalities in human subjects? we studied workers in a midwestern appliance plant where refrigerator doors and previously entire cabinets were insulated with fibreglass sheeting and loose rotary spun fibreglass. METHODS--Spirometry and lung volumes were measured, respiratory and occupational questionnaires were administered, and chest x-ray films were read for pneumoconiosis using International Labour Office (ILO) 1980 criteria in 284 workers with exposure of 20 years or more. RESULTS--Expiratory flows were reduced including FEV1 (mean 90.3% of predicted (pr), FEF25-75 (85.5% pr), and FEF75-85 (76.2% pr). Forced vital capacity was significantly reduced (92.8% pr) and total lung capacity was significantly increased (109.2% pr). In white male smokers, a group large enough for comparisons, parameters of pulmonary function were reduced further in the presence of irregular opacities. Forty three workers (15.1%) had evidence of pneumoconiosis on chest radiographs: 26 of these (9.1%), had no known exposure to asbestos and 17 (6.0%) had some exposure. The best judgement was that in 36 (13.0%), pulmonary opacities or pleural abnormalities were due to fibreglass. CONCLUSION--Commercial rotary spun fibreglass used for insulating appliances appears to produce human disease that is similar to asbestosis. PMID:1419860

Contribution of psychological, social, and mechanical work exposures to low work ability: a prospective study.

PubMed

Emberland, Jan S; Knardahl, Stein

2015-03-01

To determine the contribution of specific psychological, social, and mechanical work exposures to the self-reported low level of work ability. Employees from 48 organizations were surveyed over a 2-year period (n = 3779). Changes in 16 work exposures and 3 work ability measures-the work ability index score, perceived current, and future work ability-were tested with Spearman rank correlations. Binary logistic regressions were run to determine contribution of work exposures to low work ability. Role conflict, human resource primacy, and positive challenge were the most consistent predictors of low work ability across test designs. Role clarity and fair leadership were less consistent but prominent predictors. Mechanical exposures were not predictive. To protect employee work ability, work place interventions would benefit from focusing on reducing role conflicts and on promoting positive challenges and human resource primacy.

Contribution of Psychological, Social, and Mechanical Work Exposures to Low Work Ability

PubMed Central

Knardahl, Stein

2015-01-01

Objective: To determine the contribution of specific psychological, social, and mechanical work exposures to the self-reported low level of work ability. Methods: Employees from 48 organizations were surveyed over a 2-year period (n = 3779). Changes in 16 work exposures and 3 work ability measures—the work ability index score, perceived current, and future work ability—were tested with Spearman rank correlations. Binary logistic regressions were run to determine contribution of work exposures to low work ability. Results: Role conflict, human resource primacy, and positive challenge were the most consistent predictors of low work ability across test designs. Role clarity and fair leadership were less consistent but prominent predictors. Mechanical exposures were not predictive. Conclusions: To protect employee work ability, work place interventions would benefit from focusing on reducing role conflicts and on promoting positive challenges and human resource primacy. PMID:25470453

Comparison of drinking water, raw rice and cooking of rice as arsenic exposure routes in three contrasting areas of West Bengal, India.

PubMed

Mondal, Debapriya; Banerjee, Mayukh; Kundu, Manjari; Banerjee, Nilanjana; Bhattacharya, Udayan; Giri, Ashok K; Ganguli, Bhaswati; Sen Roy, Sugata; Polya, David A

2010-12-01

Remediation aimed at reducing human exposure to groundwater arsenic in West Bengal, one of the regions most impacted by this environmental hazard, are currently largely focussed on reducing arsenic in drinking water. Rice and cooking of rice, however, have also been identified as important or potentially important exposure routes. Quantifying the relative importance of these exposure routes is critically required to inform the prioritisation and selection of remediation strategies. The aim of our study, therefore, was to determine the relative contributions of drinking water, rice and cooking of rice to human exposure in three contrasting areas of West Bengal with different overall levels of exposure to arsenic, viz. high (Bhawangola-I Block, Murshidibad District), moderate (Chakdha Block, Nadia District) and low (Khejuri-I Block, Midnapur District). Arsenic exposure from water was highly variable, median exposures being 0.02 μg/kg/d (Midnapur), 0.77 μg/kg/d (Nadia) and 2.03 μg/kg/d (Murshidabad). In contrast arsenic exposure from cooked rice was relatively uniform, with median exposures being 0.30 μg/kg/d (Midnapur), 0.50 μg/kg/d (Nadia) and 0.84 μg/kg/d (Murshidabad). Cooking rice typically resulted in arsenic exposures of lower magnitude, indeed in Midnapur, median exposure from cooking was slightly negative. Water was the dominant route of exposure in Murshidabad, both water and rice were major exposure routes in Nadia, whereas rice was the dominant exposure route in Midnapur. Notwithstanding the differences in balance of exposure routes, median excess lifetime cancer risk for all the blocks were found to exceed the USEPA regulatory threshold target cancer risk level of 10(-4)-10(-6). The difference in balance of exposure routes indicate a difference in balance of remediation approaches in the three districts.

The ABCs of Non-Toxic Pest Control.

ERIC Educational Resources Information Center

Cooper, Susan

1990-01-01

Although chemical-intensive pest control methods have proven reasonably effective, a growing awareness of health and environmental risks associated with pesticides has sharpened public interest in safer alternatives. An integrated pest management approach reduces risks from pests while minimizing human exposure and reducing the toxicity of applied…

Exposure Science: A View of the Past and Milestones for the Future

PubMed Central

Lioy, Paul J.

2010-01-01

Background The study of human exposure to environmental toxicants has evolved as a scientific field over the past 30 years. Objectives This review provides a historical perspective on the growth of exposure science as a field, with some emphasis on the results from initial observational studies in obtaining information needed for generating hypotheses on significant human contact with environmental agents, testing the performance of models, and reducing exposures to protect public health. Discussion Advances in activity pattern and behavioral research that established a suite of variables needed to accurately define contact and factors that influence contact are also discussed. The identification and characterization of these factors have played a pivotal role in the growth of the field and in developing exposure reduction strategies. Answers to two key questions on the relevance and fundamental value of exposure science to the fields of environmental health and risk management are presented as a path forward: a) What does one do with such exposure information? b) What roles does exposure science play in situations beyond observational analyses and interpretation? Conclusions The discussion identifies the need for more focused use of observational studies of exposure for epidemiologic analyses. Further, the introduction and use of new tools and approaches for hypothesis testing that can improve the use of exposure science in prevention research for risk management is needed to affect the source-to-effect continuum. A major restructuring of the field is not required to achieve innovation. However, additional resources for training and education are required to ensure that the potential for exposure science to play a central role in reducing and preventing excess risk within environmental/occupational health is achieved. PMID:20308034

Mercury in Children: Current State on Exposure through Human Biomonitoring Studies

PubMed Central

Ruggieri, Flavia; Majorani, Costanza; Domanico, Francesco; Alimonti, Alessandro

2017-01-01

Mercury (Hg) in children has multiple exposure sources and the toxicity of Hg compounds depends on exposure routes, dose, timing of exposure, and developmental stage (be it prenatal or postnatal). Over the last decades, Hg was widely recognized as a threat to the children’s health and there have been acknowledgements at the international level of the need of a global policy intervention—like the Minamata treaty—aimed at reducing or preventing Hg exposure and protecting the child health. National human biomonitoring (HBM) data has demonstrated that low levels of exposure of Hg are still an important health concern for children, which no one country can solve alone. Although independent HBM surveys have provided the basis for the achievements of exposure mitigation in specific contexts, a new paradigm for a coordinated global monitoring of children’s exposure, aimed at a reliable decision-making tool at global level is yet a great challenge for the next future. The objective of the present review is to describe current HBM studies on Hg exposure in children, taking into account the potential pathways of Hg exposure and the actual Hg exposure levels assessed by different biomarkers. PMID:28498344

Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection.

PubMed

Roy, Anirban; Bauer, Stephen M; Lawrence, B Paige

2012-01-01

Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.

Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells

USDA-ARS?s Scientific Manuscript database

Mammary adipose tissue may contribute to breast cancer development and progression by altering neighboring epithelial cell behavior and phenotype through paracrine signaling. Dietary exposure to soy foods is associated with lower mammary tumor risk and reduced body weight and adiposity in humans and...

33 CFR 1.01-70 - CERCLA delegations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... health or welfare or the environment because of an actual or threatened release of a hazardous substance... steps as may be necessary to reduce exposure that presents a significant risk to human health, and to eliminate or substantially mitigate that significant risk to human health. (3) Authority, pursuant to CERCLA...

33 CFR 1.01-70 - CERCLA delegations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... health or welfare or the environment because of an actual or threatened release of a hazardous substance... steps as may be necessary to reduce exposure that presents a significant risk to human health, and to eliminate or substantially mitigate that significant risk to human health. (3) Authority, pursuant to CERCLA...

33 CFR 1.01-70 - CERCLA delegations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... health or welfare or the environment because of an actual or threatened release of a hazardous substance... steps as may be necessary to reduce exposure that presents a significant risk to human health, and to eliminate or substantially mitigate that significant risk to human health. (3) Authority, pursuant to CERCLA...

ELECTRORETINOGRAMS ARE ALTERED BY SUBCHRONIC TOLUENE EXPOSURE TO LONG EVANS RATS: EXPERIMENTAL EVIDENCE SUPPORTING OBSERVATIONS FROM STUDIES OF EXPOSED HUMANS

EPA Science Inventory

Impaired visual functions, including low contrast sensitivity and reduced color discrimination, have been reported in studies of humans chronically exposed to several volatile organic solvents. These reports remain controversial, however, in part due to a lack of confirmation fro...

Subchronic Toluene Exposure alters Retinal Function in Long Evans Rats: Experimental Evidence Supporting Observations from Studies of Exposed Humans.

EPA Science Inventory

Studies of humans chronically exposed to volatile organic solvents commonly report impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports have been controversial, however, in part due to a lack of confirmation from controlled...

Nanoparticles, human health hazard and regulation

PubMed Central

Seaton, Anthony; Tran, Lang; Aitken, Robert; Donaldson, Kenneth

2010-01-01

New developments in technology usually entail some hazard as well as advantage to a society. Hazard of a material translates into risk by exposure of humans and/or their environment to the agent in question, and risk is reduced by control of exposure, usually guided by regulation based on understanding of the mechanisms of harm. We illustrate risks relating to the causation of diseases associated with exposure to aerosols of combustion particles and asbestos, leading to paradigms of particle toxicity, and discuss analogies with potential exposure to manufactured nanoparticles (NPs). We review the current understanding of the hazard of NPs derived from the new science of nanotoxicology and the limited research to date into human exposure to these particles. We identify gaps in knowledge relating to the properties of NPs that might determine toxicity and in understanding the most appropriate ways both to measure this in the laboratory and to assess it in the workplace. Nevertheless, we point out that physical principles governing the behaviour of such particles allow determination of practical methods of protecting those potentially exposed. Finally, we discuss the early steps towards regulation and the difficulties facing regulators in controlling potentially harmful exposures in the absence of sufficient scientific evidence. PMID:19726441

A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway

PubMed Central

McClure, Kimberly D.; French, Rachael L.; Heberlein, Ulrike

2011-01-01

SUMMARY Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. Additionally, we show that, as in mammals, flies reared on ethanol have altered responses to ethanol vapor exposure as adults, including increased locomotor activation, resistance to the sedating effects of the drug and reduced tolerance development upon repeated ethanol exposure. We have found that the developmental and behavioral defects are largely due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression. Transgenic expression of Dilp proteins in the larval brain suppressed both the developmental and behavioral abnormalities displayed by ethanol-reared adult flies. Our results thus establish Drosophila as a useful model system to uncover the complex etiology of fetal alcohol syndrome. PMID:21303840

Medical Students' Exposure to the Humanities Correlates with Positive Personal Qualities and Reduced Burnout: A Multi-Institutional U.S. Survey.

PubMed

Mangione, Salvatore; Chakraborti, Chayan; Staltari, Giuseppe; Harrison, Rebecca; Tunkel, Allan R; Liou, Kevin T; Cerceo, Elizabeth; Voeller, Megan; Bedwell, Wendy L; Fletcher, Keaton; Kahn, Marc J

2018-05-01

Literature, music, theater, and visual arts play an uncertain and limited role in medical education. One of the arguments often advanced in favor of teaching the humanities refers to their capacity to foster traits that not only improve practice, but might also reduce physician burnout-an increasing scourge in today's medicine. Yet, research remains limited. To test the hypothesis that medical students with higher exposure to the humanities would report higher levels of positive physician qualities (e.g., wisdom, empathy, self-efficacy, emotional appraisal, spatial skills), while reporting lower levels of negative qualities that are detrimental to physician well-being (e.g., intolerance of ambiguity, physical fatigue, emotional exhaustion, and cognitive weariness). An online survey. All students enrolled at five U.S. medical schools during the 2014-2015 academic year were invited by email to take part in our online survey. Students reported their exposure to the humanities (e.g., music, literature, theater, visual arts) and completed rating scales measuring selected personal qualities. In all, 739/3107 medical students completed the survey (23.8%). Regression analyses revealed that exposure to the humanities was significantly correlated with positive personal qualities, including empathy (p < 0.001), tolerance for ambiguity (p < 0.001), wisdom (p < 0.001), emotional appraisal (p = 0.01), self-efficacy (p = 0.02), and spatial skills (p = 0.02), while it was significantly and inversely correlated with some components of burnout (p = 0.01). Thus, all hypotheses were statistically significant, with effect sizes ranging from 0.2 to 0.59. This study confirms the association between exposure to the humanities and both a higher level of students' positive qualities and a lower level of adverse traits. These findings may carry implications for medical school recruitment and curriculum design. "[Science and humanities are] twin berries on one stem, grievous damage has been done to both in regarding [them]... in any other light than complemental." (William Osler, Br Med J. 1919;2:1-7).

GPS-based Microenvironment Tracker (MicroTrac) Model to ...

EPA Pesticide Factsheets

A critical aspect of air pollution exposure assessment is the estimation of the time spent by individuals in various microenvironments (ME). Accounting for the time spent in different ME with different pollutant concentrations can reduce exposure misclassifications, while failure to do so can add uncertainty and bias to risk estimates. In this study, a classification model, called MicroTrac, was developed to estimate time of day and duration spent in eight ME (indoors and outdoors at home, work, school; inside vehicles; other locations) from global positioning system (GPS) data and geocoded building boundaries. Based on a panel study, MicroTrac estimates were compared to 24 h diary data from 7 participants on workdays and 2 participants on nonworkdays, with corresponding GPS data and building boundaries of home, school, and work. MicroTrac correctly classified the ME for 99.5% of the daily time spent by the participants. The capability of MicroTrac could help to reduce the time-location uncertainty in air pollution exposure models and exposure metrics for individuals in health studies. The National Exposure Research Laboratory’s (NERL’s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA’s mission to protect human health and the environment. HEASD’s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA’s strategic plan. More specifically, our division conducts research to characterize

Suppression of LPS-induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane.

PubMed

Folkard, Danielle L; Melchini, Antonietta; Traka, Maria H; Al-Bakheit, Ala'a; Saha, Shikha; Mulholland, Francis; Watson, Andrew; Mithen, Richard F

2014-12-01

Diets rich in cruciferous vegetables are associated with lower levels of pro-inflammatory cytokines, which may contribute to potential health-promoting properties of these vegetables. We investigate whether sulforaphane (SF), an isothiocyanate (ITC) obtained from broccoli, could suppress LPS-induced transcription and subsequent pro-inflammatory cytokine secretion at a physiologically relevant concentration using in vitro models of chronic inflammation. We find that exposure of the LPS receptor Toll-like receptor-4 (TLR4) to physiologically appropriate concentrations of SF under non-reducing conditions results in covalent modification of cysteine residues 246 and 609. We further demonstrate that the changes in expression of 1210 genes (p ≤ 0.01) in THP-1 monocytes and the secretion of pro-inflammatory cytokines in both human peripheral blood mononuclear cells (PBMCs) and THP-1 monocytes induced by LPS exposure can be completely suppressed through exposure with physiologically appropriate concentrations of SF. Finally, we show that in vivo exposure of human PBMCs to ITCs within human circulation reduces secretion of pro-inflammatory cytokines following subsequent ex vivo LPS challenge (p < 0.001). Covalent modification of TLR4 by ITCs and resultant suppression of LPS-induced cell signalling could lead to reductions in levels of pro-inflammatory cytokines in people with chronic diseases who consume diets rich in cruciferous vegetables. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prevention Strategies Against HIV Transmission: A Proactive Approach.

PubMed

Carrion, Antonio J; Miles, Jovan D; Mosley, Juan F; Smith, Lillian L; Prather, April S; Gurley, Marcus M; Phan, Linh D; Everton, Emily C

2018-02-01

Human immunodeficiency virus (HIV) has now transformed into a manageable chronic condition. Highly active antiretroviral therapy (HAART) has proven efficacious at controlling the disease progression. Based on compelling evidence, the Department of Health and Human Services (DHHS) and the Infectious Disease Society of America (IDSA) developed guidelines for the management of persons infected with HIV. However, there are approximately 50 000 new cases of HIV in the United States each year. In this article, we review proactive methods to reduce the transmission of HIV, which include reinforcing patient education, gel-coated condoms that destroy HIV, HIV vaccinations, and adequately utilizing pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP). Further development and consistent utilization of innovative prevention tools can significantly reduce the incidence of HIV infections regardless of HIV status.

Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

PubMed

Plessinger, M A

1998-03-01

Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and the effects of amphetamine and methamphetamine in general.

Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure

PubMed Central

Calderon-Gierszal, Esther L.; Prins, Gail S.

2015-01-01

Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA) can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC) into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20–30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures. PMID:26222054

Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene

PubMed Central

Bloomfield, Sally F; Rook, Graham AW; Scott, Elizabeth A; Shanahan, Fergus; Stanwell-Smith, Rosalind; Turner, Paul

2016-01-01

Aims: To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease. Methods: Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim. Results: Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe–host interactions, the term ‘hygiene hypothesis’ is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures. Conclusion: Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term ‘hygiene hypothesis’ must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about hygiene. We need to restore public understanding of hygiene as a means to prevent infectious disease. PMID:27354505

Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene.

PubMed

Bloomfield, Sally F; Rook, Graham Aw; Scott, Elizabeth A; Shanahan, Fergus; Stanwell-Smith, Rosalind; Turner, Paul

2016-07-01

To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease. Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim. Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe-host interactions, the term 'hygiene hypothesis' is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures. Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term 'hygiene hypothesis' must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about hygiene. We need to restore public understanding of hygiene as a means to prevent infectious disease. © Royal Society for Public Health 2016.

Cardiac Development in Zebrafish and Human Embryonic Stem Cells Is Inhibited by Exposure to Tobacco Cigarettes and E-Cigarettes

PubMed Central

Palpant, Nathan J.; Hofsteen, Peter; Pabon, Lil; Reinecke, Hans; Murry, Charles E.

2015-01-01

Background Maternal smoking is a risk factor for low birth weight and other adverse developmental outcomes. Objective We sought to determine the impact of standard tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo. Methods Zebrafish (Danio rerio) were used to assess developmental effects in vivo and cardiac differentiation of human embryonic stem cells (hESCs) was used as a model for in vitro cardiac development. Results In zebrafish, exposure to both types of cigarettes results in broad, dose-dependent developmental defects coupled with severe heart malformation, pericardial edema and reduced heart function. Tobacco cigarettes are more toxic than e-cigarettes at comparable nicotine concentrations. During cardiac differentiation of hESCs, tobacco smoke exposure results in a delayed transition through mesoderm. Both types of cigarettes decrease expression of cardiac transcription factors in cardiac progenitor cells, suggesting a persistent delay in differentiation. In definitive human cardiomyocytes, both e-cigarette- and tobacco cigarette-treated samples showed reduced expression of sarcomeric genes such as MLC2v and MYL6. Furthermore, tobacco cigarette-treated samples had delayed onset of beating and showed low levels and aberrant localization of N-cadherin, reduced myofilament content with significantly reduced sarcomere length, and increased expression of the immature cardiac marker smooth muscle alpha-actin. Conclusion These data indicate a negative effect of both tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo. Tobacco cigarettes are more toxic than E-cigarettes and exhibit a broader spectrum of cardiac developmental defects. PMID:25978043

Public health implications of environmental noise associated with unconventional oil and gas development.

PubMed

Hays, Jake; McCawley, Michael; Shonkoff, Seth B C

2017-02-15

Modern oil and gas development frequently occurs in close proximity to human populations and increased levels of ambient noise have been documented throughout some phases of development. Numerous studies have evaluated air and water quality degradation and human exposure pathways, but few have evaluated potential health risks and impacts from environmental noise exposure. We reviewed the scientific literature on environmental noise exposure to determine the potential concerns, if any, that noise from oil and gas development activities present to public health. Data on noise levels associated with oil and gas development are limited, but measurements can be evaluated amidst the large body of epidemiology assessing the non-auditory effects of environmental noise exposure and established public health guidelines for community noise. There are a large number of noise dependent and subjective factors that make the determination of a dose response relationship between noise and health outcomes difficult. However, the literature indicates that oil and gas activities produce noise at levels that may increase the risk of adverse health outcomes, including annoyance, sleep disturbance, and cardiovascular disease. More studies that investigate the relationships between noise exposure and human health risks from unconventional oil and gas development are warranted. Finally, policies and mitigation techniques that limit human exposure to noise from oil and gas operations should be considered to reduce health risks. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective influence of healthful nutrition on mechanisms of environmental pollutant toxicity and disease risks.

PubMed

Hoffman, Jessie B; Hennig, Bernhard

2017-06-01

Human exposures to environmental contaminants around the world contribute to the global burden of disease and thus require urgent attention. Exploring preventive measures against environmental exposure and disease risk is essential. While a sedentary lifestyle and/or poor dietary habits can exacerbate the deleterious effects resulting from exposure to toxic chemicals, much emerging evidence suggests that positive lifestyle changes (e.g., healthful nutrition) can modulate and/or reduce the toxicity of environmental pollutants. Our work has shown that diets high in anti-inflammatory bioactive food components (e.g., phytochemicals or polyphenols) are possible strategies for modulating and reducing the disease risks associated with exposure to toxic pollutants in the environment. Thus, consuming healthy diets rich in plant-derived bioactive nutrients may reduce the vulnerability to diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationships between nutrition and other lifestyle modifications and toxicant-induced diseases. © 2017 New York Academy of Sciences.

The Effect of Social Programs and Exposure to Professionals on the Educational Aspirations of the Poor

ERIC Educational Resources Information Center

Chiapa, Carlos; Garrido, Jose Luis; Prina, Silvia

2012-01-01

Investment in human capital is an important tool for reducing poverty. However, the poor may lack the capacity to aspire, which often results in underinvestment in their children's education. This paper studies the effect of a social program on the educational aspirations poor parents have for their children, and explores the role of exposure to…

Does spending time outdoors reduce stress? A review of real-time stress response to outdoor environments

Treesearch

Michelle C. Kondo; Sara F. Jacoby; Eugenia C. South

2018-01-01

Everyday environmental conditions impact human health. One mechanism underlying this relationship is the experience of stress. Through systematic review of published literature, we explore how stress has been measured in real-time non-laboratory studies of stress responses to deliberate exposure to outdoor environments. The types of exposures evaluated in this review...

Brominated flame retardants as possible endocrine disrupters.

PubMed

Darnerud, P O

2008-04-01

Brominated flame retardants (BFR) are endocrine disrupters in experimental systems, both in vitro and in vivo. Although BFR effects on thyroid hormones are well confirmed, studies of effects on oestrogen/androgen systems are fewer but today growing in numbers. The effects of BFR on other hormone systems are still unknown. Hormonal effect levels in animals start from ca 1 mg/kg b.w., but there are exceptions: effects on spermatogenesis, suggesting hormonal causes, have been observed at a low dose (60 microg/kg b.w.) of a polybrominated diphenyl ether (PBDE) congener, BDE-99. It could be concluded that hormonal effects are of importance in risk assessment, and in some cases where effects are seen at low levels safety margins may be insufficient. One additional uncertainty is the lack of reliable human data that could be used to support animal BFR observations. In spite of the recent regulation of PBDE production, levels of both PBDE and of other BFR groups are still present in environmental samples. Thus, we have to deal with the possible effects of human BFR exposure for times to come. In order to reduce BFR exposure, the routes of exposure should be carefully examined and ways to reduce levels in major exposure routes considered.

Environmental exposure to preformed nitroso compounds.

PubMed

Tricker, A R; Spiegelhalder, B; Preussmann, R

1989-01-01

In the human environment, nitrosatable amine precursors to N-nitroso compounds and nitrosating species such as nitrite and oxides of nitrogen are abundant. As a result, the formation of N-nitroso compounds and human exposure to these compounds show a rather complex pattern. The largest known human exposures to exogenous N-nitrosamines occur in the work place. This is particularly evident in the rubber and tyre manufacturing industry and in metal cutting and grinding shops. Nearly all industries which are concerned with the production and/or use of amines have a related nitrosamine problem. Outside the industrial environment, commodities such as cosmetics, pharmaceuticals, rubber and household products, which are either prepared from amines or contain high concentrations of amino compounds, may be subject to contamination by low concentrations of N-nitroso compounds. This contamination may result from the use of contaminated starting materials, in particular amines, or from the formation of N-nitroso compounds during manufacturing processes. A similar problem exists with agricultural chemicals. As our knowledge of the occurrence and formation of N-nitroso compounds in the environment increases, preventive measures can be introduced, particularly in manufacturing industries, to reduce the levels of human exposure to nitrosamines in the work place and to protect the consumer from nitrosamine exposure from household commodities.

Low dose or low dose rate ionizing radiation-induced health effect in the human.

PubMed

Tang, Feng Ru; Loganovsky, Konstantin

2018-06-05

The extensive literature review on human epidemiological studies suggests that low dose ionizing radiation (LDIR) (≤100 mSv) or low dose rate ionizing radiation (LDRIR) (<6mSv/H) exposure could induce either negative or positive health effects. These changes may depend on genetic background, age (prenatal day for embryo), sex, nature of radiation exposure, i.e., acute or chronic irradiation, radiation sources (such as atomic bomb attack, fallout from nuclear weapon test, nuclear power plant accidents, 60 Co-contaminated building, space radiation, high background radiation, medical examinations or procedures) and radionuclide components and human epidemiological experimental designs. Epidemiological and clinical studies show that LDIR or LDRIR exposure may induce cancer, congenital abnormalities, cardiovascular and cerebrovascular diseases, cognitive and other neuropsychiatric disorders, cataracts and other eye and somatic pathology (endocrine, bronchopulmonary, digestive, etc). LDIR or LDRIR exposure may also reduce mutation and cancer mortality rates. So far, the mechanisms of LDIR- or LDRIR -induced health effect are poorly understood. Further extensive studies are still needed to clarify under what circumstances, LDIR or LDRIR exposure may induce positive or negative effects, which may facilitate development of new therapeutic approaches to prevent or treat the radiation-induced human diseases or enhance radiation-induced positive health effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Microbiome of the Built Environment and Human Behavior: Implications for Emotional Health and Well-Being in Postmodern Western Societies.

PubMed

Stamper, C E; Hoisington, A J; Gomez, O M; Halweg-Edwards, A L; Smith, D G; Bates, K L; Kinney, K A; Postolache, T T; Brenner, L A; Rook, G A W; Lowry, C A

2016-01-01

It is increasingly evident that inflammation is an important determinant of cognitive function and emotional behaviors that are dysregulated in stress-related psychiatric disorders, such as anxiety and affective disorders. Inflammatory responses to physical or psychological stressors are dependent on immunoregulation, which is indicated by a balanced expansion of effector T-cell populations and regulatory T cells. This balance is in part driven by microbial signals. The hygiene or "old friends" hypothesis posits that exposure to immunoregulation-inducing microorganisms is reduced in modern urban societies, leading to an epidemic of inflammatory disease and increased vulnerability to stress-related psychiatric disorders. With the global trend toward urbanization, humans are progressively spending more time in built environments, thereby, experiencing limited exposures to these immunoregulatory "old friends." Here, we evaluate the implications of the global trend toward urbanization, and how this transition may affect human microbial exposures and human behavior. © 2016 Elsevier Inc. All rights reserved.

Human rabies in Tianjin, China.

PubMed

Montgomery, J P; Zhang, Y; Wells, E V; Liu, Y; Clayton, J L; Wang, X; Boulton, M L

2012-12-01

Human rabies has recently re-emerged as a significant public health threat in Tianjin, China. Using surveillance data compiled by the Tianjin Centers for Disease Control and Prevention, we describe 60 cases of human rabies reported from 2005 to 2011 in the municipality of Tianjin, China. All 60 cases of human rabies resulted in death. Cases were primarily male (80%), middle aged (mean 40.6 years), and exposed to rabies in a rural setting (82%). Most exposures were associated with dog bites (93%) and no animal had a history of rabies vaccination; no cases were laboratory confirmed. Fifteen percent of patients sought medical attention for their wound, and none received a complete regimen of WHO-recommended post-exposure prophylaxis (PEP). These findings suggest the need for China's public health authority to improve animal rabies surveillance and control strategies through laboratory case confirmation, more rapid response to potential exposures with provision of appropriate PEP, and education to the public and to health care providers on identifying and reducing rabies risk.

Reducing health risk assigned to organic emissions from a chemical weapons incinerator.

PubMed

Laman, David M; Weiler, B Douglas; Skeen, Rodney S

2013-03-01

Organic emissions from a chemical weapons incinerator have been characterized with an improved set of analytical methods to reduce the human health risk assigned to operations of the facility. A gas chromatography/mass selective detection method with substantially reduced detection limits has been used in conjunction with scanning electron microscopy/energy dispersive X-ray spectrometry and Fourier transform infrared microscopy to improve the speciation of semi-volatile and non-volatile organics emitted from the incinerator. The reduced detection limits have allowed a significant reduction in the assumed polycyclic aromatic hydrocarbon (PAH) and aminobiphenyl (ABP) emission rates used as inputs to the human health risk assessment for the incinerator. A mean factor of 17 decrease in assigned human health risk is realized for six common local exposure scenarios as a result of the reduced PAH and ABP detection limits.

44 CFR 351.23 - The Department of Health and Human Services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... protective actions and associated guidance to State and local governments for human food and animal feed (in...-protective substances and prophylactic use of drugs (e.g., potassium iodide) to reduce the radiation dose to specific organs including dosage and projected radiation exposures at which such drugs should be used. (g...

44 CFR 351.23 - The Department of Health and Human Services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... protective actions and associated guidance to State and local governments for human food and animal feed (in...-protective substances and prophylactic use of drugs (e.g., potassium iodide) to reduce the radiation dose to specific organs including dosage and projected radiation exposures at which such drugs should be used. (g...

44 CFR 351.23 - The Department of Health and Human Services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... protective actions and associated guidance to State and local governments for human food and animal feed (in...-protective substances and prophylactic use of drugs (e.g., potassium iodide) to reduce the radiation dose to specific organs including dosage and projected radiation exposures at which such drugs should be used. (g...

44 CFR 351.23 - The Department of Health and Human Services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... protective actions and associated guidance to State and local governments for human food and animal feed (in...-protective substances and prophylactic use of drugs (e.g., potassium iodide) to reduce the radiation dose to specific organs including dosage and projected radiation exposures at which such drugs should be used. (g...

Household air pollution: a call for studies into biomarkers of exposure and predictors of respiratory disease.

PubMed

Rylance, Jamie; Gordon, Stephen B; Naeher, Luke P; Patel, Archana; Balmes, John R; Adetona, Olorunfemi; Rogalsky, Derek K; Martin, William J

2013-05-01

Household air pollution (HAP) from indoor burning of biomass or coal is a leading global cause of morbidity and mortality, mostly due to its association with acute respiratory infection in children and chronic respiratory and cardiovascular diseases in adults. Interventions that have significantly reduced exposure to HAP improve health outcomes and may reduce mortality. However, we lack robust, specific, and field-ready biomarkers to identify populations at greatest risk and to monitor the effectiveness of interventions. New scientific approaches are urgently needed to develop biomarkers of human exposure that accurately reflect exposure or effect. In this Perspective, we describe the global need for such biomarkers, the aims of biomarker development, and the state of development of tests that have the potential for rapid transition from laboratory bench to field use.

Environmental footprint of pharmaceuticals: the significance of factors beyond direct excretion to sewers.

PubMed

Daughton, Christian G; Ruhoy, Ilene S

2009-12-01

The combined excretion of active pharmaceutical ingredients (APIs) via urine and feces is considered the primary route by which APIs from human pharmaceuticals enter the environment. Disposal of unwanted, leftover medications by flushing into sewers has been considered a secondary route-one that does not contribute substantially to overall environmental loadings. The present study presents the first comprehensive examination of secondary routes of API release to the environment and for direct but unintentional human exposure. These include bathing, washing, and laundering, all of which release APIs remaining on the skin from the use of high-content dermal applications or from excretion to the skin via sweating, and disposal of unused and partially used high-content devices. Also discussed are the health hazards associated with: partially used devices, medication disposal practices of consumers, and interpersonal dermal transfer of API residues. Understanding these secondary routes is important from the perspective of pollution prevention, because actions can be designed more easily for reducing the environmental impact of APIs compared with the route of direct excretion (via urine and feces), for reducing the incidence of unintentional and purposeful poisonings of humans and pets, and for improving the quality and cost-effectiveness of health care. Overall, unintentional exposure to APIs for humans via these routes is possibly more important than exposure to trace residues recycled from the environment in drinking water or foods.

Human Exploration of Near-Earth Objects Accessibility Study

NASA Technical Reports Server (NTRS)

Abell, Paul; Drake, Bret; Friedensen, Victoria; Mazanek, Dan

2011-01-01

Key questions addressed: How short can the trip times be reduced in order to reduce crew exposure to the deep-space radiation and microgravity environment? Are there options to conduct easy, early missions?. What is the affect of infusion of advanced propulsion technologies on target availability When do the departure opportunities open up, how frequent and how long are they? How many launches are required to conduct a round trip human mission to a NEA? And, based on the above, how many Near-Earth Asteroids are available

Arsenic transformation predisposes human skin keratinocytes to UV-induced DNA damage yet enhances their survival apparently by diminishing oxidant response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun Yang; Kojima, Chikara; Chignell, Colin

2011-09-15

Inorganic arsenic and UV, both human skin carcinogens, may act together as skin co-carcinogens. We find human skin keratinocytes (HaCaT cells) are malignantly transformed by low-level arsenite (100 nM, 30 weeks; termed As-TM cells) and with transformation concurrently undergo full adaptation to arsenic toxicity involving reduced apoptosis and oxidative stress response to high arsenite concentrations. Oxidative DNA damage (ODD) is a possible mechanism in arsenic carcinogenesis and a hallmark of UV-induced skin cancer. In the current work, inorganic arsenite exposure (100 nM) did not induce ODD during the 30 weeks required for malignant transformation. Although acute UV-treatment (UVA, 25 J/cm{supmore » 2}) increased ODD in passage-matched control cells, once transformed by arsenic to As-TM cells, acute UV actually further increased ODD (> 50%). Despite enhanced ODD, As-TM cells were resistant to UV-induced apoptosis. The response of apoptotic factors and oxidative stress genes was strongly mitigated in As-TM cells after UV exposure including increased Bcl2/Bax ratio and reduced Caspase-3, Nrf2, and Keap1 expression. Several Nrf2-related genes (HO-1, GCLs, SOD) showed diminished responses in As-TM cells after UV exposure consistent with reduced oxidant stress response. UV-exposed As-TM cells showed increased expression of cyclin D1 (proliferation gene) and decreased p16 (tumor suppressor). UV exposure enhanced the malignant phenotype of As-TM cells. Thus, the co-carcinogenicity between UV and arsenic in skin cancer might involve adaptation to chronic arsenic exposure generally mitigating the oxidative stress response, allowing apoptotic by-pass after UV and enhanced cell survival even in the face of increased UV-induced oxidative stress and increased ODD. - Highlights: > Arsenic transformation adapted to UV-induced apoptosis. > Arsenic transformation diminished oxidant response. > Arsenic transformation enhanced UV-induced DNA damage.« less

Continuous activation of Nrf2 and its target antioxidant enzymes leads to arsenite-induced malignant transformation of human bronchial epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xu; Wang, Dapeng; Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou

Long-term exposure to arsenite leads to human lung cancer, but the underlying mechanisms of carcinogenesis remain obscure. The transcription factor of nuclear factor-erythroid-2 p45-related factor (Nrf2)-mediated antioxidant response represents a critical cellular defense mechanism and protection against various diseases. Paradoxically, emerging data suggest that the constitutive activation of Nrf2 is associated with cancer development, progression and chemotherapy resistance. However, the role of Nrf2 in the occurrence of cancer induced by long-term arsenite exposure remains to be fully understood. By establishing transformed human bronchial epithelial (HBE) cells via chronic low-dose arsenite treatment, we showed that, in acquiring this malignant phenotype, continuousmore » low level of ROS and sustained enhancement of Nrf2 and its target antioxidant enzyme levels were observed in the later-stage of arsenite-induced cell transformation. The downregulation of Keap1 level may be responsible for the over-activation of Nrf2 and its target enzymes. To validate these observations, Nrf2 was knocked down in arsenite-transformed HBE cells by SiRNA transfection, and the levels of Nrf2 and its target antioxidant enzymes, ROS, cell proliferation, migration, and colony formation were determined following these treatments. Results showed that blocked Nrf2 expression significantly reduced Nrf2 and its target antioxidant enzyme levels, restored ROS levels, and eventually suppressed cell proliferation, migration, and colony formation of the transformed cells. In summary, the results of the study strongly suggested that the continuous activation of Nrf2 and its target antioxidant enzymes led to the over-depletion of intracellular ROS levels, which contributed to arsenite-induced HBE cell transformation. - Highlights: • Low level, long term arsenite exposure induces malignant transformation in vitro. • Long term arsenite exposure reduces ROS and MDA levels. • Long term arsenite exposure enhances Nrf2-mediated antioxidant levels. • Knockdown of Nrf2 reduces malignant degree of arsenite-transformed cells.« less

Long-term reduction in infrared autofluorescence caused by infrared light below the maximum permissible exposure.

PubMed

Masella, Benjamin D; Williams, David R; Fischer, William S; Rossi, Ethan A; Hunter, Jennifer J

2014-05-20

Many retinal imaging instruments use infrared wavelengths to reduce the risk of light damage. However, we have discovered that exposure to infrared illumination causes a long-lasting reduction in infrared autofluorescence (IRAF). We have characterized the dependence of this effect on radiant exposure and investigated its origin. A scanning laser ophthalmoscope was used to obtain IRAF images from two macaques before and after exposure to 790-nm light (15-450 J/cm(2)). Exposures were performed with either raster-scanning or uniform illumination. Infrared autofluorescence images also were obtained in two humans exposed to 790-nm light in a separate study. Humans were assessed with direct ophthalmoscopy, Goldmann visual fields, multifocal ERG, and photopic microperimetry to determine whether these measures revealed any effects in the exposed locations. A significant decrease in IRAF after exposure to infrared light was seen in both monkeys and humans. In monkeys, the magnitude of this reduction increased with retinal radiant exposure. Partial recovery was seen at 1 month, with full recovery within 21 months. Consistent with a photochemical origin, IRAF decreases caused by either raster-scanning or uniform illumination were not significantly different. We were unable to detect any effect of the light exposure with any measure other than IRAF imaging. We cannot exclude the possibility that changes could be detected with more sensitive tests or longer follow-up. This long-lasting effect of infrared illumination in both humans and monkeys occurs at exposure levels four to five times below current safety limits. The photochemical basis for this phenomenon remains unknown. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Exposure to Concentrated Ambient PM2.5 Shortens Lifespan and Induces Inflammation-Associated Signaling and Oxidative Stress in Drosophila.

PubMed

Wang, Xiaoke; Chen, Minjie; Zhong, Mianhua; Hu, Ziying; Qiu, Lianglin; Rajagopalan, Sanjay; Fossett, Nancy G; Chen, Lung-Chi; Ying, Zhekang

2017-03-01

Exposure to ambient PM 2.5 is associated with human premature mortality. However, it has not yet been toxicologically replicated, likely due to the lack of suitable animal models. Drosophila is frequently used in longevity research due to many incomparable merits. The present study aims to validate Drosophila models for PM 2.5 toxicity study through characterizing their biological responses to exposure to concentrated ambient PM 2.5 (CAP). The survivorship curve demonstrated that exposure to CAP markedly reduced lifespan of Drosophila. This antilongevity effect of CAP exposure was observed in both male and female Drosophila, and by comparison, the male was more sensitive [50% survivals: 20 and 48 days, CAP- and filtered air (FA)-exposed males, respectively; 21 and 40 days, CAP- and FA-exposed females, respectively]. Similar to its putative pathogenesis in humans, CAP exposure-induced premature mortality in Drosophila was also coincided with activation of pro-inflammatory signaling pathways including Jak, Jnk, and Nf-κb and increased systemic oxidative stress. Furthermore, like in humans and mammals, exposure to CAP significantly increased whole-body and circulating glucose levels and increased mRNA expression of Ilp2 and Ilp5 , indicating that CAP exposure induces dysregulated insulin signaling in Drosophila. Similar to effects on humans exposure to CAP leads to premature mortality likely through induction of inflammation-associated signaling, oxidative stress, and metabolic abnormality in Drosophila, strongly supporting that it can be a useful model organism for PM 2.5 toxicity study. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High exposure to inorganic arsenic by food: the need for risk reduction.

PubMed

Gundert-Remy, Ursula; Damm, Georg; Foth, Heidi; Freyberger, Alexius; Gebel, Thomas; Golka, Klaus; Röhl, Claudia; Schupp, Thomas; Wollin, Klaus-Michael; Hengstler, Jan Georg

2015-12-01

Arsenic is a human carcinogen that occurs ubiquitously in soil and water. Based on epidemiological studies, a benchmark dose (lower/higher bound estimate) between 0.3 and 8 μg/kg bw/day was estimated to cause a 1 % increased risk of lung, skin and bladder cancer. A recently published study by EFSA on dietary exposure to inorganic arsenic in the European population reported 95th percentiles (lower bound min to upper bound max) for different age groups in the same range as the benchmark dose. For toddlers, a highly exposed group, the highest values ranged between 0.61 and 2.09 µg arsenic/kg bw/day. For all other age classes, the margin of exposure is also small. This scenario calls for regulatory action to reduce arsenic exposure. One priority measure should be to reduce arsenic in food categories that contribute most to exposure. In the EFSA study the food categories 'milk and dairy products,' 'drinking water' and 'food for infants' represent major sources of inorganic arsenic for infants and also rice is an important source. Long-term strategies are required to reduce inorganic arsenic in these food groups. The reduced consumption of rice and rice products which has been recommended may be helpful for a minority of individuals consuming unusually high amounts of rice. However, it is only of limited value for the general European population, because the food categories 'grain-based processed products (non rice-based)' or 'milk and dairy products' contribute more to the exposure with inorganic arsenic than the food category 'rice.' A balanced regulatory activity focusing on the most relevant food categories is required. In conclusion, exposure to inorganic arsenic represents a risk to the health of the European population, particularly to young children. Regulatory measures to reduce exposure are urgently required.

Global Gradients of Coral Exposure to Environmental Stresses and Implications for Local Management

PubMed Central

Maina, Joseph; McClanahan, Tim R.; Venus, Valentijn; Ateweberhan, Mebrahtu; Madin, Joshua

2011-01-01

Background The decline of coral reefs globally underscores the need for a spatial assessment of their exposure to multiple environmental stressors to estimate vulnerability and evaluate potential counter-measures. Methodology/Principal Findings This study combined global spatial gradients of coral exposure to radiation stress factors (temperature, UV light and doldrums), stress-reinforcing factors (sedimentation and eutrophication), and stress-reducing factors (temperature variability and tidal amplitude) to produce a global map of coral exposure and identify areas where exposure depends on factors that can be locally managed. A systems analytical approach was used to define interactions between radiation stress variables, stress reinforcing variables and stress reducing variables. Fuzzy logic and spatial ordinations were employed to quantify coral exposure to these stressors. Globally, corals are exposed to radiation and reinforcing stress, albeit with high spatial variability within regions. Based on ordination of exposure grades, regions group into two clusters. The first cluster was composed of severely exposed regions with high radiation and low reducing stress scores (South East Asia, Micronesia, Eastern Pacific and the central Indian Ocean) or alternatively high reinforcing stress scores (the Middle East and the Western Australia). The second cluster was composed of moderately to highly exposed regions with moderate to high scores in both radiation and reducing factors (Caribbean, Great Barrier Reef (GBR), Central Pacific, Polynesia and the western Indian Ocean) where the GBR was strongly associated with reinforcing stress. Conclusions/Significance Despite radiation stress being the most dominant stressor, the exposure of coral reefs could be reduced by locally managing chronic human impacts that act to reinforce radiation stress. Future research and management efforts should focus on incorporating the factors that mitigate the effect of coral stressors until long-term carbon reductions are achieved through global negotiations. PMID:21860667

Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis.

PubMed

Rochester, Johanna R; Bolden, Ashley L; Kwiatkowski, Carol F

2018-05-01

Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans. Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD. Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017. For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at <3 months of age for humans, up to postnatal day 35 for rats and up to postnatal day 40 for mice. Exposure could occur either gestationally (via maternal exposure) or directly to the offspring. Studies were evaluated using the OHAT risk of bias tool. The effects in humans were assessed qualitatively. For rodents exposed to 20 μg/kg/day BPA, we evaluated the study findings in a random effects meta-analytical model. A review of the literature identified 29 rodent and 3 human studies. A random effects meta-analysis showed significantly increased hyperactivity in male rodents. In humans, early BPA exposure was associated with hyperactivity in boys and girls. We concluded that early life BPA exposure is a presumed human hazard for the development of hyperactivity. Possible limitations of this systematic review include deficiencies in author reporting, exclusion of some literature based on language, and insufficient similarity between human studies. SRs that result in hazard-based conclusions are the first step in assessing and mitigating risks. Given the widespread exposure of BPA and increasing diagnoses of ADHD, we recommend immediate actions to complete such risk analyses and take next steps for the protection of human health. In the meantime, precautionary measures should be taken to reduce exposure in pregnant women, infants and children. The present analysis also discusses potential mechanisms by which BPA affects hyperactivity, and the most effective avenues for future research. Not available. Copyright © 2017. Published by Elsevier Ltd.

Cisplatin toxicity reduced in human cultured renal tubular cells by oxygen pretreatment.

PubMed

Kaeidi, Ayat; Rasoulian, Bahram; Hajializadeh, Zahra; Pourkhodadad, Soheila; Rezaei, Maryam

2013-01-01

Cisplatin is an effective and widely used chemotherapy agent and its side effects, particularly nephrotoxicity, limit its usage and related platinum-based drugs. Cisplatin nephrotoxicity is mainly due to extremely increase in reactive oxygen species (ROS) generation leading to kidney tubular cell death. Preconditioning with oxidative stress has been demonstrated to stimulate the cellular adaptation to subsequent severe oxidative stress. Short term oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on Cisplatin induced cell death was investigated in present research. We studied the effects of hyperoxic environment pre-exposure on Cisplatin toxicity in an in-vitro model of cultured human embryonic tubular epithelial cells (AD293). Viability of AD293 cells, as evaluated by MTT-assay, was affected by Cisplatin in a time (1-4 h) dependent model. Biochemical markers of cell apoptosis were evaluated using immunoblotting. Pretreatment with nearly pure oxygen (≥90%) for 2 h significantly reduced the level of cell damage. Activated caspase 3 and Bax/Bcl-2 ratio were significantly increased in Cisplatin-treated cells. Oxygen pretreatment inhibited caspase 3 activation and decreased Bax/Bcl-2 ratio. Oxygen pre-treatment itself not showed any cytotoxicity in exposure times up to 3 h. Our data indicate that hyperoxic preconditioning reduces Cisplatin toxicity in cultured human tubular epithelial cells. The exact mechanism of protection is unclear, though enhancement of some endogenous defense mechanisms and subsequently scavenging of free oxygen radicals may play an important role.

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans

NASA Technical Reports Server (NTRS)

Crandall, C. G.; Shibasaki, M.; Wilson, T. E.; Cui, J.; Levine, B. D.

2003-01-01

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

Methylmercury Exposure and Health Effects from Rice and Fish Consumption: A Review

PubMed Central

Li, Ping; Feng, Xinbin; Qiu, Guangle

2010-01-01

Methylmercury (MeHg) is highly toxic, and its principal target tissue in humans is the nervous system, which has made MeHg intoxication a public health concern for many decades. The general population is primarily exposed to MeHg through consumption of contaminated fish and marine mammals, but recent studies have reported high levels of MeHg in rice and confirmed that in China the main human exposure to MeHg is related to frequent rice consumption in mercury (Hg) polluted areas. This article reviews the progress in the research on MeHg accumulation in rice, human exposure and health effects, and nutrient and co-contaminant interactions. Compared with fish, rice is of poor nutritional quality and lacks specific micronutrients identified as having health benefits (e.g., n-3 long chain polyunsaturated fatty acid, selenium, essential amino acids). The effects of these nutrients on the toxicity of MeHg should be better addressed in future epidemiologic and clinical studies. More emphasis should be given to assessing the health effects of low level MeHg exposure in the long term, with appropriate recommendations, as needed, to reduce MeHg exposure in the rice-eating population. PMID:20644695

Health consequences of exposure to brominated flame retardants: a systematic review.

PubMed

Kim, Young Ran; Harden, Fiona A; Toms, Leisa-Maree L; Norman, Rosana E

2014-07-01

Brominated flame retardants (BFRs), are chemicals widely used in consumer products including electronics, vehicles, plastics and textiles to reduce flammability. Experimental animal studies have confirmed that these compounds may interfere with thyroid hormone homeostasis and neurodevelopment but to date health effects in humans have not been systematically examined. To conduct a systematic review of studies on the health impacts of exposure to BFRs in humans, with a particular focus on children. A systematic review was conducted using the MEDLINE and EMBASE electronic databases up to 1 February 2012. Published cohort, cross-sectional, and case-control studies exploring the relationship between BFR exposure and various health outcomes were included. In total, 36 epidemiological studies meeting the pre-determined inclusion criteria were included. Plausible outcomes associated with BFR exposure include diabetes, neurobehavioral and developmental disorders, cancer, reproductive health effects and alteration in thyroid function. Evidence for a causal relationship between exposure to BFRs and health outcomes was evaluated within the Bradford Hill framework. Although there is suggestive evidence that exposure to BFRs is harmful to health, further epidemiological investigations particularly among children, and long-term monitoring and surveillance of chemical impacts on humans are required to confirm these relationships. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Trials Methods for Evaluation of Potential Reduced Exposure Products

PubMed Central

Hatsukami, Dorothy K.; Hanson, Karen; Briggs, Anna; Parascandola, Mark; Genkinger, Jeanine M.; O'Connor, Richard; Shields, Peter

2009-01-01

Potential reduced exposure tobacco products (PREPs) may have promise in reducing tobacco-related morbidity or mortality or may promote greater harm to individuals or the population. Critical to determining the risks or benefits from these products are valid human clinical trial PREP assessment methods. Assessment involves determining the effects of these products on biomarkers of exposure and of effect, which serve as proxies for harm, and assessing the potential for consumer uptake and abuse of the product. This article raises the critical methodological issues associated with PREP assessment, reviews the methods that have been used to assess PREPs, and describes the strengths and limitations of these methods. Additionally, recommendations for clinical trials PREP assessment methods and future research directions in this area based on this review and on the deliberations from a National Cancer Institute sponsored Clinical Trials PREP Methods Workshop are provided. PMID:19959672

INHIBITION OF TESTICULAR STEROIDOGENESIS BY THE XENOESTROGEN BISPHENOL A IS ASSOCIATED WITH REDUCED PITUITARY LH SECRETION AND DECREASED STEROIDOGENIC ENZYME GENE EXPRESSION IN RAT LEYDIG CELLS

EPA Science Inventory

Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and constituent of resins used in food packaging and denistry, is significant. In this report, exposure of rats to 2.4 ug/kg/day (a dose that approximates BPA levels in the environment) from postnatal da...

Exposure Factors Handbook - 2009 Update (External Review ...

EPA Pesticide Factsheets

The mission of National Center for Environmental Assessment (NCEA) of EPA's Office of Research and Development is to provide guidance and risk assessments aimed at protecting human health and the environment. To accomplish this mission, NCEA works to develop and improve the models, databases, tools, assumptions, and extrapolations used in risk assessments. This handbook is a tool developed by NCEA aimed at refining the assumptions used in exposure assessments and reducing uncertainty. This handbook was first published in 1989 and updated in 1997 to provide statistical data on the various human factors used in assessing exposure. This revised version of the handbook provides the up-to-date data on these exposure factors. The recommended values are based solely on our interpretations of the available data. In many situations different values may be appropriate to use in consideration of policy, precedent or other factors. External Review Draft

Are men talking their reproductive health away?

PubMed

Agarwal, Ashok; Durairajanayagam, Damayanthi

2015-01-01

The advent of mobile phones has revolutionized communication trends across the globe. As the popularity of mobile phone usage continues to escalate, there is now growing concern about the effects of radiofrequency electromagnetic waves (RF-EMW) exposure on biological tissues, such as the brain and testes. Researchers have sought to link the much debated decline in human sperm quality in the last decade, with increased exposure to RF-EMW, particularly through mobile phone usage. In a recent systematic review and meta-analysis on the effect of mobile phone RF-EMW radiation on sperm quality, Adams et al. [1] demonstrated an association between mobile phone exposure and reduced sperm motility and viability, with inconsistent effects on sperm concentration. [1] Results from 10 pooled experimental (in vitro) and observational (in vivo)human studies (n = 1492) led these researchers to suggest that exposure to RF-EMW radiation from carrying a mobile phone in the trouser pocket negatively impacts sperm quality.

Contested evidence: Exposure to competing scientific claims and public support for banning bisphenol A.

PubMed

Brewer, Paul R; Ley, Barbara L

2014-05-01

The public controversy surrounding bisphenol A (BPA) revolves around competing claims about what scientific evidence shows regarding the effects of the chemical on human health. This study uses an experiment embedded within a public opinion survey to test the effects of exposure to such claims on public support for banning the use of BPA in products. Exposure to the claim that "there is not enough scientific evidence that BPA harms human health" reduced support, whereas exposure to the claim that there "is enough scientific evidence" failed to increase support. No effect emerged among those simultaneously exposed to both claims. The "not enough evidence" claim influenced less educated respondents and women but not college-educated respondents or men. Aspects of the underlying structure of opinion also differed depending on which claim(s) respondents received. The results illuminate how members of the public respond to competing scientific claims regarding controversial issues.

Ethyl carbamate induces cell death through its effects on multiple metabolic pathways.

PubMed

Liu, Huichang; Cui, Bo; Xu, Yi; Hu, Chaoyang; Liu, Ying; Qu, Guorun; Li, Dawei; Wu, Yongning; Zhang, Dabing; Quan, Sheng; Shi, Jianxin

2017-11-01

Ethyl carbamate (EC), a multisite carcinogenic chemical causing tumors in various animal species, is probably carcinogenic to humans. However, information about the possible carcinogenic and toxicological effects of EC in humans is quite limited. Because EC is found in many dietary foods (such as fermented foods) and tobacco and its products, and exposure of humans to EC often occurs inevitably, its toxicological effects in humans need to be studied. This study was conducted to understand the metabolomic and transcriptomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 100 mM EC for short term (4 h) and long term (12 h) period, respectively. The results revealed multiple influences of EC on the metabolome and transcriptome of HepG2 cells, which was exposure time-dependent and well correlated with the kinetic changes of cell viability and mortality. EC treatment affected multiple metabolic pathways, inducing oxidative stress, reducing detoxification capacity, depleting energy, decreasing reducing power, disrupting membrane integrity, and damaging DNA and protein. These metabolomic and transcriptomic biomarkers of EC on human cell metabolism identified in this study would facilitate further studies on the risk assessment and the mitigation of dietary EC. Copyright © 2017 Elsevier B.V. All rights reserved.

Reduced chromosome aberration complexity in normal human bronchial epithelial cells exposed to low-LET γ-rays and high-LET α-particles

PubMed Central

2013-01-01

Purpose: Cells of the lung are at risk from exposure to low and moderate doses of ionizing radiation from a range of environmental and medical sources. To help assess human health risks from such exposures, a better understanding of the frequency and types of chromosome aberration initially-induced in human lung cell types is required to link initial DNA damage and rearrangements with transmission potential and, to assess how this varies with radiation quality. Materials and methods: We exposed normal human bronchial lung epithelial (NHBE) cells in vitro to 0.5 and 1 Gy low-linear energy transfer (LET) γ-rays and a low fluence of high-LET α-particles and assayed for chromosome aberrations in premature chromosome condensation (PCC) spreads by 24-color multiplex-fluorescence in situ hybridization (M-FISH). Results: Both simple and complex aberrations were induced in a LET and dose-dependent manner; however, the frequency and complexity observed were reduced in comparison to that previously reported in spherical cell types after exposure to comparable doses or fluence of radiation. Approximately 1–2% of all exposed cells were categorized as being capable of transmitting radiation-induced chromosomal damage to future NHBE cell generations, irrespective of dose. Conclusion: One possible mechanistic explanation for this reduced complexity is the differing geometric organization of chromosome territories within ellipsoid nuclei compared to spherical nuclei. This study highlights the need to better understand the role of nuclear organization in the formation of exchange aberrations and, the influence three-dimensional (3D) tissue architecture may have on this in vivo. PMID:23679558

Germline and reproductive tract effects intensify in male mice with successive generations of estrogenic exposure

PubMed Central

Horan, Tegan S.; Marre, Alyssa; Hassold, Terry; Lawson, Crystal; Hunt, Patricia A.

2017-01-01

The hypothesis that developmental estrogenic exposure induces a constellation of male reproductive tract abnormalities is supported by experimental and human evidence. Experimental data also suggest that some induced effects persist in descendants of exposed males. These multi- and transgenerational effects are assumed to result from epigenetic changes to the germline, but few studies have directly analyzed germ cells. Typically, studies of transgenerational effects have involved exposing one generation and monitoring effects in subsequent unexposed generations. This approach, however, has limited human relevance, since both the number and volume of estrogenic contaminants has increased steadily over time, intensifying rather than reducing or eliminating exposure. Using an outbred CD-1 mouse model, and a sensitive and quantitative marker of germline development, meiotic recombination, we tested the effect of successive generations of exposure on the testis. We targeted the germline during a narrow, perinatal window using oral exposure to the synthetic estrogen, ethinyl estradiol. A complex three generation exposure protocol allowed us to compare the effects of individual, paternal, and grandpaternal (ancestral) exposure. Our data indicate that multiple generations of exposure not only exacerbate germ cell exposure effects, but also increase the incidence and severity of reproductive tract abnormalities. Taken together, our data suggest that male sensitivity to environmental estrogens is increased by successive generations of exposure. PMID:28727826

Clinical Evidence for Any Effect of Anesthesia on the Developing Brain.

PubMed

Davidson, Andrew J; Sun, Lena S

2018-04-01

A recent U.S. Food and Drug Administration warning advised that prolonged or repeated exposure to general anesthetics may affect neurodevelopment in children. This warning is based on a wealth of preclinical animal studies and relatively few human studies. The human studies include a variety of different populations with several different outcome measures. Interpreting the results requires consideration of the outcome used, the power of the study, the length of exposure and the efforts to reduce the confounding effects of comorbidity and surgery. Most, but not all, of the large population-based studies find evidence for associations between surgery in early childhood and slightly worse subsequent academic achievement or increased risk for later diagnosis of a behavioral disability. In several studies, the amount of added risk is very small; however, there is some evidence for a greater association with multiple exposures. These results may be consistent with the preclinical data, but the possibility of confounding means the positive associations can only be regarded as weak evidence for causation. Finally, there is strong evidence that brief exposure is not associated with any long term risk in humans.

Habitat Design Considerations for Implementing Solar Particle Event Radiation Protection

NASA Technical Reports Server (NTRS)

Simon, Mathew A.; Clowdsley, Martha S.; Walker, Steven A.

2013-01-01

Radiation protection is an important habitat design consideration for human exploration missions beyond Low Earth Orbit. Fortunately, radiation shelter concepts can effectively reduce astronaut exposure for the relatively low proton energies of solar particle events, enabling moderate duration missions of several months before astronaut exposure (galactic cosmic ray and solar particle event) approaches radiation exposure limits. In order to minimize habitat mass for increasingly challenging missions, design of radiation shelters must minimize dedicated, single-purpose shielding mass by leveraging the design and placement of habitat subsystems, accommodations, and consumables. NASA's Advanced Exploration Systems RadWorks Storm Shelter Team has recently designed and performed radiation analysis on several low dedicated mass shelter concepts for a year-long mission. This paper describes habitat design considerations identified during the study's radiation analysis. These considerations include placement of the shelter within a habitat for improved protection, integration of human factors guidance for sizing shelters, identification of potential opportunities for habitat subsystems to compromise on individual subsystem performances for overall vehicle mass reductions, and pre-configuration of shelter components for reduced deployment times.

Circadian Entrainment to the Natural Light-Dark Cycle Across Seasons and the Weekend

PubMed Central

Stothard, Ellen R.; McHill, Andrew W.; Depner, Christopher M.; Birks, Brian R.; Moehlman, Thomas M.; Ritchie, Hannah K.; Guzzetti, Jacob R.; Chinoy, Evan D.; LeBourgeois, Monique K.; Axelsson, John; Wright, Kenneth P.

2017-01-01

Summary Reduced exposure to daytime sunlight and increased exposure to electrical lighting at night leads to late circadian and sleep timing [1–3]. We have previously shown that exposure to a natural summer 14 hr 40 min:9 hr 20 min light-dark cycle entrains the human circadian clock to solar time, such that the internal biological night begins near sunset and ends near sunrise [1]. Here we show the beginning of the biological night and sleep occur earlier after a week exposure to a natural winter 9 hr 20 min:14 hr 40 min light-dark cycle as compared to the modern electrical lighting environment. Further, we find the human circadian clock is sensitive to seasonal changes in the natural light-dark cycle showing an expansion of the biological night in winter compared to summer—akin to that seen in non-humans [4–8]. We also show circadian and sleep timing occur earlier after spending a weekend camping in a summer 14 hr 39 min:9 hr 21 min natural light-dark cycle compared to a typical weekend in the modern environment. Weekend exposure to natural light was sufficient to achieve ~69% of the shift in circadian timing we previously reported after one week exposure to natural light [1]. These findings provide evidence that the human circadian clock adapts to seasonal changes in the natural light-dark cycle and is timed later in the modern environment in both winter and summer. Further, we demonstrate earlier circadian timing can be rapidly achieved through natural light exposure during a weekend spent camping. PMID:28162893

Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption

PubMed Central

Heger, Nicholas E; Hall, Susan J; Sandrof, Moses A; McDonnell, Elizabeth V; Hensley, Janan B; McDowell, Erin N; Martin, Kayla A; Gaido, Kevin W; Johnson, Kamin J

2012-01-01

Background: In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates. Objectives: In this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response. Methods: Fetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points. Results: Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression. Conclusions: Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis. PMID:22511013

Using the Moon as a high-fidelity analogue environment to study biological and behavioral effects of long-duration space exploration

NASA Astrophysics Data System (ADS)

Goswami, Nandu; Roma, Peter G.; De Boever, Patrick; Clément, Gilles; Hargens, Alan R.; Loeppky, Jack A.; Evans, Joyce M.; Peter Stein, T.; Blaber, Andrew P.; Van Loon, Jack J. W. A.; Mano, Tadaaki; Iwase, Satoshi; Reitz, Guenther; Hinghofer-Szalkay, Helmut G.

2012-12-01

Due to its proximity to Earth, the Moon is a promising candidate for the location of an extra-terrestrial human colony. In addition to being a high-fidelity platform for research on reduced gravity, radiation risk, and circadian disruption, the Moon qualifies as an isolated, confined, and extreme (ICE) environment suitable as an analog for studying the psychosocial effects of long-duration human space exploration missions and understanding these processes. In contrast, the various Antarctic research outposts such as Concordia and McMurdo serve as valuable platforms for studying biobehavioral adaptations to ICE environments, but are still Earth-bound, and thus lack the low-gravity and radiation risks of space. The International Space Station (ISS), itself now considered an analog environment for long-duration missions, better approximates the habitable infrastructure limitations of a lunar colony than most Antarctic settlements in an altered gravity setting. However, the ISS is still protected against cosmic radiation by the Earth magnetic field, which prevents high exposures due to solar particle events and reduces exposures to galactic cosmic radiation. On Moon the ICE environments are strengthened, radiations of all energies are present capable of inducing performance degradation, as well as reduced gravity and lunar dust. The interaction of reduced gravity, radiation exposure, and ICE conditions may affect biology and behavior - and ultimately mission success - in ways the scientific and operational communities have yet to appreciate, therefore a long-term or permanent human presence on the Moon would ultimately provide invaluable high-fidelity opportunities for integrated multidisciplinary research and for preparations of a manned mission to Mars.

USDA Collaboration with EPA/ORD

EPA Science Inventory

For more than seven years, EPA scientists have been leveraging the USDA Environmental Policy Integrated Climate (EPIC) model to reduce uncertainty in our estimates of agricultural emissions, ambient PM concentrations and subsequent human exposure risk. This presentation summariz...

Estimated Daily Phthalate Exposures in a Population of Mothers of Male Infants Exhibiting Reduced Anogenital Distance

PubMed Central

Marsee, Kevin; Woodruff, Tracey J.; Axelrad, Daniel A.; Calafat, Antonia M.; Swan, Shanna H.

2006-01-01

Phthalate diesters have been shown to be developmental and reproductive toxicants in animal studies. A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects in human male infants exposed prenatally to phthalates. We used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were statistically significantly associated with developmental effects in the 214 mother–infant pairs [di-n-butyl phthalate (DnBP), diethyl phthalate (DEP), butylbenzyl phthalate (BBzP), diisobutyl phthalate (DiBP)] and for another important phthalate [di-2-ethylhexyl phthalate (DEHP)]. We estimated the median and 95th percentile of daily exposures to DBP to be 0.99 and 2.68 μg/kg/day, respectively; for DEP, 6.64 and 112.3 μg/kg/day; for BBzP, 0.50 and 2.47 μg/kg/day; and for DEHP, 1.32 and 9.32 μg/kg/day. The U.S. Environmental Protection Agency (EPA) reference doses for these chemicals are 100 (DBP), 800 (DEP), 200 (BBzP), and 20 (DEHP) μg/kg/day. The median and 95th percentile exposure estimates for the phthalates associated with reduced anogenital distance in the study population are substantially lower than current U.S. EPA reference doses for these chemicals and could be informative to any updates of the hazard assessments and risk assessments for these chemicals. PMID:16759976

Some physiological aspects of artificial gravity. [gravitational effects on human orthostatic tolerance and physical fitness

NASA Technical Reports Server (NTRS)

Cramer, D. B.; Graybiel, A.

1973-01-01

The effects of increasing artificial gravity exposure on four aspects of physiological fitness are examined in four young men who, prior to exposure, were deconditioned with bed rest and water immersion. The four aspects of physiological fitness are orthostatic tolerance, exercise tolerance, forearm endurance, and maximum strength. Orthostatic tolerance was sharply reduced by deconditioning and was substantially improved by walking in simulated lunar gravity (1/6 g) for 2.5 hours daily for 7 days or by walking in 1/2 g and 1 g for 1 hour daily for 3 days. Exercise tolerance was also sharply reduced by deconditioning but did not significantly improve with increasing g-exposure. Walking in 1 g for 1 hour daily for 3 days raised exercise tolerance only a little above the low produced by deconditioning. Forearm endurance and maximum strength were relatively unaffected by deconditioning and subsequent g-exposure.

A Controlled Trial to Reduce the Risk of Human Nipah Virus Exposure in Bangladesh.

PubMed

Nahar, Nazmun; Paul, Repon C; Sultana, Rebeca; Sumon, Shariful Amin; Banik, Kajal Chandra; Abedin, Jaynal; Asaduzzaman, Mohammad; Garcia, Fernando; Zimicki, Susan; Rahman, Mahmudur; Gurley, Emily S; Luby, Stephen P

2017-09-01

Human Nipah virus (NiV) infection, often fatal in Bangladesh, is primarily transmitted by drinking raw date palm sap contaminated by Pteropus bats. We assessed the impact of a behavior change communication intervention on reducing consumption of potentially NiV-contaminated raw sap. During the 2012-2014 sap harvesting seasons, we implemented interventions in two areas and compared results with a control area. In one area, we disseminated a "do not drink raw sap" message and, in the other area, encouraged only drinking sap if it had been protected from bat contamination by a barrier ("only safe sap"). Post-intervention, 40% more respondents in both intervention areas reported knowing about a disease contracted through raw sap consumption compared with control. Reported raw sap consumption decreased in all areas. The reductions in the intervention areas were not significantly greater compared to the control. Respondents directly exposed to the "only safe sap" message were more likely to report consuming raw sap from a protected source than those with no exposure (25 vs. 15%, OR 2.0, 95% CI 1.5-2.6, P < 0.001). While the intervention increased knowledge in both intervention areas, the "only safe sap" intervention reduced exposure to potentially NiV-contaminated sap and should be considered for future dissemination.

Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model.

PubMed

Hu, Jianzhong; Raikhel, Vincent; Gopalakrishnan, Kalpana; Fernandez-Hernandez, Heriberto; Lambertini, Luca; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Belpoggi, Fiorella; L Teitelbaum, Susan; Chen, Jia

2016-06-14

This proof-of-principle study examines whether postnatal, low-dose exposure to environmental chemicals modifies the composition of gut microbiome. Three chemicals that are widely used in personal care products-diethyl phthalate (DEP), methylparaben (MPB), triclosan (TCS)-and their mixture (MIX) were administered at doses comparable to human exposure to Sprague-Dawley rats from birth through adulthood. Fecal samples were collected at two time points: postnatal day (PND) 62 (adolescence) and PND 181 (adulthood). The gut microbiome was profiled by 16S ribosomal RNA gene sequencing, taxonomically assigned and assessed for diversity. Metagenomic profiling revealed that the low-dose chemical exposure resulted in significant changes in the overall bacterial composition, but in adolescent rats only. Specifically, the individual taxon relative abundance for Bacteroidetes (Prevotella) was increased while the relative abundance of Firmicutes (Bacilli) was reduced in all treated rats compared to controls. Increased abundance was observed for Elusimicrobia in DEP and MPB groups, Betaproteobacteria in MPB and MIX groups, and Deltaproteobacteria in TCS group. Surprisingly, these differences diminished by adulthood (PND 181) despite continuous exposure, suggesting that exposure to the environmental chemicals produced a more profound effect on the gut microbiome in adolescents. We also observed a small but consistent reduction in the bodyweight of exposed rats in adolescence, especially with DEP and MPB treatment (p < 0.05), which is consistent with our findings of a reduced Firmicutes/Bacteroidetes ratio at PND 62 in exposed rats. This study provides initial evidence that postnatal exposure to commonly used environmental chemicals at doses comparable to human exposure is capable of modifying the gut microbiota in adolescent rats; whether these changes lead to downstream health effects requires further investigation.

Comparative Risk Assessment of spill response options for a deepwater oil well blowout: Part 1. Oil spill modeling.

PubMed

French-McCay, Deborah; Crowley, Deborah; Rowe, Jill J; Bock, Michael; Robinson, Hilary; Wenning, Richard; Walker, Ann Hayward; Joeckel, John; Nedwed, Tim J; Parkerton, Thomas F

2018-06-01

Oil spill model simulations of a deepwater blowout in the Gulf of Mexico De Soto Canyon, assuming no intervention and various response options (i.e., subsea dispersant injection SSDI, in addition to mechanical recovery, in-situ burning, and surface dispersant application) were compared. Predicted oil fate, amount and area of surfaced oil, and exposure concentrations in the water column above potential effects thresholds were used as inputs to a Comparative Risk Assessment to identify response strategies that minimize long-term impacts. SSDI reduced human and wildlife exposure to volatile organic compounds; dispersed oil into a large water volume at depth; enhanced biodegradation; and reduced surface water, nearshore and shoreline exposure to floating oil and entrained/dissolved oil in the upper water column. Tradeoffs included increased oil exposures at depth. However, since organisms are less abundant below 200 m, results indicate that overall exposure of valued ecosystem components was minimized by use of SSDI. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reducing chemical exposures at home: opportunities for action

PubMed Central

Zota, Ami R; Singla, Veena; Adamkiewicz, Gary; Mitro, Susanna D; Dodson, Robin E

2017-01-01

Indoor environments can influence human environmental chemical exposures and, ultimately, public health. Furniture, electronics, personal care and cleaning products, floor coverings and other consumer products contain chemicals that can end up in the indoor air and settled dust. Consumer product chemicals such as phthalates, phenols, flame retardants and per- and polyfluorinated alkyl substances are widely detected in the US general population, including vulnerable populations, and are associated with adverse health effects such as reproductive and endocrine toxicity. We discuss the implications of our recent meta-analysis describing the patterns of chemical exposures and the ubiquity of multiple chemicals in indoor environments. To reduce the likelihood of exposures to these toxic chemicals, we then discuss approaches for exposure mitigation: targeting individual behaviour change, household maintenance and purchasing decisions, consumer advocacy and corporate responsibility in consumer markets, and regulatory action via state/federal policies. There is a need to further develop evidence-based strategies for chemical exposure reduction in each of these areas, given the multi-factorial nature of the problem. Further identifying those at greatest risk; understanding the individual, household and community factors that influence indoor chemical exposures; and developing options for mitigation may substantially improve individuals’ exposures and health. PMID:28756396

Genetic and Dietary Regulation of Glyburide Efflux by the Human Placental Breast Cancer Resistance Protein Transporter

PubMed Central

Bircsak, Kristin M.; Gupta, Vivek; Yuen, Poi Yu Sofia; Gorczyca, Ludwik; Weinberger, Barry I.; Vetrano, Anna M.

2016-01-01

Glyburide is frequently used to treat gestational diabetes owing to its low fetal accumulation resulting from placental efflux by the breast cancer resistance protein (BCRP)/ABCG2 transporter. Here we sought to determine how exposure to the dietary phytoestrogen genistein and expression of a loss-of-function polymorphism in the ABCG2 gene (C421A) impacted the transport of glyburide by BCRP using stably transfected human embryonic kidney 293 (HEK) cells, human placental choriocarcinoma BeWo cells, and human placental explants. Genistein competitively inhibited the BCRP-mediated transport of 3H-glyburide in both wild-type (WT) and C421A-BCRP HEK-expressing cells, with greater accumulation of 3H-glyburide in cells expressing the C421A variant. In BeWo cells, exposure to genistein for 60 minutes increased the accumulation of 3H-glyburide 30%–70% at concentrations relevant to dietary exposure (IC50 ∼180 nM). Continuous exposure of BeWo cells to genistein for 48 hours reduced the expression of BCRP mRNA and protein by up to 40%, which impaired BCRP transport activity. Pharmacologic antagonism of the estrogen receptor attenuated the genistein-mediated downregulation of BCRP expression, suggesting that phytoestrogens may reduce BCRP levels through this hormone receptor pathway in BeWo cells. Interestingly, genistein treatment for 48 hours did not alter BCRP protein expression in explants dissected from healthy term placentas. These data suggest that whereas genistein can act as a competitive inhibitor of BCRP-mediated transport, its ability to downregulate placental BCRP expression may only occur in choriocarcinoma cells. Overall, this research provides important mechanistic data regarding how the environment (dietary genistein) and a frequent genetic variant (ABCG2, C421A) may alter the maternal-fetal disposition of glyburide. PMID:26850786

Chlorine isotopic composition of perchlorate in human urine as a means of distinguishing among exposure sources.

PubMed

Poghosyan, Armen; Morel-Espinosa, Maria; Valentin-Blasini, Liza; Blount, Benjamin C; Ferreccio, Catterina; Steinmaus, Craig M; Sturchio, Neil C

2016-01-01

Perchlorate (ClO4(-)) is a ubiquitous environmental contaminant with high human exposure potential. Natural perchlorate forms in the atmosphere from where it deposits onto the surface of Earth, whereas synthetic perchlorate is manufactured as an oxidant for industrial, aerospace, and military applications. Perchlorate exposure can potentially cause adverse health effects in humans by interfering with the production of thyroid hormones through competitively blocking iodide uptake. To control and reduce perchlorate exposure, the contributions of different sources of perchlorate exposure need to be quantified. Thus, we demonstrate a novel approach for determining the contribution of different perchlorate exposure sources by quantifying stable and radioactive chlorine isotopes of perchlorate extracted from composite urine samples from two distinct populations: one in Atlanta, USA and one in Taltal, Chile (Atacama region). Urinary perchlorate from the Atlanta region resembles indigenous natural perchlorate from the western USA (δ(37)Cl=+4.1±1.0‰; (36)Cl/Cl=1 811 (±136) × 10(-15)), and urinary perchlorate from the Taltal, Chile region is similar to natural perchlorate in nitrate salt deposits from the Atacama Desert of northern Chile (δ(37)Cl=-11.0±1.0‰; (36)Cl/Cl=254 (±40) × 10(-15)). Neither urinary perchlorate resembled the isotopic pattern found in synthetic perchlorate. These results indicate that natural perchlorate of regional provenance is the dominant exposure source for the two sample populations, and that chlorine isotope ratios provide a robust tool for elucidating perchlorate exposure pathways.

Occupational exposure to glycol ethers: implications for occupational health nurses.

PubMed

Snow, J E

1994-09-01

1. Evaluation of workplace exposure to reproductive hazards is difficult and is often confounded by occupational exposure to multiple agents and exposure to non-occupational factors. 2. A growing body of evidence from animal and human study data supports a causal association between occupational exposure to certain glycol ethers and adverse reproductive outcomes. 3. Occupational health nurses providing services to employees exposed to glycol ethers should remain knowledgeable about the results of epidemiologic studies and current trends in the regulation of glycol ethers in industry. 4. Occupational health nurses are in a key position to reduce exposure to reproductive hazards by monitoring trends in group data and by implementing training and education programs to employees exposed to reproductive hazards.

Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents With the Tobacco Heating System 2.1

PubMed Central

Baker, Gizelle; Magnette, John; Picavet, Patrick; Weitkunat, Rolf

2017-01-01

Introduction: Heating rather than burning tobacco reduces levels of harmful and potentially harmful constituents, and consumer products using this approach aim to reduce exposure to tobacco toxicants. The Tobacco Heating System (THS) version 2.1 has been enhanced from earlier prototypes with an improved heat control and sensorial experience and thereby user acceptance. Exposure measurements are required to determine whether it may be possible to reduce the individual health risk compared to smoking combustible cigarettes (CCs). Methods: This controlled clinical study randomly assigned 40 smokers to either a group continuing to use of their own CC brand (n = 20) or a group switching to THS 2.1 (n = 20) for 5 days. Biomarkers of exposure were measured at baseline and on day 1 through day 5. Product consumption, Human Puffing Topography, the occurrence of adverse events, and an assessment of subjective effects, such as smoking satisfaction and enjoyment of respiratory tract sensations, were also determined. Results: The group of smokers who switched to THS 2.1 adapted their puffing behavior initially through longer puff duration and more puffs. During the duration of the study, total puff volume returned to baseline levels and the mean daily product consumption increased but with similar nicotine exposure compared to baseline CC use. Biomarkers of exposure to tobacco smoke toxicants which inform product risk assessment were significantly reduced with THS use compared to the CC group. THS 2.1 users experienced less reinforcing effects with THS 2.1 than with their own cigarette brand. Conclusions: THS 2.1 is a promising alternative to smoking CCs. Notwithstanding possible use adaption through consumption or puffing behavior, the exposure to harmful smoke constituents was markedly reduced with the new heated tobacco platform. Implications: Exposure markers to harmful and potentially harmful smoke constituents were lowered with the THS 2.1. Heating tobacco instead of burning can offer a potentially lower risk of delivering nicotine compared to CCs. PMID:27613951

Improving performance of HVAC systems to reduce exposure to aerosolized infectious agents in buildings; recommendations to reduce risks posed by biological attacks.

PubMed

Hitchcock, Penny J; Mair, Michael; Inglesby, Thomas V; Gross, Jonathan; Henderson, D A; O'Toole, Tara; Ahern-Seronde, Joa; Bahnfleth, William P; Brennan, Terry; Burroughs, H E Barney; Davidson, Cliff; Delp, William; Ensor, David S; Gomory, Ralph; Olsiewski, Paula; Samet, Jonathan M; Smith, William M; Streifel, Andrew J; White, Ronald H; Woods, James E

2006-01-01

The prospect of biological attacks is a growing strategic threat. Covert aerosol attacks inside a building are of particular concern. In the summer of 2005, the Center for Biosecurity of the University of Pittsburgh Medical Center convened a Working Group to determine what steps could be taken to reduce the risk of exposure of building occupants after an aerosol release of a biological weapon. The Working Group was composed of subject matter experts in air filtration, building ventilation and pressurization, air conditioning and air distribution, biosecurity, building design and operation, building decontamination and restoration, economics, medicine, public health, and public policy. The group focused on functions of the heating, ventilation, and air conditioning systems in commercial or public buildings that could reduce the risk of exposure to deleterious aerosols following biological attacks. The Working Group's recommendations for building owners are based on the use of currently available, off-the-shelf technologies. These recommendations are modest in expense and could be implemented immediately. It is also the Working Group's judgment that the commitment and stewardship of a lead government agency is essential to secure the necessary financial and human resources and to plan and build a comprehensive, effective program to reduce exposure to aerosolized infectious agents in buildings.

Respiratory effects of air pollution on children.

PubMed

Goldizen, Fiona C; Sly, Peter D; Knibbs, Luke D

2016-01-01

A substantial proportion of the global burden of disease is directly or indirectly attributable to exposure to air pollution. Exposures occurring during the periods of organogenesis and rapid lung growth during fetal development and early post-natal life are especially damaging. In this State of the Art review, we discuss air toxicants impacting on children's respiratory health, routes of exposure with an emphasis on unique pathways relevant to young children, methods of exposure assessment and their limitations and the adverse health consequences of exposures. Finally, we point out gaps in knowledge and research needs in this area. A greater understanding of the adverse health consequences of exposure to air pollution in early life is required to encourage policy makers to reduce such exposures and improve human health. © 2015 Wiley Periodicals, Inc.

Changes in Biomarkers of Exposure on Switching From a Conventional Cigarette to Tobacco Heating Products: A Randomized, Controlled Study in Healthy Japanese Subjects.

PubMed

Gale, Nathan; McEwan, Mike; Eldridge, Alison C; Fearon, Ian M; Sherwood, Neil; Bowen, Edward; McDermott, Simon; Holmes, Emma; Hedge, Andrew; Hossack, Stuart; Wakenshaw, Louise; Glew, James; Camacho, Oscar M; Errington, Graham; McAughey, John; Murphy, James; Liu, Chuan; Proctor, Christopher J

2018-06-15

Smoking is a leading cause of numerous human disorders including pulmonary disease, cardiovascular disease, and cancer. Disease development is primarily caused by exposure to cigarette smoke constituents, many of which are known toxicants. Switching smokers to modified risk tobacco products (MRTPs) has been suggested as a potential means to reduce the risks of tobacco use, by reducing such exposure. This randomized, controlled study investigated whether biomarkers of toxicant exposure (BoE) were reduced when smokers switched from smoking combustible cigarettes to using a novel (glo™/THP1.0) or in-market comparator (iQOS/THS) tobacco heating product (THP). One hundred eighty Japanese smokers smoked combustible cigarettes during a 2-day baseline period, followed by randomization to either continue smoking cigarettes, switch to using mentholated or non-mentholated variants of glo™, switch to using a non-mentholated variant of iQOS, or quit nicotine and tobacco product use completely for 5 days. Baseline and post-randomization 24-h urine samples were collected for BoE analysis. Carbon monoxide was measured daily in exhaled breath (eCO). On day 5 after switching, urinary BoE (excluding for nicotine) and eCO levels were significantly (p < .05) reduced by medians between 20.9% and 92.1% compared with baseline in all groups either using glo™ or iQOS or quitting tobacco use. Between-group comparisons revealed that the reductions in the glo™ groups were similar (p > .05) to quitting in many cases. glo™ or iQOS use for 5 days reduced exposure to smoke toxicants in a manner comparable to quitting tobacco use. THPs are reduced exposure tobacco products with the potential to be MRTPs. This clinical study demonstrates that when smokers switched from smoking combustible cigarettes to using tobacco heating products their exposure to smoke toxicants was significantly decreased. In many cases, this was to the same extent as that seen when they quit smoking completely. This may indicate that these products have the potential to be reduced exposure and/or reduced risk tobacco products when used by smokers whose cigarette consumption is displaced completely. ISRCTN14301360 and UMIN000024988.

New strategy toward dioxin risk reduction for local residents surrounding severe dioxin hotspots in Vietnam

PubMed Central

Thi Tran, Tuyet-Hanh; Nguyen, Ngoc-Bich; Le, Vu-Anh

2013-01-01

Background A public health intervention program with active involvement of local related stakeholders was piloted in the Bien Hoa dioxin hotspot (2007–2009), and then expanded to the Da Nang dioxin hotspot in Vietnam (2009–2011). It aimed to reduce the risk of dioxin exposure of local residents through foods. This article presents the results of the intervention in Da Nang. Methodology To assess the results of this intervention program, pre- and post-intervention knowledge, attitude, and practice (KAP) surveys were implemented in 400 households, randomly selected from four wards surrounding the Da Nang Airbase in 2009 and 2011, respectively. Results After the intervention, the knowledge on the existence of dioxin in food, dioxin exposure pathways, potential high-risk foods, and preventive measures significantly increased (P<0.05). Ninety-eight percent were willing to follow advice on preventing dioxin exposure. Practices to reduce the risk of dioxin exposure also significantly improved (P<0.05). After intervention, 60.4% of households undertook exposure preventive measures, significantly higher than that of the pre-intervention survey (39.6%; χ2=40.15, P<0.001). High-risk foods had quite low rates of daily consumption (from 0 to 2.5%) and were significantly reduced (P<0.05). Conclusions This is seen as an effective intervention strategy toward reducing the risk of human exposure to dioxin at dioxin hotspots. While greater efforts are needed for remediating dioxin-polluted areas inside airbases, there is also evidence to suggest that, during the past four decades, pollution has expanded to the surrounding areas. For this reason, this model should be quickly expanded to the remaining dioxin hotspots in Vietnam to further reduce the exposure risks in other areas. PMID:23791241

Aflatoxins in Iran: Nature, Hazards and Carcinogenicity

PubMed Central

Khoshpey, B; Farhud, DD; Zaini, F

2011-01-01

Many studies have shown that mycotoxin contamination of agricultural products is a challenge for individual’s health especially in developing countries. Improper production and storage of foods, prepare conditions for aflatoxin production in crops, especially rice, wheat, pistachio, walnut, almond, etc which are the main sources of foods for people. Feeding livestock by contaminated bread is another way of human exposure to mycotoxins, especially aflatoxin and because of expensive methods for detecting and analyzing aflatoxin in laboratory; it is not measured in foods. This manuscript is a review of some Iranian and nonIranian reports about aflatoxin, its exposure ways, its adverse effect on human health and nutrition, as well as methods for reducing its exposure. Based on studies on foods, aflatoxin exposure is high in Iran. Since livestock feeding by contaminated bread is one of the potential ways for milk contamination, we should control and reduce aflatoxin contamination by improving production process, storage condition and livestock feeding as soon as possible. Pistachio is one of the most important exporting products of Iran and to maintain Iran’s position in exporting of this product, specific regulations on lowering its contamination with aflatoxin should be considered seriously. Finally, effective controlling of all food and feedstuffs which are vulnerable to aflatoxin contamination is necessary to prevent its effects. PMID:23113099

SHEDS-HT: An Integrated Probabilistic Exposure Model for ...

EPA Pesticide Factsheets

United States Environmental Protection Agency (USEPA) researchers are developing a strategy for highthroughput (HT) exposure-based prioritization of chemicals under the ExpoCast program. These novel modeling approaches for evaluating chemicals based on their potential for biologically relevant human exposures will inform toxicity testing and prioritization for chemical risk assessment. Based on probabilistic methods and algorithms developed for The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals (SHEDS-MM), a new mechanistic modeling approach has been developed to accommodate high-throughput (HT) assessment of exposure potential. In this SHEDS-HT model, the residential and dietary modules of SHEDS-MM have been operationally modified to reduce the user burden, input data demands, and run times of the higher-tier model, while maintaining critical features and inputs that influence exposure. The model has been implemented in R; the modeling framework links chemicals to consumer product categories or food groups (and thus exposure scenarios) to predict HT exposures and intake doses. Initially, SHEDS-HT has been applied to 2507 organic chemicals associated with consumer products and agricultural pesticides. These evaluations employ data from recent USEPA efforts to characterize usage (prevalence, frequency, and magnitude), chemical composition, and exposure scenarios for a wide range of consumer products. In modeling indirec

A study on the dependence of exposure dose reduction and image evaluation on the distance from the dental periapical X-ray machine

NASA Astrophysics Data System (ADS)

Joo, Kyu-Ji; Shin, Jae-Woo; Dong, Kyung-Rae; Lim, Chang-Seon; Chung, Woon-Kwan; Kim, Young-Jae

2013-11-01

Reducing the exposure dose from a periapical X-ray machine is an important aim in dental radiography. Although the radiation exposure dose is generally low, any radiation exposure is harmful to the human body. Therefore, this study developed a method that reduces the exposure dose significantly compared to that encountered in a normal procedure, but still produces an image with a similar resolution. The correlation between the image resolution and the exposure dose of the proposed method was examined with increasing distance between the dosimeter and the X-ray tube. The results were compared with those obtained from the existing radiography method. When periapical radiography was performed once according to the recommendations of the International Commission on Radiological Protection (ICRP), the measured skin surface dose was low at 7 mGy or below. In contrast, the skin surface dose measured using the proposed method was only 1.57 mGy, showing a five-fold reduction. These results suggest that further decreases in dose might be achieved using the proposed method.

Food Packaging and Bisphenol A and Bis(2-Ethyhexyl) Phthalate Exposure: Findings from a Dietary Intervention

PubMed Central

Gray, Janet M.; Engel, Connie L.; Rawsthorne, Teresa W.; Dodson, Robin E.; Ackerman, Janet M.; Rizzo, Jeanne; Nudelman, Janet L.; Brody, Julia Green

2011-01-01

Background: Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) are high-production-volume chemicals used in plastics and resins for food packaging. They have been associated with endocrine disruption in animals and in some human studies. Human exposure sources have been estimated, but the relative contribution of dietary exposure to total intake has not been studied empirically. Objectives: To evaluate the contribution of food packaging to exposure, we measured urinary BPA and phthalate metabolites before, during, and after a “fresh foods” dietary intervention. Methods: We selected 20 participants in five families based on self-reported use of canned and packaged foods. Participants ate their usual diet, followed by 3 days of “fresh foods” that were not canned or packaged in plastic, and then returned to their usual diet. We collected evening urine samples over 8 days in January 2010 and composited them into preintervention, during intervention, and postintervention samples. We used mixed-effects models for repeated measures and Wilcoxon signed-rank tests to assess change in urinary levels across time. Results: Urine levels of BPA and DEHP metabolites decreased significantly during the fresh foods intervention [e.g., BPA geometric mean (GM), 3.7 ng/mL preintervention vs. 1.2 ng/mL during intervention; mono-(2-ethyl-5-hydroxy hexyl) phthalate GM, 57 ng/mL vs. 25 ng/mL]. The intervention reduced GM concentrations of BPA by 66% and DEHP metabolites by 53–56%. Maxima were reduced by 76% for BPA and 93–96% for DEHP metabolites. Conclusions: BPA and DEHP exposures were substantially reduced when participants’ diets were restricted to food with limited packaging. PMID:21450549

Calidad del aire interior

EPA Pesticide Factsheets

This web site will educate the public about indoor environmental issues including health risks and means by which human exposures can be reduced. Content on this site will be focused on Spanish translated resources for information about indoor air quality.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure.

PubMed

Rautava, Samuli; Walker, W Allan; Lu, Lei

2016-06-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. Copyright © 2016 the American Physiological Society.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure

PubMed Central

Rautava, Samuli; Lu, Lei

2016-01-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. PMID:27056727

Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavlikova, Nela, E-mail: nela.pavlikova@lf3.cuni.cz; Smetana, Pavel; Halada, Petr

Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cellmore » line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin, cytokeratin 8 and 18 was reduced in NES2Y/DDT. • Expression of HNRH1 and cytokeratin 18 was reduced in NES2Y/DDE.« less

A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.

The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the developmentmore » and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.« less

A review on recent progress in observations, and health effects of bioaerosols.

PubMed

Humbal, Charmi; Gautam, Sneha; Trivedi, Ujwalkumar

2018-06-06

Bioaerosol is a particulate mixture of solid and semi-solid matter combined with biotic matter like pollens, microbes and their fragments. The present review stresses on a cumulative understanding of sources, components, quantification and distribution of bioaerosols with respect to size, and its significant impacts on human health. The present review will be instrumental in devising strategies to understand and manage bioaerosols and reducing their human exposure and associated health hazards. The present review aims explore the relationship between particle and associated biological agents responsible for behaviours like dispersal, total potential health hazards and toxicology level during exposure to bioaerosol. Copyright © 2018. Published by Elsevier Ltd.

New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures.

PubMed

Harrill, Alison H; McAllister, Kimberly A

2017-08-15

This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene-environment interactions in human disease and to inform human health risk assessment. This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. These unique resources have the potential to be powerful tools for generating hypotheses related to gene-environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274.

New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures

PubMed Central

Harrill, Alison H.

2017-01-01

Background: This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene–environment interactions in human disease and to inform human health risk assessment. Objectives: This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. Methods: This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. Discussion: These unique resources have the potential to be powerful tools for generating hypotheses related to gene–environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. Conclusions: These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274 PMID:28886592

Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.

PubMed

Rudell, B; Ledin, M C; Hammarström, U; Stjernberg, N; Lundbäck, B; Sandström, T

1996-10-01

Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap.

The impact of lymphocyte isolation on induced DNA damage in human blood samples measured by the comet assay.

PubMed

Bausinger, Julia; Speit, Günter

2016-09-01

The comet assay is frequently used in human biomonitoring for the detection of exposure to genotoxic agents. Peripheral blood samples are most frequently used and tested either as whole blood or after isolation of lymphocytes (i.e. peripheral blood mononuclear cells, PBMC). To investigate a potential impact of lymphocyte isolation on induced DNA damage in human blood samples, we exposed blood ex vivo to mutagens with different modes of genotoxic action. The comet assay was performed either directly with whole blood at the end of the exposure period or with lymphocytes isolated directly after exposure. In addition to the recommended standard protocol for lymphocyte isolation, a shortened protocol was established to optimise the isolation procedure. The results indicate that the effects of induced DNA strand breaks and alkali-labile sites induced by ionising radiation and alkylants, respectively, are significantly reduced in isolated lymphocytes. In contrast, oxidative DNA base damage (induced by potassium bromate) and stable bulky adducts (induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide; BPDE) seem to be less affected. Our findings suggest that in vivo-induced DNA damage might also be reduced in isolated lymphocytes in comparison with the whole blood depending of the types of DNA damage induced. Because only small genotoxic effects can generally be expected in human biomonitoring studies with the comet assay after occupational and environmental exposure to genotoxic agents, any loss might be relevant and should be avoided. The possibility of such effects and their potential impact on variability of comet assay results in human biomonitoring should be considered when performing or evaluating such kind of studies. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes.

PubMed

Hawkins, Simon J; Crompton, Lucy A; Sood, Aman; Saunders, Margaret; Boyle, Noreen T; Buckley, Amy; Minogue, Aedín M; McComish, Sarah F; Jiménez-Moreno, Natalia; Cordero-Llana, Oscar; Stathakos, Petros; Gilmore, Catherine E; Kelly, Stephen; Lane, Jon D; Case, C Patrick; Caldwell, Maeve A

2018-05-01

The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes. Crucially, neuronal DNA damage is mediated by astrocytes. Inhibiting the autophagic degradation in the BeWo barrier by overexpression of the dominant-negative human ATG4B C74A significantly reduces the levels of DNA damage in astrocytes. In vivo, indirect NP toxicity in mice results in neurodevelopmental abnormalities with reactive astrogliosis and increased DNA damage in the fetal hippocampus. Our results demonstrate the potential importance of autophagy to elicit NP toxicity and the risk of indirect developmental neurotoxicity after maternal NP exposure.

Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes

NASA Astrophysics Data System (ADS)

Hawkins, Simon J.; Crompton, Lucy A.; Sood, Aman; Saunders, Margaret; Boyle, Noreen T.; Buckley, Amy; Minogue, Aedín M.; McComish, Sarah F.; Jiménez-Moreno, Natalia; Cordero-Llana, Oscar; Stathakos, Petros; Gilmore, Catherine E.; Kelly, Stephen; Lane, Jon D.; Case, C. Patrick; Caldwell, Maeve A.

2018-05-01

The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes. Crucially, neuronal DNA damage is mediated by astrocytes. Inhibiting the autophagic degradation in the BeWo barrier by overexpression of the dominant-negative human ATG4BC74A significantly reduces the levels of DNA damage in astrocytes. In vivo, indirect NP toxicity in mice results in neurodevelopmental abnormalities with reactive astrogliosis and increased DNA damage in the fetal hippocampus. Our results demonstrate the potential importance of autophagy to elicit NP toxicity and the risk of indirect developmental neurotoxicity after maternal NP exposure.

Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies

PubMed Central

Rogers, P J; Hogenkamp, P S; de Graaf, C; Higgs, S; Lluch, A; Ness, A R; Penfold, C; Perry, R; Putz, P; Yeomans, M R; Mela, D J

2016-01-01

By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific ‘learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (−0.002 kg m−2 per year, 95% confidence interval (CI) −0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (−94 kcal, 95% CI −122 to −66), with no difference versus water (−2 kcal, 95% CI −30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; −1.35 kg, 95% CI –2.28 to −0.42), and a similar relative reduction in BW versus water (three comparisons; −1.24 kg, 95% CI –2.22 to −0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water. PMID:26365102

Epidemiological Trends Strongly Suggest Exposures as Etiologic Agents in the Pathogenesis of Sporadic Alzheimer's Disease, Diabetes Mellitus, and Non-Alcoholic Steatohepatitis

PubMed Central

de la Monte, Suzanne M.; Neusner, Alexander; Chu, Jennifer; Lawton, Margot

2015-01-01

Nitrosamines mediate their mutagenic effects by causing DNA damage, oxidative stress, lipid peroxidation, and pro-inflammatory cytokine activation, which lead to increased cellular degeneration and death. However, the very same pathophysiological processes comprise the “unbuilding” blocks of aging and insulin-resistance diseases including, neurodegeneration, diabetes mellitus (DM), and non-alcoholic steatohepatitis (NASH). Previous studies demonstrated that experimental exposure to streptozotocin, a nitrosamine-related compound, causes NASH, and diabetes mellitus Types 1, 2 and 3 (Alzheimer (AD)-type neurodegeneration). Herein, we review evidence that the upwardly spiraling trends in mortality rates due to DM, AD, and Parkinson's disease typify exposure rather than genetic-based disease models, and parallel the progressive increases in human exposure to nitrates, nitrites, and nitrosamines via processed/preserved foods. We propose that such chronic exposures have critical roles in the pathogenesis of our insulin resistance disease pandemic. Potential solutions include: 1) eliminating the use of nitrites in food; 2) reducing nitrate levels in fertilizer and water used to irrigate crops; and 3) employing safe and effective measures to detoxify food and water prior to human consumption. Future research efforts should focus on refining our ability to detect and monitor human exposures to nitrosamines and assess early evidence of nitrosamine-mediated tissue injury and insulin resistance. PMID:19363256

Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: a systematic review.

PubMed

Bach, Cathrine Carlsen; Bech, Bodil Hammer; Brix, Nis; Nohr, Ellen Aagaard; Bonde, Jens Peter Ellekilde; Henriksen, Tine Brink

2015-01-01

Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated with reduced fetal growth. However, the results of human studies are inconsistent. To summarize the evidence of an association between exposure to PFASs, particularly PFOS and PFOA, and human fetal growth. Systematic literature searches were performed in MEDLINE and EMBASE. We included original studies on pregnant women with measurements of PFOA or PFOS in maternal blood during pregnancy or the umbilical cord and associations with birth weight or related outcomes according to the PFAS level. Citations and references from the included articles were investigated to locate more relevant articles. Study characteristics and results were extracted to structured tables. The completeness of reporting as well as the risk of bias and confounding were assessed. Fourteen studies were eligible. In utero PFOA exposure was associated with decreased measures of continuous birth weight in all studies, even though the magnitude of the association differed and many results were statistically insignificant. PFOS exposure and birth weight were associated in some studies, while others found no association. Higher PFOS and PFOA concentrations were associated with decreased average birth weight in most studies, but only some results were statistically significant. The impact on public health is unclear, but the global exposure to PFASs warrants further investigation.

The outdoor air quality flag program in central California: a school-based educational intervention to potentially help reduce children's exposure to environmental asthma triggers.

PubMed

Shendell, Derek G; Rawling, Mary-Michal; Foster, Christine; Bohlke, Alicia; Edwards, Bobbie; Rico, Susie A; Felix, Justina; Eaton, Sandra; Moen, Stephanie; Roberts, Eric M; Love, Mary Beth

2007-10-01

This paper describes a novel school-based, visual environmental public health educational intervention intended to help reduce the exposure of children-and adults-to outdoor air pollution, including known environmental asthma triggers like ozone and particles. The overarching goal was to enhance the learning, recreational, and work environments of students and staff. The specific purpose of the Asthma-Friendly Outdoor (Ambient) Air Quality Flag Program was to establish an education and communication tool for Central California communities that would accomplish two things: (1) Establish permanent local policy change to existing operating procedures in school districts and schools to help reduce the exposure of students, teachers, staff, and nearby communities to outdoor environmental asthma triggers and (2) provide education on air quality and potential health effects of exposure to air pollutants. Data on the program from its initial years are presented. To date, the following important lessons have been learned: (1) Science-based, simple, visual, low-cost school-based educational interventions to help reduce human exposure to outdoor environmental asthma triggers (i.e., ozone, particles, and pollens) can work in socioeconomically and ethnically diverse urban and rural or agricultural communities, and (2) local health and environmental justice groups such as asthma coalitions can successfully lead school-based environmental interventions to help improve children's quality of life.

Neuropathological Consequences of Gestational Exposure to Concentrated Ambient Fine and Ultrafine Particles in the Mouse.

PubMed

Klocke, Carolyn; Allen, Joshua L; Sobolewski, Marissa; Mayer-Pröschel, Margot; Blum, Jason L; Lauterstein, Dana; Zelikoff, Judith T; Cory-Slechta, Deborah A

2017-04-01

Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100 nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3rd trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans. The current study sought to determine whether vulnerability to fine (≤2.5 μm) and UFP air pollution exposure extends to embryonic periods of brain development in mice, equivalent to human 1st and 2nd trimesters. Pregnant mice were exposed 6 h/day from gestational days (GDs) 0.5-16.5 using the New York University VACES system to concentrated ambient fine/ultrafine particles at an average concentration of 92.69 μg/m3 over the course of the exposure period. At postnatal days (PNDs) 11-15, neuropathological consequences were characterized. Gestational air pollution exposures produced ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in both sexes. Both sexes demonstrated CC hypermyelination and increased microglial activation and reduced total CC microglia number. Analyses of iron deposition as a critical component of myelination revealed increased iron deposition in the CC of exposed female offspring, but not in males. These findings demonstrate that vulnerability of the brain to air pollution extends to gestation and produces features of several neurodevelopmental disorders in both sexes. Further, they highlight the importance of the commonalities of components of particulate matter exposures as a source of neurotoxicity and common CNS alterations. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Methods Used in EnviroAtlas to Assess Urban Natural Infrastructure

EPA Science Inventory

Previous studies have positively correlated human exposures to natural features with health promoting outcomes such as increased physical activity, improved cognitive function, increased social engagement, and reduced ambient air pollution. When using remotely-sensed data to inve...

AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells.

PubMed

Yamada, Shigeru; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

2013-05-01

Organotin compounds such as tributyltin (TBT) are known to cause various forms of cytotoxicity, including developmental toxicity and neurotoxicity. However, the molecular target of the toxicity induced by nanomolar levels of TBT has not been identified. In the present study, we found that exposure to 100 nM TBT induced growth arrest in human pluripotent embryonic carcinoma cell line NT2/D1. Since glucose provides metabolic energy, we focused on the glycolytic system. We found that exposure to TBT reduced the levels of both glucose-6-phosphate and fructose-6-phosphate. To investigate the effect of TBT exposure on glycolysis, we examined glucose transporter (GLUT) activity. TBT exposure inhibited glucose uptake via a decrease in the level of cell surface-bound GLUT1. Furthermore, we examined the effect of AMP-activated protein kinase (AMPK), which is known to regulate glucose transport by facilitating GLUT translocation. Treatment with the potent AMPK activator, AICAR, restored the TBT-induced reduction in cell surface-bound GLUT1 and glucose uptake. In conclusion, these results suggest that exposure to nanomolar levels of TBT causes growth arrest by targeting glycolytic systems in human embryonic carcinoma cells. Thus, understanding the energy metabolism may provide new insights into the mechanisms of metal-induced cytotoxicity.

Pest Private Eye: Using an Interactive Role-Playing Video Game to Teach about Pests and Integrated Pest Management

ERIC Educational Resources Information Center

Bauer, Erin; Ogg, Clyde

2011-01-01

The trend toward encouraging adoption of Integrated Pest Management (IPM) in schools has increased in the last decade. Because IPM helps reduce risk of human pesticide exposure, reduce allergens and asthma triggers, save energy, and protect the environment, it's essential that IPM awareness continue not only with current school administrators,…

Utilising shade to optimize UV exposure for vitamin D

NASA Astrophysics Data System (ADS)

Turnbull, D. J.; Parisi, A. V.

2008-01-01

Numerous studies have stated that humans need to utilise full sun radiation, at certain times of the day, to assist the body in synthesising the required levels of vitamin D3. The time needed to be spent in the full sun depends on a number of factors, for example, age, skin type, latitude, solar zenith angle. Current Australian guidelines suggest exposure to approximately 1/6 to 1/3 of a minimum erythemal dose (MED), depending on age, would be appropriate to provide adequate vitamin D3 levels. The aim of the study was to determine the exposure times to diffuse solar UV to receive exposures of 1/6 and 1/3 MED for a changing solar zenith angle in order to assess the possible role that diffuse UV (scattered radiation) may play in vitamin D3 effective UV exposures (UVD3). Diffuse and global erythemal UV measurements were conducted at five minute intervals over a twelve month period for a solar zenith angle range of 4° to 80° at a latitude of 27.6° S. For diffuse UV exposures of 1/6 and 1/3 MED, solar zenith angles smaller than 60° and 50° respectively can be utilised for exposure times of less than 10 min. Spectral measurements showed that, for a solar zenith angle of 40°, the UVA (315-400 nm) in the diffuse component of the solar UV is reduced by approximately 62% compared to the UVA in the global UV, whereas UVD3 wavelengths are only reduced by approximately 43%. At certain latitudes, diffuse UV under shade may play an important role in providing the human body with adequate levels of UVD3 (290-330 nm) radiation without experiencing the high levels of damaging UVA observed in full sun.

Utilising shade to optimize UV exposure for vitamin D

NASA Astrophysics Data System (ADS)

Turnbull, D. J.; Parisi, A. V.

2008-06-01

Numerous studies have stated that humans need to utilise full sun radiation, at certain times of the day, to assist the body in synthesising the required levels of vitamin D3. The time needed to be spent in the full sun depends on a number of factors, for example, age, skin type, latitude, solar zenith angle. Current Australian guidelines suggest exposure to approximately 1/6 to 1/3 of a minimum erythemal dose (MED), depending on age, would be appropriate to provide adequate vitamin D3 levels. The aim of the study was to determine the exposure times to diffuse solar UV to receive exposures of 1/6 and 1/3 MED for a changing solar zenith angle in order to assess the possible role that diffuse UV (scattered radiation) may play in vitamin D3 effective UV exposures (UVD3). Diffuse and global erythemal UV measurements were conducted at five minute intervals over a twelve month period for a solar zenith angle range of 4° to 80° at a latitude of 27.6° S. For a diffuse UV exposure of 1/3 MED, solar zenith angles smaller than approximately 50° can be utilised for exposure times of less than 10 min. Spectral measurements showed that, for a solar zenith angle of 40°, the UVA (315-400 nm) in the diffuse component of the solar UV is reduced by approximately 62% compared to the UVA in the global UV, whereas UVD3 wavelengths are only reduced by approximately 43%. At certain latitudes, diffuse UV under shade may play an important role in providing the human body with adequate levels of UVD3 (290-315 nm) radiation without experiencing the high levels of UVA observed in full sun.

The origin, fate, and health effects of combustion by-products: a research framework.

PubMed

Avakian, Maureen D; Dellinger, Barry; Fiedler, Heidelore; Gullet, Brian; Koshland, Catherine; Marklund, Stellan; Oberdörster, Günter; Safe, Stephen; Sarofim, Adel; Smith, Kirk R; Schwartz, David; Suk, William A

2002-11-01

Incomplete combustion processes can emit organic pollutants, metals, and fine particles. Combustion by-products represent global human and environmental health challenges that are relevant not only in heavily industrialized nations, but also in developing nations where up to 90% of rural households rely on unprocessed biomass fuels for cooking, warmth, and light. These issues were addressed at the Seventh International Congress on Combustion By-Products, which convened 4-6 June 2001 in Research Triangle Park, North Carolina. This congress included a diverse group of multidisciplinary researchers and practitioners who discussed recent developments and future goals in the control of combustion by-products and their effects of exposure on human and ecologic health. Participants recommended that interdisciplinary, coordinated research efforts should be focused to capitalize on the important potential synergisms between efforts to reduce the adverse human health effects linked to exposures to combustion by-products and broader efforts to reduce greenhouse gas emissions and save energy through efficiency. In this article we summarize the principal findings and recommendations for research focus and direction.

Sharpening vision by adapting to flicker.

PubMed

Arnold, Derek H; Williams, Jeremy D; Phipps, Natasha E; Goodale, Melvyn A

2016-11-01

Human vision is surprisingly malleable. A static stimulus can seem to move after prolonged exposure to movement (the motion aftereffect), and exposure to tilted lines can make vertical lines seem oppositely tilted (the tilt aftereffect). The paradigm used to induce such distortions (adaptation) can provide powerful insights into the computations underlying human visual experience. Previously spatial form and stimulus dynamics were thought to be encoded independently, but here we show that adaptation to stimulus dynamics can sharpen form perception. We find that fast flicker adaptation (FFAd) shifts the tuning of face perception to higher spatial frequencies, enhances the acuity of spatial vision-allowing people to localize inputs with greater precision and to read finer scaled text, and it selectively reduces sensitivity to coarse-scale form signals. These findings are consistent with two interrelated influences: FFAd reduces the responsiveness of magnocellular neurons (which are important for encoding dynamics, but can have poor spatial resolution), and magnocellular responses contribute coarse spatial scale information when the visual system synthesizes form signals. Consequently, when magnocellular responses are mitigated via FFAd, human form perception is transiently sharpened because "blur" signals are mitigated.

The origin, fate, and health effects of combustion by-products: a research framework.

PubMed Central

Avakian, Maureen D; Dellinger, Barry; Fiedler, Heidelore; Gullet, Brian; Koshland, Catherine; Marklund, Stellan; Oberdörster, Günter; Safe, Stephen; Sarofim, Adel; Smith, Kirk R; Schwartz, David; Suk, William A

2002-01-01

Incomplete combustion processes can emit organic pollutants, metals, and fine particles. Combustion by-products represent global human and environmental health challenges that are relevant not only in heavily industrialized nations, but also in developing nations where up to 90% of rural households rely on unprocessed biomass fuels for cooking, warmth, and light. These issues were addressed at the Seventh International Congress on Combustion By-Products, which convened 4-6 June 2001 in Research Triangle Park, North Carolina. This congress included a diverse group of multidisciplinary researchers and practitioners who discussed recent developments and future goals in the control of combustion by-products and their effects of exposure on human and ecologic health. Participants recommended that interdisciplinary, coordinated research efforts should be focused to capitalize on the important potential synergisms between efforts to reduce the adverse human health effects linked to exposures to combustion by-products and broader efforts to reduce greenhouse gas emissions and save energy through efficiency. In this article we summarize the principal findings and recommendations for research focus and direction. PMID:12417488

Sharpening vision by adapting to flicker

PubMed Central

Arnold, Derek H.; Williams, Jeremy D.; Phipps, Natasha E.; Goodale, Melvyn A.

2016-01-01

Human vision is surprisingly malleable. A static stimulus can seem to move after prolonged exposure to movement (the motion aftereffect), and exposure to tilted lines can make vertical lines seem oppositely tilted (the tilt aftereffect). The paradigm used to induce such distortions (adaptation) can provide powerful insights into the computations underlying human visual experience. Previously spatial form and stimulus dynamics were thought to be encoded independently, but here we show that adaptation to stimulus dynamics can sharpen form perception. We find that fast flicker adaptation (FFAd) shifts the tuning of face perception to higher spatial frequencies, enhances the acuity of spatial vision—allowing people to localize inputs with greater precision and to read finer scaled text, and it selectively reduces sensitivity to coarse-scale form signals. These findings are consistent with two interrelated influences: FFAd reduces the responsiveness of magnocellular neurons (which are important for encoding dynamics, but can have poor spatial resolution), and magnocellular responses contribute coarse spatial scale information when the visual system synthesizes form signals. Consequently, when magnocellular responses are mitigated via FFAd, human form perception is transiently sharpened because “blur” signals are mitigated. PMID:27791115

Indoor human exposure to size-fractionated aerosols during the 2015 Southeast Asian smoke haze and assessment of exposure mitigation strategies

NASA Astrophysics Data System (ADS)

Sharma, Ruchi; Balasubramanian, Rajasekhar

2017-11-01

The 2015 smoke haze episode was one of the most severe and prolonged transboundary air pollution events ever seen in Southeast Asia (SEA), affecting the air quality of several countries within the region including Indonesia, Malaysia and Singapore. The 24 h mean outdoor PM2.5 (particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm) concentrations ranged from 72-157 μg m-3 in Singapore during this episode, exceeding the WHO 24 h mean PM2.5 guidelines (25 μg m-3) several times over. The smoke haze episode not only affected ambient air quality, but also indoor air quality due to the migration of PM of different sizes from the outdoor to the indoor environment. Despite the frequent occurrence of smoke haze episodes over the years, their potential health impacts on indoor building occupants remain largely unknown in SEA due to the lack of systematic investigations and observational data. The current work was carried out in Singapore to assess human exposure to size-resolved PM during the 2015 smoke haze episode, and to evaluate the effectiveness of exposure mitigation measures in smoke-haze-impacted naturally ventilated indoor environments. The potential health risks associated with exposure to PM2.5 were assessed based on the concentrations of redox active particulate-bound trace elements, which are known to be harmful to human health, with and without exposure mitigation. Overall, it was observed that human health exposure to PM2.5 and its carcinogenic chemical components was reduced substantially by 62% (p < 0.05) while using an air cleaner. However, extremely small hazardous particles were only partially removed by the air cleaner and remain a matter of concern for public health.

Predicting and controlling risks from human exposures to vibration and mechanical shock: flag waving and flag weaving.

PubMed

Griffin, Michael J

2015-01-01

At work or in leisure activities, many people are exposed to vibration or mechanical shocks associated with risks of injury or disease. This paper identifies information that can be used to decide whether there may be a risk from exposure to hand-transmitted vibration or whole-body vibration and shock, and suggests actions that can control the risks. The complex and time-varying nature of human exposures to vibration and shock, the complexity of the different disorders and uncertainty as to the mechanisms of injury and the factors influencing injury have prevented the definition of dose-response relationships well proven by scientific study. It is necessary to wave a flag indicating when there is a need to control risks from exposure to vibration and shock while scientific enquiry provides understanding needed to weave a better flag. It is concluded that quantifying exposure severity is often neither necessary nor sufficient to either identify risks or implement measures that control the risks. The identification of risks associated with exposure to vibration and mechanical shock cannot, and need not, rely solely on the quantification of exposure severity. Qualitative methods can provide a sufficient indication of the need for control measures, which should not be restricted to reducing standardised measures of exposure severity.

Tinnitus with a normal audiogram: Relation to noise exposure but no evidence for cochlear synaptopathy.

PubMed

Guest, Hannah; Munro, Kevin J; Prendergast, Garreth; Howe, Simon; Plack, Christopher J

2017-02-01

In rodents, exposure to high-level noise can destroy synapses between inner hair cells and auditory nerve fibers, without causing hair cell loss or permanent threshold elevation. Such "cochlear synaptopathy" is associated with amplitude reductions in wave I of the auditory brainstem response (ABR) at moderate-to-high sound levels. Similar ABR results have been reported in humans with tinnitus and normal audiometric thresholds, leading to the suggestion that tinnitus in these cases might be a consequence of synaptopathy. However, the ABR is an indirect measure of synaptopathy and it is unclear whether the results in humans reflect the same mechanisms demonstrated in rodents. Measures of noise exposure were not obtained in the human studies, and high frequency audiometric loss may have impacted ABR amplitudes. To clarify the role of cochlear synaptopathy in tinnitus with a normal audiogram, we recorded ABRs, envelope following responses (EFRs), and noise exposure histories in young adults with tinnitus and matched controls. Tinnitus was associated with significantly greater lifetime noise exposure, despite close matching for age, sex, and audiometric thresholds up to 14 kHz. However, tinnitus was not associated with reduced ABR wave I amplitude, nor with significant effects on EFR measures of synaptopathy. These electrophysiological measures were also uncorrelated with lifetime noise exposure, providing no evidence of noise-induced synaptopathy in this cohort, despite a wide range of exposures. In young adults with normal audiograms, tinnitus may be related not to cochlear synaptopathy but to other effects of noise exposure. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Combining uncertainty factors in deriving human exposure levels of noncarcinogenic toxicants.

PubMed

Kodell, R L; Gaylor, D W

1999-01-01

Acceptable levels of human exposure to noncarcinogenic toxicants in environmental and occupational settings generally are derived by reducing experimental no-observed-adverse-effect levels (NOAELs) or benchmark doses (BDs) by a product of uncertainty factors (Barnes and Dourson, Ref. 1). These factors are presumed to ensure safety by accounting for uncertainty in dose extrapolation, uncertainty in duration extrapolation, differential sensitivity between humans and animals, and differential sensitivity among humans. The common default value for each uncertainty factor is 10. This paper shows how estimates of means and standard deviations of the approximately log-normal distributions of individual uncertainty factors can be used to estimate percentiles of the distribution of the product of uncertainty factors. An appropriately selected upper percentile, for example, 95th or 99th, of the distribution of the product can be used as a combined uncertainty factor to replace the conventional product of default factors.

Carcinogenic compounds in alcoholic beverages: an update.

PubMed

Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

2016-10-01

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

Effect of home food processing on chlordecone (organochlorine) content in vegetables.

PubMed

Clostre, Florence; Letourmy, Philippe; Thuriès, Laurent; Lesueur-Jannoyer, Magalie

2014-08-15

Decades after their use and their ban, organochlorine pesticides still pollute soil, water and food and lead to human and ecosystem exposure. In the case of chlordecone, human exposure is mainly due to the consumption of polluted food. We studied the effect of preparation and cooking in five vegetable products, three root vegetables (yam, dasheen and sweet potato) and two cucurbits (cucumber and pumpkin), among the main contributors to exposure to chlordecone in food in the French West Indies. Boiling the vegetables in water had no effect on chlordecone content of the vegetables and consequently on consumer exposure. The peel was three to 40-fold more contaminated than the pulp except cucumber, where the difference was less contrasted. The edible part is thus significantly less contaminated and peeling is recommended after rinsing to reduce consumer exposure, particularly for food grown in home gardens with contaminated soils. The type of soil had no consistent effect on CLD distribution but plot did. Peel and pulp composition (lipids and fibers) appear to partially account for CLD distribution in the product. Copyright © 2014 Elsevier B.V. All rights reserved.

Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats

EPA Science Inventory

Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To addre...

Phytotechnologies – Preventing Exposures, Improving Public Health

PubMed Central

Henry, Heather F.; Burken, Joel G.; Maier, Raina M.; Newman, Lee A.; Rock, Steven; Schnoor, Jerald L.; Suk, William A.

2014-01-01

Phytotechnologies have the potential to reduce the amount and/or toxicity of deleterious chemicals/agents, and thereby, prevent human exposures to hazardous substances. As such, phytotechnologies are a tool for primary prevention within the context of public health. Research advances demonstrate that phytotechnologies can be uniquely tailored for effective exposure prevention for a variety of applications. In addition to exposure prevention, phytotechnologists have advanced the use of plants as sensors to delineate environmental contaminants and potential exposures. The applications presented in this paper are at various stages of development and are presented in a framework to reflect how phytotechnologies can help meet basic public health needs for access to clean water, air, and food resources. As plant-based technologies can often be integrated into communities at minimal cost and with low infrastructure needs, their use in improving environmental quality can be applied broadly to minimize potential contaminant exposure. These natural treatment systems concurrently provide ecosystem services of notable value to communities and society. In the future, integration and coordination of phytotechnology activities with public health research will allow technology development that focuses on prevention of environmental exposures. Such an approach will lead to an important role of phytotechnologies in providing sustainable solutions to environmental exposure challenges that improve public health and potentially reduce the burden of disease. PMID:23819283

Small Molecule Protection of Bone Marrow Hematopoietic Stem Cells

DTIC Science & Technology

2017-12-01

using isogenic (mutant/complemented) human cell line pairs from patients with Fanconi anemia (FA), a heritable human bone marrow failure (BMF) syndrome ...small molecules could be therapeutically useful in reducing the risk of BMF in diseases such as Fanconi anemia, and perhaps after radiation exposure...damage-repair, DNA damage response, Fanconi anemia and associated bone marrow failure syndromes and environmental and molecular toxicology will all be

Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence

PubMed Central

Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J.

2017-01-01

Background Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. Objectives To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. Methods We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). Results We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46–9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53–2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. Conclusions We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress. PMID:28700705

Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

PubMed

Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

2017-01-01

Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

Exposure to Ozone Modulates Human Airway Protease/Antiprotease Balance Contributing to Increased Influenza A Infection

PubMed Central

Kesic, Matthew J.; Meyer, Megan; Bauer, Rebecca; Jaspers, Ilona

2012-01-01

Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA) is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI). Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs) to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility. PMID:22496898

[Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes].

PubMed

Tian, Jun; Li, Yan

2016-01-01

Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes. The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500μM was determined by Live/Dead assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine

Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes.

PubMed

Tian, Jun; Li, Yan

2016-01-01

Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes. The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500 μM was determined by LIVE/DEAD assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine

Modulation of human alveolar macrophage properties by ozone exposure in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becker, S.; Madden, M.C.; Newman, S.L.

The study investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3)(0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2(PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, the authors found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2) production in response to phorbol ester was reduced aftermore » exposure of HAM to O3 while the basal O2 release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3-exposed HAM produced significantly lower levels of these cytokines when simulated with bacterial lipopolysaccharide (LPS).« less

Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells.

PubMed

Odewumi, Caroline; Latinwo, Lekan M; Sinclair, Andre; Badisa, Veera L D; Abdullah, Ahkinyala; Badisa, Ramesh B

2015-11-01

Cadmium is an environmentally hazardous metal, which causes toxicity in humans. Inhalation of cigarette smoke and industrial fumes containing cadmium are sources of cadmium exposure. It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys. In the present study, the effect of cadmium chloride (CdCl2) on cell viability, and the expression levels of interleukin (IL)‑1α and IL‑10 cytokines at various concentrations and incubation durations were assessed in MRC‑9 human normal lung and A549 human lung cancer cells to elucidate the mechanism of cadmium toxicity. Cell viability was measured using a crystal violet dye binding assay. The expression levels of the cytokines were measured by cytokine specific enzyme‑linked immunosorbent assay kits. The viability assay results revealed higher sensitivity of the A549 lung cancer cells to CdCl2 compared with the normal MRC‑9 lung cells. In the normal MRC‑9 lung cells, higher expression levels of the cytokines were observed at the lowest CdCl2 concentration at a shorter exposure time compared with the lung cancer cells. Higher levels of the cytokines were observed in the A549 lung cancer cells at all other times and concentrations compared with the MRC‑9 cells, indicating higher levels of inflammation. The cytokine levels were reduced at higher CdCl2 concentrations and longer exposure durations, demonstrating the toxic effect of cadmium. The results indicated that CdCl2 affected the expression levels of the cytokines and led to cytotoxicity in human lung cells, and suggested that compounds which reduce inflammation may prevent cadmium toxicity.

Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

PubMed Central

Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

2014-01-01

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

Does oral exposure to cadmium and lead mediate susceptibility to colitis? The dark-and-bright sides of heavy metals in gut ecology

NASA Astrophysics Data System (ADS)

Breton, Jérôme; Daniel, Catherine; Vignal, Cécile; Body-Malapel, Mathilde; Garat, Anne; Plé, Coline; Foligné, Benoît

2016-01-01

Although the heavy metals cadmium (Cd) and lead (Pb) are known environmental health concerns, their long-term impacts on gut ecology and susceptibility to gastrointestinal autoimmune diseases have not been extensively investigated. We sought to determine whether subchronic oral exposure to Cd or Pb is a risk factor for the development and progression of inflammatory bowel disease (IBD). Mice were exposed to various doses of CdCl2 or PbCl2 in drinking water for 1, 4 or 6 weeks prior to infection with Salmonella, the induction of colitis with dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). In human cell-based models, exposure to Cd and Pb is associated with reduced transepithelial electric resistance and changes in bacteria-induced cytokine responses. Although 1- and 6-week exposures did not have clear effects on the response to Salmonella infectious challenges, 1-week short-term treatments with CdCl2 tended to enhance intestinal inflammation in mice. Unexpectedly, subchronic exposure to Cd and (to a lesser extent) Pb significantly mitigated some of the symptoms of DSS-induced colitis and reduced the severity of TNBS colitis in a dose-dependent manner. The possible adaptive and immunosuppressive mechanisms by which heavy metals might reduce intestinal inflammation are explored and discussed.

Human exposure and internal dose assessments of acrylamide in food.

PubMed

Dybing, E; Farmer, P B; Andersen, M; Fennell, T R; Lalljie, S P D; Müller, D J G; Olin, S; Petersen, B J; Schlatter, J; Scholz, G; Scimeca, J A; Slimani, N; Törnqvist, M; Tuijtelaars, S; Verger, P

2005-03-01

This review provides a framework contributing to the risk assessment of acrylamide in food. It is based on the outcome of the ILSI Europe FOSIE process, a risk assessment framework for chemicals in foods and adds to the overall framework by focusing especially on exposure assessment and internal dose assessment of acrylamide in food. Since the finding that acrylamide is formed in food during heat processing and preparation of food, much effort has been (and still is being) put into understanding its mechanism of formation, on developing analytical methods and determination of levels in food, and on evaluation of its toxicity and potential toxicity and potential human health consequences. Although several exposure estimations have been proposed, a systematic review of key information relevant to exposure assessment is currently lacking. The European and North American branches of the International Life Sciences Institute, ILSI, discussed critical aspects of exposure assessment, parameters influencing the outcome of exposure assessment and summarised data relevant to the acrylamide exposure assessment to aid the risk characterisation process. This paper reviews the data on acrylamide levels in food including its formation and analytical methods, the determination of human consumption patterns, dietary intake of the general population, estimation of maximum intake levels and identification of groups of potentially high intakes. Possible options and consequences of mitigation efforts to reduce exposure are discussed. Furthermore the association of intake levels with biomarkers of exposure and internal dose, considering aspects of bioavailability, is reviewed, and a physiologically-based toxicokinetic (PBTK) model is described that provides a good description of the kinetics of acrylamide in the rat. Each of the sections concludes with a summary of remaining gaps and uncertainties.

Efficiency of automotive cabin air filters to reduce acute health effects of diesel exhaust in human subjects

PubMed Central

Rudell, B.; Wass, U.; Horstedt, P.; Levin, J. O.; Lindahl, R.; Rannug, U.; Sunesson, A. L.; Ostberg, Y.; Sandstrom, T.

1999-01-01

OBJECTIVES: To evaluate the efficiency of different automotive cabin air filters to prevent penetration of components of diesel exhaust and thereby reduce biomedical effects in human subjects. Filtered air and unfiltered diluted diesel exhaust (DDE) were used as negative and positive controls, respectively, and were compared with exposure to DDE filtered with four different filter systems. METHODS: 32 Healthy non- smoking subjects (age 21-53) participated in the study. Each subject was exposed six times for 1 hour in a specially designed exposure chamber: once to air, once to unfiltered DDE, and once to DDE filtered with the four different cabin air filters. Particle concentrations during exposure to unfiltered DDE were kept at 300 micrograms/m3. Two of the filters were particle filters. The other two were particle filters combined with active charcoal filters that might reduce certain gaseous components. Subjective symptoms were recorded and nasal airway lavage (NAL), acoustic rhinometry, and lung function measurements were performed. RESULTS: The two particle filters decreased the concentrations of diesel exhaust particles by about half, but did not reduce the intensity of symptoms induced by exhaust. The combination of active charcoal filters and a particle filter significantly reduced the symptoms and discomfort caused by the diesel exhaust. The most noticable differences in efficacy between the filters were found in the reduction of detection of an unpleasant smell from the diesel exhaust. In this respect even the two charcoal filter combinations differed significantly. The efficacy to reduce symptoms may depend on the abilities of the filters investigated to reduce certain hydrocarbons. No acute effects on NAL, rhinometry, and lung function variables were found. CONCLUSIONS: This study has shown that the use of active charcoal filters, and a particle filter, clearly reduced the intensity of symptoms induced by diesel exhaust. Complementary studies on vehicle cabin air filters may result in further diminishing the biomedical effects of diesel exhaust in subjects exposed in traffic and workplaces.   PMID:10450238

Multi-sector thermo-physiological head simulator for headgear research

NASA Astrophysics Data System (ADS)

Martinez, Natividad; Psikuta, Agnes; Corberán, José Miguel; Rossi, René M.; Annaheim, Simon

2017-02-01

A novel thermo-physiological human head simulator for headgear testing was developed by coupling a thermal head manikin with a thermo-physiological model. As the heat flux at head-site is directly measured by the head manikin, this method provides a realistic quantification of the heat transfer phenomena occurring in the headgear, such as moisture absorption-desorption cycles, condensation, or moisture migration across clothing layers. Before coupling, the opportunities of the head manikin for representing the human physiology were evaluated separately. The evaluation revealed reduced precision in forehead and face temperature predictions under extreme heterogeneous temperature distributions and no initial limitation for simulating temperature changes observed in the human physiology. The thermo-physiological model predicted higher sweat rates when applied for coupled than for pure virtual simulations. After coupling, the thermo-physiological human head simulator was validated using eight human experiments. It precisely predicted core, mean skin, and forehead temperatures with average rmsd values within the average experimental standard deviation (rmsd of 0.20 ± 0.15, 0.83 ± 0.34, and 1.04 ± 0.54 °C, respectively). However, in case of forehead, precision was lower for the exposures including activity than for the sedentary exposures. The representation of the human sweat evaporation could be affected by a reduced evaporation efficiency and the manikin sweat dynamics. The industry will benefit from this thermo-physiological human head simulator leading to the development of helmet designs with enhanced thermal comfort and, therefore, with higher acceptance by users.

Possible Health Benefits From Reducing Occupational Magnetic Fields

PubMed Central

Bowman, Joseph D.; Ray, Tapas K.; Park, Robert M.

2015-01-01

Background Magnetic fields (MF) from AC electricity are a Possible Human Carcinogen, based on limited epidemiologic evidence from exposures far below occupational health limits. Methods To help formulate government guidance on occupational MF, the cancer cases prevented and the monetary benefits accruing to society by reducing workplace exposures were determined. Life-table methods produced Disability Adjusted Life Years, which were converted to monetary values. Results Adjusted for probabilities of causality, the expected increase in a worker’s disability-free life are 0.04 year (2 weeks) from a 1 microtesla (μT) MF reduction in average worklife exposure, which is equivalent to $5,100/worker/μT in year 2010 U.S. dollars (95% confidence interval $1,000–$9,000/worker/μT). Where nine electrosteel workers had 13.8 μT exposures, for example, moving them to ambient MFs would provide $600,000 in benefits to society (uncertainty interval $0–$1,000,000). Conclusions When combined with the costs of controls, this analysis provides guidance for precautionary recommendations for managing occupational MF exposures. PMID:23129537

Possible health benefits from reducing occupational magnetic fields.

PubMed

Bowman, Joseph D; Ray, Tapas K; Park, Robert M

2013-07-01

Magnetic fields (MF) from AC electricity are a Possible Human Carcinogen, based on limited epidemiologic evidence from exposures far below occupational health limits. To help formulate government guidance on occupational MF, the cancer cases prevented and the monetary benefits accruing to society by reducing workplace exposures were determined. Life-table methods produced Disability Adjusted Life Years, which were converted to monetary values. Adjusted for probabilities of causality, the expected increase in a worker's disability-free life are 0.04 year (2 weeks) from a 1 microtesla (µT) MF reduction in average worklife exposure, which is equivalent to $5,100/worker/µT in year 2010 U.S. dollars (95% confidence interval $1,000-$9,000/worker/µT). Where nine electrosteel workers had 13.8 µT exposures, for example, moving them to ambient MFs would provide $600,000 in benefits to society (uncertainty interval $0-$1,000,000). When combined with the costs of controls, this analysis provides guidance for precautionary recommendations for managing occupational MF exposures. Copyright © 2012 Wiley Periodicals, Inc.

Exposure-response analysis and risk assessment for lung cancer in relationship to silica exposure: a 44-year cohort study of 34,018 workers.

PubMed

Liu, Yuewei; Steenland, Kyle; Rong, Yi; Hnizdo, Eva; Huang, Xiji; Zhang, Hai; Shi, Tingming; Sun, Yi; Wu, Tangchun; Chen, Weihong

2013-11-01

Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960-2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m(3) of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.

Genetic modification of human mesenchymal stem cells helps to reduce adiposity and improve glucose tolerance in an obese diabetic mouse model.

PubMed

Sen, Sabyasachi; Domingues, Cleyton C; Rouphael, Carol; Chou, Cyril; Kim, Chul; Yadava, Nagendra

2015-12-09

Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible. We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene expression. HG increased reactive superoxide (ROS) accumulation noted by day 7 both in cytosol and mitochondria. The OCR between the NG and HG exposed groups however did not change until 10 days at which point OCR of HG exposed cells were reduced significantly. We noted that HG exposure upregulated mRNA expression of adipogenic (PPARG, FABP-4, CREBP alpha and beta), inflammatory (IL-6 and TNF alpha) and antioxidant (SOD2 and Catalase) genes. Next, we used AdSOD2 to upregulate SOD2 prior to HG exposure and thereby noted reduction in superoxide generation. SOD2 upregulation helped reduce mRNA over-expression of PPARG, FABP-4, IL-6 and TNFα. In a series of separate experiments, we delivered the eGFP and SOD2 upregulated MSCs (5 days post ex-vivo transduction) and saline intra-peritoneally (IP) to obese diabetic (db/db) mice. We confirmed homing-in of eGFP labeled MSCs, delivered IP, to different inflamed fat pockets, particularly omental fat. Mice receiving SOD2-MSCs showed progressive reduction in body weight and improved glucose tolerance (GTT) at 4 weeks, post MSCs transplantation compared to the GFP-MSC group (control). High glucose evokes superoxide generation, OCR reduction and adipogenic differentiation. Mitochondrial superoxide dismutase upregulation quenches excess superoxide and reduces adipocyte inflammation. Delivery of superoxide dismutase (SOD2) using MSCs as a gene delivery vehicle reduces inflammation and improves glucose tolerance in vivo. Suppression of superoxide production and adipocyte inflammation using mitochondrial superoxide dismutase may be a novel and safe therapeutic tool to combat hyperglycemia mediated effects.

[Clinical impact of opening a human milk bank in a neonatal unit].

PubMed

Vázquez-Román, S; Bustos-Lozano, G; López-Maestro, M; Rodríguez-López, J; Orbea-Gallardo, C; Samaniego-Fernández, M; Pallás-Alonso, C R

2014-09-01

The benefits of donor human milk compared with artificial formulas have been well demonstrated; nevertheless the impact in the clinical practice of opening a human milk bank within a neonatal unit has not yet been studied. The main aim of this study was to analyze the impact on the clinical practice of opening a human milk bank in a neonatal unit to provide donor human milk for preterm infants ≤ 32 weeks of gestational age. A before and after study was designed, with the intervention being the opening a human milk bank. Preterm infants ≤ 32 weeks of gestational age born in the Hospital 12 Octubre from July to December 2005 and January to June 2008 (firsts 6 months after opening the human milk bank) were included. After opening the human milk bank, enteral feedings were started 31h before (P<.001), 100ml/kg/day were achieved 59.5h before (P<.001) and 150 ml/kg/day 52 h before (P=.002). Enteral feedings were never started LM with artificial formula, the exposure to formula in the first 15 days of life was reduced from 50% to 16.6%, and it's consumption during the first 28 days of life was significantly reduced. There was a higher consumption of own mother's milk during the hospital stay, and a higher rate of exclusive breastfeeding at hospital discharge (54% vs 40%). The availability of donor human milk has led to quicker progression with enteral feedings and earlier withdrawal of parenteral nutrition. It has reduced the exposure to artificial formulas, and has also increased the intake of own mother's milk during the hospital stay and the rate of exclusive breastfeeding at hospital discharge. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Mitigating HZE Radiation-Induced Deficits in Marrow-Derived Mesenchymal Progenitor Cells and Skeletal Structure

NASA Technical Reports Server (NTRS)

Globus, Ruth K.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Terada, Masahiro; Alwood, Joshua; Halloran, Bernard; Tahimic, Candice

2016-01-01

Future long-duration space exploration beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure causes progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility.

Evaluation of E-cigarette liquid vapor and mainstream cigarette smoke after direct exposure of primary human bronchial epithelial cells.

PubMed

Scheffler, Stefanie; Dieken, Hauke; Krischenowski, Olaf; Förster, Christine; Branscheid, Detlev; Aufderheide, Michaela

2015-04-08

E-cigarettes are emerging products, often described as "reduced-risk" nicotine products or alternatives to combustible cigarettes. Many smokers switch to e-cigarettes to quit or significantly reduce smoking. However, no regulations for e-cigarettes are currently into force, so that the quality and safety of e-liquids is not necessarily guaranteed. We exposed primary human bronchial epithelial cells of two different donors to vapor of e-cigarette liquid with or without nicotine, vapor of the carrier substances propylene glycol and glycerol as well as to mainstream smoke of K3R4F research cigarettes. The exposure was done in a CULTEX® RFS compact  module, allowing the exposure of the cells at the air-liquid interface. 24 h post-exposure, cell viability and oxidative stress levels in the cells were analyzed. We found toxicological effects of e-cigarette vapor and the pure carrier substances, whereas the nicotine concentration did not have an effect on the cell viability. The viability of mainstream smoke cigarette exposed cells was 4.5-8 times lower and the oxidative stress levels 4.5-5 times higher than those of e-cigarette vapor exposed cells, depending on the donor. Our experimental setup delivered reproducible data and thus provides the opportunity for routine testing of e-cigarette liquids to ensure safety and quality for the user.

Short-term direct contact with soil and plant materials leads to an immediate increase in diversity of skin microbiota.

PubMed

Grönroos, Mira; Parajuli, Anirudra; Laitinen, Olli H; Roslund, Marja I; Vari, Heli K; Hyöty, Heikki; Puhakka, Riikka; Sinkkonen, Aki

2018-05-29

Immune-mediated diseases have increased during the last decades in urban environments. The hygiene hypothesis suggests that increased hygiene level and reduced contacts with natural biodiversity are related to the increase in immune-mediated diseases. We tested whether short-time contact with microbiologically diverse nature-based materials immediately change bacterial diversity on human skin. We tested direct skin contact, as two volunteers rubbed their hands with sixteen soil and plant based materials, and an exposure via fabric packets filled with moss material. Skin swabs were taken before and after both exposures. Next-generation sequencing showed that exposures increased, at least temporarily, the total diversity of skin microbiota and the diversity of Acidobacteria, Actinobacteria, Bacteroidetes, Proteobacteria and Alpha-, Beta- and Gammaproteobacteria suggesting that contact with nature-based materials modify skin microbiome and increase skin microbial diversity. Until now, approaches to cure or prevent immune system disorders using microbe-based treatments have been limited to use of a few microbial species. We propose that nature-based materials with high natural diversity, such as the materials tested here, might be more effective in modifying human skin microbiome, and eventually, in reducing immune system disorders. Future studies should investigate how long-term changes in skin microbiota are achieved and if the exposure induces beneficial changes in the immune system markers. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Assessment of Electromagnetic Fields at NASA Langley Research Center

NASA Technical Reports Server (NTRS)

Ficklen, Carter B.

1995-01-01

This report presents the results of an assessment of ElectroMagnetic Fields (EMF) completed at NASA Langley Research Center as part of the Langley Aerospace Research Summer Scholars Program. This project was performed to determine levels of electromagnetic fields, determine the significance of the levels present, and determine a plan to reduce electromagnetic field exposure, if necessary. This report also describes the properties of electromagnetic fields and their interaction with humans. The results of three major occupational epidemiological studies is presented to determine risks posed to humans by EMF exposure. The data for this report came from peer-reviewed journal articles and government publications pertaining to the health effects of electromagnetic fields.

Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.

PubMed Central

Rudell, B; Ledin, M C; Hammarström, U; Stjernberg, N; Lundbäck, B; Sandström, T

1996-01-01

OBJECTIVES: Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. METHODS: Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. RESULTS: The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. CONCLUSION: Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap. PMID:8943829

A paler shade of green? The toxicology of biodiesel emissions ...

EPA Pesticide Factsheets

Background: Biodiesel produced primarily from plants and algal feedstocks is believed to have advantages for production and use compared to petroleum and to some other fuel sources. There is some speculation that exposure to biodiesel combustion emissions may not induce biological responses or health effects or at a minimum reduce the effects relative to other fuels. In evaluating the overall environmental and health effects of biodiesel production to end use scenario, empirical data or modeling data based on such data are needed.Scope of Review: This manuscript examines the available toxicology reports examining combustion derived biodiesel emissions since approximately 2007, when our last review of the topic occurred. Toxicity derived from other end uses of biodiesel- eg, spills, dermal absorption, etc- are not examined. Findings from biodiesel emissions are roughly divided into three areas: whole non-human animal model exposures; in vitro exposures of mammalian and bacterial cells (used for mutation studies primarily); and human exposures in controlled or other exposure fashions. Major Conclusions: Overall, these more current studies clearly demonstrate that biodiesel combustion emission exposure- to either 100% biodiesel or a blend in petroleum diesel- can induce biological effects. There are reports that show biodiesel exposure generally induces more effects or a greater magnitude of effect than petroleum diesel, however there are also a similar number

40 CFR 300.415 - Removal action.

Code of Federal Regulations, 2014 CFR

2014-07-01

... food chain from hazardous substances or pollutants or contaminants; (ii) Actual or potential contamination of drinking water supplies or sensitive ecosystems; (iii) Hazardous substances or pollutants or...—where it will reduce the likelihood of spillage; leakage; exposure to humans, animals, or food chain; or...

40 CFR 300.415 - Removal action.

Code of Federal Regulations, 2012 CFR

2012-07-01

... food chain from hazardous substances or pollutants or contaminants; (ii) Actual or potential contamination of drinking water supplies or sensitive ecosystems; (iii) Hazardous substances or pollutants or...—where it will reduce the likelihood of spillage; leakage; exposure to humans, animals, or food chain; or...

EPA Technology Available for Licensing: Portable Device to Concentrate Water Samples for Microorganism Analysis

EPA Pesticide Factsheets

Using a computer controlled system, this ultrafiltration device automates the process of concentrating a water sample and can be operated in the field. The system was also designed to reduce human exposure to potentially contaminated water.

Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents With the Tobacco Heating System 2.1.

PubMed

Lüdicke, Frank; Baker, Gizelle; Magnette, John; Picavet, Patrick; Weitkunat, Rolf

2017-02-01

Heating rather than burning tobacco reduces levels of harmful and potentially harmful constituents, and consumer products using this approach aim to reduce exposure to tobacco toxicants. The Tobacco Heating System (THS) version 2.1 has been enhanced from earlier prototypes with an improved heat control and sensorial experience and thereby user acceptance. Exposure measurements are required to determine whether it may be possible to reduce the individual health risk compared to smoking combustible cigarettes (CCs). This controlled clinical study randomly assigned 40 smokers to either a group continuing to use of their own CC brand (n = 20) or a group switching to THS 2.1 (n = 20) for 5 days. Biomarkers of exposure were measured at baseline and on day 1 through day 5. Product consumption, Human Puffing Topography, the occurrence of adverse events, and an assessment of subjective effects, such as smoking satisfaction and enjoyment of respiratory tract sensations, were also determined. The group of smokers who switched to THS 2.1 adapted their puffing behavior initially through longer puff duration and more puffs. During the duration of the study, total puff volume returned to baseline levels and the mean daily product consumption increased but with similar nicotine exposure compared to baseline CC use. Biomarkers of exposure to tobacco smoke toxicants which inform product risk assessment were significantly reduced with THS use compared to the CC group. THS 2.1 users experienced less reinforcing effects with THS 2.1 than with their own cigarette brand. THS 2.1 is a promising alternative to smoking CCs. Notwithstanding possible use adaption through consumption or puffing behavior, the exposure to harmful smoke constituents was markedly reduced with the new heated tobacco platform. Exposure markers to harmful and potentially harmful smoke constituents were lowered with the THS 2.1. Heating tobacco instead of burning can offer a potentially lower risk of delivering nicotine compared to CCs. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

Improved Inactivation of Nonenveloped Enteric Viruses and Their Surrogates by a Novel Alcohol-Based Hand Sanitizer ▿

PubMed Central

Macinga, David R.; Sattar, Syed A.; Jaykus, Lee-Ann; Arbogast, James W.

2008-01-01

Norovirus is the leading cause of food-related illness in the United States, and contamination of ready-to-eat items by food handlers poses a high risk for disease. This study reports the in vitro (suspension test) and in vivo (fingerpad protocol) assessments of a new ethanol-based hand sanitizer containing a synergistic blend of polyquaternium polymer and organic acid, which is active against viruses of public health importance, including norovirus. When tested in suspension, the test product reduced the infectivity of the nonenveloped viruses human rotavirus (HRV), poliovirus type 1 (PV-1), and the human norovirus (HNV) surrogates feline calicivirus (FCV) F-9 and murine norovirus type 1 (MNV-1) by greater than 3 log10 after a 30-s exposure. In contrast, a benchmark alcohol-based hand sanitizer reduced only HRV by greater than 3 log10 and none of the additional viruses by greater than 1.2 log10 after the same exposure. In fingerpad experiments, the test product produced a 2.48 log10 reduction of MNV-1 after a 30-s exposure, whereas a 75% ethanol control produced a 0.91 log10 reduction. Additionally, the test product reduced the infectivity titers of adenovirus type 5 (ADV-5) and HRV by ≥3.16 log10 and ≥4.32 log10, respectively, by the fingerpad assay within 15 s; and PV-1 was reduced by 2.98 log10 in 30 s by the same method. Based on these results, we conclude that this new ethanol-based hand sanitizer is a promising option for reducing the transmission of enteric viruses, including norovirus, by food handlers and care providers. PMID:18586970

Improved inactivation of nonenveloped enteric viruses and their surrogates by a novel alcohol-based hand sanitizer.

PubMed

Macinga, David R; Sattar, Syed A; Jaykus, Lee-Ann; Arbogast, James W

2008-08-01

Norovirus is the leading cause of food-related illness in the United States, and contamination of ready-to-eat items by food handlers poses a high risk for disease. This study reports the in vitro (suspension test) and in vivo (fingerpad protocol) assessments of a new ethanol-based hand sanitizer containing a synergistic blend of polyquaternium polymer and organic acid, which is active against viruses of public health importance, including norovirus. When tested in suspension, the test product reduced the infectivity of the nonenveloped viruses human rotavirus (HRV), poliovirus type 1 (PV-1), and the human norovirus (HNV) surrogates feline calicivirus (FCV) F-9 and murine norovirus type 1 (MNV-1) by greater than 3 log(10) after a 30-s exposure. In contrast, a benchmark alcohol-based hand sanitizer reduced only HRV by greater than 3 log(10) and none of the additional viruses by greater than 1.2 log(10) after the same exposure. In fingerpad experiments, the test product produced a 2.48 log(10) reduction of MNV-1 after a 30-s exposure, whereas a 75% ethanol control produced a 0.91 log(10) reduction. Additionally, the test product reduced the infectivity titers of adenovirus type 5 (ADV-5) and HRV by > or =3.16 log(10) and > or =4.32 log(10), respectively, by the fingerpad assay within 15 s; and PV-1 was reduced by 2.98 log(10) in 30 s by the same method. Based on these results, we conclude that this new ethanol-based hand sanitizer is a promising option for reducing the transmission of enteric viruses, including norovirus, by food handlers and care providers.

Quantifying the exposure of humans and the environment to oil pollution in the Niger Delta using advanced geostatistical techniques.

PubMed

Obida, Christopher B; Alan Blackburn, G; Duncan Whyatt, J; Semple, Kirk T

2018-02-01

The Niger Delta is one of the largest oil producing regions of the world. Large numbers and volumes of oil spills have been reported in this region. What has not been quantified is the putative exposure of humans and/or the environment to this hydrocarbon pollution. In this novel study, advanced geostatistical techniques were applied to an extensive database of oil spill incidents from 2007 to 2015. The aims were to (i) identify and analyse spill hotspots along the oil pipeline network and (ii) estimate the exposure of the hydrocarbon pollution to the human population and the environment within the Niger Delta. Over the study period almost 90millionlitres of oil were released. Approximately 29% of the human population living in proximity to the pipeline network has been potentially exposed to oil contamination, of which 565,000 people live within high or very high spill intensity sectors. Over 1000km 2 of land has been contaminated by oil pollution, with broadleaved forest, mangroves and agricultural land the most heavily impacted land cover types. Proximity to the coast, roads and cities are the strongest spatial factors contributing to spill occurrence, which largely determine the accessibility of sites for pipeline sabotage and oil theft. Overall, the findings demonstrate the high levels of environmental and human exposure to hydrocarbon pollutants in the Niger Delta. These results provide evidence with which to spatially target interventions to reduce future spill incidents and mitigate the impacts of previous spills on human communities and ecosystem health. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.

PubMed

Raju, S Vamsee; Lin, Vivian Y; Liu, Limbo; McNicholas, Carmel M; Karki, Suman; Sloane, Peter A; Tang, Liping; Jackson, Patricia L; Wang, Wei; Wilson, Landon; Macon, Kevin J; Mazur, Marina; Kappes, John C; DeLucas, Lawrence J; Barnes, Stephen; Kirk, Kevin; Tearney, Guillermo J; Rowe, Steven M

2017-01-01

Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-μm resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis.

Health-based ingestion exposure guidelines for Vibrio cholerae: Technical basis for water reuse applications.

PubMed

Watson, Annetta P; Armstrong, Anthony Q; White, George H; Thran, Brandolyn H

2018-02-01

U.S. military and allied contingency operations are increasingly occurring in locations with limited, unstable or compromised fresh water supplies. Non-potable graywater reuse is currently under assessment as a viable means to increase mission sustainability while significantly reducing the resources, logistics and attack vulnerabilities posed by transport of fresh water. Development of health-based (non-potable) exposure guidelines for the potential microbial components of graywater would provide a logical and consistent human-health basis for water reuse strategies. Such health-based strategies will support not only improved water security for contingency operations, but also sustainable military operations. Dose-response assessment of Vibrio cholerae based on adult human oral exposure data were coupled with operational water exposure scenario parameters common to numerous military activities, and then used to derive health risk-based water concentrations. The microbial risk assessment approach utilized oral human exposure V. cholerae dose studies in open literature. Selected studies focused on gastrointestinal illness associated with experimental infection by specific V. cholerae serogroups most often associated with epidemics and pandemics (O1 and O139). Nonlinear dose-response model analyses estimated V. cholerae effective doses (EDs) aligned with gastrointestinal illness severity categories characterized by diarrheal purge volume. The EDs and water exposure assumptions were used to derive Risk-Based Water Concentrations (CFU/100mL) for mission-critical illness severity levels over a range of water use activities common to military operations. Human dose-response studies, data and analyses indicate that ingestion exposures at the estimated ED 1 (50CFU) are unlikely to be associated with diarrheal illness while ingestion exposures at the lower limit (200CFU) of the estimated ED 10 are not expected to result in a level of diarrheal illness associated with degraded individual capability. The current analysis indicates that the estimated ED 20 (approximately 1000CFU) represents initiation of a more advanced stage of diarrheal illness associated with clinical care. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body?

PubMed

Guilbaud, Axel; Niquet-Leridon, Celine; Boulanger, Eric; Tessier, Frederic J

2016-12-06

The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients. The present article provides an overview of current dietary strategies tested either in vitro, in vivo or both to reduce the endogenous formation of AGEs and to limit exposure to food AGEs.

How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body?

PubMed Central

Guilbaud, Axel; Niquet-Leridon, Celine; Boulanger, Eric; Tessier, Frederic J.

2016-01-01

The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients. The present article provides an overview of current dietary strategies tested either in vitro, in vivo or both to reduce the endogenous formation of AGEs and to limit exposure to food AGEs. PMID:28231179

Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage.

PubMed

Weyemi, Urbain; Redon, Christophe E; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R; Bonner, Michael Y; Arbiser, Jack L; Bonner, William M

2015-03-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year.

Inactivation of NADPH Oxidases NOX4 and NOX5 Protects Human Primary Fibroblasts from Ionizing Radiation-Induced DNA Damage

PubMed Central

Weyemi, Urbain; Redon, Christophe E.; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R.; Bonner, Michael Y.; Arbiser, Jack L.; Bonner, William M.

2015-01-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year. PMID:25706776

What California sea lions exposed to domoic acid might teach us about autism: lessons for predictive and preventive medicine.

PubMed

Lahvis, Garet Paul

2017-09-01

Autism spectrum disorder (ASD) shares many biological and behavioral similarities with the deleterious effects of domoic acid (DA) exposure. DA is produced by marine algae and most commonly by species of Pseudo-nitzschia . Humans and marine mammals can be exposed to DA when they consume whole fish or shellfish. The mammalian fetus is highly sensitive to the deleterious effects of DA exposure. Both ASD and exposures to toxic levels of DA feature repetitive behaviors, challenges with social interaction, and seizures. They can also share a commonality in brain anatomy and function, particularly the balance between excitatory and inhibitory mechanisms. The current article is relevant to predictive, preventive, and personalized medicine for three reasons. First, shellfish consumption may be a risk factor for ASD and the regulatory limit for DA should be adjusted to prevent this possibility. Human contributions to increased algal production of DA in coastal waters should be identified and reduced. Second, evaluations of sentinel species wild and free-roaming in the environment, though typically outside the purview of biomedical research, should be much more fully employed to gain insights to risk factors for human disease. To better identify and prevent disease, biomedical researchers should study wild populations. Third, studies of DA exposure highlight the possibility that glutamate additives to processed foods may also have deleterious impacts on human brain development and behavior.

A New Approach in Applying Systems Engineering Tools and Analysis to Determine Hepatocyte Toxicogenomics Risk Levels to Human Health.

PubMed

Gigrich, James; Sarkani, Shahryar; Holzer, Thomas

2017-03-01

There is an increasing backlog of potentially toxic compounds that cannot be evaluated with current animal-based approaches in a cost-effective and expeditious manner, thus putting human health at risk. Extrapolation of animal-based test results for human risk assessment often leads to different physiological outcomes. This article introduces the use of quantitative tools and methods from systems engineering to evaluate the risk of toxic compounds by the analysis of the amount of stress that human hepatocytes undergo in vitro when metabolizing GW7647 1 over extended times and concentrations. Hepatocytes are exceedingly connected systems that make it challenging to understand the highly varied dimensional genomics data to determine risk of exposure. Gene expression data of peroxisome proliferator-activated receptor-α (PPARα) 2 binding was measured over multiple concentrations and varied times of GW7647 exposure and leveraging mahalanombis distance to establish toxicity threshold risk levels. The application of these novel systems engineering tools provides new insight into the intricate workings of human hepatocytes to determine risk threshold levels from exposure. This approach is beneficial to decision makers and scientists, and it can help reduce the backlog of untested chemical compounds due to the high cost and inefficiency of animal-based models.

Effects of a chronic reduction of short-wavelength light input on melatonin and sleep patterns in humans: evidence for adaptation.

PubMed

Giménez, Marina C; Beersma, Domien G M; Bollen, Pauline; van der Linden, Matthijs L; Gordijn, Marijke C M

2014-06-01

Light is an important environmental stimulus for the entrainment of the circadian clock and for increasing alertness. The intrinsically photosensitive ganglion cells in the retina play an important role in transferring this light information to the circadian system and they are elicited in particular by short-wavelength light. Exposure to short wavelengths is reduced, for instance, in elderly people due to yellowing of the ocular lenses. This reduction may be involved in the disrupted circadian rhythms observed in aged subjects. Here, we tested the effects of reduced blue light exposure in young healthy subjects (n = 15) by using soft orange contact lenses (SOCL). We showed (as expected) that a reduction in the melatonin suppressing effect of light is observed when subjects wear the SOCL. However, after chronic exposure to reduced (short wavelength) light for two consecutive weeks we observed an increase in sensitivity of the melatonin suppression response. The response normalized as if it took place under a polychromatic light pulse. No differences were found in the dim light melatonin onset or in the amplitude of the melatonin rhythms after chronic reduced blue light exposure. The effects on sleep parameters were limited. Our results demonstrate that the non-visual light system of healthy young subjects is capable of adapting to changes in the spectral composition of environmental light exposure. The present results emphasize the importance of considering not only the short-term effects of changes in environmental light characteristics.

Human Biomechanical and Cardiopulmonary Responses to Partial Gravity - A Systematic Review.

PubMed

Richter, Charlotte; Braunstein, Bjoern; Winnard, Andrew; Nasser, Mona; Weber, Tobias

2017-01-01

The European Space Agency has recently announced to progress from low Earth orbit missions on the International Space Station to other mission scenarios such as exploration of the Moon or Mars. Therefore, the Moon is considered to be the next likely target for European human space explorations. Compared to microgravity (μg), only very little is known about the physiological effects of exposure to partial gravity (μg < partial gravity <1 g). However, previous research studies and experiences made during the Apollo missions comprise a valuable source of information that should be taken into account when planning human space explorations to reduced gravity environments. This systematic review summarizes the different effects of partial gravity (0.1-0.4 g) on the human musculoskeletal, cardiovascular and respiratory systems using data collected during the Apollo missions as well as outcomes from terrestrial models of reduced gravity with either 1 g or microgravity as a control. The evidence-based findings seek to facilitate decision making concerning the best medical and exercise support to maintain astronauts' health during future missions in partial gravity. The initial search generated 1,323 publication hits. Out of these 1,323 publications, 43 studies were included into the present analysis and relevant data were extracted. None of the 43 included studies investigated long-term effects. Studies investigating the immediate effects of partial gravity exposure reveal that cardiopulmonary parameters such as heart rate, oxygen consumption, metabolic rate, and cost of transport are reduced compared to 1 g, whereas stroke volume seems to increase with decreasing gravity levels. Biomechanical studies reveal that ground reaction forces, mechanical work, stance phase duration, stride frequency, duty factor and preferred walk-to-run transition speed are reduced compared to 1 g. Partial gravity exposure below 0.4 g seems to be insufficient to maintain musculoskeletal and cardiopulmonary properties in the long-term. To compensate for the anticipated lack of mechanical and metabolic stimuli some form of exercise countermeasure appears to be necessary in order to maintain reasonable astronauts' health, and thus ensure both sufficient work performance and mission safety.

Human Biomechanical and Cardiopulmonary Responses to Partial Gravity – A Systematic Review

PubMed Central

Richter, Charlotte; Braunstein, Bjoern; Winnard, Andrew; Nasser, Mona; Weber, Tobias

2017-01-01

The European Space Agency has recently announced to progress from low Earth orbit missions on the International Space Station to other mission scenarios such as exploration of the Moon or Mars. Therefore, the Moon is considered to be the next likely target for European human space explorations. Compared to microgravity (μg), only very little is known about the physiological effects of exposure to partial gravity (μg < partial gravity <1 g). However, previous research studies and experiences made during the Apollo missions comprise a valuable source of information that should be taken into account when planning human space explorations to reduced gravity environments. This systematic review summarizes the different effects of partial gravity (0.1–0.4 g) on the human musculoskeletal, cardiovascular and respiratory systems using data collected during the Apollo missions as well as outcomes from terrestrial models of reduced gravity with either 1 g or microgravity as a control. The evidence-based findings seek to facilitate decision making concerning the best medical and exercise support to maintain astronauts' health during future missions in partial gravity. The initial search generated 1,323 publication hits. Out of these 1,323 publications, 43 studies were included into the present analysis and relevant data were extracted. None of the 43 included studies investigated long-term effects. Studies investigating the immediate effects of partial gravity exposure reveal that cardiopulmonary parameters such as heart rate, oxygen consumption, metabolic rate, and cost of transport are reduced compared to 1 g, whereas stroke volume seems to increase with decreasing gravity levels. Biomechanical studies reveal that ground reaction forces, mechanical work, stance phase duration, stride frequency, duty factor and preferred walk-to-run transition speed are reduced compared to 1 g. Partial gravity exposure below 0.4 g seems to be insufficient to maintain musculoskeletal and cardiopulmonary properties in the long-term. To compensate for the anticipated lack of mechanical and metabolic stimuli some form of exercise countermeasure appears to be necessary in order to maintain reasonable astronauts' health, and thus ensure both sufficient work performance and mission safety. PMID:28860998

Varied exposure to carcinogenic, mutagenic, and reprotoxic (CMR) chemicals in occupational settings in France.

PubMed

Havet, Nathalie; Penot, Alexis; Morelle, Magali; Perrier, Lionel; Charbotel, Barbara; Fervers, Béatrice

2017-02-01

To explore varied exposure to carcinogenic, mutagenic, and reprotoxic chemicals (CMR) for French employees. Our study assessed data from the French national cross-sectional survey of occupational risks (SUMER) that was conducted in 2010 in a national representative sample of employees. We selected 28 CMR agents that were classified by the International Agency for Research on Cancer or European Union as being known or presumed to have CMR potential in humans. The association of individual and job characteristics with exposure prevalence, duration, and intensity of the CMR agents during a 1-week period was examined using multilevel logistic regression analysis. Overall, 10.4% of employees in 2010 were exposed to one or more CMR agents at their workplace, and 3.4% were subjected to multiple CMR exposures. Blue-collar workers, night-shift workers and workers with short-term employment contracts experienced higher exposure prevalence (p < 0.01) and intensity (p < 0.05). Blue-collar workers and shift workers experienced also longer exposure duration (p < 0.001). Conversely, managers, workers of large companies, and women were less exposed to CMR agents (p < 0.001). The presence of a Committee for Health, Safety, and Working Conditions, and intervention by Occupational Health and Safety officers were significantly associated with reduced exposure intensities (p < 0.001 and p < 0.05). Establishment of European CMR regulations and the existence of an applicable substitution principle reduced the exposure duration (p < 0.001) and intensity (p < 0.05). Our results point out disparities in CMR exposure and identify high-priority targets for prevention measures to help reducing social health discrepancies.

Maternal exposure to diluted diesel engine exhaust alters placental function and induces intergenerational effects in rabbits.

PubMed

Valentino, Sarah A; Tarrade, Anne; Aioun, Josiane; Mourier, Eve; Richard, Christophe; Dahirel, Michèle; Rousseau-Ralliard, Delphine; Fournier, Natalie; Aubrière, Marie-Christine; Lallemand, Marie-Sylvie; Camous, Sylvaine; Guinot, Marine; Charlier, Madia; Aujean, Etienne; Al Adhami, Hala; Fokkens, Paul H; Agier, Lydiane; Boere, John A; Cassee, Flemming R; Slama, Rémy; Chavatte-Palmer, Pascale

2016-07-26

Airborne pollution is a rising concern in urban areas. Epidemiological studies in humans and animal experiments using rodent models indicate that gestational exposure to airborne pollution, in particular diesel engine exhaust (DE), reduces birth weight, but effects depend on exposure duration, gestational window and nanoparticle (NP) concentration. Our aim was to evaluate the effects of gestational exposure to diluted DE on feto-placental development in a rabbit model. Pregnant females were exposed to diluted (1 mg/m(3)), filtered DE (NP diameter ≈ 69 nm) or clean air (controls) for 2 h/day, 5 days/week by nose-only exposure (total exposure: 20 days in a 31-day gestation). DE exposure induced early signs of growth retardation at mid gestation with decreased head length (p = 0.04) and umbilical pulse (p = 0.018). Near term, fetal head length (p = 0.029) and plasma insulin and IGF1 concentrations (p = 0.05 and p = 0.019) were reduced. Placental function was also affected, with reduced placental efficiency (fetal/placental weight) (p = 0.049), decreased placental blood flow (p = 0.009) and fetal vessel volume (p = 0.002). Non-aggregated and "fingerprint" NP were observed at various locations, in maternal blood space, in trophoblastic cells and in the fetal blood, demonstrating transplacental transfer. Adult female offspring were bred with control males. Although fetoplacental biometry was not affected near term, second generation fetal metabolism was modified by grand-dam exposure with decreased plasma cholesterol (p = 0.008) and increased triglyceride concentrations (p = 0.015). Repeated daily gestational exposure to DE at levels close to urban pollution can affect feto-placental development in the first and second generation.

Human microvascular dysfunction and apoptotic injury induced by AL amyloidosis light chain proteins.

PubMed

Migrino, Raymond Q; Truran, Seth; Gutterman, David D; Franco, Daniel A; Bright, Megan; Schlundt, Brittany; Timmons, Mitchell; Motta, Angelica; Phillips, Shane A; Hari, Parameswaran

2011-12-01

Light chain amyloidosis (AL) involves overproduction of amyloidogenic light chain proteins (LC) leading to heart failure, yet the mechanisms underlying tissue toxicity remain unknown. We hypothesized that LC induces endothelial dysfunction in non-AL human microvasculature and apoptotic injury in human coronary artery endothelial cells (HCAECs). Adipose arterioles (n = 34, 50 ± 3 yr) and atrial coronary arterioles (n = 19, 68 ± 2 yr) from non-AL subjects were cannulated. Adipose arteriole dilator responses to acetylcholine/papaverine were measured at baseline and 1 h exposure to LC (20 μg/ml) from biopsy-proven AL subjects (57 ± 11 yr) without and with antioxidant cotreatment. Coronary arteriole dilation to bradykinin/papaverine was measured post-LC exposure. HCAECs were exposed to 1 or 24 h of LC. LC reduced dilation to acetylcholine (10(-4) M: 41.6 ± 7 vs. 85.8 ± 2.2% control, P < 0.001) and papaverine (81.4 ± 4.6 vs. 94.8 ± 1.3% control, P < 0.01) in adipose arterioles and to bradykinin (10(-6) M: 68.6 ± 6.2 vs. 90.9 ± 1.6% control, P < 0.001) but not papaverine in coronary arterioles. There was an increase in superoxide and peroxynitrite in arterioles treated with LC. Adipose arteriole dilation was restored by cotreatment with polyethylene glycol-superoxide dismutase and tetrahydrobiopterin but only partially restored by mitoquinone (mitochondria-targeted antioxidant) and gp91ds-tat (NADPH oxidase inhibitor). HCAECs exposed to LC showed reduced NO and increased superoxide, peroxynitrite, annexin-V, and propidium iodide compared with control. Brief exposure to physiological amounts of LC induced endothelial dysfunction in human adipose and coronary arterioles and increased apoptotic injury in coronary artery endothelial cells likely as a result of oxidative stress, reduced NO bioavailability, and peroxynitrite production. Microvascular dysfunction and injury is a novel mechanism underlying AL pathobiology and is a potential target for therapy.

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice.

PubMed

Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

2017-05-01

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. Copyright © 2017 Elsevier Inc. All rights reserved.

Elimination of human rabies in a canine endemic province in Thailand: five-year programme.

PubMed Central

Kamoltham, T.; Singhsa, J.; Promsaranee, U.; Sonthon, P.; Mathean, P.; Thinyounyong, W.

2003-01-01

A five-year project to prevent human deaths from rabies in Phetchabun Province, Thailand involved increasing accessibility of post-exposure treatment with the Thai Red Cross intradermal (2-2-2-0-1-1) regimen for humans exposed to potentially and confirmed rabid animals; intensifying documentation of post-exposure treatment; increasing educational awareness through advocacy in provincial schools, television programmes, and newspapers; reducing canine rabies by monitoring the dog population and implementing vaccination and sterilization programmes; increasing the cooperation between the Ministries of Public Health, Agriculture, and Education on a provincial level; and assessing the impact of the programme through intensified follow-up of patients exposed to suspected and laboratory-confirmed rabid animals. Between 1996 and 2001, 10350 patients received post-exposure treatment; 7227 of these received the Thai Red Cross intradermal regimen. Fewer than 3% of exposed patients received rabies immunoglobulin. Seventy-three percent of all patients presented with WHO category III exposures. In a retrospective study, 188 patients exposed to laboratory-confirmed rabid animals were followed to determine their health status. Of these patients, 20 received the intramuscular Essen regimen and 168 the Thai Red Cross intradermal regimen (148 received 0.1 ml purified chick embryo cell rabies vaccine, 10 received 0.1 ml purified vero cell rabies vaccine, and 10 received 0.2 ml purified duck embryo cell rabies vaccine). All patients were alive one year after exposure. Two human deaths occurred in the first two years of the programme - neither patient had received vaccine or rabies immunoglobulin after exposure. No deaths occurred during the last three years of the programme, which indicated that the programme was successful. PMID:12862022

If exposure to aluminium in antiperspirants presents health risks, its content should be reduced.

PubMed

Pineau, Alain; Fauconneau, Bernard; Sappino, André-Pascal; Deloncle, Roger; Guillard, Olivier

2014-04-01

Since aluminium (Al) pervades our environment, the scientific community has for many years raised concerns regarding its safety in humans. Al is present in numerous cosmetics such as antiperspirants, lipsticks and sunscreens. Al chlorohydrate is the active antiperspirant agent in underarm cosmetics and may constitute for Al a key exposure route to the human body and a potential source of damage. An in vitro study has demonstrated that Al from antiperspirant can be absorbed through viable human stripped skin. The potential toxicity of Al has been clearly shown and recent works convincingly argue that Al could be involved in cancerogenic processes. Nowadays, for example, Al is suspected of being involved in breast cancer. Recent work in cells in culture has lent credence to the hypothesis that this metal could accumulate in the mammary gland and selectively interfere with the biological properties of breast epithelial cells, thereby promoting a cascade of alterations reminiscent of the early phases of malignant transformation. In addition, several studies suggest that the presence of Al in human breast could influence metastatic process. As a consequence, given that the toxicity of Al has been widely recognized and that it is not a physiological component in human tissues, reducing the concentration of this metal in antiperspirants is a matter of urgency. Copyright © 2013 Elsevier GmbH. All rights reserved.

The impact of a Bus Rapid Transit system on commuters' exposure to Benzene, CO, PM 2.5 and PM 10 in Mexico City

NASA Astrophysics Data System (ADS)

Wöhrnschimmel, Henry; Zuk, Miriam; Martínez-Villa, Gerardo; Cerón, Julia; Cárdenas, Beatriz; Rojas-Bracho, Leonora; Fernández-Bremauntz, Adrián

Carbon monoxide (CO), benzene and other volatile organic compounds (VOCs) and suspended particles PM 2.5 and PM 10 were measured inside public transportation vehicles, before and after a new Bus Rapid Transit (BRT) system was implemented in Mexico City in June 2005. The objective was to evaluate the BRT system's impact on commuters' exposure to these air pollutants. The BRT system replaced conventional transport modes along 20 km of Insurgentes Avenue, and features confined corridors and new articulated diesel buses. We assessed the impact of the transportation mode on commuters' exposure using least squares regression models. We also analyzed the chemical composition of VOCs to evaluate the possible origin of these species. The implementation of the BRT system resulted in reductions in commuters' exposure to CO, benzene and PM 2.5 ranging between 20% and 70%. No significant reductions in PM 10 exposure were observed. Lower commuting times further reduced total commuters' exposure. Major sources affecting VOCs inside all transport modes are likely to be related to traffic and to emissions from the use of Liquefied Petroleum Gas. The results suggest that BRT systems could in general be an effective means of reducing human exposure to traffic related air pollutants and associated health impacts.

Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

PubMed

Hu, Xindi C; Dassuncao, Clifton; Zhang, Xianming; Grandjean, Philippe; Weihe, Pál; Webster, Glenys M; Nielsen, Flemming; Sunderland, Elsie M

2018-02-01

Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS exposures. The composition of PFASs in human sera reflects the complexity of exposure sources but source identification can be confounded by differences in toxicokinetics affecting uptake, distribution, and elimination. Common PFASs, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects. We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands) to explore whether chemical fingerprints in human sera provide insights into predominant exposure sources. We compare serum PFAS profiles from Faroese individuals to other North American populations to investigate commonalities in potential exposure sources. We compare individuals with similar demographic and physiological characteristics and samples from the same years to reduce confounding by toxicokinetic differences and changing environmental releases. Using principal components analysis (PCA) confirmed by hierarchical clustering, we assess variability in serum PFAS concentrations across three Faroese groups. The first principal component (PC)/cluster consists of C9-C12 perfluoroalkyl carboxylates (PFCAs) and is consistent with measured PFAS profiles in consumed seafood. The second PC/cluster includes perfluorohexanesulfonic acid (PFHxS) and the PFOS precursor N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same exposure sources in two North American populations, suggesting generalizability of results from the Faroese population. We conclude that PFAS homologue profiles in serum provide valuable information on major exposure sources. It is essential to compare samples collected at similar time periods and to correct for demographic groups that are highly affected by differences in physiological processes (e.g., pregnancy). Information on PFAS homologue profiles is crucial for attributing adverse health effects to the proper mixtures or individual PFASs.

Proinflammatory effects of cookstove emissions on human bronchial epithelial cells.

PubMed

Hawley, B; Volckens, J

2013-02-01

Approximately half of the world's population uses biomass fuel for indoor cooking and heating. This form of combustion typically occurs in open fires or primitive stoves. Human exposure to emissions from indoor biomass combustion is a global health concern, causing an estimated 1.5 million premature deaths each year. Many 'improved' stoves have been developed to address this concern; however, studies that examine exposure-response with cleaner-burning, more efficient stoves are few. The objective of this research was to evaluate the effects of traditional and cleaner-burning stove emissions on an established model of the bronchial epithelium. We exposed well-differentiated, normal human bronchial epithelial cells to emissions from a single biomass combustion event using either a traditional three-stone fire or one of two energy-efficient stoves. Air-liquid interface cultures were exposed using a novel, aerosol-to-cell deposition system. Cellular expression of a panel of three pro-inflammatory markers was evaluated at 1 and 24 h following exposure. Cells exposed to emissions from the cleaner-burning stoves generated significantly fewer amounts of pro-inflammatory markers than cells exposed to emissions from a traditional three-stone fire. Particulate matter emissions from each cookstove were substantially different, with the three-stone fire producing the largest concentrations of particles (by both number and mass). This study supports emerging evidence that more efficient cookstoves have the potential to reduce respiratory inflammation in settings where solid fuel combustion is used to meet basic domestic needs. Emissions from more efficient, cleaner-burning cookstoves produced less inflammation in well-differentiated bronchial lung cells. The results support evidence that more efficient cookstoves can reduce the health burden associated with exposure to indoor pollution from the combustion of biomass. © 2012 John Wiley & Sons A/S.

Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells.

PubMed

Mullins, Benjamin J; Kicic, Anthony; Ling, Kak-Ming; Mead-Hunter, Ryan; Larcombe, Alexander N

2016-01-01

Increasing use of biodiesel has prompted research into the potential health effects of biodiesel exhaust exposure. Few studies directly compare the health consequences of mineral diesel, biodiesel, or blend exhaust exposures. Here, we exposed human epithelial cell cultures to diluted exhaust generated by the combustion of Australian ultralow-sulfur-diesel (ULSD), unprocessed canola oil, 100% canola biodiesel (B100), and a blend of 20% canola biodiesel mixed with 80% ULSD. The physicochemical characteristics of the exhaust were assessed and we compared cellular viability, apoptosis, and levels of interleukin (IL)-6, IL-8, and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) in exposed cultured cells. Different fuel types produced significantly different amounts of exhaust gases and different particle characteristics. All exposures resulted in significant apoptosis and loss of viability when compared with control, with an increasing proportion of biodiesel being correlated with a decrease in viability. In most cases, exposure to exhaust resulted in an increase in mediator production, with the greatest increases most often in response to B100. Exposure to pure canola oil (PCO) exhaust did not increase mediator production, but resulted in a significant decrease in IL-8 and RANTES in some cases. Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure. This may be related to an increase in particle surface area and number in B100 exhaust when compared with ULSD exhaust. Exposure to PCO exhaust elicited the greatest loss of cellular viability, but virtually no inflammatory response, likely due to an overall increase in average particle size. © 2014 Wiley Periodicals, Inc.

Chlorine Isotopic Composition of Perchlorate in Human Urine as a Means of Distinguishing Among Natural and Synthetic Exposure Sources

PubMed Central

Poghosyan, Armen; Morel-Espinosa, Maria; Valentín-Blasini, Liza; Blount, Benjamin C.; Ferreccio, Catterina; Steinmaus, Craig M.; Sturchio, Neil C.

2015-01-01

Perchlorate (ClO4−) is a ubiquitous environmental contaminant with high human exposure potential; it has both natural and man-made sources in the environment. Natural perchlorate forms in the atmosphere from where it deposits onto the surface of Earth, whereas synthetic perchlorate is manufactured as an oxidant for industrial, aerospace, and military applications. Perchlorate exposure can potentially cause adverse health effects in humans by interfering with the production of thyroid hormones through competitively blocking iodide uptake. To control and reduce perchlorate exposure, the contributions of different sources of perchlorate exposure need to be quantified. Thus, we demonstrate a novel approach for determining the contribution of different perchlorate exposure sources by quantifying stable and radioactive chlorine isotopes of perchlorate extracted from composite urine samples from two distinct populations: one in Atlanta, USA and one in Taltal, Chile (Atacama region). Urinary perchlorate from the Atlanta region resembles indigenous natural perchlorate from the southwestern USA [δ37Cl = +4.1 ± 1.0 ‰; 36Cl/Cl = 1811 (± 136) × 10−15], and urinary perchlorate from the Taltal, Chile region is similar to natural perchlorate in nitrate salt deposits from the Atacama Desert of northern Chile [δ37Cl = −11.0 ± 1.0 ‰; 36Cl/Cl = 254 (± 40) × 10−15]. Neither urinary perchlorate resembled the isotopic pattern found in synthetic perchlorate. These results indicate that natural perchlorate of regional provenance is the dominant exposure source for the two sample populations, and that chlorine isotope ratios provide a robust tool for elucidating perchlorate exposure pathways. PMID:25805252

Inactivation of dairy manure-borne pathogens by anaerobic digestion

USDA-ARS?s Scientific Manuscript database

Background: Anaerobic digestion of animal manure has the potential to inactivate enteric pathogens, thereby reducing exposures to livestock and humans when the products of digestion are disposed by land-spreading or irrigation or returned to livestock uses such as bedding. Data on digester effectiv...

Determination of an Ergonomically Sound Glovebox Glove Port Center Line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christman, Marissa St; Land, Whitney Morgan

2016-11-30

Determine an ergonomic glovebox glove port center line location which will be used for standardization in new designs, thus allowing for predictable human work performance, reduced worker exposure to radiation and musculoskeletal injury risks, and improved worker comfort, efficiency, health, and safety.

Incorporating Human Dosimetry and Exposure into High-Throughput In Vitro Toxicity Screening

EPA Science Inventory

Many chemicals in commerce today have undergone limited or no safety testing. To reduce the number of untested chemicals and prioritize limited testing resources, several governmental programs are using high-throughput in vitro screens for assessing chemical effects across multip...

HIGHLY SENSITIVE ASSAY FOR ANTICHOLINESTERASE COMPOUNDS USING 96 WELL PLATE FORMAT

EPA Science Inventory

One of the approaches for reducing uncertainties in the assessment of human exposure is to better characterize concentrations of hazardous compounds that may be present in our immediate environment. A significant limitation to this approach, however, is that sampling and labora...

A VISION FOR A BEACH FORECASTING TOOL

EPA Science Inventory

The societal value of safe access to swimmable water is intuitive and in many countries it is a legal right. Threats to water quality reduce these recreational opportunities. The risk comes from exposure to waterborne pathogens from a myriad of sources, both human and animal. ...

Increased SHP-1 Protein Expression by High Glucose Levels Reduces Nephrin Phosphorylation in Podocytes*

PubMed Central

Denhez, Benoit; Lizotte, Farah; Guimond, Marie-Odile; Jones, Nina; Takano, Tomoko; Geraldes, Pedro

2015-01-01

Nephrin, a critical podocyte membrane component that is reduced in diabetic nephropathy, has been shown to activate phosphotyrosine signaling pathways in human podocytes. Nephrin signaling is important to reduce cell death induced by apoptotic stimuli. We have shown previously that high glucose level exposure and diabetes increased the expression of SHP-1, causing podocyte apoptosis. SHP-1 possesses two Src homology 2 domains that serve as docking elements to dephosphorylate tyrosine residues of target proteins. However, it remains unknown whether SHP-1 interacts with nephrin and whether its elevated expression affects the nephrin phosphorylation state in diabetes. Here we show that human podocytes exposed to high glucose levels exhibited elevated expression of SHP-1, which was associated with nephrin. Coexpression of nephrin-CD16 and SHP-1 reduced nephrin tyrosine phosphorylation in transfected human embryonic kidney 293 cells. A single tyrosine-to-phenylalanine mutation revealed that rat nephrin Tyr1127 and Tyr1152 are required to allow SHP-1 interaction with nephrin. Overexpression of dominant negative SHP-1 in human podocytes prevented high glucose-induced reduction of nephrin phosphorylation. In vivo, immunoblot analysis demonstrated that nephrin expression and phosphorylation were decreased in glomeruli of type 1 diabetic Akita mice (Ins2+/C96Y) compared with control littermate mice (Ins2+/+), and this was associated with elevated SHP-1 and cleaved caspase-3 expression. Furthermore, immunofluorescence analysis indicated increased colocalization of SHP-1 with nephrin in diabetic mice compared with control littermates. In conclusion, our results demonstrate that high glucose exposure increases SHP-1 interaction with nephrin, causing decreased nephrin phosphorylation, which may, in turn, contribute to diabetic nephropathy. PMID:25404734

Effect of the cytostatic agent idarubicin on fibroblasts of the human Tenon's capsule compared with mitomycin C.

PubMed

Heilmann, C; Schönfeld, P; Schlüter, T; Bohnensack, R; Behrens-Baumann, W

1999-08-01

To investigate the in vitro effect of a short time exposure to the anthracycline idarubicin on proliferation, protein synthesis, and motility of human Tenon's capsule fibroblasts in comparison with the antitumour antibiotic mitomycin C. After determination of effective concentrations of idarubicin, fibroblasts of the human Tenon's capsule were exposed to idarubicin or mitomycin C at concentrations ranging from 0.1 microg/ml to 1 microg/ml or from 2.5 microg/ml to 250 microg/ml, respectively, for 0.5, 2, or 5 minutes and cultured for 60 days. Cell death by apoptosis caused by idarubicin treatment was confirmed by Hoechst 33258 staining. Further proliferation was explored by cell counting and by (3)H-thymidine uptake. Protein synthesis was measured by (3)H-proline uptake and motility was assessed by agarose droplet motility assay. Idarubicin is able to exert toxicity and to induce apoptosis during a short time exposure of 0.5 minutes at concentrations of 0.3-1 microg/ml resulting in a significant reduction in cell number compared with the control after 60 days. For mitomycin C, higher concentrations and longer expositions were necessary. Even after treatment with 1 microg/ml idarubicin or 250 microg/ml mitomycin C a few cells were able to incorporate (3)H-thymidine. (3)H-proline uptake up to 10 days after exposure to 0.3 microg/ml idarubicin was found not to be decreased. Cell motility was reduced after treatment with 1 microg/ml idarubicin for 5 minutes or with 250 microg/ml mitomycin C for 2 or 5 minutes. For low mitomycin C concentrations, an increase in motility was found during the first 10 days. Idarubicin reduces proliferation of human Tenons's capsule fibroblasts after incubation for 0.5 minutes at concentrations as low as 0.3-1 microg/ml. In comparison, mitomycin C requires longer exposure times and higher doses for equal results. Therefore, idarubicin may be useful in the prevention of glaucoma filtering surgery failure.

Genetic and Dietary Regulation of Glyburide Efflux by the Human Placental Breast Cancer Resistance Protein Transporter.

PubMed

Bircsak, Kristin M; Gupta, Vivek; Yuen, Poi Yu Sofia; Gorczyca, Ludwik; Weinberger, Barry I; Vetrano, Anna M; Aleksunes, Lauren M

2016-04-01

Glyburide is frequently used to treat gestational diabetes owing to its low fetal accumulation resulting from placental efflux by the breast cancer resistance protein (BCRP)/ABCG2 transporter. Here we sought to determine how exposure to the dietary phytoestrogen genistein and expression of a loss-of-function polymorphism in the ABCG2 gene (C421A) impacted the transport of glyburide by BCRP using stably transfected human embryonic kidney 293 (HEK) cells, human placental choriocarcinoma BeWo cells, and human placental explants. Genistein competitively inhibited the BCRP-mediated transport of (3)H-glyburide in both wild-type (WT) and C421A-BCRP HEK-expressing cells, with greater accumulation of (3)H-glyburide in cells expressing the C421A variant. In BeWo cells, exposure to genistein for 60 minutes increased the accumulation of (3)H-glyburide 30%-70% at concentrations relevant to dietary exposure (IC50 ∼180 nM). Continuous exposure of BeWo cells to genistein for 48 hours reduced the expression of BCRP mRNA and protein by up to 40%, which impaired BCRP transport activity. Pharmacologic antagonism of the estrogen receptor attenuated the genistein-mediated downregulation of BCRP expression, suggesting that phytoestrogens may reduce BCRP levels through this hormone receptor pathway in BeWo cells. Interestingly, genistein treatment for 48 hours did not alter BCRP protein expression in explants dissected from healthy term placentas. These data suggest that whereas genistein can act as a competitive inhibitor of BCRP-mediated transport, its ability to downregulate placental BCRP expression may only occur in choriocarcinoma cells. Overall, this research provides important mechanistic data regarding how the environment (dietary genistein) and a frequent genetic variant (ABCG2, C421A) may alter the maternal-fetal disposition of glyburide. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Implications of outer-zone radiations on operations in the geostationary region utilizing the ae4 environmental model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, J.W.; Denn, F.M.

1977-05-01

The radiation exposure in the region of geostationary orbits is examined in search for means of optimizing human performance. It is found that the use of slightly inclined circular orbits is one means by which exposure and spacesuit thickness requirements can be reduced. Another effective technique is to limit the extravehicular activity to those days when the short term fluctuations result in low exposure. Space-suit shielding approaching 1/2 sq cm or less may be possible by utilizing work stoppages and inclined orbits. If aluminum and other low-atomic-number materials are used to construct the habitat, then excessive wall thicknesses are required.more » If special bremsstrahlung shielding is used, then the habitat shield may be reduced to as low as 2 g/sq cm. Numerous tables and graphs are presented for future analysis of dose in the geostationary region.« less

Modeling of urban trees' effects on reducing human exposure to UV radiation in Seoul, Korea

Treesearch

Hang Ryeol Na; Gordon M. Heisler; David J. Nowak; Richard H. Grant

2014-01-01

A mathematical model isconstructed for quantifying urban trees’ effects on mitigating the intensity of ultraviolet (UV) radiation on the ground within different landuse types across a city. The model is based upon local field data, meteorological data and equations designed to predict the reduced UV fraction due to trees at the ground level. Trees in Seoul, Korea (2010...

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Motwani, Hitesh V., E-mail: hitesh.motwani@mmk.su.se; Törnqvist, Margareta

2014-12-15

1,3-Butadiene (BD) is a rodent and human carcinogen. In the cancer tests, mice have been much more susceptible than rats with regard to BD-induced carcinogenicity. The species-differences are dependent on metabolic formation/disappearance of the genotoxic BD epoxy-metabolites that lead to variations in the respective in vivo doses, i.e. “area under the concentration-time curve” (AUC). Differences in AUC of the most gentoxic BD epoxy-metabolite, diepoxybutane (DEB), are considered important with regard to cancer susceptibility. The present work describes: the application of cob(I)alamin for accurate measurements of in vitro enzyme kinetic parameters associated with BD epoxy-metabolites in human, mouse and rat; themore » use of published data on hemoglobin (Hb) adduct levels of BD epoxides from BD exposure studies on the three species to calculate the corresponding AUCs in blood; and a parallelogram approach for extrapolation of AUC of DEB based on the in vitro metabolism studies and adduct data from in vivo measurements. The predicted value of AUC of DEB for humans from the parallelogram approach was 0.078 nM · h for 1 ppm · h of BD exposure compared to 0.023 nM · h/ppm · h as calculated from Hb adduct levels observed in occupational exposure. The corresponding values in nM · h/ppm · h were for mice 41 vs. 38 and for rats 1.26 vs. 1.37 from the parallelogram approach vs. experimental exposures, respectively, showing a good agreement. This quantitative inter-species extrapolation approach will be further explored for the clarification of metabolic rates/pharmacokinetics and the AUC of other genotoxic electrophilic compounds/metabolites, and has a potential to reduce and refine animal experiments. - Highlights: • In vitro metabolism to in vivo dose extrapolation of butadiene metabolites was proposed. • A parallelogram approach was introduced to estimate dose (AUC) in humans and rodents. • AUC of diepoxybutane predicted in humans was 0.078 nM h/ppm h butadiene exposure. • The presented approach has a potential to reduce, refine and replace animal experiments.« less

Free will and punishment: a mechanistic view of human nature reduces retribution.

PubMed

Shariff, Azim F; Greene, Joshua D; Karremans, Johan C; Luguri, Jamie B; Clark, Cory J; Schooler, Jonathan W; Baumeister, Roy F; Vohs, Kathleen D

2014-08-01

If free-will beliefs support attributions of moral responsibility, then reducing these beliefs should make people less retributive in their attitudes about punishment. Four studies tested this prediction using both measured and manipulated free-will beliefs. Study 1 found that people with weaker free-will beliefs endorsed less retributive, but not consequentialist, attitudes regarding punishment of criminals. Subsequent studies showed that learning about the neural bases of human behavior, through either lab-based manipulations or attendance at an undergraduate neuroscience course, reduced people's support for retributive punishment (Studies 2-4). These results illustrate that exposure to debates about free will and to scientific research on the neural basis of behavior may have consequences for attributions of moral responsibility. © The Author(s) 2014.

Blood-borne biomarkers and bioindicators for linking exposure to health effects in environmental health science.

PubMed

Wallace, M Ariel Geer; Kormos, Tzipporah M; Pleil, Joachim D

2016-01-01

Environmental health science aims to link environmental pollution sources to adverse health outcomes to develop effective exposure intervention strategies that reduce long-term disease risks. Over the past few decades, the public health community recognized that health risk is driven by interaction between the human genome and external environment. Now that the human genetic code has been sequenced, establishing this "G × E" (gene-environment) interaction requires a similar effort to decode the human exposome, which is the accumulation of an individual's environmental exposures and metabolic responses throughout the person's lifetime. The exposome is composed of endogenous and exogenous chemicals, many of which are measurable as biomarkers in blood, breath, and urine. Exposure to pollutants is assessed by analyzing biofluids for the pollutant itself or its metabolic products. New methods are being developed to use a subset of biomarkers, termed bioindicators, to demonstrate biological changes indicative of future adverse health effects. Typically, environmental biomarkers are assessed using noninvasive (excreted) media, such as breath and urine. Blood is often avoided for biomonitoring due to practical reasons such as medical personnel, infectious waste, or clinical setting, despite the fact that blood represents the central compartment that interacts with every living cell and is the most relevant biofluid for certain applications and analyses. The aims of this study were to (1) review the current use of blood samples in environmental health research, (2) briefly contrast blood with other biological media, and (3) propose additional applications for blood analysis in human exposure research.

Cadmium exposure inhibits branching morphogenesis and causes alterations consistent with HIF-1α inhibition in human primary breast organoids.

PubMed

Rocco, Sabrina A; Koneva, Lada; Middleton, Lauren Y M; Thong, Tasha; Solanki, Sumeet; Karram, Sarah; Nambunmee, Kowit; Harris, Craig; Rozek, Laura S; Sartor, Maureen A; Shah, Yatrik M; Colacino, Justin A

2018-05-07

Developmental cadmium exposure in vivo disrupts mammary gland differentiation, while exposure of breast cell lines to cadmium causes invasion consistent with the epithelial-mesenchymal transition (EMT). The effects of cadmium on normal human breast stem cells have not been measured. Here, we quantified the effects of cadmium exposure on reduction mammoplasty patient-derived breast stem cell proliferation and differentiation. Using the mammosphere assay and organoid formation in 3D hydrogels, we tested two physiologically relevant doses of cadmium, 0.25μM and 2.5μM, and tested for molecular alterations using RNA-seq. We functionally validated our RNA-seq findings with a HIF-1α activity reporter line and pharmaceutical inhibition of HIF-1α in organoid formation assays. 2.5μM cadmium reduced primary mammosphere formation and branching structure organoid formation rates by 33% and 87%, respectively. Despite no changes in mammosphere formation, 0.25μM cadmium inhibited branching organoid formation in hydrogels by 73%. RNA-seq revealed cadmium downregulated genes associated with extracellular matrix formation and EMT, while upregulating genes associated with metal response including metallothioneins and zinc transporters. In the RNA-seq data, cadmium downregulated HIF-1α target genes including LOXL2, ZEB1, and VIM. Cadmium significantly inhibited HIF-1α activity in a luciferase assay, and the HIF-1α inhibitor acriflavine ablated mammosphere and organoid formation. These findings show that cadmium, at doses relevant to human exposure, inhibited human mammary stem cell proliferation and differentiation, potentially through disruption of HIF-1α activity.

Cooking and co-ingested polyphenols reduce in vitro methylmercury bioaccessibility from fish and may alter exposure in humans.

PubMed

Girard, Catherine; Charette, Tania; Leclerc, Maxime; Shapiro, B Jesse; Amyot, Marc

2018-03-01

Fish consumption is a major pathway for mercury exposure in humans. Current guidelines and risk assessments assume that 100% of methylmercury (MeHg) in fish is absorbed by the human body after ingestion. However, a growing body of literature suggests that this absorption rate may be overestimated. We used an in vitro digestion method to measure MeHg bioaccessibility in commercially-purchased fish, and investigated the effects of dietary practices on MeHg bioaccessibility. Cooking had the greatest effect, decreasing bioaccessibility on average to 12.5±5.6%. Polyphenol-rich beverages also significantly reduced bioaccessibility to 22.7±3.8% and 28.6±13.9%, for green and black tea respectively. We confirmed the suspected role of polyphenols in tea as being a driver of MeHg's reduced bioaccessibility, and found that epicatechin, epigallocatechin gallate, rutin and cafeic acid could individually decrease MeHg bioaccessibility by up to 55%. When both cooking and polyphenol-rich beverage treatments were combined, only 1% of MeHg remained bioaccessible. These results call for in vivo validation, and suggest that dietary practices should be considered when setting consumer guidelines for MeHg. More realistic risk assessments could promote consumption of fish as a source of fatty acids, which can play a protective role against cardiovascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Exposure to Ambient Particulate Matter during Specific Gestational Periods Produces Adverse Obstetric Consequences in Mice

PubMed Central

Blum, Jason L.; Chen, Lung-Chi

2017-01-01

Background: Epidemiological studies associate inhalation of fine-sized particulate matter (PM2.5) during pregnancy with preterm birth (PTB) and low birth weight (LBW) but disagree over which time frames are most sensitive, or if effects are cumulative. Objectives: Our objective was to provide experimental plausibility for epidemiological observations by testing the hypothesis that exposure to PM2.5 during discrete periods of pregnancy results in PTB and LBW. Methods: For the first study, timed-pregnant B6C3F1 mice were exposed to concentrated ambient PM2.5 (CAPs) or filtered air (FA) throughout pregnancy [6 h/d from gestational day (GD) 0.5 through GD16.5]. A follow-up study examined the effects of CAPs exposure during discrete gestational periods (1: GD0.5–5.5; 2: GD6.5–14.5; 3: GD14.5–16.5; 4: GD0.5–16.5) aligning to milestones during human development. Results: In the first experiment, exposure to 160 μg CAPs/m3 throughout pregnancy decreased gestational term by 0.5 d (∼1.1  wk decrease for humans) and birth weight by 11.4% compared with FA. The follow-up experiment investigated timing of CAPs exposure (mean concentrations at 178, 193, 171, and 173 μg/m3 for periods 1–4, respectively). Pregnancy was significantly shortened (vs. FA) by ∼0.4d when exposure occurred during gestational periods 2 and 4, and by ∼0.5d if exposure occurred during period 3. Exposure during periods 1, 2, and 4 reduced birth weight by ∼10% compared with FA, and placental weight was reduced (∼8%) on GD17.5 if exposure occurred only during period 3. Conclusions: Adverse PM2.5-induced outcomes such as PTB and LBW are dependent upon the periods of maternal exposure. The results of these experimental studies could contribute significantly to air pollution policy decisions in the future. https://doi.org/10.1289/EHP1029 PMID:28893721

Photo-protection by 3-bromo-4, 5-dihydroxybenzaldehyde against ultraviolet B-induced oxidative stress in human keratinocytes.

PubMed

Hyun, Yu Jae; Piao, Mei Jing; Zhang, Rui; Choi, Yung Hyun; Chae, Sungwook; Hyun, Jin Won

2012-09-01

Exposure of the skin to ultraviolet B (UVB) radiation leads to epidermal damage and the generation of reactive oxygen species (ROS) in skin cells, including keratinocytes. Therefore, the photo-protective effect of 3-bromo-4, 5-dihydroxybenzaldehyde (BDB) against UVB was assessed in human HaCaT keratinocytes exposed to UVB radiation in vitro. BDB restored cell viability, which decreased upon exposure to UVB radiation. BDB exhibited scavenging activity against 1, 1-diphenyl-2-picrylhydrazyl radicals, intracellular ROS induced by hydrogen peroxide (H(2)O(2)) or UVB radiation, the superoxide anion generated by the xanthine/xanthine oxidase system, and the hydroxyl radical generated by the Fenton reaction (FeSO(4)+H(2)O(2)). Moreover, BDB absorbed UVB and decreased injury resulting from UVB-induced oxidative stress to lipids, proteins and DNA. Finally, BDB reduced UVB-induced apoptosis, as exemplified by fewer apoptotic bodies and a reduction in DNA fragmentation. Taken together, these results suggest that BDB protects human keratinocytes against UVB-induced oxidative stress by scavenging ROS and absorbing UVB rays, thereby reducing injury to cellular components. Copyright © 2012 Elsevier Inc. All rights reserved.

Reducing biting rates of Aedes aegypti with metofluthrin: investigations in time and space.

PubMed

Darbro, Jonathan M; Muzari, M Odwell; Giblin, Arthur; Adamczyk, Rebecca M; Ritchie, Scott A; Devine, Gregor J

2017-02-07

Indoor residual spraying is key to dengue control in Cairns and other parts of northern Queensland, Australia, where Aedes aegypti is prevalent, but the strategy faces challenges with regards to slow application time and, therefore, community coverage. A faster potential improvement might be the use of polyethylene netting impregnated with the volatile pyrethroid metofluthrin (SumiOne™). This formulation was assessed in rooms in three houses in Cairns, Australia. One emanator was placed in each room and cages of 10 female Aedes aegypti were exposed at distances of 1 and 3 m. Knockdown and landings on a human hand were counted before metofluthrin exposure and at 10, 30, 60, 90 and 120 min during exposure. In addition, two trials continued over 48 h of exposure to assess the long-term sublethal effects of metofluthrin on caged mosquitoes. Percentage landing rates fell to 0-2.5% in the first 10 min of exposure. Knockdown was most evident between 10 and 30 min (54% at 1 m and 33% at 3 m). Distance from the emanator strongly affected the results: mosquitoes at 3 m exhibited less knockdown and more landings than those at 1 m. As room volume increased, knockdown decreased and the number of landing increased. There is a cumulative mortality and landing inhibition and, for mosquitoes exposed to metofluthrin for > 48 h, mortality was 100% at 1 m and 90% at 3 m. Of those still alive, a small number continued to land and bite. After being removed from metofluthrin-treated rooms, exposed insect cages were found to reducing landing rates for up to 2 h. Despite only moderate levels of knockdown during the initial hours of exposure, metofluthrin emanators were effective in reducing mosquito landing rates, especially within 1 m, even when exposed on an open veranda. The evaluation methods and results described in this paper will help inform the optimal conditions of deployment of metofluthrin emanators. These devices have the potential to reduce contact between humans and urban disease vectors faster than indoor residual spraying so supplement our current arsenal of dengue control tools.

Ultrafine particle concentrations and exposures in seven residences in northern California.

PubMed

Bhangar, S; Mullen, N A; Hering, S V; Kreisberg, N M; Nazaroff, W W

2011-04-01

Human exposures to ultrafine particles (UFP) are poorly characterized given the potential associated health risks. Residences are important sites of exposure. To characterize residential exposures to UFP in some circumstances and to investigate governing factors, seven single-family houses in California were studied during 2007-2009. During multiday periods, time-resolved particle number concentrations were monitored indoors and outdoors and information was acquired concerning occupancy, source-related activities, and building operation. On average, occupants were home for 70% of their time. The geometric mean time-average residential exposure concentration for 21 study subjects was 14,500 particles per cm(3) (GSD = 1.8; arithmetic mean ± standard deviation = 17,000 ± 10,300 particles per cm(3)). The average contribution to residential exposures from indoor episodic sources was 150% of the contribution from particles of outdoor origin. Unvented natural-gas pilot lights contributed up to 19% to exposure for the two households where present. Episodic indoor source activities, most notably cooking, caused the highest peak exposures and most of the variation in exposure among houses. Owing to the importance of indoor sources and variations in the infiltration factor, residential exposure to UFP cannot be characterized by ambient measurements alone. Indoor and outdoor sources each contribute to residential ultrafine particle (UFP) concentrations and exposures. Under the conditions investigated, peak exposure concentrations indoors were associated with cooking, using candles, or the use of a furnace. Active particle removal systems can mitigate exposure by reducing the persistence of particles indoors. Eliminating the use of unvented gas pilot lights on cooking appliances could also be beneficial. The study results indicate that characterization of human exposure to UFP, an air pollutant of emerging public health concern, cannot be accomplished without a good understanding of conditions inside residences. © 2010 John Wiley & Sons A/S.

Managing respiratory effects of air pollution.

PubMed

Watson, Bianca K; Sheppeard, Vicky

2005-12-01

Exposure to air pollution (both indoor and outdoor) has many potential adverse effects on human health. This article looks at the adverse respiratory health effects of air pollution and gives some guidance about management of exposure in susceptible individuals. Motor vehicle and industrial emissions are the primary contributors to outdoor air pollution in Australia. High levels of ozone and other pollutants can cause respiratory symptoms in susceptible individuals. Air quality advisory systems exist in most states. Clinicians can incorporate the health effects of air pollution, and awareness of advisory systems in the education of their susceptible patients and their carers. Asthma and chronic airways disease management plans should include provision for possible exposure to high pollution events and steps that can be taken to reduce exposure.

Does BPA alter steroid hormone synthesis in human granulosa cells in vitro?

PubMed

Mansur, Abdallah; Adir, Michal; Yerushalmi, Gil; Hourvitz, Ariel; Gitman, Hila; Yung, Yuval; Orvieto, Raoul; Machtinger, Ronit

2016-07-01

Does Bisphenol A (BPA) impair steroid hormone production in human luteinized granulosa cells in vitro? At supra-physiological concentrations, BPA alters progesterone and estradiol synthesis in vitro and significantly reduces the mRNA and protein expression levels of three genes encoding steroidogenesis enzymes. In IVF patients, the effects of BPA exposure on cycle outcome are controversial. Previous animal studies have shown that granulosa cell steroid hormone synthesis is compromised after BPA exposure, but their findings have been difficult to replicate in humans due, in part, to the low availability of discarded biological material. Luteinized granulosa cells obtained from 44 fertile and infertile patients undergoing in vitro fertilization were cultured for 48 h with different concentrations of BPA (0, 0.2, 0.02, 2.0, 20 µg/ml). Culture medium and total RNA extracted from the luteinized granulosa cells were examined for estradiol and progesterone levels as well as mRNA and protein expression of steroidogenesis enzymes, using enzyme immunoassays, real-time PCR and western blots. Treatment of granulosa cells with 2 or 20 µg/ml BPA for 48 h resulted in significantly lower progesterone biosynthesis (P < 0.005 and <0.001, respectively). Estradiol production was significantly altered only after incubation with 20 µg/ml of BPA (P < 0.001). These concentrations also significantly reduced the mRNA levels of 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP11A1 and CYP19A1 without affecting StAR and 17β-hydroxysteroid dehydrogenase mRNA expression. Similarly, 3β-HSD, CYP11A1 and CYP19A1 protein levels were reduced after administration of 20 µg/ml BPA. Lower BPA concentrations similar to, and up to 100 times, the concentrations measured in human follicular fluid, serum and urine did not alter steroidogenesis in primary granulosa cell cultures. This was an in vitro study investigating the effects of acute exposure (48 h) of BPA on discarded material. As such, the model may not accurately reflect the effect of BPA on the physiological events of follicular steroid hormone synthesis in vivo. Our results show that in vitro exposure to BPA at low doses does not affect granulosa cells steroidogenesis. Combined with recent in vivo studies, these data can be reassuring but further studies are needed to assess the effects of chronic exposure to BPA on ovarian steroidogenesis. This study was supported by grant number 1936/12 from the Israeli Science Foundation (ISF). The authors have no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nonclinical and clinical pharmacological characterization of the potent and selective cathepsin K inhibitor MIV-711.

PubMed

Lindström, Erik; Rizoska, Biljana; Henderson, Ian; Terelius, Ylva; Jerling, Markus; Edenius, Charlotte; Grabowska, Urszula

2018-05-09

Cathepsin K is an attractive therapeutic target for diseases in which bone resorption is excessive such as osteoporosis and osteoarthritis (OA). The current paper characterized the pharmacological profile of the potent and selective cathepsin K inhibitor, MIV-711, in vitro and in cynomolgus monkeys, and assessed translation to human based on a single dose clinical study in man. The potency and selectivity of MIV-711 were assessed in vitro using recombinant enzyme assays and differentiated human osteoclasts. MIV-711 was administered to healthy cynomolgus monkeys (3-30 µmol/kg, p.o.). Plasma levels of MIV-711 and the bone resorption biomarker CTX-I were measured after single dose experiments, and urine levels of CTX-I, NTX-I and CTX-II biomarkers were measured after repeat dose experiments. The safety, pharmacokinetics and pharmacodynamics (serum CTX-I) of MIV-711 were assessed in human healthy subjects after single ascending doses from 20 to 600 mg. MIV-711 was a potent inhibitor of human cathepsin K (K i : 0.98 nmol/L) with > 1300-fold selectivity towards other human cathepsins. MIV-711 inhibited human osteoclast-mediated bone resorption with an IC 50 value of 43 nmol/L. Single oral doses of MIV-711 to monkeys reduced plasma levels of CTX-I in a dose-dependent fashion by up to 57% at trough. The effect on CTX-I was linearly correlated to the plasma exposure of MIV-711, while the efficacy duration outlasted plasma exposure. Repeat oral dosing with MIV-711 also reduced urinary levels of the bone resorption biomarkers CTX-I (by 93%) and NTX-I (by 71%) and the cartilage degradation biomarker CTX-II (by 71%). MIV-711 was safe and well-tolerated when given as single ascending doses to healthy subjects. MIV-711 reduced serum CTX-I levels in a dose-dependent manner by up to 79% at trough. The relationship between MIV-711 exposure and effects on these biomarkers in humans was virtually identical when compared to the corresponding monkey data. MIV-711 is a potent and selective cathepsin K inhibitor with dose-dependent effects on biomarkers of bone and cartilage degradation in monkey and human. Taken together, MIV-711 shows promise for the treatment of bone and cartilage related disorders in humans, such as OA. Trial Registration EudraCT number 2011-003024-12, registered on June 22nd 2011.

Evolution, human-microbe interactions, and life history plasticity.

PubMed

Rook, Graham; Bäckhed, Fredrik; Levin, Bruce R; McFall-Ngai, Margaret J; McLean, Angela R

2017-07-29

A bacterium was once a component of the ancestor of all eukaryotic cells, and much of the human genome originated in microorganisms. Today, all vertebrates harbour large communities of microorganisms (microbiota), particularly in the gut, and at least 20% of the small molecules in human blood are products of the microbiota. Changing human lifestyles and medical practices are disturbing the content and diversity of the microbiota, while simultaneously reducing our exposures to the so-called old infections and to organisms from the natural environment with which human beings co-evolved. Meanwhile, population growth is increasing the exposure of human beings to novel pathogens, particularly the crowd infections that were not part of our evolutionary history. Thus some microbes have co-evolved with human beings and play crucial roles in our physiology and metabolism, whereas others are entirely intrusive. Human metabolism is therefore a tug-of-war between managing beneficial microbes, excluding detrimental ones, and channelling as much energy as is available into other essential functions (eg, growth, maintenance, reproduction). This tug-of-war shapes the passage of each individual through life history decision nodes (eg, how fast to grow, when to mature, and how long to live). Copyright © 2017 Elsevier Ltd. All rights reserved.

Exposure, metabolism, and health effects of arsenic in residents from arsenic-contaminated groundwater areas of Vietnam and Cambodia: a review.

PubMed

Agusa, Tetsuro; Kunito, Takashi; Kubota, Reiji; Inoue, Suguru; Fujihara, Junko; Minh, Tu Binh; Ha, Nguyen Ngoc; Tu, Nguyen Phuc Cam; Trang, Pham Thi Kim; Chamnan, Chhoun; Takeshita, Haruo; Iwata, Hisato; Tuyen, Bui Cach; Viet, Pham Hung; Tana, Touch Seang; Tanabe, Shinsuke

2010-01-01

In this review, we summarize the current knowledge on exposure, metabolism, and health effects of arsenic (As) in residents from As-contaminated groundwater areas of Vietnam and Cambodia based on our findings from 2000 and other studies. The health effects of As in humans include severe gastrointestinal disorders, hepatic and renal failure, cardiovascular disturbances, skin pigmentation, hyperkeratosis, and cancers in the lung, bladder, liver, kidney, and skin. Arsenic contamination in groundwater is widely present at Vietnam and Cambodia and the highest As levels are frequently found in groundwater from Cambodia. Sand filter system can reduce As concentration in raw groundwater. The results of hair and urine analyses indicate that residents from these As-contaminated areas are exposed to As. In general, sex, age, body mass index, and As exposure level are significantly associated with As metabolism. Genetic polymorphisms in arsenic (+III) methyltransferase and glutathione-S-transferase isoforms may be influenced As metabolism and accumulation in a Vietnamese population. It is suggested oxidative DNA damage is caused by exposure to As in groundwater from residents in Cambodia. An epidemiologic study on an association of As exposure with human health effects is required in these areas.

Sexual orientation and gender identity after prenatal exposure to the Dutch famine.

PubMed

de Rooij, Susanne R; Painter, Rebecca C; Swaab, Dick F; Roseboom, Tessa J

2009-06-01

Sexual differentiation of the human brain has been suggested to take place through exposure to sex steroids during intrauterine development. Animal experiments have shown that interference in this process by underfeeding of the mother can result in feminization of the male offspring. We explored the possible effects of prenatal exposure to famine on sexual orientation and gender identity in humans. We used the Klein Sexual Orientation Grid to assess sexual orientation and also assessed gender identity in a group of 380 men and 472 women who were born as term singletons around the time of the 1944-1945 Dutch famine. Prenatal exposure to famine did not affect sexual orientation in men or in women. Three people indicated having some gender identity problems: one woman born before the famine and one man and woman exposed to famine in late gestation. In men, a later birth order was associated with a non-exclusively heterosexual identification. In conclusion, we found no evidence for a significant association between exposure to famine in utero and altered sexual orientation and gender identity. The small sample size of participants with non-exclusively heterosexual identification (possibly due to underreporting of homosexuality) may have reduced our power to detect any differences.

Disorders Induced by Direct Occupational Exposure to Noise: Systematic Review

PubMed Central

Domingo-Pueyo, Andrea; Sanz-Valero, Javier; Wanden-Berghe, Carmina

2016-01-01

Background: To review the available scientific literature about the effects on health by occupational exposure to noise. Materials and Methods: A systematic review of the retrieved scientific literature from the databases MEDLINE (via PubMed), ISI-Web of Knowledge (Institute for Scientific Information), Cochrane Library Plus, SCOPUS, and SciELO (collection of scientific journals) was conducted. The following terms were used as descriptors and were searched in free text: “Noise, Occupational,” “Occupational Exposure,” and “Occupational Disease.” The following limits were considered: “Humans,” “Adult (more than 18 years),” and “Comparative Studies.” Results: A total of 281 references were retrieved, and after applying inclusion/exclusion criteria, 25 articles were selected. Of these selected articles, 19 studies provided information about hearing disturbance, four on cardiovascular disorders, one regarding respiratory alteration, and one on other disorders. Conclusions: It can be interpreted that the exposure to noise causes alterations in humans with different relevant outcomes, and therefore appropriate security measures in the work environment must be employed to minimize such an exposure and thereby to reduce the number of associated disorders. PMID:27762251

DERMAL, ORAL, AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation ki...

The Pesticide Problem: Is Any Amount Safe?

ERIC Educational Resources Information Center

Cooper, Susan

1991-01-01

Discusses the use of integrated pest management to foster a safe school environment free from pesticides. This effective, environmentally sound system minimizes human exposure and reduces the toxicity of materials used to control pests. Parents, teachers, and students can educate themselves to improve school pest control practices. (SM)

Optimal selection of biochars for remediating metals contaminated mine soils

EPA Science Inventory

Approximately 500,000 abandoned mines across the U.S. pose a considerable, pervasive risk to human health and the environment due to possible exposure to the residuals of heavy metal extraction. Historically, a variety of chemical and biological methods have been used to reduce ...

Pesticide Exposure, Safety Issues, and Risk Assessment Indicators

PubMed Central

Damalas, Christos A.; Eleftherohorinos, Ilias G.

2011-01-01

Pesticides are widely used in agricultural production to prevent or control pests, diseases, weeds, and other plant pathogens in an effort to reduce or eliminate yield losses and maintain high product quality. Although pesticides are developed through very strict regulation processes to function with reasonable certainty and minimal impact on human health and the environment, serious concerns have been raised about health risks resulting from occupational exposure and from residues in food and drinking water. Occupational exposure to pesticides often occurs in the case of agricultural workers in open fields and greenhouses, workers in the pesticide industry, and exterminators of house pests. Exposure of the general population to pesticides occurs primarily through eating food and drinking water contaminated with pesticide residues, whereas substantial exposure can also occur in or around the home. Regarding the adverse effects on the environment (water, soil and air contamination from leaching, runoff, and spray drift, as well as the detrimental effects on wildlife, fish, plants, and other non-target organisms), many of these effects depend on the toxicity of the pesticide, the measures taken during its application, the dosage applied, the adsorption on soil colloids, the weather conditions prevailing after application, and how long the pesticide persists in the environment. Therefore, the risk assessment of the impact of pesticides either on human health or on the environment is not an easy and particularly accurate process because of differences in the periods and levels of exposure, the types of pesticides used (regarding toxicity and persistence), and the environmental characteristics of the areas where pesticides are usually applied. Also, the number of the criteria used and the method of their implementation to assess the adverse effects of pesticides on human health could affect risk assessment and would possibly affect the characterization of the already approved pesticides and the approval of the new compounds in the near future. Thus, new tools or techniques with greater reliability than those already existing are needed to predict the potential hazards of pesticides and thus contribute to reduction of the adverse effects on human health and the environment. On the other hand, the implementation of alternative cropping systems that are less dependent on pesticides, the development of new pesticides with novel modes of action and improved safety profiles, and the improvement of the already used pesticide formulations towards safer formulations (e.g., microcapsule suspensions) could reduce the adverse effects of farming and particularly the toxic effects of pesticides. In addition, the use of appropriate and well-maintained spraying equipment along with taking all precautions that are required in all stages of pesticide handling could minimize human exposure to pesticides and their potential adverse effects on the environment. PMID:21655127

Environmental noise and human prenatal growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schell, L.M.

1981-09-01

To determine whether chronic exposure to relatively loud noise has demonstrable biological effects in humans, a study was conducted on the effect of mother's exposure to airport noise while pregnant, and of social and biological characteristics of the family upon birthweight and gestation length. The sample of births was drawn from a community located adjacent to an international airport in the U.S., where noise levels had been measured previously. Mother's noise exposure was based upon noise levels near her residence in the community while she was pregnant. Data from 115 births were used, these being from mothers whose noise exposuremore » history was most complete throughout the pregnancy. Using multivariate analysis to correct for family characteristics, the partial correlation coefficient for noise exposure and gestation length was negative, large, and significant in girls (r . -0.49, p less than 0.001). In boys the partial correlation coefficient was also negative but was smaller and did not quite reach statistical significance. Partial correlations with birthweight were smaller in both boys and girls and not significant. These results agree best with previous studies that suggest that noise may reduce prenatal growth. The size of the observed effects may be related to a conservative research design biased towards underestimation, as well as to the real effects of noise upon human prenatal growth.« less

UV-induced inhibition of adipokine production in subcutaneous fat aggravates dermal matrix degradation in human skin.

PubMed

Kim, Eun Ju; Kim, Yeon Kyung; Kim, Min-Kyoung; Kim, Sungsoo; Kim, Jin Yong; Lee, Dong Hun; Chung, Jin Ho

2016-05-10

Ultraviolet (UV) exposure to the human skin reduces triglycerides contents and lipid synthesis in the subcutaneous (SC) fat. Because adiponectin and leptin are the most abundant adipokines from the SC fat, we aim to investigate how they interact with UV exposure and skin aging. The expressions of adiponectin and leptin were significantly decreased in SC fat of sun-exposed forearm skin, in comparison with that of sun-protected buttock skin of the same elderly individuals, indicating that chronic UV exposure decreases both adipokines. Acute UV irradiation also decreased the expressions of adiponectin and leptin in SC fat. The expressions of adiponectin receptor 1/2 and leptin receptor were significantly decreased in the dermis as well as in SC fat. Moreover, while exogenous adiponectin and leptin administration prevented UV- and TNF-α induced matrix metalloproteinase (MMP)-1 expression, they also increased UV- and TNF-α induced reduction of type 1 procollagen production. Silencing of adiponectin, leptin or their receptors led to an increased MMP-1 and a decreased type 1 procollagen expression, which was reversed by treatment with recombinant human adiponectin or leptin. In conclusion, UV exposure decreases the expression of adiponectin and leptin, leading to the exacerbation of photoaging by stimulating MMP-1 expression and inhibiting procollagen synthesis.

Double strand breaks and cell-cycle arrest induced by the cyanobacterial toxin cylindrospermopsin in HepG2 cells.

PubMed

Alja, Štraser; Filipič, Metka; Novak, Matjaž; Žegura, Bojana

2013-08-21

The newly emerging cyanobacterial cytotoxin cylindrospermopsin (CYN) is increasingly found in surface freshwaters, worldwide. It poses a potential threat to humans after chronic exposure as it was shown to be genotoxic in a range of test systems and is potentially carcinogenic. However, the mechanisms of CYN toxicity and genotoxicity are not well understood. In the present study CYN induced formation of DNA double strand breaks (DSBs), after prolonged exposure (72 h), in human hepatoma cells, HepG2. CYN (0.1-0.5 µg/mL, 24-96 h) induced morphological changes and reduced cell viability in a dose and time dependent manner. No significant increase in lactate dehydrogenase (LDH) leakage could be observed after CYN exposure, indicating that the reduction in cell number was due to decreased cell proliferation and not due to cytotoxicity. This was confirmed by imunocytochemical analysis of the cell-proliferation marker Ki67. Analysis of the cell-cycle using flow-cytometry showed that CYN has an impact on the cell cycle, indicating G0/G1 arrest after 24 h and S-phase arrest after longer exposure (72 and 96 h). Our results provide new evidence that CYN is a direct acting genotoxin, causing DSBs, and these facts need to be considered in the human health risk assessment.

Health impact assessment of a skin sensitizer: Analysis of potential policy measures aimed at reducing geraniol concentrations in personal care products and household cleaning products.

PubMed

Jongeneel, W P; Delmaar, J E; Bokkers, B G H

2018-06-08

A methodology to assess the health impact of skin sensitizers is introduced, which consists of the comparison of the probabilistic aggregated exposure with a probabilistic (individual) human sensitization or elicitation induction dose. The health impact of potential policy measures aimed at reducing the concentration of a fragrance allergen, geraniol, in consumer products is analysed in a simulated population derived from multiple product use surveys. Our analysis shows that current dermal exposure to geraniol from personal care and household cleaning products lead to new cases of contact allergy and induce clinical symptoms for those already sensitized. We estimate that this exposure results yearly in 34 new cases of geraniol contact allergy per million consumers in Western and Northern Europe, mainly due to exposure to household cleaning products. About twice as many consumers (60 per million) are projected to suffer from clinical symptoms due to re-exposure to geraniol. Policy measures restricting geraniol concentrations to <0.01% will noticeably reduce new cases of sensitization and decrease the number of people with clinical symptoms as well as the frequency of occurrence of these clinical symptoms. The estimated numbers should be interpreted with caution and provide only a rough indication of the health impact. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Abundant Rodent Furan-Derived Urinary Metabolites Are Associated with Tobacco Smoke Exposure in Humans.

PubMed

Grill, Alex E; Schmitt, Thaddeus; Gates, Leah A; Lu, Ding; Bandyopadhyay, Dipankar; Yuan, Jian-Min; Murphy, Sharon E; Peterson, Lisa A

2015-07-20

Furan, a possible human carcinogen, is found in heat treated foods and tobacco smoke. Previous studies have shown that humans are capable of converting furan to its reactive metabolite, cis-2-butene-1,4-dial (BDA), and therefore may be susceptible to furan toxicity. Human risk assessment of furan exposure has been stymied because of the lack of mechanism-based exposure biomarkers. Therefore, a sensitive LC-MS/MS assay for six furan metabolites was applied to measure their levels in urine from furan-exposed rodents as well as in human urine from smokers and nonsmokers. The metabolites that result from direct reaction of BDA with lysine (BDA-N(α)-acetyllysine) and from cysteine-BDA-lysine cross-links (N-acetylcysteine-BDA-lysine, N-acetylcysteine-BDA-N(α)-acetyllysine, and their sulfoxides) were targeted in this study. Five of the six metabolites were identified in urine from rodents treated with furan by gavage. BDA-N(α)-acetyllysine, N-acetylcysteine-BDA-lysine, and its sulfoxide were detected in most human urine samples from three different groups. The levels of N-acetylcysteine-BDA-lysine sulfoxide were more than 10 times higher than that of the corresponding sulfide in many samples. The amount of this metabolite was higher in smokers relative to that in nonsmokers and was significantly reduced following smoking cessation. Our results indicate a strong relationship between BDA-derived metabolites and smoking. Future studies will determine if levels of these biomarkers are associated with adverse health effects in humans.

Sweet taste exposure and the subsequent acceptance and preference for sweet taste in the diet: systematic review of the published literature.

PubMed

Appleton, K M; Tuorila, H; Bertenshaw, E J; de Graaf, C; Mela, D J

2018-03-01

There are consistent, evidence-based global public health recommendations to reduce intakes of free sugars. However, the corresponding evidence for recommending reduced exposure to sweetness is less clear. Our aim was to identify and review the published evidence investigating the impact of dietary exposure to sweet-tasting foods or beverages on the subsequent generalized acceptance, preference, or choice of sweet foods and beverages in the diet. Systematic searches were conducted to identify all studies testing relations of variation in exposure to sweetness through foods and beverages with subsequent variation in the generalized acceptance, preference, or choice of sweetened foods or beverages, in humans aged >6 mo. Twenty-one studies met our inclusion criteria, comprising 7 population cohort studies involving 2320 children and 14 controlled trials involving 1113 individuals. These studies were heterogeneous in study design, population, exposure, and outcomes measured, and few were explicitly designed to address our research question. The findings from these were inconsistent. We found equivocal evidence from population cohort studies. The evidence from controlled studies suggests that a higher sweet taste exposure tends to lead to reduced preferences for sweetness in the shorter term, but very limited effects were found in the longer term. A small and heterogeneous body of research currently has considered the impact of varying exposure to sweet taste on subsequent generalized sweet taste preferences, and this evidence is equivocal regarding the presence and possible direction of a relation. Future work should focus on adequately powered studies with well-characterized exposures of sufficient duration. This review was registered with PROSPERO as CRD42016051840, 24 November 2016.

Multi-sector thermo-physiological head simulator for headgear research.

PubMed

Martinez, Natividad; Psikuta, Agnes; Corberán, José Miguel; Rossi, René M; Annaheim, Simon

2017-02-01

A novel thermo-physiological human head simulator for headgear testing was developed by coupling a thermal head manikin with a thermo-physiological model. As the heat flux at head-site is directly measured by the head manikin, this method provides a realistic quantification of the heat transfer phenomena occurring in the headgear, such as moisture absorption-desorption cycles, condensation, or moisture migration across clothing layers. Before coupling, the opportunities of the head manikin for representing the human physiology were evaluated separately. The evaluation revealed reduced precision in forehead and face temperature predictions under extreme heterogeneous temperature distributions and no initial limitation for simulating temperature changes observed in the human physiology. The thermo-physiological model predicted higher sweat rates when applied for coupled than for pure virtual simulations. After coupling, the thermo-physiological human head simulator was validated using eight human experiments. It precisely predicted core, mean skin, and forehead temperatures with average rmsd values within the average experimental standard deviation (rmsd of 0.20 ± 0.15, 0.83 ± 0.34, and 1.04 ± 0.54 °C, respectively). However, in case of forehead, precision was lower for the exposures including activity than for the sedentary exposures. The representation of the human sweat evaporation could be affected by a reduced evaporation efficiency and the manikin sweat dynamics. The industry will benefit from this thermo-physiological human head simulator leading to the development of helmet designs with enhanced thermal comfort and, therefore, with higher acceptance by users.

Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaccone, Eric J.; Goldsmith, W. Travis; Shimko, Michael J.

Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6 h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance, we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity. We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 h to diacetyl ormore » 2,3-pentanedione vapors (25 or ≥ 60 ppm) and the effects on short circuit current and transepithelial resistance (R{sub t}) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na{sup +} transport, without affecting Cl{sup −} transport or Na{sup +},K{sup +}-pump activity. R{sub t} was unaffected. Na{sup +} transport recovered 18 h after exposure. Concentrations (100–360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro. - Highlights: • Butter flavoring vapor effects on human cultured airway epithelium were studied. • Na transport was reduced by a 6-h exposure to 25 ppm diacetyl and 2,3-pentanedione. • Na transport recovered 18 h after exposure. • > 60 ppm transepithelial voltage and resistance were abolished; cells were damaged. • Cells metabolized diacetyl and 2,3-pentanedione into acetoin and 2-OH-3-pentanone.« less

Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abou-Elwafa Abdallah, Mohamed, E-mail: mae_abdallah@yahoo.co.uk; Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut; Pawar, Gopal

Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm{sup 2}, finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPPmore » and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K{sub p}, cm/h) showed a significant negative correlation with log K{sub ow} for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K{sub ow} of PFRs. • Skin washing reduced the overall dermal absorption of target PFRs to varying degrees. • Toddlers are more exposed to PFRs via dermal contact with indoor dust than adults.« less

The exposome concept in a human nutrigenomics study: evaluating the impact of exposure to a complex mixture of phytochemicals using transcriptomics signatures.

PubMed

van Breda, Simone G J; Wilms, Lonneke C; Gaj, Stan; Jennen, Danyel G J; Briedé, Jacob J; Kleinjans, Jos C S; de Kok, Theo M C M

2015-11-01

The application of transcriptome analyses in molecular epidemiology studies has become a promising tool in order to evaluate the impact of environmental exposures. These analyses have a great value in establishing the exposome, the totality of human exposures, both by identifying the chemical nature of the exposures and the induced molecular responses. Transcriptomic signatures can be regarded as biomarker of exposure as well as markers of effect which reflect the interaction between individual genetic background and exposure levels. However, the biological interpretation of modulated gene expression profiles is a challenging task and translating affected molecular pathways into risk assessment, for instance in terms of cancer promoting or disease preventing responses, is a far from standardised process. Here, we describe the in-depth analyses of the gene expression responses in a human dietary intervention in which the interaction between genotype and exposure to a blueberry-apple juice containing a complex mixture of phytochemicals is investigated. We also describe how data on differences in genetic background combined with different effect markers can provide a better understanding of gene-environment interactions. Pathway analyses of differentially expressed genes in combination with gene were used to identify complex but strong changes in several biological processes like immune response, cell adhesion, lipid metabolism and apoptosis. These observed changes may lead to upgraded growth control, induced immunity, reduced platelet aggregation and activation, diminished production of reactive oxidative species by platelets, blood glucose homeostasis, regulation of blood lipid levels and increased apoptosis. Our findings demonstrate that applying transcriptomics to well-controlled human dietary intervention studies can provide insight into mechanistic pathways involved in disease prevention by dietary factors. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fate and Transport of Mercury in Environmental Media and Human Exposure

PubMed Central

Kim, Moon-Kyung

2012-01-01

Mercury is emitted to the atmosphere from various natural and anthropogenic sources, and degrades with difficulty in the environment. Mercury exists as various species, mainly elemental (Hg0) and divalent (Hg2+) mercury depending on its oxidation states in air and water. Mercury emitted to the atmosphere can be deposited into aqueous environments by wet and dry depositions, and some can be re-emitted into the atmosphere. The deposited mercury species, mainly Hg2+, can react with various organic compounds in water and sediment by biotic reactions mediated by sulfur-reducing bacteria, and abiotic reactions mediated by sunlight photolysis, resulting in conversion into organic mercury such as methylmercury (MeHg). MeHg can be bioaccumulated through the food web in the ecosystem, finally exposing humans who consume fish. For a better understanding of how humans are exposed to mercury in the environment, this review paper summarizes the mechanisms of emission, fate and transport, speciation chemistry, bioaccumulation, levels of contamination in environmental media, and finally exposure assessment of humans. PMID:23230463

Mycobacterium avium subsp. paratuberculosis in dairy products, meat, and drinking water.

PubMed

Gill, C O; Saucier, L; Meadus, W J

2011-03-01

Mycobacterium avium subsp. paratuberculosis (Map) is the cause of Johne's disease, a chronic infection of the gut, in ruminant animals that provide milk and/or meat for human consumption. Map also may be involved in Crohn's disease and type 1 diabetes in humans. Although the role of Map in human diseases has not been established, minimizing the exposure of humans to the organism is considered desirable as a precautionary measure. Infected animals can shed Map in feces and milk, and the organism can become disseminated in tissues remote from the gut and its associated lymph nodes. The presence of at least some Map in raw milk and meat and in natural waters is likely, but the numbers of Map in those foods and waters should be reduced through cooking or purification. The available information relating to Map in milk and dairy products, meats, and drinking water is reviewed here for assessment of the risks of exposure to Map from consumption of such foods and water.

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.

Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomousmore » growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a valuable model for arsenic-induced lung cancer.« less

Unconsented HIV Testing in Cases of Occupational Exposure: Ethics, Law, and Policy

PubMed Central

Cowan, Ethan; Macklin, Ruth

2012-01-01

Post-exposure prophylaxis (PEP) has substantially reduced the risk of acquiring human immunodeficiency virus (HIV) after an occupational exposure; nevertheless, exposure to HIV remains a concern for emergency department providers. According to published guidelines, PEP should be taken only when source patients are HIV positive or have risk factors for HIV. Initiating PEP when source patients are uninfected puts exposed persons at risk from taking toxic drugs with no compensating benefit. Forgoing PEP if the source is infected results in increased risk of acquiring HIV. What should be done if source patients refuse HIV testing? Is it justifiable to test the blood of these patients over their autonomous objection? The authors review current law and policy and perform an ethical analysis to determine if laws permitting unconsented testing in cases of occupational exposure can be ethically justified. PMID:22994417

Galvanic zinc-copper microparticles inhibit melanogenesis via multiple pigmentary pathways.

PubMed

Won, Yen-Kim; Lin, Connie B; Seiberg, Miri; Chen, Nannan; Hu, Yaping; Rossetti, Dianne; Saliou, Claude; Loy, Chong-Jin

2014-01-01

The endogenous electrical field of human skin plays an important role in many skin functions. However, the biological effects and mechanism of action of externally applied electrical stimulation on skin remain unclear. Recent study showed that galvanic zinc-copper microparticles produce electrical stimulation and reduce inflammatory and immune responses in intact skin, suggesting the important role of electrical stimulation in non-wounded skin. The objective of this study is to investigate the biological effect of galvanic zinc-copper microparticles on skin pigmentation. Our findings showed that galvanic zinc-copper microparticles inhibited melanogenesis in a human melanoma cell line (MNT-1), human keratinocytes and melanoma cells co-cultures, and in pigmented epidermal equivalents. Treatment of galvanic zinc-copper microparticles inhibited melanogenesis by reducing the promoter transactivation of tyrosinase and tyrosinase-related protein-1 in human melanoma cells. In a co-culture Transwell system of keratinocytes and melanoma cells, galvanic zinc-copper microparticles reduced melanin production via downregulation of endothelin-1 secretion from keratinocytes and reduced tyrosinase gene expression in melanoma cells. In addition, exposure of pigmented epidermal equivalents to galvanic zinc-copper microparticles resulted in reduced melanin deposition. In conclusion, our data demonstrated for the first time that galvanic zinc-copper microparticles reduced melanogenesis in melanoma cells and melanin deposition in pigmented epidermal equivalents by affecting multiple pigmentary pathways.

A Topical Mitochondria-Targeted Redox Cycling Nitroxide Mitigates Oxidative Stress Induced Skin Damage

PubMed Central

Brand, Rhonda M.; Epperly, Michael W.; Stottlemyer, J. Mark; Skoda, Erin M.; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E.; Greenberger, Joel S.; Falo, Louis D.

2017-01-01

Skin is the largest human organ and provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation induced skin damage ranges from photoaging and cutaneous carcinogenesis from UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species (ROS). Mitochondria are particularly susceptible to oxidative stress, and mitochondrial dependent apoptosis plays a major role in radiation induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent ROS accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrial targeted antioxidant prevents and mitigates radiation induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin’s antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. PMID:27794421

Rationale and support for a One Health program for canine vaccination as the most cost-effective means of controlling zoonotic rabies in endemic settings.

PubMed

Lavan, Robert P; King, Alasdair I MacG; Sutton, David J; Tunceli, Kaan

2017-03-23

Although dog vaccination has been demonstrated to reduce and eliminate rabies in humans, during meetings there are often calls for further pilot studies. The assembled data proves that a widespread approach is now required. While zoonotic rabies has a minimal presence in developed nations, it is endemic throughout most of Asia and Africa, where it is considered to be a neglected tropical disease. In these areas, rabies causes an estimated annual mortality of at least 55,000 human deaths. Worldwide rabid dogs are the source of the vast majority of human rabies exposures. The World Health Organization (WHO), the Food and Agriculture Organization (FAO) of the United Nations and the World Organization for Animal Health (OIE) advocate a collaborative One Health approach involving human public health and veterinary agencies, with mass canine vaccination programs in endemic areas being the mainstay of strategies to eliminate dog-mediated human rabies. While post-exposure prophylaxis (PEP) is effective in preventing deaths in people exposed to rabies, it is comparatively expensive and has little impact on the canine reservoir that is the primary source of zoonotic rabies. Indiscriminate culling of the dog population is expensive and there is little evidence that it is effective in controlling rabies in non-island locations. Mass canine vaccination programs using a One Health framework that achieves a minimum 70% vaccination coverage during annual campaigns have proven to be cost-effective in controlling zoonotic rabies in endemic, resource-poor regions. Case studies, such as in Tanzania and Bhutan, illustrate how an approach based on mass canine rabies vaccination has effectively reduced both canine and human rabies to minimal levels. The multiple benefits of mass canine rabies vaccination in these cases included eliminating rabies in the domestic dog reservoirs, eliminating human rabies cases, and decreasing the rabies economic burden by reducing expenditures on PEP. Copyright © 2017. Published by Elsevier Ltd.

Melatonin Protects Human Cells from Clustered DNA Damages, Killing and Acquisition of Soft Agar Growth Induced by X-rays or 970 MeV/n Fe ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, B.; Sutherland, B.; Bennett, P. V.

We tested the ability of melatonin (N-acetyl-5 methoxytryptamine), a highly effective radical scavenger and human hormone, to protect DNA in solution and in human cells against induction of complex DNA clusters and biological damage induced by low or high linear energy transfer radiation (100 kVp X-rays, 970 MeV/nucleon Fe ions). Plasmid DNA in solution was treated with increasing concentrations of melatonin (0.0-3.5 mM) and were irradiated with X-rays. Human cells (28SC monocytes) were also irradiated with X-rays and Fe ions with and without 2 mM melatonin. Agarose plugs containing genomic DNA were subjected to Contour Clamped Homogeneous Electrophoretic Field (CHEF)more » followed by imaging and clustered DNA damages were measured by using Number Average length analysis. Transformation experiments on human primary fibroblast cells using soft agar colony assay were carried out which were irradiated with Fe ions with or without 2 mM melatonin. In plasmid DNA in solution, melatonin reduced the induction of single- and double-strand breaks. Pretreatment of human 28SC cells for 24 h before irradiation with 2 mM melatonin reduced the level of X-ray induced double-strand breaks by {approx}50%, of abasic clustered damages about 40%, and of Fe ion-induced double-strand breaks (41% reduction) and abasic clusters (34% reduction). It decreased transformation to soft agar growth of human primary cells by a factor of 10, but reduced killing by Fe ions only by 20-40%. Melatonin's effective reduction of radiation-induced critical DNA damages, cell killing, and striking decrease of transformation suggest that it is an excellent candidate as a countermeasure against radiation exposure, including radiation exposure to astronaut crews in space travel.« less

Reiki improves heart rate homeostasis in laboratory rats.

PubMed

Baldwin, Ann Linda; Wagers, Christina; Schwartz, Gary E

2008-05-01

To determine whether application of Reiki to noise-stressed rats can reduce their heart rates (HRs) and blood pressures. In a previous study, we showed that exposure of rats to 90 dB white noise for 15 minutes caused their HRs and blood pressures to significantly increase. Reiki has been shown to significantly decrease HR and blood pressure in a small group of healthy human subjects. However, use of humans in such studies has the disadvantage that experimental interpretations are encumbered by the variable of belief or skepticism regarding Reiki. For that reason, noise-stressed rats were used as an animal model to test the efficacy of Reiki in reducing elevated HR and blood pressure. Three unrestrained, male Sprague-Dawley rats implanted with radiotelemetric transducers were exposed daily for 8 days to a 15-minute white noise regimen (90 dB). For the last 5 days, the rats received 15 minutes of Reiki immediately before the noise and during the noise period. The experiment was repeated on the same animals but using sham Reiki. The animals were housed in a quiet room in University of Arizona Animal Facility. Mean HRs and blood pressure were determined before Reiki/sham Reiki, during Reiki/sham Reiki, and during the noise in each case. Reiki, but not sham Reiki, significantly reduced HR compared to initial values. With Reiki, there was a high correlation between change in HR and initial HR, suggesting a homeostatic effect. Reiki, but not sham Reiki, significantly reduced the rise in HR produced by exposure of the rats to loud noise. Neither Reiki nor sham Reiki significantly affected blood pressure. Reiki is effective in modulating HR in stressed and unstressed rats, supporting its use as a stress-reducer in humans.

Pathogenesis of Mortalin in Manganese-induced Parkinsonism

NASA Astrophysics Data System (ADS)

Cook, Travis J.

Manganese (Mn) is an essential dietary micronutrient for which excessive exposure has long been known to be neurotoxic. Historically, short-term, high-intensity exposure in occupational settings was recognized to cause acute-onset parkinsonism (PS) termed manganism. Although modern day exposures are typically several orders of magnitude lower than those necessary to cause manganism, chronic, low-level exposures are not uncommon among a number of occupations and communities. Recent epidemiologic studies have demonstrated an association between Mn exposure and risk of PS, and in this regard Mn remains a public health concern. The work described here was designed to provide insight toward questions which remain with respect to Mn exposure and its toxic effect on the brain, and includes studies utilizing Mn exposed human populations and in vitro model systems to address these objectives. Blood plasma samples obtained from a cohort of welders, whose work is recognized as generating appreciable amounts of airborne Mn, and post-mortem brain tissue of Mn mine workers were both found to have discernable alterations related to the mitochondrial chaperone protein mortalin. Furthermore, in vitro studies demonstrated that reduced astroglial expression of mortalin confers neuronal susceptibility to toxicity elicited by low levels of Mn, possibly via mechanisms of endoplasmic reticulum and oxidative stress mediated by alpha-synuclein. Taken together, the results of these studies indicate that Mn exposures experienced by modern day populations are sufficient to cause biological alterations in humans that are potentially neurotoxic.

Development of an on-line exposure system to determine freshly produced diesel engine emission-induced cellular effects.

PubMed

Oostingh, Gertie J; Papaioannou, Eleni; Chasapidis, Leonidas; Akritidis, Theofylaktos; Konstandopoulos, Athanasios G; Duschl, Albert

2013-09-01

Diesel engine emission particle filters are often placed at exhaust outlets to remove particles from the exhaust. The use of filters results in the exposure to a reduced number of nanometer-sized particles, which might be more harmful than the exposure to a larger number of micrometer-sized particles. An in vitro exposure system was established to expose human alveolar epithelial cells to freshly generated exhaust. Computer simulations were used to determine the optimal flow characteristics and ensure equal exposure conditions for each well of a 6-well plate. A selective particle size sampler was used to continuously deliver diesel soot particles with different particle size distributions to cells in culture. To determine, whether the system could be used for cellular assays, alterations in cytokine production and cell viability of human alveolar A549 cells were determined after 3h on-line exposure followed by a 21-h conventional incubation period. Data indicated that complete diesel engine emission slightly affected pre-stimulated cells, but naive cells were not affected. The fractions containing large or small particles never affected the cells. The experimental set-up allowed a reliable exposure of the cells to the complete exhaust fraction or to the fractions containing either large or small diesel engine emission particles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Environmental source of arsenic exposure.

PubMed

Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

2014-09-01

Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

Environmental Source of Arsenic Exposure

PubMed Central

Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

2014-01-01

Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made. PMID:25284196

Effect of Bluetooth headset and mobile phone electromagnetic fields on the human auditory nerve.

PubMed

Mandalà, Marco; Colletti, Vittorio; Sacchetto, Luca; Manganotti, Paolo; Ramat, Stefano; Marcocci, Alessandro; Colletti, Liliana

2014-01-01

The possibility that long-term mobile phone use increases the incidence of astrocytoma, glioma and acoustic neuroma has been investigated in several studies. Recently, our group showed that direct exposure (in a surgical setting) to cell phone electromagnetic fields (EMFs) induces deterioration of auditory evoked cochlear nerve compound action potential (CNAP) in humans. To verify whether the use of Bluetooth devices reduces these effects, we conducted the present study with the same experimental protocol. Randomized trial. Twelve patients underwent retrosigmoid vestibular neurectomy to treat definite unilateral Ménière's disease while being monitored with acoustically evoked CNAPs to assess direct mobile phone exposure or alternatively the EMF effects of Bluetooth headsets. We found no short-term effects of Bluetooth EMFs on the auditory nervous structures, whereas direct mobile phone EMF exposure confirmed a significant decrease in CNAPs amplitude and an increase in latency in all subjects. The outcomes of the present study show that, contrary to the finding that the latency and amplitude of CNAPs are very sensitive to EMFs produced by the tested mobile phone, the EMFs produced by a common Bluetooth device do not induce any significant change in cochlear nerve activity. The conditions of exposure, therefore, differ from those of everyday life, in which various biological tissues may reduce the EMF affecting the cochlear nerve. Nevertheless, these novel findings may have important safety implications. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

The EPA's human exposure research program for assessing cumulative risk in communities.

PubMed

Zartarian, Valerie G; Schultz, Bradley D

2010-06-01

Communities are faced with challenges in identifying and prioritizing environmental issues, taking actions to reduce their exposures, and determining their effectiveness for reducing human health risks. Additional challenges include determining what scientific tools are available and most relevant, and understanding how to use those tools; given these barriers, community groups tend to rely more on risk perception than science. The U.S. Environmental Protection Agency's Office of Research and Development, National Exposure Research Laboratory (NERL) and collaborators are developing and applying tools (models, data, methods) for enhancing cumulative risk assessments. The NERL's "Cumulative Communities Research Program" focuses on key science questions: (1) How to systematically identify and prioritize key chemical stressors within a given community?; (2) How to develop estimates of exposure to multiple stressors for individuals in epidemiologic studies?; and (3) What tools can be used to assess community-level distributions of exposures for the development and evaluation of the effectiveness of risk reduction strategies? This paper provides community partners and scientific researchers with an understanding of the NERL research program and other efforts to address cumulative community risks; and key research needs and opportunities. Some initial findings include the following: (1) Many useful tools exist for components of risk assessment, but need to be developed collaboratively with end users and made more comprehensive and user-friendly for practical application; (2) Tools for quantifying cumulative risks and impact of community risk reduction activities are also needed; (3) More data are needed to assess community- and individual-level exposures, and to link exposure-related information with health effects; and (4) Additional research is needed to incorporate risk-modifying factors ("non-chemical stressors") into cumulative risk assessments. The products of this research program will advance the science for cumulative risk assessments and empower communities with information so that they can make informed, cost-effective decisions to improve public health.

Timing of Galectin-1 Exposure Differentially Modulates Nipah Virus Entry and Syncytium Formation in Endothelial Cells

PubMed Central

Garner, Omai B.; Yun, Tatyana; Pernet, Olivier; Aguilar, Hector C.; Park, Arnold; Bowden, Thomas A.; Freiberg, Alexander N.

2014-01-01

ABSTRACT Nipah virus (NiV) is a deadly emerging enveloped paramyxovirus that primarily targets human endothelial cells. Endothelial cells express the innate immune effector galectin-1 that we have previously shown can bind to specific N-glycans on the NiV envelope fusion glycoprotein (F). NiV-F mediates fusion of infected endothelial cells into syncytia, resulting in endothelial disruption and hemorrhage. Galectin-1 is an endogenous carbohydrate-binding protein that binds to specific glycans on NiV-F to reduce endothelial cell fusion, an effect that may reduce pathophysiologic sequelae of NiV infection. However, galectins play multiple roles in regulating host-pathogen interactions; for example, galectins can promote attachment of HIV to T cells and macrophages and attachment of HSV-1 to keratinocytes but can also inhibit influenza entry into airway epithelial cells. Using live Nipah virus, in the present study, we demonstrate that galectin-1 can enhance NiV attachment to and infection of primary human endothelial cells by bridging glycans on the viral envelope to host cell glycoproteins. In order to exhibit an enhancing effect, galectin-1 must be present during the initial phase of virus attachment; in contrast, addition of galectin-1 postinfection results in reduced production of progeny virus and syncytium formation. Thus, galectin-1 can have dual and opposing effects on NiV infection of human endothelial cells. While various roles for galectin family members in microbial-host interactions have been described, we report opposing effects of the same galectin family member on a specific virus, with the timing of exposure during the viral life cycle determining the outcome. IMPORTANCE Nipah virus is an emerging pathogen that targets endothelial cells lining blood vessels; the high mortality rate (up to 70%) in Nipah virus infections results from destruction of these cells and resulting catastrophic hemorrhage. Host factors that promote or prevent Nipah virus infection are not well understood. Endogenous human lectins, such as galectin-1, can function as pattern recognition receptors to reduce infection and initiate immune responses; however, lectins can also be exploited by microbes to enhance infection of host cells. We found that galectin-1, which is made by inflamed endothelial cells, can both promote Nipah virus infection of endothelial cells by “bridging” the virus to the cell, as well as reduce production of progeny virus and reduce endothelial cell fusion and damage, depending on timing of galectin-1 exposure. This is the first report of spatiotemporal opposing effects of a host lectin for a virus in one type of host cell. PMID:25505064

The effect of embryonic and fetal exposure to x-ray, microwaves, and ultrasound: Counseling the pregnant and nonpregnant patient about these risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brent, R.L.

The term radiation evokes emotional responses both from lay persons and from professionals. Many spokespersons are unfamiliar with radiation biology or the quantitative nature of the risks. Frequently, microwave, ultrasound, and ionizing radiation risks are confused. Although it is impossible to prove no risk for any environmental hazard, it appears that exposure to microwave radiation below the maximal permissible levels present no measurable risk to the embryo. Ultrasound exposure from diagnostic ultrasonographic-imaging equipment also is quite innocuous. It is true that continued surveillance and research into potential risks of these low-level exposures should continue; however, at present ultrasound not onlymore » improves obstetric care, but also reduces the necessity of diagnostic x-ray procedures. In the field of ionizing radiation, we have a better comprehension of the biologic effects and the quantitative maximum risks than for any other environmental hazard. Although the animal and human data support the conclusion that no increases in the incidence of gross congenital malformations, IUGR, or abortion will occur with exposures less than 5 rad, that does not mean that there are definitely no risks to the embryo exposed to lower doses of radiation, Whether there exists a linear or exponential dose-response relationship or a threshold exposure for genetic, carcinogenic, cell-depleting, and life-shortening effects has not been determined. It is obvious that the risks of 1-rad (.10Gy) or 5-rad (.05Gy) acute exposure are far below the spontaneous risks of the developing embryo because 15% of human embryos abort, 2.7% to 3.0% of human embryos have major malformations, 4% have intrauterine growth retardation, and 8% to 10% have early- or late-stage onset genetic disease. 92 references.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brent, R.L.

Many professionals are unfamiliar with radiation biology or the quantitative nature of the risks. Frequently, microwave, ultrasound, and ionizing radiation risks are confused. Although it is impossible to prove no risk for any environmental hazard, it appears that exposure to microwave radiation below the maximal permissible levels present no measurable risk to the embryo. Ultrasound exposure from diagnostic ultrasonographic imaging equipment also is quite innocuous. It is true that continued surveillance and research into potential risks of these low-level exposures should continue, but at present ultrasound not only improves obstetric care but also reduces the necessity of diagnostic x-ray procedures.more » In the field of ionizing radiation, we have as good a comprehension of the biologic effects and the quantitative maximum risks as of any other environmental hazard. Although the animal and human data support the conclusion that no increases in the incidence of gross congenital malformations, intrauterine growth retardation, or abortion will occur with exposures less than 5 rad, that does not mean that there are definitely no risks to the embryo exposed to lower doses of radiation. Whether there exists a linear or exponential dose-response relationship or a threshold exposure for genetic, carcinogenic, cell-depleting, and life-shortening effects has not been determined. In establishing maximum permissible levels for the embryo at low exposures, refer to Tables 4, 5, 6, 8, and 9. It is obvious that the risks of 1-rad or 5-rad acute exposure are far below the spontaneous risks of the developing embryo because 15 per cent of human embryos abort, 2.7 to 3.0 per cent of human embryos have major malformations, 4 per cent have intrauterine growth retardation, and 8 to 10 per cent have early- or late-onset genetic disease. 98 references.« less

Utilizing 1-Meter Land Cover Data to Increase Sensitivity of Studies Exploring Relationships between Urban Natural Spaces and Health across Multiple Communities

EPA Science Inventory

Purpose: Previous studies have positively correlated human nature exposures with health promoting outcomes such as increased physical activity, improved cognitive function, increased social engagement, and reduced ambient air pollution. When using remotely-sensed data to investig...

Assessment of chemical effects on neurite outgrowth in PC12 cells using high content screening

EPA Science Inventory

Identification of chemicals that pose a hazard to the developing nervous system is the first step in reducing human exposure and preventing health risks to infants and children. In response to the need for more efficient methods to identify potential developmental neurotoxicants,...

DERMAL, ORAL AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhal...

Integrating Exposure, Pharmacokinetics, And Dosimetry With In Vitro Dose-Response Data To Evaluate Chemical Risk

EPA Science Inventory

High throughput in vitro toxicity testing of hundreds to thousands of chemicals across any number of biological endpoints allows for rapidly assessing human and ecosystem health impacts, thus reducing resources associated with traditional animal testing. In order to apply these i...

Mechanisms of perfluoroalkyl acid (PFAA) toxicity: Involvement of peroxisome proliferator activator receptor alpha (PPAR) molecular signals.

EPA Science Inventory

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of environmentally persistent perfluorinated compounds and are found in the serum of wildlife and humans. PFOS and PFOA are developmentally toxic in rats and mice. Exposure in utero reduces...

SHORT-TERM EXPOSURE TO ALCOHOL IN RATS AFFECTS BRAIN LEVELS OF ANANDAMIDE, OTHER N-ACYLETHANOLAMINES AND 2-ARACHIDONOYL-GLYCEROL

PubMed Central

Rubio, Marina; McHugh, Douglas; Fernández-Ruiz, Javier; Bradshaw, Heather; Walker, J. Michael

2010-01-01

Chronic alcohol exposure leads to significant changes in the levels of endocannabinoids and their receptors in the brains of humans and laboratory animals, as well as in cultured neuronal cells. However, little is known about the effects of short-term periods of alcohol exposure. In the present study, we examined the changes in endocannabinoid levels (anandamide and 2-arachidonoylglycerol), as well as four additional N-acylethanolamines, in four brain regions of rats exposed to alcohol through the liquid diet for a period of 24 hours. The levels of N-acylethanolamines were diminished 24 hours after the onset of alcohol exposure. This was particularly evident for anandamide in the hypothalamus, amygdala and caudate-putamen, for N-palmitoylethanolamine in the caudate-putamen, for N-oleoylethanolamine in the hypothalamus, caudate-putamen and prefrontal cortex, and for N-stearoylethanolamine in the amygdala. The only exception was N-linoleoylethanolamine for which the levels increased in the amygdala after the exposure to alcohol. The levels of the other major endocannabinoid, 2-arachidonoylglycerol, were also reduced with marked effects in the prefrontal cortex. These results support the notion that short-term alcohol exposure reduces endocannabinoid levels in the brain accompanied by a reduction in several related N-acylethanolamines. PMID:17574742

Climate change and environmental impacts on maternal and newborn health with focus on Arctic populations.

PubMed

Rylander, Charlotta; Odland, Jon Ø; Sandanger, Torkjel M

2011-01-01

In 2007, the Intergovernmental Panel on Climate Change (IPCC) presented a report on global warming and the impact of human activities on global warming. Later the Lancet commission identified six ways human health could be affected. Among these were not environmental factors which are also believed to be important for human health. In this paper we therefore focus on environmental factors, climate change and the predicted effects on maternal and newborn health. Arctic issues are discussed specifically considering their exposure and sensitivity to long range transported contaminants. Considering that the different parts of pregnancy are particularly sensitive time periods for the effects of environmental exposure, this review focuses on the impacts on maternal and newborn health. Environmental stressors known to affects human health and how these will change with the predicted climate change are addressed. Air pollution and food security are crucial issues for the pregnant population in a changing climate, especially indoor climate and food security in Arctic areas. The total number of environmental factors is today responsible for a large number of the global deaths, especially in young children. Climate change will most likely lead to an increase in this number. Exposure to the different environmental stressors especially air pollution will in most parts of the world increase with climate change, even though some areas might face lower exposure. Populations at risk today are believed to be most heavily affected. As for the persistent organic pollutants a warming climate leads to a remobilisation and a possible increase in food chain exposure in the Arctic and thus increased risk for Arctic populations. This is especially the case for mercury. The perspective for the next generations will be closely connected to the expected temperature changes; changes in housing conditions; changes in exposure patterns; predicted increased exposure to Mercury because of increased emissions and increased biological availability. A number of environmental stressors are predicted to increase with climate change and increasingly affecting human health. Efforts should be put on reducing risk for the next generation, thus global politics and research effort should focus on maternal and newborn health.

The leaded apron revisited: does it reduce gonadal radiation dose in dental radiology?

PubMed

Wood, R E; Harris, A M; van der Merwe, E J; Nortjé, C J

1991-05-01

A tissue-equivalent anthropomorphic human phantom was used with a lithium fluoride thermoluminescent dosimetry system to evaluate the radiation absorbed dose to the ovarian and testicular region during dental radiologic procedures. Measurements were made with and without personal lead shielding devices consisting of thyroid collar and apron of 0.25 mm lead thickness equivalence. The radiation absorbed dose with or without lead shielding did not differ significantly from control dosimeters in vertex occlusal and periapical views (p greater than 0.05). Personal lead shielding devices did reduce gonadal dose in the case of accidental exposure (p less than 0.05). A leaded apron of 0.25 mm lead thickness equivalent was permeable to radiation in direct exposure testing.

Repeated exposure to delta 9-tetrahydrocannabinol reduces prefrontal cortical dopamine metabolism in the rat.

PubMed

Jentsch, J D; Verrico, C D; Le, D; Roth, R H

1998-05-01

Long-term abuse of marijuana by humans can induce profound behavioral deficits characterized by cognitive and memory impairments. In particular, deficits on tasks dependent on frontal lobe function have been reported in cannabis abusers. In the current study, we examined whether long-term exposure to delta9-tetrahydrocannabinol, the active ingredient in marijuana, altered the neurochemistry of the frontal cortex in rats. Two weeks administration of delta9-tetrahydrocannabinol reduced dopamine transmission in the medial prefrontal cortex, while dopamine metabolism in striatal regions was unaffected. These data are consistent with earlier findings of dopaminergic regulation of frontal cortical cognition. Thus, cognitive deficits in heavy abusers of cannabis may be subserved by drug-induced alterations in frontal cortical dopamine transmission.

Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.

PubMed

Gopalakrishnan, Kalpana; Teitelbaum, Susan L; Lambertini, Luca; Wetmur, James; Manservisi, Fabiana; Falcioni, Laura; Panzacchi, Simona; Belpoggi, Fiorella; Chen, Jia

2017-01-01

Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products - methyl paraben (MPB) and triclosan (TCS) - on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson's Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes in Mammary Histology and Transcriptome Profiles by Low-Dose Exposure to Environmental Phenols at Critical Windows of Development1

PubMed Central

Gopalakrishnan, Kalpana; Teitelbaum, Susan L.; Lambertini, Luca; Wetmur, James; Manservisi, Fabiana; Falcioni, Laura; Panzacchi, Simona; Belpoggi, Fiorella; Chen, Jia

2016-01-01

Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products – methyl paraben (MPB) and triclosan (TCS) – on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson’s Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer. PMID:27810681

Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis

PubMed Central

Guerquin, Marie-Justine; Matilionyte, Gabriele; Kilcoyne, Karen; N’Tumba-Byn, Thierry; Messiaen, Sébastien; Deceuninck, Yoann; Pozzi-Gaudin, Stéphanie; Benachi, Alexandra; Livera, Gabriel; Antignac, Jean-Philippe; Mitchell, Rod; Rouiller-Fabre, Virginie

2018-01-01

Background Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models. Methods Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks. Results With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice. Conclusions Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures. PMID:29385186

DEMONSTRATION OF HUMAN EXPOSURE TOOLS

EPA Science Inventory

The Human Exposure and Atmospheric Sciences Division (HEASD) of the National Exposure Research Laboratory (NERL) conducts research on exposure measurements, human activity patterns, exposure and dose models, and cumulative exposures critical for the Agency to make scientificall...

Oxidative stress due to aluminum exposure induces eryptosis which is prevented by erythropoietin.

PubMed

Vota, Daiana M; Crisp, Renée L; Nesse, Alcira B; Vittori, Daniela C

2012-05-01

The widespread use of aluminum (Al) provides easy exposure of humans to the metal and its accumulation remains a potential problem. In vivo and in vitro assays have associated Al overload with anemia. To better understand the mechanisms by which Al affects human erythrocytes, morphological and biochemical changes were analyzed after long-term treatment using an in vitro model. The appearance of erythrocytes with abnormal shapes suggested metal interaction with cell surface, supported by the fact that high amounts of Al attached to cell membrane. Long-term incubation of human erythrocytes with Al induced signs of premature erythrocyte death (eryptosis), such as phosphatidylserine externalization, increased intracellular calcium, and band 3 degradation. Signs of oxidative stress, such as significant increase in reactive oxygen species in parallel with decrease in the amount of reduced glutathione, were also observed. These oxidative effects were completely prevented by the antioxidant N-acetylcysteine. Interestingly, erythrocytes were also protected from the prooxidative action of Al by the presence of erythropoietin (EPO). In conclusion, results provide evidence that chronic Al exposure may lead to biochemical and morphological alterations similar to those shown in eryptosis induced by oxidant compounds in human erythrocytes. The antieryptotic effect of EPO may contribute to enhance the knowledge of its physiological role on erythroid cells. Irrespective of the antioxidant mechanism, this property of EPO, shown in this model of Al exposure, let us suggest potential benefits by EPO treatment of patients with anemia associated to altered redox environment. Copyright © 2011 Wiley Periodicals, Inc.

Mechanism of erythrocyte death in human population exposed to arsenic through drinking water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biswas, Debabrata; Banerjee, Mayukh; Sen, Gargi

2008-07-01

Arsenic contamination in drinking water is one of the biggest natural calamities, which has become an imperative threat to human health throughout the world. Abbreviation of erythrocyte lifespan leading to the development of anemia is a common sequel in arsenic exposed population. This study was undertaken to explore the mechanism of cell death in human erythrocytes during chronic arsenic exposure. Results revealed transformation of smooth discoid red cells into evaginated echinocytic form in the exposed individuals. Further distortion converted reversible echinocytes to irreversible spheroechinocytes. Arsenic toxicity increased membrane microviscosity along with an elevation of cholesterol/phospholipid ratio, which hampered the flexibilitymore » of red cell membrane and made them less deformable. Significant increase in the binding of merocyanine 540 with erythrocyte membrane due to arsenic exposure indicated disruption of lipid packing in the outer leaflet of the cell membrane resulting from altered transbilayer phospholipid asymmetry. Arsenic induced eryptosis was characterized by cell shrinkage and exposure of phosphatidylserine at the cell surface. Furthermore, metabolic starvation with depletion of cellular ATP triggered apoptotic removal of erythrocytes from circulation. Significant decrease in reduced glutathione content indicating defective antioxidant capacity was coupled with enhancement of malondialdehyde and protein carbonyl levels, which pointed to oxidative damage to erythrocyte membrane. Arsenic toxicity intervened into red cell membrane integrity eventually leading to membrane destabilization and hemoglobin release. The study depicted the involvement of both erythrophagocytosis and hemolysis in the destruction of human erythrocytes during chronic arsenic exposure.« less

Food Chain Mycotoxin Exposure, Gut Health, and Impaired Growth: A Conceptual Framework1

PubMed Central

Smith, Laura E.; Stoltzfus, Rebecca J.; Prendergast, Andrew

2012-01-01

Childhood stunting is an important and intractable public health problem that underlies ∼20% of deaths among children aged <5 y in developing countries. Environmental enteropathy (EE), a subclinical condition of the small intestine characterized by reduced absorptive capacity and increased intestinal permeability, is almost universal among children in developing countries and may mediate stunting. However, the etiology of EE is poorly understood. Mycotoxins are metabolites of fungi that frequently contaminate the staple foods of children living in developing countries. We review evidence from human and animal studies that exposure to mycotoxins, particularly aflatoxin (AF), fumonisin (FUM), and deoxynivaenol (DON), may impair child growth. Although these toxins have distinct actions, they all mediate intestinal damage through: 1) inhibition of protein synthesis (AF, DON); 2) an increase in systemic proinflammatory cytokines (DON); and 3) inhibition of ceramide synthase (FUM). The intestinal pathology that arises from mycotoxin exposure is very similar to that of EE. We propose that future studies should address the role of mycotoxins in the pathogenesis of EE and evaluate interventions to limit mycotoxin exposure and reduce childhood stunting. PMID:22797988

Proposal for coordinated health research in PFAS-contaminated communities in the United States.

PubMed

Bruton, Thomas A; Blum, Arlene

2017-11-14

The drinking water of more than six million Americans in numerous communities has been found to contain highly fluorinated chemicals at concentrations of concern. Certain of these chemicals, including perfluorooctanoic acid and perfluorooctane sulfonic acid, are known to be persistent, bioaccumulative, and associated with adverse health outcomes in humans and animal models. The possible health impacts of exposure to highly fluorinated chemicals are of great concern to communities whose water has been impacted. Community members want information, and are asking for biomonitoring, exposure pathway analysis, and health studies. Governmental agencies are striving to deal with these multiple concerns in the face of information and resource constraints. We propose the development of a high-level research strategy to maximize what can be learned about health effects of highly fluorinated chemicals and methods to reduce or eliminate exposure. We suggest coordinating the research across multiple communities for greater statistical power. If implemented, such a strategy could help to generate information and evidence integration to enable regulatory decision making and contribute to reducing future exposures.

Short-term high-altitude pre-exposure improves neurobehavioral ability

PubMed Central

Guo, Wenyun; Chen, Guozhu; Qin, Jun; Zhang, Jihang; Guo, Xubin; Yu, Jie; Song, Pan; Lu, Wei; Xu, Baida; Li, Jiabei; Ding, Xiaohan

2016-01-01

This study aims to evaluate the effect of the duration of high-altitude (HA) pre-exposure on human neurobehavioral parameters including mood states and cognitive performance at HA. One hundred and eleven healthy individuals (ranging in age from 18 to 35 years) were recruited to participate in this study. They were divided into two groups: a 4-day short-term HA pre-exposure group (n=57) and a 3-month long-term HA pre-exposure group (n=54). All participants lived in the area at 400 m altitude above sea level before pre-exposure to HA. They were then transported to 3700 m plateau for either a 4-day or a 3-month HA pre-exposure, and finally delivered to 4400 m plateau. On the last day of pre-exposure at 3700 m and on the 10th day at 4400 m, neurobehavioral parameters of the participants in the two groups were evaluated. At the end of pre-exposure and on the 10th day of HA exposure, participants in the short-term group had significantly lower negative mood states, better cognitive performance with higher sensorimotor, attention, and psychomotor abilities, and less acute mountain sickness in comparison with the participants in the long-term pre-exposure group. Our field study with large samples showed that in comparison with 3-month long-term pre-exposure, 4-day short-term HA pre-exposure at 3700 m has a better effect in improving human neurobehavioral parameters including mood states and cognitive performance and reducing acute mountain sickness when exposed to a HA at 4400 m. PMID:26966781

Blood and body fluid exposure risks among health care workers: results from the Duke Health and Safety Surveillance System.

PubMed

Dement, John M; Epling, Carol; Ostbye, Truls; Pompeii, Lisa A; Hunt, Debra L

2004-12-01

Health care workers (HCWs) are at risk of exposures to human blood and body fluids (BBF). Needlestick injuries and splashes place HCWs at risk for numerous blood-borne infections including human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV). Utilizing a new comprehensive occupational health surveillance system, the objective of this research was to better define the BBF exposure risk and risk factors among employees of a large tertiary medical center. A population of 24,425 HCWs employed in jobs with potential BBF exposures was followed for BBF exposure events from 1998 to 2002. BBF exposure rates were calculated for strata defined by age, race, gender, occupation, work location, and duration of employment. Poisson regression was used for detailed analyses of risk factors for BBF exposure. The study population reported 2,730 BBF exposures during the study period, resulting in an overall annual rate of 5.5 events/100 FTEs and a rate of 3.9 for percutaneous exposures. Higher rates were observed for males, persons employed less than 4 years, Hispanic employees, and persons less than 45 years of age. Much higher rates were observed for house staff, nurse anesthetists, inpatient nurses, phlebotomists, and surgical/operating room technicians. Poisson regression results strengthened and extended results from stratified analyses. Rates of percutaneous exposures from hollow needles were found to decrease over the study period; however, exposure rates from suture needles appear to be increasing. While continued training efforts need to be directed toward new HCWs, our data also suggest that employees who have been in their job 1-4 years continue to be at higher risk of BBF exposures. This research also points to the need for better safety devices/products and work practices to reduce suture-related injuries.

Improvement of human cell line activation test (h-CLAT) using short-time exposure methods for prevention of false-negative results.

PubMed

Narita, Kazuto; Ishii, Yuuki; Vo, Phuc Thi Hong; Nakagawa, Fumiko; Ogata, Shinichi; Yamashita, Kunihiko; Kojima, Hajime; Itagaki, Hiroshi

2018-01-01

Recently, animal testing has been affected by increasing ethical, social, and political concerns regarding animal welfare. Several in vitro safety tests for evaluating skin sensitization, such as the human cell line activation test (h-CLAT), have been proposed. However, similar to other tests, the h-CLAT has produced false-negative results, including in tests for acid anhydride and water-insoluble chemicals. In a previous study, we demonstrated that the cause of false-negative results from phthalic anhydride was hydrolysis by an aqueous vehicle, with IL-8 release from THP-1 cells, and that short-time exposure to liquid paraffin (LP) dispersion medium could reduce false-negative results from acid anhydrides. In the present study, we modified the h-CLAT by applying this exposure method. We found that the modified h-CLAT is a promising method for reducing false-negative results obtained from acid anhydrides and chemicals with octanol-water partition coefficients (LogK ow ) greater than 3.5. Based on the outcomes from the present study, a combination of the original and the modified h-CLAT is suggested for reducing false-negative results. Notably, the combination method provided a sensitivity of 95% (overall chemicals) or 93% (chemicals with LogK ow > 2.0), and an accuracy of 88% (overall chemicals) or 81% (chemicals with LogK ow > 2.0). We found that the combined method is a promising evaluation scheme for reducing false-negative results seen in existing in vitro skin-sensitization tests. In the future, we expect a combination of original and modified h-CLAT to be applied in a newly developed in vitro test for evaluating skin sensitization.

Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez–Arguelles, D.B.; Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4; McIntosh, M.

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressuremore » in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.« less

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2016-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2015-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

Do flame retardant chemicals increase the risk for thyroid dysregulation and cancer?

PubMed

Hoffman, Kate; Sosa, Julie A; Stapleton, Heather M

2017-01-01

Flame retardant chemicals are added to consumer products to reduce fire incidence and severity; approximately 1.5 million tons of these chemicals are used annually. However, their widespread use has led to their ubiquitous presence in the environment and chronic accumulation in human tissues. We summarize current trends in human flame retardant chemical exposure, and review recent data highlighting concerns for thyroid dysregulation and cancer risk in human populations. Polybrominated diphenyl ethers were once commonly used as flame retardant chemicals, but recently were phased out. Exposure is associated with thyroid dysregulation (mainly T4 reductions) in animals, with new work focusing on specific mechanisms of action. Polybrominated diphenyl ethers also impact human thyroid regulation and are related to clinical thyroid disease, but associations appear both dose and life-stage dependent. Emerging data suggest that common alternate flame retardant chemicals may be more potent thyroid disruptors than their predecessors, which is particularly concerning given increasing levels of exposure. Potential health impacts of flame retardant chemicals are only beginning to be understood for 'legacy flame retardant chemicals' (i.e., polybrominated diphenyl ethers), and are largely unevaluated for newer-use chemicals. Cumulatively, current data suggest impact on thyroid regulation is likely, potentially implicating flame retardant chemicals in thyroid disease and cancers for which thyroid dysregulation impacts risk or prognosis.

Houttuynia cordata extract increased systemic exposure and liver concentrations of metformin through OCTs and MATEs in rats.

PubMed

You, Byoung Hoon; Chin, Young-Won; Kim, Hojun; Choi, Han Seok; Choi, Young Hee

2018-06-01

The synergistic activity of Houttuynia cordata ethanol extract (HCT) and metformin combination in diabetic rats has been previously reported, but the fundamental causes remain unsolved. Organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) transport metformin to the liver and kidneys. Therefore, pharmacological activity and systemic exposure of metformin in HCT-metformin combination were determined from pharmacokinetic change and glucose-lowering activity using in vitro HEK-293 cells expressing human OCTs or human MATEs and in vivo rats. HCT inhibited human OCT2 and human MATE1-mediated metformin transports in vitro. In in vivo rats, treatment with HCT and metformin for 28 days in rats (28MH rats) reduced the rat Oct2-mediated renal excretion of metformin and thereby the increased systemic exposure of metformin compared with only metformin-treated rats for 28 days (28M rats). In 28MH rats, rat Oct1-mediated metformin uptake into the liver was enhanced, leading to an improved glucose-lowering effect without hypoglycaemia compared with 28M rats. There was no impairment of renal function in HCT and metformin treatments. These results suggest that HCT-metformin combination therapy is applicable in terms of efficacy and safety. Copyright © 2018 John Wiley & Sons, Ltd.

Critical Evaluation of the Linkage Between Tick-Based Risk Measures and the Occurrence of Lyme Disease Cases.

PubMed

Eisen, Lars; Eisen, Rebecca J

2016-06-21

The nymphal stage of the blacklegged tick, Ixodes scapularis Say, is considered the primary vector to humans in the eastern United States of the Lyme disease spirochete Borrelia burgdorferi sensu stricto. The abundance of infected host-seeking nymphs is commonly used to estimate the fundamental risk of human exposure to B. burgdorferi, for the purpose of environmental risk assessment and as an outcome measure when evaluating environmentally based tick or pathogen control methods. However, as this tick-based risk measure does not consider the likelihoods of either human encounters with infected ticks or tick bites resulting in pathogen transmission, its linkage to the occurrence of Lyme disease cases is worth evaluating. In this Forum article, we describe different tick-based risk measures, discuss their strengths and weaknesses, and review the evidence for their capacity to predict the occurrence of Lyme disease cases. We conclude that: 1) the linkage between abundance of host-seeking B. burgdorferi-infected nymphs and Lyme disease occurrence is strong at community or county scales but weak at the fine spatial scale of residential properties where most human exposures to infected nymphs occur in Northeast, 2) the combined use of risk measures based on infected nymphs collected from the environment and ticks collected from humans is preferable to either one of these risk measures used singly when assessing the efficacy of environmentally based tick or pathogen control methods aiming to reduce the risk of human exposure to B. burgdorferi, 3) there is a need for improved risk assessment methodology for residential properties that accounts for both the abundance of infected nymphs and the likelihood of human-tick contact, and 4) we need to better understand how specific human activities conducted in defined residential microhabitats relate to risk for nymphal exposures and bites. Published by Oxford University Press on behalf of Entomological Society of America 2016.This work is written by US Government employees and is in the public domain in the US.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad.

PubMed

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N'Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N’Djamena, Chad

PubMed Central

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N’Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general. PMID:28421186

Used tire recycling to produce granulates: evaluation of occupational exposure to chemical agents.

PubMed

Savary, Barbara; Vincent, Raymond

2011-10-01

Exposure was assessed in four facilities where used tires are turned into rubber granulates. Particulate exposure levels were measured using filter samples and gravimetric analysis. In parallel, volatile organic compounds (VOCs) screening was carried out using samples taken on activated carbon supports, followed by an analysis using a gas chromatograph coupled to a spectrometric detector. The exposure level medians are between 0.58 and 3.95 mg m(-3). Clogging of the textile fiber separation systems can lead to worker exposure; in this case, the measured concentrations can reach 41 mg m(-3). However, in contrast to the data in the literature, VOC levels >1 p.p.m. were not detected. The particulate mixtures deposited on the installation surfaces are complex; some of the chemical agents are toxic to humans. The results of this study indicate significant exposure to complex mixtures of rubber dust. Optimizing exhaust ventilation systems inside the shredders, with a cyclone for example, is essential for reducing the exposure of workers in this rapidly developing sector.

Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants.

PubMed

Abdallah, Mohamed Abou-Elwafa; Pawar, Gopal; Harrad, Stuart

2015-11-01

Ethical and technical difficulties inherent to studies in human tissues are impeding assessment of the dermal bioavailability of brominated flame retardants (BFRs). This is further complicated by increasing restrictions on the use of animals in toxicity testing, and the uncertainties associated with extrapolating data from animal studies to humans due to inter-species variations. To overcome these difficulties, we evaluate 3D-human skin equivalents (3D-HSE) as a novel in vitro alternative to human and animal testing for assessment of dermal absorption of BFRs. The percutaneous penetration of hexabromocyclododecanes (HBCD) and tetrabromobisphenol-A (TBBP-A) through two commercially available 3D-HSE models was studied and compared to data obtained for human ex vivo skin according to a standard protocol. No statistically significant differences were observed between the results obtained using 3D-HSE and human ex vivo skin at two exposure levels. The absorbed dose was low (less than 7%) and was significantly correlated with log Kow of the tested BFR. Permeability coefficient values showed increasing dermal resistance to the penetration of γ-HBCD>β-HBCD>α-HBCD>TBBPA. The estimated long lag times (>30 min) suggests that frequent hand washing may reduce human exposure to HBCDs and TBBPA via dermal contact. Copyright © 2015 Elsevier Ltd. All rights reserved.

PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senthilkumar, P.K.; Robertson, L.W.; Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA

Polychlorinated biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cellmore » cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism. -- Highlights: ► Human immortal (HaCaT) and primary (NFK) keratinocytes were exposed to PCB153. ► PCB153 significantly reduced telomerase activity and telomere length in HaCaT. ► No effect on telomere length and telomerase activity was found in NFK. ► Increased intracellular superoxide levels and reduced cell growth was seen in both. ► PCB153 may damage telomerase expressing cells like stem cells.« less

Extinction Can Reduce the Impact of Reward Cues on Reward-Seeking Behavior.

PubMed

Lovibond, Peter F; Satkunarajah, Michelle; Colagiuri, Ben

2015-07-01

Reward-associated cues are thought to promote relapse after treatment of appetitive disorders such as drug-taking, binge eating, and gambling. This process has been modelled in the laboratory using a Pavlovian-instrumental transfer (PIT) design in which Pavlovian cues facilitate instrumental reward-directed action. Attempts to reduce facilitation by cue exposure (extinction) have produced mixed results. We tested the effect of extinction in a recently developed PIT procedure using a natural reward, chocolate, in human participants. Facilitation of instrumental responding was only observed in participants who were aware of the Pavlovian contingencies. Pavlovian extinction successfully reduced, but did not completely eliminate, expectancy of reward and facilitation of instrumental responding. The results indicate that exposure can reduce the ability of cues to promote reward-directed behavior in the laboratory. However, the residual potency of extinguished cues means that additional active strategies may be needed in clinical practice to train patients to resist the impact of these cues in their environment. Copyright © 2015. Published by Elsevier Ltd.

The impact of urban open space and 'lift-up' building design on building intake fraction and daily pollutant exposure in idealized urban models.

PubMed

Sha, Chenyuan; Wang, Xuemei; Lin, Yuanyuan; Fan, Yifan; Chen, Xi; Hang, Jian

2018-08-15

Sustainable urban design is an effective way to improve urban ventilation and reduce vehicular pollutant exposure to urban residents. This paper investigated the impacts of urban open space and 'lift-up' building design on vehicular CO (carbon monoxide) exposure in typical three-dimensional (3D) urban canopy layer (UCL) models under neutral atmospheric conditions. The building intake fraction (IF) represents the fraction of total vehicular pollutant emissions inhaled by residents when they stay at home. The building daily CO exposure (E t ) means the extent of human beings' contact with CO within one day indoor at home. Computational fluid dynamics (CFD) simulations integrating with these two concepts were performed to solve turbulent flow and assess vehicular CO exposure to urban residents. CFD technique with the standard k-ε model was successfully validated by wind tunnel data. The initial numerical UCL model consists of 5-row and 5-column (5×5) cubic buildings (building height H=street width W=30m) with four approaching wind directions (θ=0°, 15°, 30°, 45°). In Group I, one of the 25 building models is removed to attain urban open space settings. In Group II, the first floor (Lift-up1), or second floor (Lift-up2), or third floor (Lift-up3) of all buildings is elevated respectively to create wind pathways through buildings. Compared to the initial case, urban open space can slightly or significantly reduce pollutant exposure for urban residents. As θ=30° and 45°, open space settings are more effective to reduce pollutant exposure than θ=0° and 15°.The pollutant dilution near or surrounding open space and in its adjacent downstream regions is usually enhanced. Lift-up1 and Lift-up2 experience much greater pollutant exposure reduction in all wind directions than Lift-up3 and open space. Although further investigations are still required to provide practical guidelines, this study is one of the first attempts for reducing urban pollutant exposure by improving urban design. Copyright © 2018. Published by Elsevier B.V.

Reducing prenatal phthalate exposure through maternal dietary changes: results from a pilot study

PubMed Central

Barrett, Emily S.; Velez, Marissa; Qiu, Xing; Chen, Shaw-Ree

2016-01-01

Objectives Diet is a major source of exposure to certain phthalates, a class of environmental chemicals associated with endocrine disruption in animal models and humans. Several studies have attempted to lower phthalate exposure through carefully designed dietary interventions, with inconsistent results. We conducted a dietary intervention pilot study with the objective to lower phthalate exposure in low-income pregnant women, a particularly vulnerable population. Methods Ten pregnant women consumed a provided diet consisting of mostly fresh, organic foods for three days. We collected urine samples before, during, and after the intervention and conducted semi-structured interviews to assess the feasibility and acceptability of the intervention. We used repeated measures ANOVA and paired t-tests to assess differences in urinary phthalate metabolite concentrations across the study, focusing on the metabolites of di-2-ethylhexyl phthalate (DEHP), a phthalate of particular interest, and their molar sum (∑DEHP). Results Phthalate metabolite concentrations did not change appreciably during the intervention period. We observed no significant difference in ∑DEHP metabolite concentrations across the three time periods (F=0.21; adjusted p-value=0.65), and no reduction during the intervention as compared to baseline (t=−1.07, adjusted p-value=0.51). Results of interviews indicated that participants were not motivated to make dietary changes to potentially reduce chemical exposures outside of the study. Conclusions Despite the small sample size, our results suggest that promoting dietary changes to lower phthalate exposure may not be an effective public health measure. Reducing the use of phthalates in food processing and packaging may be a better solution to lowering exposure on a population level. PMID:25652062

Deoxynivalenol exposure induces autophagy/apoptosis and epigenetic modification changes during porcine oocyte maturation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Jun; Wang, Qiao-Chu; Zhu, Cheng-Cheng

Deoxynivalenol (DON) is a widespread trichothecene mycotoxin which contaminates agricultural staples and elicits a complex spectrum of toxic effects on humans and animals. It has been shown that DON impairs oocyte maturation, reproductive function and causes abnormal fetal development in mammals; however, the mechanisms remain unclear. In the present study, we investigate the possible reasons of the toxic effects of DON on porcine oocytes. Our results showed that DON significantly inhibited porcine oocyte maturation and disrupted meiotic spindle by reducing p-MAPK protein level, which caused retardation of cell cycle progression. In addition, up-regulated LC3 protein expression and aberrant Lamp2, LC3more » and mTOR mRNA levels were observed with DON exposure, together with Annexin V-FITC staining assay analysis, these results indicated that DON treatment induced autophagy/apoptosis in porcine oocytes. We also showed that DON exposure increased DNA methylation level in porcine oocytes through altering DNMT3A mRNA levels. Histone methylation levels were also changed showing with increased H3K27me3 and H3K4me2 protein levels, and mRNA levels of their relative methyltransferase genes, indicating that epigenetic modifications were affected. Taken together, our results suggested that DON exposure reduced porcine oocytes maturation capability through affecting cytoskeletal dynamics, cell cycle, autophagy/apoptosis and epigenetic modifications. - Highlights: • DON exposure disrupted meiotic spindle by reducing p-MAPK expression. • DON exposure caused retardation of cell cycle progression in porcine oocytes. • DON triggered autophagy and early-apoptosis in porcine oocytes. • DON exposure led to aberrant epigenetic modifications in porcine oocytes.« less

Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis

PubMed Central

Ray, Jessica L.; Kopec, Anna K.; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H.; Williams, Kurt J.; Leung, Patrick S.; Gershwin, M. Eric

2017-01-01

Abstract Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL+/+ mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model. PMID:28115651

International Space Station Noise Constraints Flight Rule Process

NASA Technical Reports Server (NTRS)

Limardo, Jose G.; Allen, Christopher S.; Danielson, Richard W.

2014-01-01

Crewmembers onboard the International Space Station (ISS) live in a unique workplace environment for as long as 6 -12 months. During these long-duration ISS missions, noise exposures from onboard equipment are posing concerns for human factors and crewmember health risks, such as possible reductions in hearing sensitivity, disruptions of crew sleep, interference with speech intelligibility and voice communications, interference with crew task performance, and reduced alarm audibility. The purpose of this poster is to describe how a recently-updated noise constraints flight rule is being used to implement a NASA-created Noise Exposure Estimation Tool and Noise Hazard Inventory to predict crew noise exposures and recommend when hearing protection devices are needed.

Bisphenol A Exposure Disrupts Genomic Imprinting in the Mouse

PubMed Central

Susiarjo, Martha; Sasson, Isaac; Mesaros, Clementina; Bartolomei, Marisa S.

2013-01-01

Exposure to endocrine disruptors is associated with developmental defects. One compound of concern, to which humans are widely exposed, is bisphenol A (BPA). In model organisms, BPA exposure is linked to metabolic disorders, infertility, cancer, and behavior anomalies. Recently, BPA exposure has been linked to DNA methylation changes, indicating that epigenetic mechanisms may be relevant. We investigated effects of exposure on genomic imprinting in the mouse as imprinted genes are regulated by differential DNA methylation and aberrant imprinting disrupts fetal, placental, and postnatal development. Through allele-specific and quantitative real-time PCR analysis, we demonstrated that maternal BPA exposure during late stages of oocyte development and early stages of embryonic development significantly disrupted imprinted gene expression in embryonic day (E) 9.5 and 12.5 embryos and placentas. The affected genes included Snrpn, Ube3a, Igf2, Kcnq1ot1, Cdkn1c, and Ascl2; mutations and aberrant regulation of these genes are associated with imprinting disorders in humans. Furthermore, the majority of affected genes were expressed abnormally in the placenta. DNA methylation studies showed that BPA exposure significantly altered the methylation levels of differentially methylated regions (DMRs) including the Snrpn imprinting control region (ICR) and Igf2 DMR1. Moreover, exposure significantly reduced genome-wide methylation levels in the placenta, but not the embryo. Histological and immunohistochemical examinations revealed that these epigenetic defects were associated with abnormal placental development. In contrast to this early exposure paradigm, exposure outside of the epigenetic reprogramming window did not cause significant imprinting perturbations. Our data suggest that early exposure to common environmental compounds has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta. PMID:23593014

The perils of climate change: In utero exposure to temperature variability and birth outcomes in the Andean region.

PubMed

Molina, Oswaldo; Saldarriaga, Victor

2017-02-01

The discussion on the effects of climate change on human activity has primarily focused on how increasing temperature levels can impair human health. However, less attention has been paid to the effect of increased climate variability on health. We investigate how in utero exposure to temperature variability, measured as the fluctuations relative to the historical local temperature mean, affects birth outcomes in the Andean region. Our results suggest that exposure to a temperate one standard deviation relative to the municipality's long-term temperature mean during pregnancy reduces birth weight by 20g. and increases the probability a child is born with low birth weight by a 0.7 percentage point. We also explore potential channels driving our results and find some evidence that increased temperature variability can lead to a decrease in health care and increased food insecurity during pregnancy. Copyright © 2016 Elsevier B.V. All rights reserved.

Metal Pollutants and Cardiovascular Disease: Mechanisms and Consequences of Exposure

PubMed Central

Solenkova, Natalia V.; Newman, Jonathan D.; Berger, Jeffrey S.; Thurston, George; Hochman, Judith S.; Lamas, Gervasio A.

2014-01-01

Introduction There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, are significant risk factors for CVD. Methods We reviewed the English-speaking medical literature to assess and present the epidemiological evidence that 4 metals having no role in the human body (xenobiotic), mercury, lead, cadmium, and arsenic, have epidemiologic and mechanistic links to atherosclerosis and CVD. Moreover, we briefly review how the results of the Trial to Assess Chelation Therapy strengthen the link between atherosclerosis and xenobiotic metal contamination in humans. Conclusions There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor. PMID:25458643

Sudan azo dyes and Para Red degradation by prevalent bacteria of the human gastrointestinal tract☆

PubMed Central

Xu, Haiyan; Heinze, Thomas M.; Paine, Donald D.; Cerniglia, Carl E.; Chen, Huizhong

2018-01-01

Sudan azo dyes have genotoxic effects and ingestion of food products contaminated with Sudan I, II, III, IV, and Para Red could lead to exposure in the human gastrointestinal tract. In this study, we examined thirty-five prevalent species of human intestinal bacteria to evaluate their capacity to degrade Sudan dyes and Para Red. Among these tested bacterial strains, 23, 13, 33, 30, and 29 out of 35 species tested were able to reduce Sudan I, II, III, IV, and Para Red, respectively, to some extent. Bifidobacterium infantis, Clostridium indolis, Enterococcus faecalis, Lactobacillus rhamnosus, and Ruminococcus obeum were able to reduce completely all four tested Sudan dyes and Para Red. Escherichia coli and Peptostreptococcus magnus were the only two strains that were not able to reduce any of the tested Sudan dyes and Para Red to any significant extent. Metabolites of the reduction of the tested Sudan dyes and Para Red by E. faecalis were isolated and identified by HPLC and LC/ESI-MS analyses and compared with authentic standards. Thus it appears that the ability to reduce Sudan dyes and Para Red except Sudan II is common among bacteria in the human colon. PMID:19580882

HUMAN EXPOSURE ACTIVITY PATTERNS

EPA Science Inventory

Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

Insecticide-Treated Nets Can Reduce Malaria Transmission by Mosquitoes Which Feed Outdoors

PubMed Central

Govella, Nicodem J.; Okumu, Fredros O.; Killeen, Gerry F.

2010-01-01

Insecticide treated nets (ITNs) represent a powerful means for controlling malaria in Africa because the mosquito vectors feed primarily indoors at night. The proportion of human exposure that occurs indoors, when people are asleep and can conveniently use ITNs, is therefore very high. Recent evidence suggests behavioral changes by malaria mosquito populations to avoid contact with ITNs by feeding outdoors in the early evening. We adapt an established mathematical model of mosquito behavior and malaria transmission to illustrate how ITNs can achieve communal suppression of malaria transmission exposure, even where mosquito evade them and personal protection is modest. We also review recent reports from Tanzania to show that conventional mosquito behavior measures can underestimate the potential of ITNs because they ignore the importance of human movements. PMID:20207866

Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan

Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LCmore » cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the relationship between cadmium and lung cancer.« less

Forecasting human exposure to atmospheric pollutants in Portugal - A modelling approach

NASA Astrophysics Data System (ADS)

Borrego, C.; Sá, E.; Monteiro, A.; Ferreira, J.; Miranda, A. I.

2009-12-01

Air pollution has become one main environmental concern because of its known impact on human health. Aiming to inform the population about the air they are breathing, several air quality modelling systems have been developed and tested allowing the assessment and forecast of air pollution ambient levels in many countries. However, every day, an individual is exposed to different concentrations of atmospheric pollutants as he/she moves from and to different outdoor and indoor places (the so-called microenvironments). Therefore, a more efficient way to prevent the population from the health risks caused by air pollution should be based on exposure rather than air concentrations estimations. The objective of the present study is to develop a methodology to forecast the human exposure of the Portuguese population based on the air quality forecasting system available and validated for Portugal since 2005. Besides that, a long-term evaluation of human exposure estimates aims to be obtained using one-year of this forecasting system application. Additionally, a hypothetical 50% emission reduction scenario has been designed and studied as a contribution to study emission reduction strategies impact on human exposure. To estimate the population exposure the forecasting results of the air quality modelling system MM5-CHIMERE have been combined with the population spatial distribution over Portugal and their time-activity patterns, i.e. the fraction of the day time spent in specific indoor and outdoor places. The population characterization concerning age, work, type of occupation and related time spent was obtained from national census and available enquiries performed by the National Institute of Statistics. A daily exposure estimation module has been developed gathering all these data and considering empirical indoor/outdoor relations from literature to calculate the indoor concentrations in each one of the microenvironments considered, namely home, office/school, and other indoors (leisure activities like shopping areas, gym, theatre/cinema and restaurants). The results show how this developed modelling system can be useful to anticipate air pollution episodes and to estimate their effects on human health on a long-term basis. The two metropolitan areas of Porto and Lisbon are identified as the most critical ones in terms of air pollution effects on human health over Portugal in a long-term as well as in a short-term perspective. The coexistence of high concentration values and high population density is the key factor for these stressed areas. Regarding the 50% emission reduction scenario, the model results are significantly different for both pollutants: there is a small overall reduction in the individual exposure values of PM 10 (<10 μg m -3 h), but for O 3, in contrast, there is an extended area where exposure values increase with emission reduction. This detailed knowledge is a prerequisite for the development of effective policies to reduce the foreseen adverse impact of air pollution on human health and to act on time.

A paler shade of green? The toxicology of biodiesel emissions: Recent findings from studies with this alternative fuel.

PubMed

Madden, Michael C

2016-12-01

Biodiesel produced primarily from plants and algal feedstocks is believed to have advantages for production and use compared to petroleum and to some other fuel sources. There is some speculation that exposure to biodiesel combustion emissions may not induce biological responses or health effects or at a minimum reduce the effects relative to other fuels. In evaluating the overall environmental and health effects of biodiesel production to end use scenario, empirical data or modeling data based on such data are needed. This manuscript examines the available toxicology reports examining combustion derived biodiesel emissions since approximately 2007, when our last review of the topic occurred. Toxicity derived from other end uses of biodiesel - e.g., spills, dermal absorption, etc. - are not examined. Findings from biodiesel emissions are roughly divided into three areas: whole non-human animal model exposures; in vitro exposures of mammalian and bacterial cells (used for mutation studies primarily); and human exposures in controlled or other exposure fashions. Overall, these more current studies clearly demonstrate that biodiesel combustion emission exposure- to either 100% biodiesel or a blend in petroleum diesel- can induce biological effects. There are reports that show biodiesel exposure generally induces more effects or a greater magnitude of effect than petroleum diesel, however there are also a similar number of reports showing the opposite trend. It is unclear whether effects induced by exposure to a blend are greater than exposure to 100% biodiesel. Taken together, the evidence suggest biodiesel emissions can have some similar effects as diesel emissions on inflammatory, vascular, mutagenic, and other responses. While acute biodiesel exposures can show toxicity with a variety of endpoints, the potential effects on human health need further validation. Additionally there are few or no findings to date on whether biodiesel emissions can induce effects or even a weaker response that petroleum diesel with repeated exposure scenarios such as in an occupational setting. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Copyright © 2016. Published by Elsevier B.V.

Endocrine disrupting compounds in drinking water supply system and human health risk implication.

PubMed

Wee, Sze Yee; Aris, Ahmad Zaharin

2017-09-01

To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water. Copyright © 2017 Elsevier Ltd. All rights reserved.

EFFECT OF VARYING MATERNAL FOLATE STATUS AND DIETARY FOLATE INTAKE ON RESPONSE TO DIVERSE DEVELOPMENTAL TOXICANTS IN THE RAT

EPA Science Inventory

Periconceptional and early pregnancy folate supplements are associated with reduced recurrence and occurrence of birth defects in humans. This study was undertaken to assess the influence of maternal folate status and dietary folate intake on outcome of exposures to diverse terat...

Wildfire exposure and fuel management on western US national forests

Treesearch

Alan A. Ager; Michelle A. Day; Charles W. McHugh; Karen Short; Julie Gilbertson-Day; Mark A. Finney; David E. Calkin

2014-01-01

Substantial investments in fuel management activities on national forests in the western US are part of a national strategy to reduce human and ecological losses from catastrophic wildfire and create fire resilient landscapes. Prioritizing these investments within and among national forests remains a challenge, partly because a comprehensive assessment that establishes...

The threats to food safety and biocontrol of aflatoxins

USDA-ARS?s Scientific Manuscript database

Aflatoxins are a serious food safety concern for human and animal health. Great attention should be paid to the dietary exposure to these toxins in order to reduce the risk of aflatoxin contamination in the food chain. Although the research on aflatoxins was started more than 50 years ago, it is sti...

Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh

USDA-ARS?s Scientific Manuscript database

Background: Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neura...

DEVELOPMENTAL EXPOSURE TO POLYBROMINATED DIPHENYL ETHERS DOES IMPAIRS SYNAPTIC TRANSMISSION AND LTP IN HIPPOCAMPUS.

EPA Science Inventory

Polybrominated diphenyl ether (PBDE) flame retardants bioaccumulate in wildlife and in humans and reduce circulating levels of thyroxine (T4). The present work examined hippocampal function in adult offspring of LE rats treated daily by oral gavage with 0, 30 or 100 mg/kg of a ...

Ca(2+)-mediated prostaglandin E2 induction reduces haematoporphyrin-derivative-induced cytotoxicity of T24 human bladder transitional carcinoma cells in vitro.

PubMed Central

Penning, L C; Keirse, M J; VanSteveninck, J; Dubbelman, T M

1993-01-01

The effects of haematoporphyrin-derivative-mediated photodynamic treatment on arachidonic acid metabolism and its relation to clonogenicity have been studied in human bladder-tumour cells. Photodynamic treatment resulted in a transient release of arachidonic acid-derived compounds; prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) especially were strongly increased. This release was reduced by chelation of intracellular Ca2+ with Quin-2 or by lowering the extracellular Ca2+ concentration in the medium with EGTA, presumably resulting in inhibition of phospholipase A2. A similar reduction was obtained when indomethacin, an inhibitor of the cyclo-oxygenase pathway, was added prior to light exposure. These three treatments enhanced the photosensitivity, as revealed by the clonogenicity assay. Incubation with PGE2 prior to light exposure, but not with TXB2, protected against reproductive-cell death. The results of these experiments suggest that Ca(2+)-mediated activation of cyclo-oxygenase, resulting in increased levels of PGE2, participates in a cellular-defence mechanism against photodynamic cell killing. PMID:8503851

Hazards of heavy metal contamination.

PubMed

Järup, Lars

2003-01-01

The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. These metals have been extensively studied and their effects on human health regularly reviewed by international bodies such as the WHO. Heavy metals have been used by humans for thousands of years. Although several adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues, and is even increasing in some parts of the world, in particular in less developed countries, though emissions have declined in most developed countries over the last 100 years. Cadmium compounds are currently mainly used in re-chargeable nickel-cadmium batteries. Cadmium emissions have increased dramatically during the 20th century, one reason being that cadmium-containing products are rarely re-cycled, but often dumped together with household waste. Cigarette smoking is a major source of cadmium exposure. In non-smokers, food is the most important source of cadmium exposure. Recent data indicate that adverse health effects of cadmium exposure may occur at lower exposure levels than previously anticipated, primarily in the form of kidney damage but possibly also bone effects and fractures. Many individuals in Europe already exceed these exposure levels and the margin is very narrow for large groups. Therefore, measures should be taken to reduce cadmium exposure in the general population in order to minimize the risk of adverse health effects. The general population is primarily exposed to mercury via food, fish being a major source of methyl mercury exposure, and dental amalgam. The general population does not face a significant health risk from methyl mercury, although certain groups with high fish consumption may attain blood levels associated with a low risk of neurological damage to adults. Since there is a risk to the fetus in particular, pregnant women should avoid a high intake of certain fish, such as shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from polluted fresh waters should especially be avoided. There has been a debate on the safety of dental amalgams and claims have been made that mercury from amalgam may cause a variety of diseases. However, there are no studies so far that have been able to show any associations between amalgam fillings and ill health. The general population is exposed to lead from air and food in roughly equal proportions. During the last century, lead emissions to ambient air have caused considerable pollution, mainly due to lead emissions from petrol. Children are particularly susceptible to lead exposure due to high gastrointestinal uptake and the permeable blood-brain barrier. Blood levels in children should be reduced below the levels so far considered acceptable, recent data indicating that there may be neurotoxic effects of lead at lower levels of exposure than previously anticipated. Although lead in petrol has dramatically decreased over the last decades, thereby reducing environmental exposure, phasing out any remaining uses of lead additives in motor fuels should be encouraged. The use of lead-based paints should be abandoned, and lead should not be used in food containers. In particular, the public should be aware of glazed food containers, which may leach lead into food. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Occupational exposure to arsenic, primarily by inhalation, is causally associated with lung cancer. Clear exposure-response relationships and high risks have been observed.

Transgenerational effects and recovery of microplastics exposure in model populations of the freshwater cladoceran Daphnia magna Straus.

PubMed

Martins, Alexandra; Guilhermino, Lúcia

2018-08-01

The environmental contamination by microplastics is a global challenge to ecosystem and human health, and the knowledge on the long-term effects of such particles is limited. Thus, the effects of microplastics and post-exposure recovery were investigated over 4 generations (F 0 , F 1 , F 2 , F 3 ) using Daphnia magna as model. Effect criteria were parental mortality, growth, several reproductive parameters, and population growth rate. Microplastics exposure (0.1mg/l of pristine polymer microspheres 1-5μm diameter) caused parental mortality (10-100%), and significantly (p≤0.05) decreased growth, reproduction, and population growth rate leading to the extinction of the microplastics-exposed model population in the F 1 generation. Females descending from those exposed to microplastics in F 0 and exposed to clean medium presented some recovery but up to the F 3 generation they still had significantly (p≤0.05) reduced growth, reproduction, and population growth rate. Overall, these results indicate that D. magna recovery from chronic exposure to microplastics may take several generations, and that the continuous exposure over generations to microplastics may cause population extinction. These findings have implications to aquatic ecosystem functioning and services, and raise concern on the long-term animal and human exposure to microplastics through diverse routes. Copyright © 2018. Published by Elsevier B.V.

Exposure to Carbon Ions Triggers Proinflammatory Signals and Changes in Homeostasis and Epidermal Tissue Organization to a Similar Extent as Photons

PubMed Central

Simoniello, Palma; Wiedemann, Julia; Zink, Joana; Thoennes, Eva; Stange, Maike; Layer, Paul G.; Kovacs, Maximilian; Podda, Maurizio; Durante, Marco; Fournier, Claudia

2016-01-01

The increasing application of charged particles in radiotherapy requires a deeper understanding of early and late side effects occurring in skin, which is exposed in all radiation treatments. We measured cellular and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure. Model systems for human skin from healthy donors of different complexity, i.e., keratinocytes, coculture of skin cells, 3D skin equivalents, and skin explants, were used to investigate the alterations induced by carbon ions (spread-out Bragg peak, dose-averaged LET 100 keV/μm) in comparison to X-ray and UV-B exposure. After exposure to ionizing radiation, in none of the model systems, apoptosis/necrosis was observed. Carbon ions triggered inflammatory signaling and accelerated differentiation of keratinocytes to a similar extent as X-rays at the same doses. High doses of carbon ions were more effective than X-rays in reducing proliferation and inducing abnormal differentiation. In contrast, changes identified following low-dose exposure (≤0.5 Gy) were induced more effectively after X-ray exposure, i.e., enhanced proliferation and change in the polarity of basal cells. PMID:26779439

900 MHz radiation does not induce micronucleus formation in different cell types.

PubMed

Hintzsche, Henning; Jastrow, Christian; Kleine-Ostmann, Thomas; Schrader, Thorsten; Stopper, Helga

2012-07-01

The exposure of the population to non-ionising electromagnetic radiation is still increasing, mainly due to mobile communication. Whether low-intensity electromagnetic fields can cause other effects apart from heating has been a subject of debate. One of the effects, which were proposed to be caused by mobile phone radiation, is the occurrence of mitotic disturbances. The aim of this study was to investigate possible consequences of these mitotic disturbances as manifest genomic damage, i.e. micronucleus induction. Cells were irradiated at a frequency of 900 MHz, which is located in one of the main frequency bands applied for mobile communication. Two cell types were used, HaCaT cells as human cells and A(L) cells (human-hamster hybrid cells), in which mitotic disturbances had been reported to occur. After different post-exposure incubation periods, cells were fixed and micronucleus frequencies were evaluated. Both cell types did not show any genomic damage after exposure. To adapt the protocol for the micronucleus test into the direction of the protocol for mitotic disturbances, the post-exposure incubation period was reduced and exposure time was extended to one cell cycle length. This did not result in any increase of the genomic damage. In conclusion, micronucleus induction was not observed as a consequence of exposure to non-ionising radiation, even though this agent was reported to cause mitotic disturbances under similar experimental conditions.

The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

PubMed

Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

2018-01-01

The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

Health-Based Cyanotoxin Guideline Values Allow for Cyanotoxin-Based Monitoring and Efficient Public Health Response to Cyanobacterial Blooms

PubMed Central

Farrer, David; Counter, Marina; Hillwig, Rebecca; Cude, Curtis

2015-01-01

Human health risks from cyanobacterial blooms are primarily related to cyanotoxins that some cyanobacteria produce. Not all species of cyanobacteria can produce toxins. Those that do often do not produce toxins at levels harmful to human health. Monitoring programs that use identification of cyanobacteria genus and species and enumeration of cyanobacterial cells as a surrogate for cyanotoxin presence can overestimate risk and lead to unnecessary health advisories. In the absence of federal criteria for cyanotoxins in recreational water, the Oregon Health Authority (OHA) developed guideline values for the four most common cyanotoxins in Oregon’s fresh waters (anatoxin-a, cylindrospermopsin, microcystins, and saxitoxins). OHA developed three guideline values for each of the cyanotoxins found in Oregon. Each of the guideline values is for a specific use of cyanobacteria-affected water: drinking water, human recreational exposure and dog recreational exposure. Having cyanotoxin guidelines allows OHA to promote toxin-based monitoring (TBM) programs, which reduce the number of health advisories and focus advisories on times and places where actual, rather than potential, risks to health exist. TBM allows OHA to more efficiently protect public health while reducing burdens on local economies that depend on water recreation-related tourism. PMID:25664510

Building human resilience: the role of public health preparedness and response as an adaptation to climate change.

PubMed

Keim, Mark E

2008-11-01

Global climate change will increase the probability of extreme weather events, including heatwaves, drought, wildfire, cyclones, and heavy precipitation that could cause floods and landslides. Such events create significant public health needs that can exceed local capacity to respond, resulting in excess morbidity or mortality and in the declaration of disasters. Human vulnerability to any disaster is a complex phenomenon with social, economic, health, and cultural dimensions. Vulnerability to natural disasters has two sides: the degree of exposure to dangerous hazards (susceptibility) and the capacity to cope with or recover from disaster consequences (resilience). Vulnerability reduction programs reduce susceptibility and increase resilience. Susceptibility to disasters is reduced largely by prevention and mitigation of emergencies. Emergency preparedness and response and recovery activities--including those that address climate change--increase disaster resilience. Because adaptation must occur at the community level, local public health agencies are uniquely placed to build human resilience to climate-related disasters. This article discusses the role of public health in reducing human vulnerability to climate change within the context of select examples for emergency preparedness and response.

Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

PubMed Central

Vaiserman, Alexander M.

2010-01-01

Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour

PubMed Central

Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C.; Hughes, Ieuan A.; Acerini, Carlo L.

2016-01-01

Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. PMID:26833843

Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

PubMed

Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

2016-02-19

Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. © 2016 The Author(s).

The rationale for the use of measles post-exposure prophylaxis in pregnant women: a review.

PubMed

Manikkavasagan, G; Ramsay, M

2009-10-01

A review of published literature was undertaken to investigate the maternal and fetal effects of measles infection in pregnancy and to inform the need for post-exposure prophylaxis. There is no evidence to support an association between measles in pregnancy and congenital defects. However, the need for effective post-exposure protection is supported by studies suggesting a high risk of severe maternal morbidity, fetal loss and prematurity. Measles in late pregnancy can also lead to perinatal infection in the infant, which may be associated with a high mortality and the risk of subacute sclerosing panencephalitis. UK guidance recommends using human normal immunoglobulin for susceptible pregnant women exposed to measles. Although there is no direct evidence that this will reduce the complications of measles in pregnancy, it may attenuate disease and therefore reduce the rate of complications. Measures to identify women likely to be susceptible include assessment of age, vaccination history, and/or antibody testing.

Quantitation of ortho-Cresyl Phosphate Adducts to Butyrylcholinesterase in Human Serum by Immunomagnetic-UHPLC-MS/MS

PubMed Central

Johnson, Darryl; Carter, Melissa D.; Crow, Brian S.; Isenberg, Samantha L.; Graham, Leigh Ann; Erol, H. Akin; Watson, Caroline M.; Pantazides, Brooke G.; van der Schans, Marcel J.; Langenberg, Jan P.; Noort, Daan; Blake, Thomas A.; Thomas, Jerry D.; Johnson, Rudolph C.

2017-01-01

Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids, and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to form the aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic-UHPLC-MS/MS method for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. The method has a reportable range from 2.0 ng/mL to 150 ng/mL, which is consistent with the sensitivity of methods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥ 85%) and precision (RSD ≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72 hours at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20, and demonstrates a 3-fold improvement in sensitivity. PMID:26149113

Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

PubMed Central

Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Olive Ngalame, Ntube N.; Waalkes, Michael P.

2013-01-01

Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell’s ability to adapt to chronic cadmium exposure. PMID:23811327

Report on carcinogens monograph on cumene.

PubMed

2013-09-01

The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

Protective practices against zoonotic infections among rural and slum communities from South Central Chile.

PubMed

Mason, Meghan R; Gonzalez, Marcelo; Hodges, James S; Muñoz-Zanzi, Claudia

2015-07-28

Despite well-recognized recommendations to reduce human exposure to zoonotic pathogens, the use of personal and herd-level protective practices is inconsistent in communities where human interactions with animals are common. This study assessed household-level participation in rodent- (extermination, proper food storage, trash disposal), occupational- (preventive veterinary care, boot-wearing, glove-wearing), and garden-associated (restricting animal access, boot-wearing, glove-wearing) protective practices in farms, villages, and slums in the Los Rios region, Chile, where zoonotic pathogens are endemic. Questionnaires administered at 422 households across 12 communities recorded household-level socio-demographic characteristics and participation in nine protective practices. Household inclusion in the analysis of occupational practices required having livestock and a household member with occupational exposure to livestock (n = 127), and inclusion in analysis of garden practices required having a garden and at least one animal (n = 233). The proportion of households participating in each protective practice was compared across community types through chi-square analyses. Mixed effects logistic regression assessed household-level associations between socio-demographic characteristics and participation in each protective practice. Most households (95.3 %) reported participation in rodent control, and a positive association between the number of rodent signs in a household and rodent extermination was observed (OR: 1.75, 95 % CI: 1.41, 2.16). Occupational protective practices were reported in 61.8 % of eligible households; household size (OR: 1.63, 95 % CI: 1.17, 5.84) and having children (OR: 0.22, 95 % CI: 0.06, 0.78) were associated with preventive veterinary care. Among eligible households, 73.8 % engaged in protective practices when gardening, and species diversity was positively associated with wearing boots (OR: 1.27, 95 % CI: 1.03, 1.56). Household-level participation in all three protective practices within any exposure category was limited (<10.4 %) and participation in any individual protective practice varied considerably within and across community types. The levels of participation in protective practices reported in this study are consistent with descriptions in the literature of imperfect use of methods that reduce human exposure to zoonotic pathogens. The wide differences across communities in the proportion of households participating in protective practices against human exposure to zoonotic pathogens, suggests that future research should identify community-level characteristics that influence household participation in such practices.

Critical Evaluation of the Linkage Between Tick-Based Risk Measures and the Occurrence of Lyme Disease Cases

PubMed Central

Eisen, Lars; Eisen, Rebecca J.

2018-01-01

The nymphal stage of the blacklegged tick, Ixodes scapularis Say, is considered the primary vector to humans in the eastern United States of the Lyme disease spirochete Borrelia burgdorferi sensu stricto. The abundance of infected host-seeking nymphs is commonly used to estimate the fundamental risk of human exposure to B. burgdorferi, for the purpose of environmental risk assessment and as an outcome measure when evaluating environmentally based tick or pathogen control methods. However, as this tick-based risk measure does not consider the likelihoods of either human encounters with infected ticks or tick bites resulting in pathogen transmission, its linkage to the occurrence of Lyme disease cases is worth evaluating. In this Forum article, we describe different tick-based risk measures, discuss their strengths and weaknesses, and review the evidence for their capacity to predict the occurrence of Lyme disease cases. We conclude that: 1) the linkage between abundance of host-seeking B. burgdorferi-infected nymphs and Lyme disease occurrence is strong at community or county scales but weak at the fine spatial scale of residential properties where most human exposures to infected nymphs occur in Northeast, 2) the combined use of risk measures based on infected nymphs collected from the environment and ticks collected from humans is preferable to either one of these risk measures used singly when assessing the efficacy of environmentally based tick or pathogen control methods aiming to reduce the risk of human exposure to B. burgdorferi, 3) there is a need for improved risk assessment methodology for residential properties that accounts for both the abundance of infected nymphs and the likelihood of human–tick contact, and 4) we need to better understand how specific human activities conducted in defined residential microhabitats relate to risk for nymphal exposures and bites. PMID:27330093

A systematic review of Bisphenol A "low dose" studies in the context of human exposure: a case for establishing standards for reporting "low-dose" effects of chemicals.

PubMed

Teeguarden, Justin G; Hanson-Drury, Sesha

2013-12-01

Human exposure to the chemical Bisphenol A is almost ubiquitous in surveyed industrialized societies. Structural features similar to estrogen confer the ability of Bisphenol A (BPA) to bind estrogen receptors, giving BPA membership in the group of environmental pollutants called endocrine disruptors. References by scientists, the media, political entities, and non-governmental organizations to many toxicity studies as "low dose" has led to the belief that exposure levels in these studies are similar to humans, implying that BPA is toxic to humans at current exposures. Through systematic, objective comparison of our current, and a previous compilation of the "low-dose" literature to multiple estimates of human external and internal exposure levels, we found that the "low-dose" moniker describes exposures covering 8-12 orders of magnitude, the majority (91-99% of exposures) being greater than the upper bound of human exposure in the general infant, child and adult U.S. Population. "low dose" is therefore a descriptor without specific meaning regarding human exposure. Where human exposure data are available, for BPA and other environmental chemicals, reference to toxicity study exposures by direct comparison to human exposure would be more informative, more objective, and less susceptible to misunderstanding. Copyright © 2013 Elsevier Ltd. All rights reserved.

Incorporating biologically based models into assessments of risk from chemical contaminants

NASA Technical Reports Server (NTRS)

Bull, R. J.; Conolly, R. B.; De Marini, D. M.; MacPhail, R. C.; Ohanian, E. V.; Swenberg, J. A.

1993-01-01

The general approach to assessment of risk from chemical contaminants in drinking water involves three steps: hazard identification, exposure assessment, and dose-response assessment. Traditionally, the risks to humans associated with different levels of a chemical have been derived from the toxic responses observed in animals. It is becoming increasingly clear, however, that further information is needed if risks to humans are to be assessed accurately. Biologically based models help clarify the dose-response relationship and reduce uncertainty.

Comparison of skin decontamination efficacy of commercial decontamination products following exposure to VX on human skin.

PubMed

Thors, L; Koch, M; Wigenstam, E; Koch, B; Hägglund, L; Bucht, A

2017-08-01

The decontamination efficacy of four commercially available skin decontamination products following exposure to the nerve agent VX was evaluated in vitro utilizing a diffusion cell and dermatomed human skin. The products included were Reactive Skin Decontamination Lotion (RSDL), the Swedish decontamination powder 104 (PS104), the absorbent Fuller's Earth and the aqueous solution alldecontMED. In addition, various decontamination procedures were assessed to further investigate important mechanisms involved in the specific products, e.g. decontamination removal from skin, physical removal by sponge swabbing and activation of degradation mechanisms. The efficacy of each decontamination product was evaluated 5 or 30 min after dermal application of VX (neat or diluted to 20% in water). The RSDL-lotion was superior in reducing the penetration of VX through human skin, both when exposed as neat agent and when diluted to 20% in water. Swabbing with the RSDL-sponge during 2 min revealed decreased efficacy compared to applying the RSDL-lotion directly on the skin for 30 min. Decontamination with Fuller's Earth and alldecontMED significantly reduced the penetration of neat concentration of VX through human skin. PS104-powder was insufficient for decontamination of VX at both time-points, independently of the skin contact time of PS104. The PS104-slurry (a mixture of PS104-powder and water), slightly improved the decontamination efficacy. Comparing the time-points for initiated decontamination revealed less penetrated VX for RSDL and Fuller's Earth when decontamination was initiated after 5 min compared to 30 min post-exposure, while alldecontMED displayed similar efficacy at both time-points. Decontamination by washing with water only resulted in a significant reduction of penetrated VX when washing was performed 5 min after exposure, but not when decontamination was delayed to 30 min post-exposure of neat VX. In conclusion, early initiated decontamination with the RSDL-lotion, containing both absorption and degrading properties, allowed to act on skin for 30 min was superior in preventing VX from penetrating human skin. Adding water during decontamination resulted in increased penetration of neat VX, however, water in the decontaminant removal process did not influence the decontamination efficacy. From our study on commercially available decontaminants, it is recommended that future product developments should include both strong absorbents and efficient nerve agent degrading components. Copyright © 2017 Elsevier B.V. All rights reserved.

The Air Pollution Exposure Laboratory (APEL) for controlled human exposure to diesel exhaust and other inhalants: characterization and comparison to existing facilities.

PubMed

Birger, Nicholas; Gould, Timothy; Stewart, James; Miller, Mark R; Larson, Timothy; Carlsten, Chris

2011-03-01

The Air Pollution Exposure Laboratory (APEL) was designed for the controlled inhalation of human subjects to aged and diluted diesel exhaust (DE) to mimic "real-world" occupational and environmental conditions. An EPA Tier 3-compliant, 6.0 kW diesel generator is operated under discrete cyclic loads to simulate diesel on-road emissions. The engine accepts standard ultra-low sulfur diesel or a variety of alternative fuels (such as biodiesel) via a partitioned tank. A portion of raw exhaust is drawn into the primary dilution system and is diluted 9:1 with compressed air at standard temperature (20°C) and humidity (40%) levels. The exhaust is further diluted approximately 25:1 by high efficiency particulate air (HEPA)-filtered air (FA) and then aged for 4 min before entering the 4 × 6 × 7-foot exposure booth. An optional HEPA filter path immediately proximal to the booth can generate a particle-reduced (gas-enriched) exposure. In-booth particulate is read by a nephelometer to provide an instantaneous light scattering coefficient for closed-loop system control. A Scanning Mobility Particle Sizer and multi-stage impactor measures particle size distribution. Filter sampling allows determination of sessional average concentrations of size-fractionated and unfractionated particulate oxidative potential, elemental carbon, organic carbon and trace elements. Approximately 300 μg/m(3) PM(2.5) is routinely achievable at APEL and is well characterized in terms of oxidative potential and elemental components. APEL efficiently creates fresh DE, appropriately aged and diluted for human experimentation at safe yet realistic concentrations. Description of exposure characteristics allows comparison to other international efforts to deepen the current evidence base regarding the health effects of DE.

Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

PubMed Central

Crowley, Stephanie J.; Eastman, Charmane I.

2015-01-01

OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

DNA methylation and copy number variation analyses of human embryonic stem cell-derived neuroprogenitors after low-dose decabromodiphenyl ether and/or bisphenol A exposure.

PubMed

Du, L; Sun, W; Li, X M; Li, X Y; Liu, W; Chen, D

2018-05-01

The polybrominated diphenyl ether flame retardants decabromodiphenyl ether (BDE-209) and bisphenol A (BPA) are environmental contaminants that can cross the placenta and exert toxicity in the developing fetal nervous system. Copy number variants (CNVs) play a role in a number of genetic disorders and may be implicated in BDE-209/BPA teratogenicity. In this study, we found that BDE-209 and/or BPA exposure decreased neural differentiation efficiency of human embryonic stem cells (hESCs), although there was a >90% induction of neuronal progenitor cells (NPCs) from exposed hESCs. However, the mean of CNV numbers in the NPCs with BDE-209 + BPA treatment was significantly higher compared to the other groups, whereas DNA methylation was lower and DNA methyltransferase(DNMT1 and DNMT3A) expression were significantly decreased in all of the BDE-209 and/or BPA treatment groups compared with the control groups. The number of CNVs in chromosomes 3, 4, 11, 22, and X in NPCs with BDE-209 and/or BPA exposure was higher compared to the control group. In addition, CNVs in chromosomes 7, 8, 14, and 16 were stable in hESCs and hESCs-derived NPCs irrespective of BDE-209/BPA exposure, and CNVs in chromosomes 20 q11.21 and 16 p13.11 might be induced by neural differentiation. Thus, BDE-209/BPA exposure emerges as a potential source of CNVs distinct from neural differentiation by itself. BDE-209 and/or BPA exposure may cause genomic instability in cultured stem cells via reduced activity of DNA methyltransferase, suggesting a new mechanism of human embryonic neurodevelopmental toxicity caused by this class of environmental toxins.

Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

PubMed

Crowley, Stephanie J; Eastman, Charmane I

2015-02-01

Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Lei; Xiao, Yongsheng; Wang, Yinsheng, E-mail: yinsheng.wang@ucr.edu

Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 humanmore » skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA(III) perturbs Nrf2 pathway and selenoprotein synthesis.« less

Reducing sound and light exposure to improve sleep on the adult intensive care unit: An inclusive narrative review.

PubMed

Bion, Victoria; Lowe, Alex Sw; Puthucheary, Zudin; Montgomery, Hugh

2018-05-01

Sleep disturbance is common in intensive care units. It is associated with detrimental psychological impacts and has potential to worsen outcome. Irregular exposure to sound and light may disrupt circadian rhythm and cause frequent arousals from sleep. We sought to review the efficacy of environmental interventions to reduce sound and light exposure with the aim of improving patient sleep on adult intensive care units. We searched both PubMed (1966-30 May 2017) and Embase (1974-30 May 2017) for all relevant human (adult) studies and meta-analyses published in English using search terms ((intensive care OR critical care), AND (sleep OR sleep disorders), AND (light OR noise OR sound)). Bibliographies were explored. Articles were included if reporting change in patient sleep in response to an intervention to reduce disruptive intensive care unit sound /light exposure. Fifteen studies were identified. Nine assessed mechanical interventions, four of which used polysomnography to assess sleep. Five studies looked at environmental measures to facilitate sleep and a further two (one already included as assessing a mechanical intervention) studied the use of sound to promote sleep. Most studies found a positive impact of the intervention on sleep. However, few studies used objective sleep assessments, sample sizes were small, methodologies sometimes imperfect and analysis limited. Data are substantially derived from specialist (neurosurgical, post-operative, cardiothoracic and cardiological) centres. Patients were often at the 'less sick' end of the spectrum in a variety of settings (open ward beds or side rooms). Simple measures to reduce intensive care unit patient sound/light exposure appear effective. However, larger and more inclusive high-quality studies are required in order to identify the measures most effective in different patient groups and any impacts on outcome.

Reducing Pb poisoning in birds and Pb exposure in game meat consumers: the dual benefit of effective Pb shot regulation.

PubMed

Mateo, Rafael; Vallverdú-Coll, Núria; López-Antia, Ana; Taggart, Mark A; Martínez-Haro, Monica; Guitart, Raimon; Ortiz-Santaliestra, Manuel E

2014-02-01

The use of lead (Pb) ammunition in the form of shot pellets has been identified as a Pb exposure risk in wildlife and their human consumers. We explore the hypothesis that Pb shot ban enforcement reduces the risk of avian Pb poisoning as well as Pb exposure in game meat consumers. We assessed compliance with a partial ban on Pb shot commencing in 2003 by examination of 937 waterbirds harvested by hunters between 2007 and 2012 in the Ebro delta (Spain). Prevalence of Pb shot ingestion was determined, as were Pb concentrations in liver and muscle tissue to evaluate the potential for Pb exposure in game meat consumers. Hunted birds with only embedded Pb shot (no steel) declined from 26.9% in 2007-08 to <2% over the following three hunting seasons after ban reinforcement. Pb shot ingestion in mallards decreased from a pre-ban value of 30.2% to 15.5% in the post-ban period. Liver Pb levels were predominantly defined by the presence of ingested shot, whereas muscle levels were defined by the presence of both ingested and embedded shot. Only 2.5% of mallard muscle tissue had Pb levels above European Union regulations for meat (0.1μg/g wet weight) in the 2008-09 season, when Pb shot ingestion prevalence was also at a minimum (5.1%). Effective restrictions in Pb ammunition use have a dual benefit since this reduces Pb exposure for game meat consumers due to embedded ammunition as well as reducing Pb poisoning in waterbirds. Copyright © 2013 Elsevier Ltd. All rights reserved.

Militarization, human rights violations and community responses as determinants of health in southeastern Myanmar: results of a cluster survey.

PubMed

Davis, William W; Mullany, Luke C; Schissler, Matt; Albert, Saw; Beyrer, Chris

2015-01-01

The Myanmar army and ethnic armed groups agreed to a preliminary ceasefire in 2012, but a heavy military presence remains in southeastern Myanmar. Qualitative data suggested this militarization can result in human rights abuses in the absence of armed engagements between the parties, and that rural ethnic civilians use a variety of self-protection strategies to avoid these abuses or reduce their negative impacts. We used data from a household survey to determine prevalence of select self-protection activities and to examine exposure to armed groups, human rights violations and self-protection activities as determinants of health in southeastern Myanmar. Data collected from 463 households via a two-stage cluster survey of conflict-affected areas in eastern Myanmar in January 2012, were analyzed using logistic regression models to identify associations between exposure to state and non-state armed groups, village self-protection, human rights abuses and health outcomes. Close proximity to a military base was associated with human rights abuses (PRR 1.30, 95 % CI: 1.14-1.48), inadequate food production (PRR 1.08, 95 % CI: 1.03-1.13), inability to access health care (PRR 1.29, 95 % CI: 1.04-1.60) and diarrhea (PRR 1.15, 95 % CI: 1.05-1.27. Direct exposure to armed groups was associated with household hunger (PRR1.71, 95 % CI: 1.30-2.23). Among households that reported no human rights abuses, risk of household hunger (PRR 5.64, 95 % CI: 1.88-16.91), inadequate food production (PRR 1.95, 95 % CI: 1.11-3.41) and diarrhea (PRR 2.53, 95 % CI: 1.45-4.42) increased when neighbors' households reported experiencing human rights abuses. Households in villages that reported negotiating with the Myanmar army had lower risk of human rights violations (PRR 0.91, 95 % CI: 0.85-0.98), household hunger (PRR 0.85, 95 % CI: 0.74-0.96), inadequate food production (PRR 0.93, 95 % CI:0.89-0.98) and diarrhea (PRR 0.89, 95 % CI:0.82-0.97). Stratified analysis suggests that self-protection strategies may modify the effect of exposure to armed groups on risk of human rights violations and some health outcomes. Militarization may negatively affect health in southeastern Myanmar, and village self-protection activities may reduce these impacts. As southeastern Myanmar opens to international health and development interventions, implementing agencies should consider militarization as a determinant of health and design interventions that can mediate its effects. Such interventions should take into account existing self-protection strategies, seek to provide support where possible and, at all times, take care not to unintentionally undermine them.

Newborns health in the Danube Region: Environment, biomonitoring, interventions and economic benefits in a large prospective birth cohort study.

PubMed

Andersen, Zorana J; Sram, Radim J; Ščasný, Milan; Gurzau, Eugen S; Fucic, Aleksandra; Gribaldo, Laura; Rossner, Pavel; Rossnerova, Andrea; Kohlová, Markéta Braun; Máca, Vojtěch; Zvěřinová, Iva; Gajdosova, Dagmar; Moshammer, Hanns; Rudnai, Peter; Knudsen, Lisbeth E

2016-03-01

The EU strategy for the Danube Region addresses numerous challenges including environment, health and socioeconomic disparities. Many old environmental burdens and heavily polluted areas in Europe are located in the Danube Region, consisting of 14 countries, with over 100 million people. Estimating the burden of environmental exposures on early-life health is a growing research area in Europe which has major public health implications, but the data from the Danube Region are largely missing. This review presents an inventory of current environmental challenges, related early-life health risks, and knowledge gaps in the Danube Region, based on publicly available databases, registers, and literature, as a rationale and incentive for a new integrated project. The review also proposes the concept for the project aiming to characterize in utero exposures to multiple environmental factors and estimate their effect on early-life health, evaluate economic impact, as well as identify interventions with a potential to harness social norms to reduce emissions, exposures and health risks in the Danube Region. Experts in environmental epidemiology, human biomonitoring and social science in collaboration with clinicians propose to establish a new large multi-center birth cohort of mother-child pairs from Danube countries, measure biomarkers of exposure and health in biological samples at birth, collect centrally measured climate, air and water pollution data, conduct pre- and postnatal surveys on lifestyle, indoor exposures, noise, occupation, socio-economic status, risk-averting behavior, and preferences; and undertake clinical examinations of children at and after birth. Birth cohort will include at least 2000 newborns per site, and a subset of at least 200 mother-child pairs per site for biomonitoring. Novel biomarkers of exposure, susceptibility, and effect will be applied, to gain better mechanistic insight. Effects of multiple environmental exposures on fetal and child growth, respiratory, allergic, immunologic, and neurodevelopmental health outcomes will be estimated. Parent's willingness to pay for reducing health risks in children will be elicited by survey, while values of cost-of-illness will be gathered from literature and national statistics. Effects of risk reducing interventions will be examined. The proposed project would provide novel estimates of the burden of early childhood diseases attributable to environmental exposures and assess health impacts of different intervention scenarios in the Danube Region, in an integrated approach combining human biomonitoring, epidemiological and social science research. Copyright © 2015 Elsevier Ltd. All rights reserved.

RECOVERY OF VASCULAR FUNCTION AFTER EXPOSURE TO A SINGLE BOUT OF SEGMENTAL VIBRATION

PubMed Central

Krajnak, Kristine; Waugh, Stacey; Miller, G. Roger; Johnson, Claud

2015-01-01

Work rotation schedules may be used to reduce the negative effects of vibration on vascular function. This study determined how long it takes vascular function to recover after a single exposure to vibration in rats (125 Hz, acceleration 5g). The responsiveness of rat-tail arteries to the vasoconstricting factor UK14304, an α2C-adrenoreceptor agonist, and the vasodilating factor acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a single bout of vibration. Vasoconstriction induced by UK14304 returned to control levels after 1 d of recovery. However, re-dilation induced by ACh did not return to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged effects on peripheral vascular function, and altered vascular responses to a subsequent exposure. To optimize the positive results of work rotation schedules, it is suggested that studies assessing recovery of vascular function after exposure to a single bout of vibration be performed in humans. PMID:25072825

Single bright light exposure decreases sweet taste threshold in healthy volunteers.

PubMed

Srivastava, Shrikant; Donaldson, Lucy F; Rai, Dheeraj; Melichar, Jan K; Potokar, John

2013-10-01

Bright light exposure can alter circulating serotonin levels, and alteration of available serotonin by acute selective serotonin reuptake inhibition significantly lowers sweet but not salt taste recognition thresholds. We tested the hypothesis that bright light exposure would increase sweet but not salt taste sensitivity in healthy adults. Fourteen healthy volunteers were exposed to bright (10,000 lux) and dim (<20 lux) light for 30 min each, in counterbalanced order. Measures of taste perception (salt and sweet) and mood were determined at baseline, and before and after each light exposure period. Recognition thresholds for sucrose were significantly lower after bright but not dim light exposure. Thresholds for salt were unaffected by either condition. There were no significant changes in taste acuity, intensity or pleasantness for both the taste modalities and on visual analogue scales (VASs) for mood, anxiety, sleepiness and alertness, under either light condition. Brief bright light exposure reduces sweet but not salt taste recognition thresholds in healthy humans.

Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Yi; Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, Tucson, AZ 85721; Tao, Shasha

2012-12-15

Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted inmore » pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure. -- Highlights: ► Exposed to arsenic particles and/or SF have elevated Nrf2 and its target genes. ► Sulforaphane prevents pathological alterations, oxidative damage and cell death. ► Sulforaphane alleviates infiltration of inflammatory cells into the lungs. ► Sulforaphane suppresses arsenic-induced proinflammatory cytokine production.« less

Brain morphology in school-aged children with prenatal opioid exposure: A structural MRI study.

PubMed

Sirnes, Eivind; Oltedal, Leif; Bartsch, Hauke; Eide, Geir Egil; Elgen, Irene B; Aukland, Stein Magnus

Both animal and human studies have suggested that prenatal opioid exposure may be detrimental to the developing fetal brain. However, results are somewhat conflicting. Structural brain changes in children with prenatal opioid exposure have been reported in a few studies, and such changes may contribute to neuropsychological impairments observed in exposed children. To investigate the association between prenatal opioid exposure and brain morphology in school-aged children. A cross-sectional magnetic resonance imaging (MRI) study of prenatally opioid-exposed children and matched controls. A hospital-based sample (n=16) of children aged 10-14years with prenatal exposure to opioids and 1:1 sex- and age-matched unexposed controls. Automated brain volume measures obtained from T1-weighted MRI scans using FreeSurfer. Volumes of the basal ganglia, thalamus, and cerebellar white matter were reduced in the opioid-exposed group, whereas there were no statistically significant differences in global brain measures (total brain, cerebral cortex, and cerebral white matter volumes). In line with the limited findings reported in the literature to date, our study showed an association between prenatal opioid exposure and reduced regional brain volumes. Adverse effects of opioids on the developing fetal brain may explain this association. However, further research is needed to explore the causal nature and functional consequences of these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

ANALYSIS OF HUMAN ACTIVITY DATA FOR USE IN MODELING ENVIRONMENTAL EXPOSURES

EPA Science Inventory

Human activity data are a critical part of exposure models being developed by the US EPA's National Exposure Research Laboratory (NERL). An analysis of human activity data within NERL's Consolidated Human Activity Database (CHAD) was performed in two areas relevant to exposure ...

Mitochondrial toxicity in human pregnancy: an update on clinical and experimental approaches in the last 10 years.

PubMed

Morén, Constanza; Hernández, Sandra; Guitart-Mampel, Mariona; Garrabou, Glòria

2014-09-22

Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

Development of a liquid chromatography-multiple reaction monitoring procedure for concurrent verification of exposure to different forms of mustard agents.

PubMed

Yeo, Thong-Hiang; Ho, Mer-Lin; Loke, Weng-Keong

2008-01-01

A novel liquid chromatography-multiple reaction monitoring (LC-MRM) procedure has been developed for retrospective diagnosis of exposure to different forms of mustard agents. This concise method is able to validate prior exposure to nitrogen mustards (HN-1, HN-2, and HN-3) or sulfur mustard (HD) in a single run, which significantly reduces analysis time compared to separate runs to screen for different mustards' biomarkers based on tandem mass spectrometry. Belonging to one of the more toxic classes of chemical warfare agents, these potent vesicants bind covalently to the cysteine-34 residue of human serum albumin. This results in the formation of stable adducts whose identities were confirmed by a de novo sequencing bioinformatics software package. Our developed technique tracks these albumin-derived adduct biomarkers in blood samples which persist in vitro following exposure, enabling a detection limit of 200 nM of HN-1, 100 nM of HN-2, 200 nM of HN-3, or 50 nM of HD in human blood. The CWA-adducts formed in blood samples can be conveniently and sensitively analyzed by this MRM technique to allow rapid and reliable screening.

An evaluation of behavioural endpoints: The pharmaceutical pollutant fluoxetine decreases aggression across multiple contexts in round goby (Neogobius melanostomus).

PubMed

McCallum, Erin S; Bose, Aneesh P H; Warriner, Theresa R; Balshine, Sigal

2017-05-01

Fluoxetine (Prozac™) is designed to alter human behaviour; however, because many physiological pathways are conserved across vertebrates, this drug may affect the behaviour of fish living in fluoxetine-polluted environments. Although a number of studies have used behaviour to document the sub-lethal effects of fluoxetine, the repeatability of these effects across experiments, across behavioural contexts, and over different exposure durations are rarely considered. Here, we conducted two experiments and assessed how fluoxetine exposure affected a range of fitness-related behaviours in wild round goby (Neogobius melanostomus). We found that fluoxetine impacts round goby behaviour at high (40 μg/l) doses, but not at environmentally relevant low doses (1 μg/l). In both experiments, an acute 3-day exposure to fluoxetine reduced round goby aggression in multiple behavioural contexts, but had no detectable effect on overall activity or social affiliative behaviour. While a chronic 28-day exposure to fluoxetine exposure still reduced aggression, this reduction was only detectable in one behavioural context. Our findings demonstrate the importance of repeated behavioural testing (both between and within experiments) and contribute to a growing body of literature evaluating the effects of fluoxetine and other pharmaceuticals on animal behaviour. Copyright © 2017 Elsevier Ltd. All rights reserved.

Space radiation protection: Destination Mars.

PubMed

Durante, Marco

2014-04-01

National space agencies are planning a human mission to Mars in the XXI century. Space radiation is generally acknowledged as a potential showstopper for this mission for two reasons: a) high uncertainty on the risk of radiation-induced morbidity, and b) lack of simple countermeasures to reduce the exposure. The need for radiation exposure mitigation tools in a mission to Mars is supported by the recent measurements of the radiation field on the Mars Science Laboratory. Shielding is the simplest physical countermeasure, but the current materials provide poor reduction of the dose deposited by high-energy cosmic rays. Accelerator-based tests of new materials can be used to assess additional protection in the spacecraft. Active shielding is very promising, but as yet not applicable in practical cases. Several studies are developing technologies based on superconducting magnetic fields in space. Reducing the transit time to Mars is arguably the best solution but novel nuclear thermal-electric propulsion systems also seem to be far from practical realization. It is likely that the first mission to Mars will employ a combination of these options to reduce radiation exposure. Copyright © 2014 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

In vitro toxicity of photodynamic antimicrobial chemotherapy on human keratinocytes proliferation.

PubMed

Migliario, Mario; Rizzi, Manuela; Rocchetti, Vincenzo; Cannas, Mario; Renò, Filippo

2013-02-01

This in vitro experimental study has been designed to assess the effects of photodynamic antimicrobial chemotherapy (PACT) on human keratinocytes proliferation. Human keratinocytes (HaCaT) monolayers (∼0.5 cm(2)) have been irradiated with 635 nm red laser light with a fluence of 82.5 or 112.5 J/cm(2) in the absence or presence of toluidine (TB). Cell proliferation, monolayer area coverage, cytokeratin 5 (K5) and filaggrin (Fil) expression, and metalloproteinase (MMP)-2 and MMP-9 activity were measured after 72 h from laser irradiation. HaCaT proliferation was reduced by TB staining. Cell exposure to both low- and high-fluence laser irradiation in both presence and absence of TB staining reduced their proliferation and monolayer area extension. Moreover both laser treatments were able to reduce K5 and Fil expression and MMP-9 production in keratinocytes not treated with TB. These data indicate that PACT could exert toxic effects on normal proliferating keratinocytes present around parodontal pockets. The observed reduced cell proliferation along with a reduced production of enzymes involved in wound healing could alter the clinical outcome of the patients treated with PACT.

A polyvalent Clade B virus-like particle HIV vaccine combined with partially protective oral preexposure prophylaxis prevents simian-human immunodeficiency virus Infection in macaques and primes for virus-amplified immunity.

PubMed

Ross, Ted M; Pereira, Lara E; Luckay, Amara; McNicholl, Janet M; García-Lerma, J Gerardo; Heneine, Walid; Eugene, Hermancia S; Pierce-Paul, Brooke R; Zhang, Jining; Hendry, R Michael; Smith, James M

2014-11-01

Vaccination and preexposure prophylaxis (PrEP) with antiretrovirals have shown only partial protection from HIV-1 infection in human trials. Oral Truvada (emtricitabine/tenofovir disoproxil fumarate) is FDA approved as PrEP but partial adherence reduces efficacy. If combined as biomedical preventions (CBP), an HIV vaccine could protect when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. The efficacy of combining oral PrEP with an HIV vaccine has not been evaluated in humans. We determined the efficacy of combining a DNA/virus-like particle (VLP) vaccine with partially effective intermittent PrEP in Indian rhesus macaques (RM). Eight RM received intramuscular inoculations of five DNA plasmids encoding four HIV-1 Clade B primary isolate Envs and SIVmac239 Gag (at weeks 0 and 4), followed by intramuscular and intranasal inoculations of homologous Gag VLPs and four Env VLPs (at weeks 12, 16, and 53). At week 61, we initiated weekly rectal exposures with heterologous SHIV162p3 (10 TCID50) along with oral Truvada (TDF, 22 mg/kg; FTC 20 mg/kg) dosing 2 h before and 22 h after each exposure. This PrEP regimen previously demonstrated 50% efficacy. Five controls (no vaccine, no PrEP) received weekly SHIV162p3. All controls were infected after a median of four exposures; the mean peak plasma viral load (VL) was 3.9×10(7) vRNA copies/ml. CBP protected seven of eight (87.5%) RM. The one infected CBP RM had a reduced peak VL of 8.8×10(5) copies/ml. SHIV exposures during PrEP amplified Gag and Env antibody titers in protected RM. These results suggest that combining oral PrEP with HIV vaccines could enhance protection against HIV-1 infection.

Neural defects and cardiac arrhythmia in fish larvae following embryonic exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47).

PubMed

Lema, Sean C; Schultz, Irvin R; Scholz, Nathaniel L; Incardona, John P; Swanson, Penny

2007-05-31

Polybrominated diphenyl ethers (PBDEs) are added to plastics, polyurethane foam, and textiles as a flame retardant. While PBDEs play a key role in reducing loss of human life and property from fires, these flame retardants have become pervasive organic contaminants in the environment and in the tissues of fish, birds, marine mammals, and humans. Levels of PBDEs in wildlife and humans continue to rise, raising concerns about potential ecological and health risks associated with exposure to these chemicals. Nevertheless, there is little currently known about the toxicological effects of PBDE exposure. Here, we examined the developmental toxicity of the PBDE congener 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) using the zebrafish (Danio rerio) as an ontogenetic model. Zebrafish embryos were exposed continuously to dissolved phase PBDE 47 (100-5000 microg/l) beginning 3-5 h post-fertilization (hpf). Fish treated with the highest concentrations of PBDE 47 delayed hatching, had reduced growth post-hatching, and displayed an abnormal dorsal curvature of the body with flexion at the hindbrain. By 96h post-fertilization larvae exposed to PBDE 47 had significant tachycardia, which progressed into atrioventricular block arrhythmias. Microinjection of fluorescent dye into the hindbrain ventricle revealed that cerebrospinal fluid in the neural tube and brain ventricles flowed more slowly in fish larvae exposed to PBDE 47, a likely etiology for the dorsal curvature. Similar, though much less pronounced, developmental toxicity also occurred in larvae exposed to PBDE 47 only for a 20h period during early embryogenesis (3-23 hpf), suggesting that PBDEs incorporated in lipid of the egg are bioavailable and cause toxicity later in life. Taken together, this work indicates that exposure to PBDE 47 can cause morphological abnormalities, impair cardiovascular function and cerebrospinal fluid flow, and provides a tractable starting point for using the zebrafish model to explore molecular mechanisms of PBDE toxicity.

Heat wave exposure in India in current, 1.5 °C, and 2.0 °C worlds

NASA Astrophysics Data System (ADS)

Mishra, Vimal; Mukherjee, Sourav; Kumar, Rohini; Stone, Dáithí A.

2017-12-01

Heatwaves with large impacts have increased in the recent past and will continue to increase under future warming. However, the implication for population exposure to severe heatwaves remains unexplored. Here, we characterize maximum potential human exposure (without passive/active reduction measures) to severe heatwaves in India. We show that if the global mean temperature is limited to 2.0 °C above pre-industrial conditions, the frequency of severe heatwaves will rise by 30 times the current climate by the end-21st century. In contrast, the frequency is projected to be about 2.5 times more (than the low-warming scenario of 2 °C) under conditions expected if the RCP8.5 ‘business-as-usual’ emissions scenario is followed. Under the 2.0 °C low-warming target, population exposure to severe heatwaves is projected to increase by about 15 and 92 times the current level by the mid and end-21st century respectively. Strategies to reduce population growth in India during the 21st century may provide only limited mitigation of heatwave exposure mostly late in the century. Limiting global temperatures to 1.5 °C above preindustrial would reduce the exposure by half relative to RCP8.5 by the mid-21st century. If global temperatures are to exceed 1.5 °C then substantial measures will be required to offset the large increase in exposure to severe heatwaves in India.

Local-Scale Air Quality Modeling in Support of Human Health and Exposure Research (Invited)

NASA Astrophysics Data System (ADS)

Isakov, V.

2010-12-01

Spatially- and temporally-sparse information on air quality is a key concern for air-pollution-related environmental health studies. Monitor networks are sparse in both space and time, are costly to maintain, and are often designed purposely to avoid detecting highly localized sources. Recent studies have shown that more narrowly defining the geographic domain of the study populations and improvements in the measured/estimated ambient concentrations can lead to stronger associations between air pollution and hospital admissions and mortality records. Traditionally, ambient air quality measurements have been used as a primary input to support human health and exposure research. However, there is increasing evidence that the current ambient monitoring network is not capturing sharp gradients in exposure due to the presence of high concentration levels near, for example, major roadways. Many air pollutants exhibit large concentration gradients near large emitters such as major roadways, factories, ports, etc. To overcome these limitations, researchers are now beginning to use air quality models to support air pollution exposure and health studies. There are many advantages to using air quality models over traditional approaches based on existing ambient measurements alone. First, models can provide spatially- and temporally-resolved concentrations as direct input to exposure and health studies and thus better defining the concentration levels for the population in the geographic domain. Air quality models have a long history of use in air pollution regulations, and supported by regulatory agencies and a large user community. Also, models can provide bidirectional linkages between sources of emissions and ambient concentrations, thus allowing exploration of various mitigation strategies to reduce risk to exposure. In order to provide best estimates of air concentrations to support human health and exposure studies, model estimates should consider local-scale features, regional-scale transport, and photochemical transformations. Since these needs are currently not met by a single model, hybrid air quality modeling has recently been developed to combine these capabilities. In this paper, we present the results of two studies where we applied the hybrid modeling approach to provide spatial and temporal details in air quality concentrations to support exposure and health studies: a) an urban-scale air quality accountability study involving near-source exposures to multiple ambient air pollutants, and b) an urban-scale epidemiological study involving human health data based on emergency department visits.

Re-imagining malaria: heterogeneity of human and mosquito behaviour in relation to residual malaria transmission in Cambodia.

PubMed

Gryseels, Charlotte; Durnez, Lies; Gerrets, René; Uk, Sambunny; Suon, Sokha; Set, Srun; Phoeuk, Pisen; Sluydts, Vincent; Heng, Somony; Sochantha, Tho; Coosemans, Marc; Peeters Grietens, Koen

2015-04-24

In certain regions in Southeast Asia, where malaria is reduced to forested regions populated by ethnic minorities dependent on slash-and-burn agriculture, malaria vector populations have developed a propensity to feed early and outdoors, limiting the effectiveness of long-lasting insecticide-treated nets (LLIN) and indoor residual spraying (IRS). The interplay between heterogeneous human, as well as mosquito behaviour, radically challenges malaria control in such residual transmission contexts. This study examines human behavioural patterns in relation to the vector behaviour. The anthropological research used a sequential mixed-methods study design in which quantitative survey research methods were used to complement findings from qualitative ethnographic research. The qualitative research existed of in-depth interviews and participant observation. For the entomological research, indoor and outdoor human landing collections were performed. All research was conducted in selected villages in Ratanakiri province, Cambodia. Variability in human behaviour resulted in variable exposure to outdoor and early biting vectors: (i) indigenous people were found to commute between farms in the forest, where malaria exposure is higher, and village homes; (ii) the indoor/outdoor biting distinction was less clear in forest housing often completely or partly open to the outside; (iii) reported sleeping times varied according to the context of economic activities, impacting on the proportion of infections that could be accounted for by early or nighttime biting; (iv) protection by LLINs may not be as high as self-reported survey data indicate, as observations showed around 40% (non-treated) market net use while (v) unprotected evening resting and deep forest activities impacted further on the suboptimal use of LLINs. The heterogeneity of human behaviour and the variation of vector densities and biting behaviours may lead to a considerable proportion of exposure occurring during times that people are assumed to be protected by the distributed LLINs. Additional efforts in improving LLIN use during times when people are resting in the evening and during the night might still have an impact on further reducing malaria transmission in Cambodia.

Chronic Ketamine Exposure Causes White Matter Microstructural Abnormalities in Adolescent Cynomolgus Monkeys.

PubMed

Li, Qi; Shi, Lin; Lu, Gang; Yu, Hong-Luan; Yeung, Fu-Ki; Wong, Nai-Kei; Sun, Lin; Liu, Kai; Yew, David; Pan, Fang; Wang, De-Feng; Sham, Pak C

2017-01-01

Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control) was administered intravenously for 3 months to male adolescent cynomolgus monkeys ( n = 5/group). Diffusion tensor imaging (DTI) experiments were performed and tract-based spatial statistics (TBSS) was used for data analysis. Fractional anisotropy (FA) was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR), retrolenticular limb of the internal capsule (RLIC) and superior longitudinal fasciculus (SLF), and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.

Pharmacokinetics of [ 14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hummel, Jessica M.; Madeen, Erin P.; Siddens, Lisbeth K.

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is a known human carcinogen. In non-smoking adults greater than 95% of BaP exposure is through diet. The carcinogenicity of BaP is utilized by the U.S. EPA to assess relative potency of complex PAH mixtures. PAH relative potency factors (RPFs, BaP=1) are determined from high dose animal data. Here we employed accelerator mass spectrometry (AMS) to determine pharmacokinetics of [ 14C]-BaP in humans following dosing with 46 ng (an order of magnitude lower than human dietary daily exposure and million-fold lower than animal cancer models). To assess the impact of co-administration of foodmore » with a complex PAH mixture, humans were dosed with 46 ng of [ 14C]-BaP with or without smoked salmon. Subjects were asked to avoid high BaP-containing diets and a 3-day dietary questionnaire given to assess dietary exposure prior to dosing and three days post-dosing with [ 14C]-BaP. Co-administration of smoked salmon, containing a complex mixture of PAHs with an RPF of 460 ng BaP eq, reduced and delayed absorption. Administration of canned commercial salmon, containing very low amounts of PAHs, showed the impacts on pharmacokinetics were not due to high amounts of PAHs but rather a food matrix effect.« less

Pharmacokinetics of [ 14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction

DOE PAGES

Hummel, Jessica M.; Madeen, Erin P.; Siddens, Lisbeth K.; ...

2018-03-01

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is a known human carcinogen. In non-smoking adults greater than 95% of BaP exposure is through diet. The carcinogenicity of BaP is utilized by the U.S. EPA to assess relative potency of complex PAH mixtures. PAH relative potency factors (RPFs, BaP=1) are determined from high dose animal data. Here we employed accelerator mass spectrometry (AMS) to determine pharmacokinetics of [ 14C]-BaP in humans following dosing with 46 ng (an order of magnitude lower than human dietary daily exposure and million-fold lower than animal cancer models). To assess the impact of co-administration of foodmore » with a complex PAH mixture, humans were dosed with 46 ng of [ 14C]-BaP with or without smoked salmon. Subjects were asked to avoid high BaP-containing diets and a 3-day dietary questionnaire given to assess dietary exposure prior to dosing and three days post-dosing with [ 14C]-BaP. Co-administration of smoked salmon, containing a complex mixture of PAHs with an RPF of 460 ng BaP eq, reduced and delayed absorption. Administration of canned commercial salmon, containing very low amounts of PAHs, showed the impacts on pharmacokinetics were not due to high amounts of PAHs but rather a food matrix effect.« less

NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A.

PubMed

Shelby, Michael D

2008-09-01

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http://cerhr.niehs.nih.gov/). See bisphenol A under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs. nih.gov/chemicals/bisphenol/bisphenol.html). The NTP reached the following conclusions on the possible effects of exposure to bisphenol A on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. The NTP has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring. The NTP has negligible concern that exposure to bisphenol A will cause reproductive effects in non-occupationally exposed adults and minimal concern for workers exposed to higher levels in occupational settings. NTP will transmit the NTP-CERHR Monograph on Bisphenol A to federal and state agencies, interested parties, and the public and make it available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD from CERHR.

Human health risk assessment related to contaminated land: state of the art.

PubMed

Swartjes, F A

2015-08-01

Exposure of humans to contaminants from contaminated land may result in many types of health damage ranging from relatively innocent symptoms such as skin eruption or nausea, on up to cancer or even death. Human health protection is generally considered as a major protection target. State-of-the-art possibilities and limitations of human health risk assessment tools are described in this paper. Human health risk assessment includes two different activities, i.e. the exposure assessment and the hazard assessment. The combination of these is called the risk characterization, which results in an appraisal of the contaminated land. Exposure assessment covers a smart combination of calculations, using exposure models, and measurements in contact media and body liquids and tissue (biomonitoring). Regarding the time frame represented by exposure estimates, biomonitoring generally relates to exposure history, measurements in contact media to actual exposures, while exposure calculations enable a focus on exposure in future situations. The hazard assessment, which is different for contaminants with or without a threshold for effects, results in a critical exposure value. Good human health risk assessment practice accounts for tiered approaches and multiple lines of evidence. Specific attention is given here to phenomena such as the time factor in human health risk assessment, suitability for the local situation, background exposure, combined exposure and harmonization of human health risk assessment tools.

A comparison of human exposures to fiberglass with those used in a recent rat chronic inhalation study.

PubMed

Hesterberg, T W; Hart, G A

1994-12-01

In a recent rat inhalation study, 2 years of exposure to high concentrations of fiberglass (FG) resulted in no treatment-related fibrosis or thoracic tumors. To determine the relevancy of this study for human risk assessment, it is important to compare the rat experimental exposure levels with those of humans. Data on human exposures were taken from several studies and included FG manufacturing, installation and removal, and ambient air. FG levels in the rat aerosol were 200,000-fold higher than indoor air, > 2000-fold higher than during FG insulation manufacturing, and > 1000-fold higher than FG batt installation. The rat aerosol was 30-fold more concentrated than the highest human exposure (blowing installation of unbound FG). Rat FG lung burden also vastly exceeded that of FG workers, which was not significantly elevated above nonworker levels. The amount of fibers/mg dry lung for the rat after lifetime exposure was > 4000-fold greater than for the FG worker, average exposure 11 years. Aerosol and lung fiber dimensions in the rat study were comparable to those of human exposures. From these comparisons, it can be concluded that the exposure level in the rat inhalation study was sufficiently, if not excessively, high in comparison to human exposures. Increasing the experimental exposure in the rat studies would not serve to mirror human environmental or occupational exposures.

Emotional response of undergraduates to cadaver dissection.

PubMed

Wisenden, Patricia A; Budke, Katherine J; Klemetson, Chelsea J; Kurtti, Tana R; Patel, Chandi M; Schwantz, Trenda L; Wisenden, Brian D

2018-03-01

The most effective way to learn human anatomy is through cadaver dissection. Historically, cadaver dissection has been the provenance of professional schools. Increasingly, cadaver-based courses in human anatomy are shifting to the undergraduate level, which creates both problems and opportunities because of differences between undergraduate and graduate student populations. Anxiety associated with dissecting cadavers can create a barrier to learning, and ultimately, entry into the health and medical sciences for some demographic subpopulations of undergraduates. We surveyed 76 students in 2007 and 51 students in 2009 at four times in the semester to investigate the timing and sociodemographic predictors of anxiety over cadaver dissection. We followed this with a second survey of 44 students in 2014 to test the effect of humanization of cadaver donors (providing information about donor occupation and cause of death) to reduce student anxiety. Students experienced anxiety upon first exposure to cadaver dissection. Female students experienced greater anxiety than male students upon first exposure to cadavers but this effect was short-lived. Self-identified non-white, non-Christian students experienced sustained anxiety throughout the semester, likely because cadaver stress compounded social and financial stressors unique to international students. Humanization was effective in reducing anxiety in non-white, non-Christian students but had the unexpected effect of increasing anxiety in female students. We recommend that humanizing information be offered to students who seek it out, but not forced upon students for whom the information would only add to their stress. Clin. Anat. 31:224-230, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

ASSESSING CHILDREN'S EXPOSURES TO PESTICIDES: AN IMPORTANT APPLICATION OF THE STOCHASTIC HUMAN EXPOSURE AND DOSE SIMULATION MODEL (SHEDS)

EPA Science Inventory

Accurately quantifying human exposures and doses of various populations to environmental pollutants is critical for the Agency to assess and manage human health risks. For example, the Food Quality Protection Act of 1996 (FQPA) requires EPA to consider aggregate human exposure ...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in humans...

Contact variables for exposure to avian influenza H5N1 virus at the human-animal interface.

PubMed

Rabinowitz, P; Perdue, M; Mumford, E

2010-06-01

Although the highly pathogenic avian influenza H5N1 virus continues to cause infections in both avian and human populations, the specific zoonotic risk factors remain poorly understood. This review summarizes available evidence regarding types of contact associated with transmission of H5N1 virus at the human-animal interface. A systematic search of the published literature revealed five analytical studies and 15 case reports describing avian influenza transmission from animals to humans for further review. Risk factors identified in analytical studies were compared, and World Health Organization-confirmed cases, identified in case reports, were classified according to type of contact reported using a standardized algorithm. Although cases were primarily associated with direct contact with sick/unexpectedly dead birds, some cases reported only indirect contact with birds or contaminated environments or contact with apparently healthy birds. Specific types of contacts or activities leading to exposure could not be determined from data available in the publications reviewed. These results support previous reports that direct contact with sick birds is not the only means of human exposure to avian influenza H5N1 virus. To target public health measures and disease awareness messaging for reducing the risk of zoonotic infection with avian influenza H5N1 virus, the specific types of contacts and activities leading to transmission need to be further understood. The role of environmental virus persistence, shedding of virus by asymptomatic poultry and disease pathophysiology in different avian species relative to human zoonotic risk, as well as specific modes of zoonotic transmission, should be determined.

Monomethylarsonous Acid (MMAIII) Has an Adverse Effect on the Innate Immune Response of Human Bronchial Epithelial Cells to Pseudomonas aeruginosa.

PubMed

Notch, Emily G; Goodale, Britton C; Barnaby, Roxanna; Coutermarsh, Bonita; Berwin, Brent; Taylor, Vivien F; Jackson, Brian P; Stanton, Bruce A

2015-01-01

Arsenic is the number one contaminant of concern with regard to human health according to the World Health Organization. Epidemiological studies on Asian and South American populations have linked arsenic exposure with an increased incidence of lung disease, including pneumonia, and chronic obstructive pulmonary disease, both of which are associated with bacterial infection. However, little is known about the effects of low dose arsenic exposure, or the contributions of organic arsenic to the innate immune response to bacterial infection. This study examined the effects on Pseudomonas aeruginosa (P. aeruginosa) induced cytokine secretion by human bronchial epithelial cells (HBEC) by inorganic sodium arsenite (iAsIII) and two major metabolites, monomethylarsonous acid (MMAIII) and dimethylarsenic acid (DMAV), at concentrations relevant to the U.S. Neither iAsIII nor DMAV altered P. aeruginosa induced cytokine secretion. By contrast, MMAIII increased P. aeruginosa induced secretion of IL-8, IL-6 and CXCL2. A combination of iAsIII, MMAIII and DMAV (10 pbb total) reduced IL-8 and CXCL1 secretion. These data demonstrate for the first time that exposure to MMAIII alone, and a combination of iAsIII, MMAIII and DMAV at levels relevant to the U.S. may have negative effects on the innate immune response of human bronchial epithelial cells to P. aeruginosa.

Short and prolonged exposure to hyperglycaemia in human fibroblasts and endothelial cells: metabolic and osmotic effects.

PubMed

Moruzzi, Noah; Del Sole, Marianna; Fato, Romana; Gerdes, Jantje M; Berggren, Per-Olof; Bergamini, Christian; Brismar, Kerstin

2014-08-01

High blood glucose levels are the main feature of diabetes. However, the underlying mechanism linking high glucose concentration to diabetic complications is still not fully elucidated, particularly with regard to human physiology. Excess of glucose is likely to trigger a metabolic response depending on the cell features, activating deleterious pathways involved in the complications of diabetes. In this study, we aim to elucidate how acute and prolonged hyperglycaemia alters the biology and metabolism in human fibroblasts and endothelial cells. We found that hyperglycaemia triggers a metabolic switch from oxidative phosphorylation to glycolysis that is maintained over prolonged time. Moreover, osmotic pressure is a major factor in the early metabolic response, decreasing both mitochondrial transmembrane potential and cellular proliferation. After prolonged exposure to hyperglycaemia we observed decreased mitochondrial steady-state and uncoupled respiration, together with a reduced ATP/ADP ratio. At the same time, we could not detect major changes in mitochondrial transmembrane potential and reactive oxygen species. We suggest that the physiological and metabolic alterations observed in healthy human primary fibroblasts and endothelial cells are an adaptive response to hyperglycaemia. The severity of metabolic and bioenergetics impairment associated with diabetic complications may occur after longer glucose exposure or due to interactions with cell types more sensitive to hyperglycaemia. Copyright © 2014 Elsevier Ltd. All rights reserved.

First report of the concentrations and implications of DDT residues in chicken eggs from a malaria-controlled area.

PubMed

Bouwman, Hindrik; Bornman, Riana; van Dyk, Cobus; Barnhoorn, Irene

2015-10-01

In malaria-endemic areas, where DDT is still used for vector control by indoor residual spraying (IRS), the concentrations of DDT in human blood and breast milk are high, and there are indications of human health impacts. To identify the possible avenues of exposure reduction, we created the concept of a Total Homestead Environment Approach (THEA). THEA characterizes the interactions between DDT, humans, and the biota within and around homesteads. One dietary route of human exposure and uptake of DDT, namely, chicken egg consumption, has to our knowledge never been studied. The ΣDDT in eggs from a DDT-sprayed village ranged between 5200 and 48,000 ng/g wm (wet mass), with a median of 11,000 ng/g wm. On a lipid mass-basis (lm), the mean ΣDDT for eggs from the sprayed village was 100,000 ng/g lm. The maximum egg concentration observed was three orders of magnitude higher than the median. The acceptable daily intake (ADI) was not exceeded based on the consumption of three eggs per week for a 60 kg person. This equates to an intake of 0.089 g DDT per person per year. Chicken egg consumption is therefore a possible target for exposure reduction, probably best achieved by reducing the DDT concentrations in soils. Copyright © 2015 Elsevier Ltd. All rights reserved.

A retrospective review of notified human leptospirosis cases in the Waikato region of New Zealand, 2004 to 2010.

PubMed

Cowie, George; Bell, Anita

2012-07-29

To retrospectively review notified human leptospirosis cases in the Waikato region of New Zealand between 2004 and 2010 and to identify risk factors for human leptospirosis infection. Waikato leptospirosis notification data for the period 1 January 2004 to 31 December 2010 were analysed to identify any trends in the rates and distribution of key variables. Annual Waikato leptospirosis notification rates were consistently higher than national rates. Infection was associated with males (93%) of working age (97%) who had exposure to animals through their occupation. Most cases were employed in dry stock farming, dairy farming or in the meat processing industry. Those who work with cattle continue to be at risk of infection from Leptospira. The data suggests that dry stock cattle farmers are at the highest risk. It is speculated that the immunisation of all cattle herds may further reduce the incidence of leptospirosis, although more accurate collection of work exposure data and further analysis is needed to determine this.

Timing of galectin-1 exposure differentially modulates Nipah virus entry and syncytium formation in endothelial cells.

PubMed

Garner, Omai B; Yun, Tatyana; Pernet, Olivier; Aguilar, Hector C; Park, Arnold; Bowden, Thomas A; Freiberg, Alexander N; Lee, Benhur; Baum, Linda G

2015-03-01

Nipah virus (NiV) is a deadly emerging enveloped paramyxovirus that primarily targets human endothelial cells. Endothelial cells express the innate immune effector galectin-1 that we have previously shown can bind to specific N-glycans on the NiV envelope fusion glycoprotein (F). NiV-F mediates fusion of infected endothelial cells into syncytia, resulting in endothelial disruption and hemorrhage. Galectin-1 is an endogenous carbohydrate-binding protein that binds to specific glycans on NiV-F to reduce endothelial cell fusion, an effect that may reduce pathophysiologic sequelae of NiV infection. However, galectins play multiple roles in regulating host-pathogen interactions; for example, galectins can promote attachment of HIV to T cells and macrophages and attachment of HSV-1 to keratinocytes but can also inhibit influenza entry into airway epithelial cells. Using live Nipah virus, in the present study, we demonstrate that galectin-1 can enhance NiV attachment to and infection of primary human endothelial cells by bridging glycans on the viral envelope to host cell glycoproteins. In order to exhibit an enhancing effect, galectin-1 must be present during the initial phase of virus attachment; in contrast, addition of galectin-1 postinfection results in reduced production of progeny virus and syncytium formation. Thus, galectin-1 can have dual and opposing effects on NiV infection of human endothelial cells. While various roles for galectin family members in microbial-host interactions have been described, we report opposing effects of the same galectin family member on a specific virus, with the timing of exposure during the viral life cycle determining the outcome. Nipah virus is an emerging pathogen that targets endothelial cells lining blood vessels; the high mortality rate (up to 70%) in Nipah virus infections results from destruction of these cells and resulting catastrophic hemorrhage. Host factors that promote or prevent Nipah virus infection are not well understood. Endogenous human lectins, such as galectin-1, can function as pattern recognition receptors to reduce infection and initiate immune responses; however, lectins can also be exploited by microbes to enhance infection of host cells. We found that galectin-1, which is made by inflamed endothelial cells, can both promote Nipah virus infection of endothelial cells by "bridging" the virus to the cell, as well as reduce production of progeny virus and reduce endothelial cell fusion and damage, depending on timing of galectin-1 exposure. This is the first report of spatiotemporal opposing effects of a host lectin for a virus in one type of host cell. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Health effects from the inhalation of oxidant air pollutants as related to the immune system. Final report. Research report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osebold, J.W.; Zee, Y.C.

1985-07-01

The investigations dealt with links between ozone inhalation and lung diseases. Mice exposed to ozone both continuously and intermittently in four-day cycles showed allergic sensitization to the test antigen (ovalbumin) when compaired to mice maintained in ambeint air. An adjuvant (inactivated Bordetella pertussis cells) administered to mice augmented the immunological response to the test antigen with periodic exposure to ozone. Guinea pigs were tested for allergic sensitization from ozone exposure similar to human asthma, but this trial was not definitive. Ozone inhalation reduced the severity of pneumonia in mice from influenza virus infection, even when ozone and virus exposures weremore » timed to produce maximal edema in the lung.« less

T05 DETERMINATION OF REDUCED ARSENIC-THIO SPECIES IN WATERS BY ION CHROMATOGRAPHY-INDUCTIVELY-COUPLED PLASMA-MASS SSPECTROMETRY (IC-ICP-MS).

EPA Science Inventory

Elevated arsenic concentrations in ground water are a significant concern for human health, because they may lead to increased arsenic exposure via drinking water. As the inorganic arsenic species arsenite (As(III)) and arsenate (As(V)) are known carcinogens, it is desirable to r...

78 FR 19294 - Notice of Availability of the Clear Creek Management Area Proposed Resource Management Plan and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-29

... plan decisions were adopted. For example, the EPA's CCMA Asbestos Exposure and Human Health Risk... to asbestos by reducing airborne emissions of asbestos. For example, the CCMA Proposed RMP designates... asbestos; and use would be limited to highway-licensed vehicles by permit only. Under the Proposed RMP, the...

FIELD ANALYTICAL METHODS: ADVANCED FIELD MONITORING METHODS DEVELOPMENT AND EVALUATION OF NEW AND INNOVATIVE TECHNOLOGIES THAT SUPPORT THE SITE CHARACTERIZATION AND MONITORING REQUIREMENTS OF THE SUPERFUND PROGRAM.

EPA Science Inventory

The overall goal of this task is to help reduce the uncertainties in the assessment of environmental health and human exposure by better characterizing hazardous wastes through cost-effective analytical methods. Research projects are directed towards the applied development and ...

Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men

PubMed Central

Li, De-kun; Yang, Fen; Pan, Hongjie; Li, Tianqi; Miao, Maohua; Li, Runsheng; Yuan, Wei

2017-01-01

Environmental BPA exposure has been shown to impact human sperm concentration and motility, as well as rodent spermatogenesis. However, it is unclear whether BPA exposure is associated with alteration in DNA hydroxymethylation, a marker for epigenetic modification, in human sperm. A genome-wide DNA hydroxymethylation study was performed using sperm samples of men who were occupationally exposed to BPA. Compared with controls who had no occupational BPA exposure, the total levels of 5-hydroxymethylcytosine (5hmc) increased significantly (19.37% increase) in BPA-exposed men, with 72.69% of genome regions harboring 5hmc. A total of 9,610 differential 5hmc regions (DhMRs) were revealed in BPA-exposed men relative to controls, which were mainly located in intergenic and intron regions. These DhMRs were composed of 8,670 hyper-hMRs and 940 hypo-hMRs, affecting 2,008 genes and the repetitive elements. The hyper-hMRs affected genes were enriched in pathways associated with nervous system, development, cardiovascular diseases and signal transduction. Additionally, enrichment of 5hmc was observed in the promoters of eight maternally expressed imprinted genes in BPA-exposed sperm. Some of the BPA-affected genes, for example, MLH1, CHD2, SPATA12 and SPATA20 might participate in the response to DNA damage in germ cells caused by BPA. Our analysis showed that enrichment of 5hmc both in promoters and gene bodies is higher in the genes whose expression has been detected in human sperm than those whose expression is absent. Importantly, we observed that BPA exposure affected the 5hmc level in 11.4% of these genes expressed in sperm, and in 6.85% of the sperm genome. Finally, we also observed that BPA exposure tends to change the 5hmc enrichment in the genes which was previously reported to be distributed with the trimethylated Histone 3 (H3K27me3, H3K4me2 or H3K4me3) in sperm. Thus, these results suggest that BPA exposure likely interferes with gene expression via affecting DNA hydroxymethylation in a way partially dependent on trimethylation of H3 in human spermatogenesis. Our current study reveals a new mechanism by which BPA exposure reduces human sperm quality. PMID:28582417

Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men.

PubMed

Zheng, Huajun; Zhou, Xiaoyu; Li, De-Kun; Yang, Fen; Pan, Hongjie; Li, Tianqi; Miao, Maohua; Li, Runsheng; Yuan, Wei

2017-01-01

Environmental BPA exposure has been shown to impact human sperm concentration and motility, as well as rodent spermatogenesis. However, it is unclear whether BPA exposure is associated with alteration in DNA hydroxymethylation, a marker for epigenetic modification, in human sperm. A genome-wide DNA hydroxymethylation study was performed using sperm samples of men who were occupationally exposed to BPA. Compared with controls who had no occupational BPA exposure, the total levels of 5-hydroxymethylcytosine (5hmc) increased significantly (19.37% increase) in BPA-exposed men, with 72.69% of genome regions harboring 5hmc. A total of 9,610 differential 5hmc regions (DhMRs) were revealed in BPA-exposed men relative to controls, which were mainly located in intergenic and intron regions. These DhMRs were composed of 8,670 hyper-hMRs and 940 hypo-hMRs, affecting 2,008 genes and the repetitive elements. The hyper-hMRs affected genes were enriched in pathways associated with nervous system, development, cardiovascular diseases and signal transduction. Additionally, enrichment of 5hmc was observed in the promoters of eight maternally expressed imprinted genes in BPA-exposed sperm. Some of the BPA-affected genes, for example, MLH1, CHD2, SPATA12 and SPATA20 might participate in the response to DNA damage in germ cells caused by BPA. Our analysis showed that enrichment of 5hmc both in promoters and gene bodies is higher in the genes whose expression has been detected in human sperm than those whose expression is absent. Importantly, we observed that BPA exposure affected the 5hmc level in 11.4% of these genes expressed in sperm, and in 6.85% of the sperm genome. Finally, we also observed that BPA exposure tends to change the 5hmc enrichment in the genes which was previously reported to be distributed with the trimethylated Histone 3 (H3K27me3, H3K4me2 or H3K4me3) in sperm. Thus, these results suggest that BPA exposure likely interferes with gene expression via affecting DNA hydroxymethylation in a way partially dependent on trimethylation of H3 in human spermatogenesis. Our current study reveals a new mechanism by which BPA exposure reduces human sperm quality.

Dispersion and Deposition of Fine Particulates, Heavy Metals and Nitrogen in Urban Landscapes

NASA Astrophysics Data System (ADS)

Whitlow, T. H.; Tong, Z.

2015-12-01

Cities are characterized by networks of heavily trafficked roads, abrupt environmental gradients and local sources of airborne pollutants. Because urban dwellers are inevitably in close proximity to near ground pollution, there has been recent interest in using trees and green roofs to reduce human exposure yet there have been few empirical studies documenting the effect of vegetation and spatial heterogeneity on pollution concentration, human exposure and food safety. In this paper we describe the results of 2 studies in the New York metropolitan area. The first describes the effect of roadside trees on the concentration of fine particulates downwind of a major highway. The second examines vertical attenuation of fine particulates between street level and a rooftop vegetable farm and the deposition of nitrogen and heavy metals to vegetables and soil on the roof.

Physiologically based Pharmacokinetic Modeling of 1,4-Dioxane in Rats, Mice, and Humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sweeney, Lisa M.; Thrall, Karla D.; Poet, Torka S.

2008-01-01

ABSTRACT 1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver and kidney damage at sufficiently high exposure levels. Two physiologically-based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed:partitionmore » coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassays. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.« less

Understanding population and individual risk assessment: the case of polychlorinated biphenyls.

PubMed

Shields, Peter G

2006-05-01

Decisions about how to improve or protect the public health can be, and sometimes necessarily are, made on imprecise science. The regulation of potential human carcinogens in the environment entails a population-risk assessment process intended to reduce risks to less than one additional cancer in 100,000 or 1,000,000 persons. These risk assessment processes, however, may be miscommunicated or misinterpreted in the context of individual cancer risks by scientists, regulators, the lay media, and the public. This commentary will review methods for establishing a causal relationship between carcinogen exposures and cancer risk. It will use the case of polychlorinated biphenyls (PCB) as an example of how to place scientific data into the context of human exposure and cancer risk. PCBs are widespread environmental contaminants and most people have detectable levels of PCBs in their bodies. The primary source for exposure in the general population is through the diet. PCBs are carcinogens in experimental animal models, but how this information can be extrapolated to human risk remains uncertain. PCB experimental studies provide data that are used to regulate and control human exposure, although the epidemiologic evidence fails to establish PCBs as human carcinogens. Thus, what is used for population-risk assessment may not be appropriate for individual-risk assessment or concluding that a causal relationship exists between PCB exposure and cancer risk. The hazards from a carcinogen designated by regulatory and review agencies as a "probable" human carcinogen is often misunderstood out of context about the magnitude of the risk and in what settings. How scientists communicate their results in scientific articles can strongly influence how others interpret their data. Misunderstandings from both the use of regulatory and review-agency opinions and the conclusions espoused by scientists occur in the media, among private physicians counseling their patients about cancer risk, and in the legal settings where plaintiffs seek compensation for exposure and alleged harm (or future harm). This can lead to false conclusions about what caused a cancer in a specific patient, undue anxiety about future cancer risk, inappropriate cancer screening, and attendant increased morbidity due to increased uses of the medical system and complication rates from medical procedures. The communication of research findings by scientists must be presented with caution, resisting the temptation to extrapolate, inappropriately, research data to the general population.

AN OVERVIEW OF HUMAN EXPOSURE MODELING ACTIVITIES AT THE U.S. EPA'S NATIONAL EXPOSURE RESEARCH LABORATORY

EPA Science Inventory

The computational modeling of human exposure to environmental pollutants is one of the primary activities of the US Environmental Protection Agency (USEPA)'s National Exposure Research Laboratory (NERL). Assessment of human exposures is a critical part of the overall risk assessm...

40 CFR 158.1060 - Post-application exposure-criteria for testing

Code of Federal Regulations, 2012 CFR

2012-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1060 Post-application exposure...) Occupational human post-application exposure to pesticide residues on plants or in soil could occur as the...) Residential human post-application exposure to pesticide residues on plants or in soil could occur. Such uses...

40 CFR 158.1060 - Post-application exposure-criteria for testing

Code of Federal Regulations, 2011 CFR

2011-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1060 Post-application exposure...) Occupational human post-application exposure to pesticide residues on plants or in soil could occur as the...) Residential human post-application exposure to pesticide residues on plants or in soil could occur. Such uses...

40 CFR 158.1060 - Post-application exposure-criteria for testing.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1060 Post-application exposure...) Occupational human post-application exposure to pesticide residues on plants or in soil could occur as the...) Residential human post-application exposure to pesticide residues on plants or in soil could occur. Such uses...

40 CFR 158.1060 - Post-application exposure-criteria for testing

Code of Federal Regulations, 2010 CFR

2010-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1060 Post-application exposure...) Occupational human post-application exposure to pesticide residues on plants or in soil could occur as the...) Residential human post-application exposure to pesticide residues on plants or in soil could occur. Such uses...

40 CFR 158.1060 - Post-application exposure-criteria for testing.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1060 Post-application exposure...) Occupational human post-application exposure to pesticide residues on plants or in soil could occur as the...) Residential human post-application exposure to pesticide residues on plants or in soil could occur. Such uses...

Long-Term Evolution Electromagnetic Fields Exposure Modulates the Resting State EEG on Alpha and Beta Bands.

PubMed

Yang, Lei; Chen, Qinghua; Lv, Bin; Wu, Tongning

2017-05-01

Long-term evolution (LTE) wireless telecommunication systems are widely used globally, which has raised a concern that exposure to electromagnetic fields (EMF) emitted from LTE devices can change human neural function. To date, few studies have been conducted on the effect of exposure to LTE EMF. Here, we evaluated the changes in electroencephalogram (EEG) due to LTE EMF exposure. An LTE EMF exposure system with a stable power emission, which was equivalent to the maximum emission from an LTE mobile phone, was used to radiate the subjects. Numerical simulations were conducted to ensure that the specific absorption rate in the subject's head was below the safety limits. Exposure to LTE EMF reduced the spectral power and the interhemispheric coherence in the alpha and beta bands of the frontal and temporal brain regions. No significant change was observed in the spectral power and the inter-hemispheric coherence in different timeslots during and after the exposure. These findings also corroborated those of our previous study using functional magnetic resonant imaging.

Reduction of Coxiella burnetii prevalence by vaccination of goats and sheep, The Netherlands.

PubMed

Hogerwerf, Lenny; van den Brom, René; Roest, Hendrik I J; Bouma, Annemarie; Vellema, Piet; Pieterse, Maarten; Dercksen, Daan; Nielen, Mirjam

2011-03-01

Recently, the number of human Q fever cases in the Netherlands increased dramatically. In response to this increase, dairy goats and dairy sheep were vaccinated against Coxiella burnetii. All pregnant dairy goats and dairy sheep in herds positive for Q fever were culled. We identified the effect of vaccination on bacterial shedding by small ruminants. On the day of culling, samples of uterine fluid, vaginal mucus, and milk were obtained from 957 pregnant animals in 13 herds. Prevalence and bacterial load were reduced in vaccinated animals compared with unvaccinated animals. These effects were most pronounced in animals during their first pregnancy. Results indicate that vaccination may reduce bacterial load in the environment and human exposure to C. burnetii.

Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus).

PubMed

Maréchal, Laëtitia; Levy, Xandria; Meints, Kerstin; Majolo, Bonaventura

2017-01-01

Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion) affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus , affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants' level of experience was defined as either: (1) naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2) exposed: shown pictures of the different Barbary macaques' facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3) expert: worked with Barbary macaques for at least two months. Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques' facial expressions improved the ability of inexperienced participants to better discriminate neutral and distressed faces, and a trend was found for aggressive faces. However, these participants, even when previously exposed to pictures, had difficulties in recognising aggressive, distressed and friendly faces above chance level. These results do not support the universality hypothesis as exposed and naïve participants had difficulties in correctly identifying aggressive, distressed and friendly faces. Exposure to facial expressions improved their correct recognition. In addition, the findings suggest that providing simple exposure to 2D pictures (for example, information signs explaining animals' facial signalling in zoos or animal parks) is not a sufficient educational tool to reduce tourists' misinterpretations of macaque emotion. Additional measures, such as keeping a safe distance between tourists and wild animals, as well as reinforcing learning via videos or supervised visits led by expert guides, could reduce such issues and improve both animal welfare and tourist experience.

Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujimura, Masatake, E-mail: fujimura@nimd.go.jp; Usuki, Fusako; Cheng, Jinping

Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes weremore » not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.« less

Health impacts due to personal exposure to fine particles caused by insulation of residential buildings in Europe

NASA Astrophysics Data System (ADS)

Gens, Alexandra; Hurley, J. Fintan; Tuomisto, Jouni T.; Friedrich, Rainer

2014-02-01

The insulation of residential buildings affects human exposure to fine particles. According to current EU guidelines, insulation is regulated for energy saving reasons. As buildings become tighter, the air exchange rate is reduced and, thus, the indoor concentration of pollutants is increased if there are significant indoor sources. While usually the effects of heat insulation and increase of the air-tightness of buildings on greenhouse gas emissions are highlighted, the negative impacts on human health due to higher indoor concentrations are not addressed. Thus, we investigated these impacts using scenarios in three European countries, i. e. Czech Republic, Switzerland and Greece. The assessment was based on modelling the human exposure to fine particles originating from sources of particles within outdoor and indoor air, including environmental tobacco smoke. Exposure response relationships were derived to link (adverse) health effects to the exposure. Furthermore, probable values for the parameters influencing the infiltration of fine particles into residential buildings were modelled. Results show that the insulation and increase of the air-tightness of residential buildings leads to an overall increase of the mean population exposure - and consequently adverse health effects - in all considered countries (ranging for health effects from 0.4% in Czech Republic to 11.8% in Greece for 100% insulated buildings) due to an accumulation of particles indoors, especially from environmental tobacco smoke. Considering only the emission reductions in outdoor air (omitting changes in infiltration parameters) leads to a decrease of adverse health effects. This study highlights the importance of ensuring a sufficient air exchange rate when insulating buildings, e. g. by prescribing heat ventilation and air conditioning systems in new buildings and information campaigns on good airing practice in renovated buildings. It also shows that assessing policy measures based on the exposure may provide different recommendations compared to an assessment based on only the outdoor air concentration.

Occupational exposures to emissions from combustion of diesel and alternative fuels in underground mining--a simulated pilot study.

PubMed

Lutz, Eric A; Reed, Rustin J; Lee, Vivien S T; Burgess, Jefferey L

2015-01-01

Diesel fuel is commonly used for underground mining equipment, yet diesel engine exhaust is a known human carcinogen. Alternative fuels, including biodiesel, and a natural gas/diesel blend, offer the potential to reduce engine emissions and associated health effects. For this pilot study, exposure monitoring was performed in an underground mine during operation of a load-haul-dump vehicle. Use of low-sulfur diesel, 75% biodiesel/25% diesel blend (B75), and natural gas/diesel blend (GD) fuels were compared. Personal samples were collected for total and respirable diesel particulate matter (tDPM and rDPM, respectively) and total and respirable elemental and organic carbon (tEC, rEC, tOC, rOC, respectively), as well as carbon monoxide (CO), formaldehyde, acetaldehyde, naphthalene, nitric oxide (NO), and nitrogen dioxide (NO2). Compared to diesel, B75 use was associated with a 33% reduction in rDPM, reductions in rEC, tEC, and naphthalene, increased tDPM, tOC, and NO, and no change in rOC, CO, and NO2. Compared to diesel, GD was associated with a 66% reduction in rDPM and a reduction in all other exposures except CO. The alternative fuels tested both resulted in reduced rDPM, which is the basis for the current Mine Safety and Health Administration (MSHA) occupational exposure standard. Although additional study is needed with a wider variety of equipment, use of alternative fuels have the promise of reducing exposures from vehicular exhaust in underground mining settings.

The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

PubMed

Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

2015-01-01

There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.

Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (Ecstasy) users: preliminary results.

PubMed

Reneman, Liesbeth; Majoie, Charles B L M; Flick, Herman; den Heeten, Gerard J

2002-02-01

The perceived safety of the recreational drug methylenedioxymethamphetamine (MDMA), or Ecstasy, conflicts with animal evidence indicating that MDMA damages cortical serotonin (5-HT) neurons at doses similar to those used by humans. Few data are available about the effects of MDMA on the human brain. This study was designed to evaluate MDMA-related alterations in metabolite ratios with single-voxel proton ((1)H) MR spectroscopy. Fifteen male MDMA users (mean lifetime exposure, 723 tablets; mean time since last tablet, 12.0 weeks) and 12 age-matched control subjects underwent single-voxel (1)H MR spectroscopy. N-Acetylaspartate (NAA)/creatine (Cr), NAA/Choline (Cho), and myoinositol (MI)/Cr ratios were measured in midfrontal gray matter, midoccipital gray matter, and right parietal white matter. Data were analyzed with linear model-based multivariate analysis of variance. NAA/Cr (P =.04) and NAA/Cho (P =.03) ratios, markers associated with neuronal loss or dysfunction, were reduced in the frontal cortex of MDMA users. Neither NAA/Cr (P =.72) nor NAA/Cho (P =.12) ratios were different between both groups in occipital gray matter and parietal white matter (P =.18). Extent of previous MDMA use and frontal cortical NAA/Cr (rho = -.50, P =.012) or NAA/Cho (rho = -.550, P <.01) ratios were significantly associated. Reduced NAA/Cr and NAA/Cho ratios at (1)H MR spectroscopy provide evidence for neuronal abnormality in the frontal cortex of MDMA users; these are correlated with the degree of MDMA exposure. These data suggest that MDMA may be a neurotoxin in humans, as it is in animals.

Effects of varenicline on alcohol cue reactivity in heavy drinkers.

PubMed

Roberts, Walter; Harrison, Emily L R; McKee, Sherry A

2017-09-01

Clinical trials and human laboratory studies have established that varenicline can reduce rates of alcohol use among heavy drinkers. Less is known about the mechanisms by which varenicline has this effect on drinking behavior. Reactivity to alcohol cues is often cited as the primary cause of relapse among those being treated for alcohol use disorder, and several front-line treatments for alcohol use disorder work, at least in part, by minimizing cue-induced alcohol craving. The current double-blind, placebo-controlled human laboratory study tested the effects of varenicline on alcohol cue reactivity in a group of heavy-drinking adult smokers and nonsmokers. As part of a larger series of sequential human laboratory experiments testing the effects of varenicline on drinking outcomes, participants were assigned (between-participant) to receive either active varenicline (2 mg/day) or placebo. Following a titration period, participants (n = 77) attended a laboratory session during which they were exposed to alcohol and neutral cues using a standard cue reactivity paradigm. Alcohol cue exposure increased craving for alcohol in both medication groups. However, participants receiving varenicline showed a smaller increase in alcohol craving compared to participants receiving placebo. The medication effect did not differ between smokers and nonsmokers. Among smokers, alcohol cue exposure also increased tobacco craving. Varenicline did not attenuate this effect. Results support the use of varenicline for reducing alcohol use in heavy drinkers and identify a potential mechanism by which varenicline reduces drinking. Varenicline continues to show promise as a pharmacological treatment for alcohol use disorder.

The Human Exposure Model (HEM): A Tool to Support Rapid Assessment of Human Health Impacts from Near-Field Consumer Product Exposures

EPA Science Inventory

The US EPA is developing an open and publically available software program called the Human Exposure Model (HEM) to provide near-field exposure information for Life Cycle Impact Assessments (LCIAs). Historically, LCIAs have often omitted impacts from near-field sources of exposur...

Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis.

PubMed

Lewis, Anthony J; Zhang, Xianghong; Griepentrog, John E; Yuan, Du; Collage, Richard D; Waltz, Paul K; Angus, Derek C; Zuckerbraun, Brian S; Rosengart, Matthew R

2018-05-04

The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis. To further translational relevance, we performed a pilot clinical trial of blue light therapy in human subjects with appendicitis. Laboratory animal research, pilot human feasibility trial. University basic science laboratory and tertiary care hospital. Male C57BL/6J mice, adult (> 17 yr) patients with acute appendicitis. Mice underwent cecal ligation and puncture and were randomly assigned to a 24-hour photoperiod of bright blue, bright red, or ambient white fluorescent light. Subjects with appendicitis were randomized to receive postoperatively standard care or standard care plus high-illuminance blue light. Exposure to bright blue light enhanced bacterial clearance from the peritoneum, reduced bacteremia and systemic inflammation, and attenuated the degree of acute kidney injury. The mechanism involved an elevation in cholinergic tone that augmented tissue expression of the nuclear orphan receptor REV-ERBα and occurred independent of alterations in melatonin or corticosterone concentrations. Clinically, exposure to blue light after appendectomy was feasible and reduced serum interleukin-6 and interleukin-10 concentrations. Modifying the spectrum of light may offer therapeutic utility in sepsis.

Radio frequency electromagnetic field exposure in humans: Estimation of SAR distribution in the brain, effects on sleep and heart rate.

PubMed

Huber, Reto; Schuderer, Jürgen; Graf, Thomas; Jütz, Kathrin; Borbély, Alexander A; Kuster, Niels; Achermann, Peter

2003-05-01

In two previous studies we demonstrated that radiofrequency electromagnetic fields (RF EMF) similar to those emitted by digital radiotelephone handsets affect brain physiology of healthy young subjects exposed to RF EMF (900 MHz; spatial peak specific absorption rate [SAR] 1 W/kg) either during sleep or during the waking period preceding sleep. In the first experiment, subjects were exposed intermittently during an 8 h nighttime sleep episode and in the second experiment, unilaterally for 30 min prior to a 3 h daytime sleep episode. Here we report an extended analysis of the two studies as well as the detailed dosimetry of the brain areas, including the assessment of the exposure variability and uncertainties. The latter enabled a more in depth analysis and discussion of the findings. Compared to the control condition with sham exposure, spectral power of the non-rapid eye movement sleep electroencephalogram (EEG) was initially increased in the 9-14 Hz range in both experiments. No topographical differences with respect to the effect of RF EMF exposure were observed in the two experiments. Even unilateral exposure during waking induced a similar effect in both hemispheres. Exposure during sleep reduced waking after sleep onset and affected heart rate variability. Exposure prior to sleep reduced heart rate during waking and stage 1 sleep. The lack of asymmetries in the effects on sleep EEG, independent of bi- or unilateral exposure of the cortex, may indicate involvement of subcortical bilateral projections to the cortex in the generation of brain function changes, especially since the exposure of the thalamus was similar in both experiments (approx. 0.1 W/kg). Copyright 2003 Wiley-Liss, Inc.

[CALCULATION OF RADIATION LOADS ON THE ANTHROPOMORPHIC PHANTOM ONBOARD THE SPACE STATION IN THE CASE OF ADDITIONAL SHIELDING].

PubMed

Kartashov, D A; Shurshakov, V A

2015-01-01

The paper presents the results of calculating doses from space ionizing radiation for a modeled orbital station cabin outfitted with an additional shield aimed to reduce radiation loads on cosmonaut. The shield is a layer with the mass thickness of -6 g/cm2 (mean density = 0.62 g/cm3) that covers the outer cabin wall and consists of wet tissues and towels used by cosmonauts for hygienic purposes. A tissue-equivalent anthropomorphic phantom imitates human body. Doses were calculated for the standard orbit of the International space station (ISS) with consideration of the longitudinal and transverse phantom orientation relative to the wall with or without the additional shield. Calculation of dose distribution in the human body improves prediction of radiation loads. The additional shield reduces radiation exposure of human critical organs by -20% depending on their depth and body spatial orientation in the ISS compartment.

OVERVIEW OF THE U.S. EPA NERL'S HUMAN EXPOSURE MODELING

EPA Science Inventory

Computational modeling of human exposure to environmental pollutants is one of the primary activities of the US Environmental Protection Agency's National Exposure Research Laboratory (NERL). Assessment of human exposures is a critical part of the overall risk assessment para...

Deoxynivalenol: rationale for development and application of a urinary biomarker.

PubMed

Turner, Paul C; Burley, Victoria J; Rothwell, Joseph A; White, Kay L M; Cade, Janet E; Wild, Christopher P

2008-07-01

Mycotoxins are common dietary contaminants in most regions of the world. The frequency of exposure to the various families of mycotoxins is often dependent on geographic location, national wealth and related agricultural and regulatory infrastructure, combined with diversity of diet and degree of food sufficiency. Deoxynivalenol (DON) is a Fusarium mycotoxin that frequently contaminates wheat, corn and barley in temperate regions. A number of acute poisoning incidences have been linked to DON-contaminated foods and chronic exposure to lower levels of DON has been predicted in many regions. DON is a potent animal toxin and exposure in humans may cause gastroenteritis, growth faltering and immune toxicity. An ability to conduct accurate exposure assessment at the individual level is required to fully understand the potential health consequences for humans. To date, such exposure biomarkers have been lacking for many important mycotoxins, including DON. To better assess exposure to DON at the individual level, we have developed a robust urinary assay, incorporating immunoaffinity column (IAC) enrichment and LC-MS detection. Further refinement of this urinary assay, by inclusion of (13)C-DON as an internal standard, was then undertaken and tested within the UK. DON was frequently observed in urine and was significantly associated with cereal intake. A dietary intervention study demonstrated that avoiding wheat in the diet markedly reduced urinary levels of DON. This biomarker requires further validation but our initial data suggest it may provide a useful tool in epidemiological investigations of the potential health consequences of this common environmental toxin.

Bisphenol-A and disparities in birth outcomes: a review and directions for future research

PubMed Central

Ranjit, Nalini; Siefert, Kristine; Padmanabhan, Vasantha

2014-01-01

Racial disparities in pregnancy outcome in the United States are significant, persistent and costly, but the causes are poorly understood. We propose that disproportionate exposure of African-American women to environmental endocrine disrupting compounds (EDCs) may contribute to birth outcome disparities. Marked racial segregation, as well as health behaviors associated with poverty could result in differences in exposure to particular EDCs. One EDC that has aroused concern in recent years is bisphenol-A (BPA), a widely used industrial plasticizer with known estrogenic properties. Published studies indicate that excessive BPA exposure is associated with reduced fetal survival, as well as reductions in maternal weight and fetal body weight. Related findings include adverse effects of BPA exposure on ovarian function, mammary gland development, earlier age of puberty onset, and some metabolic parameters. However, these findings are largely limited to experimental animal studies, and need to be validated in human populations. Our review supports the need to move beyond the currently dominant toxicological approach to examining the effects of BPA exposure, and rely more on observational human studies and epidemiological methods. Many of the risk factors for racial disparities in pregnancy outcome are global or difficult to modify, but exposure to BPA is a potentially malleable risk factor. If BPA contributes to racial disparities in pregnancy outcome, there are important implications for prevention. It is our hope that this review will stimulate further research in this important and neglected area. PMID:19587689

Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention

PubMed Central

2014-01-01

Exposure to environmental mutagens is an important cause of human cancer, and measures to reduce mutagenic and carcinogenic exposures have been highly successful at controlling cancer. Until recently, it has been possible to connect the chemical characteristics of mutagens to actual mutations observed in human tumors only indirectly. Now, next-generation sequencing technology enables us to observe in detail the DNA-sequence-level effects of well-known mutagens, such as ultraviolet radiation and tobacco smoke, as well as endogenous mutagenic processes, such as those involving activated DNA cytidine deaminases (APOBECs). We can also observe the effects of less well-known but potent mutagens, including those recently found to be present in some herbal remedies. Crucially, we can now tease apart the superimposed effects of several mutational exposures and processes and determine which ones occurred during the development of individual tumors. Here, we review advances in detecting these mutation signatures and discuss the implications for surveillance and prevention of cancer. The number of sequenced tumors from diverse cancer types and multiple geographic regions is growing explosively, and the genomes of these tumors will bear the signatures of even more diverse mutagenic exposures. Thus, we envision development of wide-ranging compendia of mutation signatures from tumors and a concerted effort to experimentally elucidate the signatures of a large number of mutagens. This information will be used to link signatures observed in tumors to the exposures responsible for them, which will offer unprecedented opportunities for prevention. PMID:25031618

Environmental health impacts: occurrence, exposure and significance, Lancaster University, UK, 9-10 September 2003.

PubMed

Martin, Francis L; Semple, Kirk T

2004-09-01

Speakers: John Ashby (Syngenta CTL, UK), Peter A. Behnisch (Eurofins GfA, Germany), Paul L. Carmichael (Unilever Colworth, UK), Curtis C.Harris (National Cancer Institute, USA), Kevin C. Jones (Lancaster University, UK), Andreas Kortenkamp (School of Pharmacy, London, UK), Caroline J. Langdon (Reading University, UK), Anthony M. Lynch (GlaxoSmithKline, UK), Francis L. Martin (Lancaster University, UK), Trevor J. McMillan (Lancaster University, UK), David H. Phillips (Institute of Cancer Research, UK), Huw J. Ricketts (University of Cardiff, UK), Michael N. Routledge (University of Leeds, UK), J. Thomas Sanderson (Utrecht University, The Netherlands) and Kirk T. Semple (Lancaster University, UK) The effects of many environmental exposures to either single contaminants or to mixtures still remain to be properly assessed in ecotoxicological and human toxicological settings. Such assessments need to be carried out using relevant biological assays. On a mechanistic basis, future studies need to be able to extrapolate exposure to disease risk. It is envisaged that such an approach would lead to the development of appropriate strategies to either reduce exposures or to initiate preventative measures in susceptible individuals or populations. To mark the opening of a new Institute, the Lancaster Environmental Centre, an environmental health workshop was held over 2 days (9-10 September 2003) at Lancaster University, UK. The fate, behaviour and movement of chemicals in the environment, together with environmental exposures and human health, biomarkers of such exposures, hormone-like compounds and appropriate genetic toxicology methodologies, were discussed.

Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment.

PubMed

Scharton, Dionna; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Kumaki, Yohichi; Van Wettere, Arnaud; Furuta, Yousuke; Gowen, Brian B

2014-04-01

Rift Valley fever is a zoonotic, arthropod-borne disease that affects livestock and humans. The etiologic agent, Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) is primarily transmitted through mosquito bites, but can also be transmitted by exposure to infectious aerosols. There are presently no licensed vaccines or therapeutics to prevent or treat severe RVFV infection in humans. We have previously reported on the activity of favipiravir (T-705) against the MP-12 vaccine strain of RVFV and other bunyaviruses in cell culture. In addition, efficacy has also been documented in mouse and hamster models of infection with the related Punta Toro virus. Here, hamsters challenged with the highly pathogenic ZH501 strain of RVFV were used to evaluate the activity of favipiravir against lethal infection. Subcutaneous RVFV challenge resulted in substantial serum and tissue viral loads and caused severe disease and mortality within 2-3 days of infection. Oral favipiravir (200 mg/kg/day) prevented mortality in 60% or greater of hamsters challenged with RVFV when administered within 1 or 6h post-exposure and reduced RVFV titers in serum and tissues relative to the time of treatment initiation. In contrast, although ribavirin (75 mg/kg/day) was effective at protecting animals from the peracute RVFV disease, most ultimately succumbed from a delayed-onset neurologic disease associated with high RVFV burden observed in the brain in moribund animals. When combined, T-705 and ribavirin treatment started 24 h post-infection significantly improved survival outcome and reduced serum and tissue virus titers compared to monotherapy. Our findings demonstrate significant post-RVFV exposure efficacy with favipiravir against both peracute disease and delayed-onset neuroinvasion, and suggest added benefit when combined with ribavirin. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of Liquid- and Fog-Based Application of Sterilox Hypochlorous Acid Solution for Surface Inactivation of Human Norovirus▿

PubMed Central

Park, Geun Woo; Boston, Deyanna M.; Kase, Julie A.; Sampson, Mark N.; Sobsey, Mark D.

2007-01-01

Noroviruses (NVs) are the most frequent cause of outbreaks of gastroenteritis in common settings, with surface-mediated transfer via contact with fecally contaminated surfaces implicated in exposure. NVs are environmentally stable and persistent and have a low infectious dose. Several disinfectants have been evaluated for efficacy to control viruses on surfaces, but the toxicity and potential damage to treated materials limits their applicability. Sterilox hypochlorous acid (HOCl) solution (HAS) has shown broad-spectrum antimicrobial activity while being suitable for general use. The objectives of this study were to evaluate the efficacy of HAS to reduce NV both in aqueous suspensions and on inanimate carriers. HOCl was further tested as a fog to decontaminate large spaces. HOCl effectiveness was evaluated using nonculturable human NV measured by reverse transcriptase PCR (RT-PCR) and two surrogate viruses, coliphage MS2 and murine NV, that were detected by both infectivity and RT-PCR. Exposing virus-contaminated carriers of ceramic tile (porous) and stainless steel (nonporous) to 20 to 200 ppm of HOCl solution resulted in ≥99.9% (≥3 log10) reductions of both infectivity and RNA titers of tested viruses within 10 min of exposure time. HOCl fogged in a confined space reduced the infectivity and RNA titers of NV, murine NV, and MS2 on these carriers by at least 99.9% (3 log10), regardless of carrier location and orientation. We conclude that HOCl solution as a liquid or fog is likely to be effective in disinfecting common settings to reduce NV exposures and thereby control virus spread via fomites. PMID:17483283

Modulators of mercury risk to wildlife and humans in the context of rapid global change

USGS Publications Warehouse

Eagles-Smith, Collin A.; Silbergeld, Ellen K.; Basu, Niladri; Bustamante, Paco; Diaz-Barriga, Fernando; Hopkins, William A.; Kidd, Karen A.; Nyland, Jennifer F.

2018-01-01

Environmental mercury (Hg) contamination is an urgent global health threat. The complexity of Hg in the environment can hinder accurate determination of ecological and human health risks, particularly within the context of the rapid global changes that are altering many ecological processes, socioeconomic patterns, and other factors like infectious disease incidence, which can affect Hg exposures and health outcomes. However, the success of global Hg-reduction efforts depends on accurate assessments of their effectiveness in reducing health risks. In this paper, we examine the role that key extrinsic and intrinsic drivers play on several aspects of Hg risk to humans and organisms in the environment. We do so within three key domains of ecological and human health risk. First, we examine how extrinsic global change drivers influence pathways of Hg bioaccumulation and biomagnification through food webs. Next, we describe how extrinsic socioeconomic drivers at a global scale, and intrinsic individual-level drivers, influence human Hg exposure. Finally, we address how the adverse health effects of Hg in humans and wildlife are modulated by a range of extrinsic and intrinsic drivers within the context of rapid global change. Incorporating components of these three domains into research and monitoring will facilitate a more holistic understanding of how ecological and societal drivers interact to influence Hg health risks.

Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells

PubMed Central

Browning, Cynthia L.; Qin, Qin; Kelly, Deborah F.; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria

2016-01-01

Abstract Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. PMID:27449664

Influence of gastrointestinal tract on metabolism of bisphenol A as determined by in vitro simulated system.

PubMed

Wang, Yonghua; Rui, Min; Nie, Yang; Lu, Guanghua

2018-05-07

Oral exposure is a major route of human bisphenol A (BPA) exposure. However, influence of gastrointestinal tract on BPA metabolism is unavailable. In this study, in vitro simulator of the human intestinal microbial ecosystem (SHIME) was applied to investigate the changes in bioaccessibility and metabolism of BPA in different parts of gastrointestinal tract (stomach, small intestine and colon). Then the human hepatoma cell line HepG2 was employed to compare toxic effects of BPA itself and effluents of SHIME system on hepatic gene expression profiles. Results showed that level of bioaccessible BPA decreased with the process of gastrointestinal digestion. But the gastrointestinal digestion could not completely degrade BPA. Then, BPA exposure significantly changed microbial community in colons and increased the percentage of microbes shared in ascending, transverse and descending colons. Abundances of BPA-degradable bacteria, such as Microbacterium and Alcaligenes, were up-regulated. Further, SHIME effluents significantly up-regulated expressions of genes related to estrogenic effect and oxidative stress compared to BPA itself, but reduced or had little change on the risk of cell apoptosis and fatty deposits. This study sheds new lights on influence of gastrointestinal digestion on bioaccessibility and toxic effects of BPA. Copyright © 2018 Elsevier B.V. All rights reserved.

Modulation of persistent organic pollutant toxicity through nutritional intervention: emerging opportunities in biomedicine and environmental remediation.

PubMed

Petriello, Michael C; Newsome, Bradley J; Dziubla, Thomas D; Hilt, J Zach; Bhattacharyya, Dibakar; Hennig, Bernhard

2014-09-01

Environmental pollution is increasing worldwide, and there is evidence that exposure to halogenated persistent organic pollutants (POPs) such as polychlorinated biphenyls can contribute to the pathology of inflammatory diseases such as atherosclerosis, diabetes, and cancer. Pollutant removal from contaminated sites and subsequent pollutant degradation are critical for reducing the long-term health risks associated with exposure. However, complete remediation of a toxicant from the environment is very difficult and cost-prohibitive. Furthermore, remediation technologies often result in the generation of secondary toxicants. Considering these circumstances, environmentally-friendly and sustainable remediation technologies and biomedical solutions to reduce vulnerability to environmental chemical insults need to be explored to reduce the overall health risks associated with exposure to environmental pollutants. We propose that positive lifestyle changes such as healthful nutrition and consumption of diets rich in fruits and vegetables or bioactive nutrients with antioxidant and/or anti-inflammatory properties will reduce the body's vulnerability to environmental stressors and thus reduce toxicant-mediated disease pathologies. Interestingly, emerging evidence now implicates the incorporation of bioactive nutrients, such as plant-derived polyphenols, in technologies focused on the capture, sensing and remediation of halogenated POPs. We propose that human nutritional intervention in concert with the use of natural polyphenol sensing and remediation platforms may provide a sensible means to develop primary and long-term prevention strategies of diseases associated with many environmental toxic insults including halogenated POPs. Copyright © 2014 Elsevier B.V. All rights reserved.

Modulation of persistent organic pollutant toxicity through nutritional intervention: emerging opportunities in biomedicine and environmental remediation

PubMed Central

Petriello, Michael C.; Newsome, Bradley J.; Dziubla, Thomas D.; Hilt, J. Zach; Bhattacharyya, Dibakar; Hennig, Bernhard

2014-01-01

Environmental pollution is increasing worldwide, and there is evidence that exposure to halogenated persistent organic pollutants (POPs) such as polychlorinated biphenyls can contribute to the pathology of inflammatory diseases such as atherosclerosis, diabetes, and cancer. Pollutant removal from contaminated sites and subsequent pollutant degradation are critical for reducing the long-term health risks associated with exposure. However, complete remediation of a toxicant from the environment is very difficult and cost-prohibitive. Furthermore, remediation technologies often result in the generation of secondary toxicants. Considering these circumstances, environmentally-friendly and sustainable remediation technologies and biomedical solutions to reduce vulnerability to environmental chemical insults need to be explored to reduce the overall health risks associate with exposure to environmental pollutants. We propose that positive lifestyle changes such as healthful nutrition and consumption of diets rich in fruits and vegetables or bioactive nutrients with antioxidant and/or anti-inflammatory properties will reduce the body’s vulnerability to environmental stressors and thus reduce toxicant-mediated disease pathologies. Interestingly, emerging evidence now implicates the incorporation of bioactive nutrients, such as plant-derived polyphenols, in technologies focused on the capture, sensing and remediation of halogenated POPs. We propose that human nutritional intervention in concert with the use of natural polyphenol sensing and remediation platforms may provide a sensible means to develop primary and long-term prevention strategies of diseases associated with many environmental toxic insults including halogenated POPs. PMID:24530186

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development.

PubMed

Burt, T; Yoshida, K; Lappin, G; Vuong, L; John, C; de Wildt, S N; Sugiyama, Y; Rowland, M

2016-04-01

A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications and design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. All phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.

Understanding Arsenic Dynamics in Agronomic Systems to ...

EPA Pesticide Factsheets

This review is on arsenic in agronomic systems, and covers processes that influence the entry of arsenic into the human food supply. The scope is from sources of arsenic (natural and anthropogenic) in soils, biogeochemical and rhizosphere processes that control arsenic speciation and availability, through to mechanisms of uptake by crop plants and potential mitigation strategies. This review makes a case for taking steps to prevent or limit crop uptake of arsenic, wherever possible, and to work toward a long-term solution to the presence of arsenic in agronomic systems. The past two decades have seen important advances in our understanding of how biogeochemical and physiological processes influence human exposure to soil arsenic, and thus must now prompt an informed reconsideration and unification of regulations to protect the quality of agricultural and residential soils. Consumption of staple foods such as rice, beverages such as apple juice, or vegetables grown in historically arsenic-contaminated soils is now recognized as a tangible route of arsenic exposure that, in many cases, is more significant than exposure from drinking water. Understanding the sources of arsenic to crop plants and the factors that influence them is key to reducing exposure now and preventing exposure in future. In addition to the abundant natural sources of arsenic, there are a large number of industrial and agricultural sources of arsenic to the soil; from mining wastes, coal fly

Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood

PubMed Central

Krstew, Elena V.; Tait, Robert J.; Hulse, Gary K.

2012-01-01

Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero. PMID:23300784

Evaluation of chromium in red blood cells as an indicator of exposure to hexavalent chromium: An in vitro study.

PubMed

Devoy, Jérôme; Géhin, Antoine; Müller, Samuel; Melczer, Mathieu; Remy, Aurélie; Antoine, Guillaume; Sponne, Isabelle

2016-07-25

Chromium(VI) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and whole blood (i.e., including plasma) are indicative of recent exposure, chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure. Before recommending Cr in RBC as a biological indicator of Cr(VI) exposure, in-vitro studies must be undertaken to assess its reliability. The present study examines the relationship between the chromium added to a blood sample and that subsequently found in the RBC. After incubation of total blood with chromium, RBC were isolated, counted and their viability assessed. Direct analysis of chromium in RBC was conducted using Atomic Absorption Spectrometry. Hexavalent, but not trivalent Cr, was seen to accumulate in the RBC and we found a strong correlation between the Cr(VI) concentration added to a blood sample and the amount of Cr in RBC. This relationship appears to be independent of the chemical properties of the human blood samples (e.g., different blood donors or different reducing capacities). Even though in-vivo studies are still needed to integrate our understanding of Cr(VI) toxicokinetics, our findings reinforce the idea that a single determination of the chromium concentration in RBC would enable biomonitoring of critical cases of Cr(VI) exposure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice after Chronic Oral Exposure

PubMed Central

Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Collins, Bradley J.; Travlos, Gregory S.; Witt, Kristine L.; Melnick, Ronald L.; Abdo, Kamal M.; Malarkey, David E.; Hooth, Michelle J.

2009-01-01

Background Hexavalent chromium [Cr(VI)] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI). Objective We characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents. Methods The National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice. Results Cr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice. Conclusions Cr(VI) was carcinogenic after administration in drinking water to male and female rats and mice. PMID:19479012

NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY (NHEXAS): OPPORTUNITIES AND LESSONS LEARNED

EPA Science Inventory

The National Human Exposure Assessment Survey (NHEXAS) in its fullest sense is a conceptual design, which upon implementation, will have long-term implications to exposure research and assessment. The ultimate goal is to document national distribution of human exposure to pote...

AN APPROACH TO METHODS DEVELOPMENT FOR HUMAN EXPOSURE ASSESSMENT STUDIES

EPA Science Inventory

Human exposure assessment studies require methods that are rapid, cost-effective and have a high sample through-put. The development of analytical methods for exposure studies should be based on specific information for individual studies. Human exposure studies suggest that di...

[Indoor dust as a pathway of human exposure to polybrominated diphenyl ethers (PBDEs)].

PubMed

Góralczyk, Katarzyna; Struciński, Paweł; Hernik, Agnieszka; Czaja, Katarzyna; Korcz, Wojciech; Minorczyk, Maria; Ludwicki, Jan K

2012-01-01

The brominated diphenyl ethers (PBDEs) belong to a class of synthetic, additive brominated flame retardants (BFRs). PBDEs are used to reduce the flammability of commercial and household products such as textiles, various plastic polymers, furnishing foam, and electronic equipment. People spend a large percentage of their life-time indoors at home, in offices and cars, etc, providing many opportunities for lengthy exposure to PBDEs from residential settings and commercial products in an indoor environment. In recent time, the foodstuffs, mainly food of animal origin, have been indicated as the main pathway of human exposure to PBDEs. However, many studies have shown that the indoor environment, mainly indoor dust, can be also a significant source of exposure to PBDEs, especially for younger children (toddlers) because of their behavioral patterns, eg. putting fingers, toys, and other items in their mouth. Numerous studies show that the median intakes of PBDEs via dust for adult range from 1.41 to 277 ng x day(-1) is lower than that via food which range from 135 to 333 ng x day-', while the median intake of these compounds via indoor dust for children range from 101 to 404 ng x day(-1) is much higher than via food: 77-190 ng x day(-1). The congener pattern observed in the indoor dust is different to that found in food. The indoor dust is dominated by the congener BDE-209 vs. food where the most dominated congeners are BDE-47 and BDE-99. Human exposure to PBDEs and other brominated flame retardants (BFRs) is widely widespread throughout the world and it depends on a country range of usage, production and legislation concerning these chemicals as well as a citizen's behavior. Generally, human exposure has been found higher in North America than in Europe and Asia. Within European countries the significant highest concentrations in dust have been found in the United Kingdom. It should be noted that many uncertainty factors such as personal habits, dietary preferences, and time spent in various rooms, cars and outdoors could affect the exposure assessment. In some cases the occupational exposure is the most important source of PBDEs for adults, for example air crews, car sale employees and disposal/recycling of electronic waste workers.

Chronic exposure to low environmental concentrations and legal aquaculture doses of antibiotics cause systemic adverse effects in Nile tilapia and provoke differential human health risk.

PubMed

Limbu, Samwel M; Zhou, Li; Sun, Sheng-Xiang; Zhang, Mei-Ling; Du, Zhen-Yu

2018-06-01

Antibiotics used globally to treat human and animal diseases exist ubiquitously in the environment at low doses because of misuse, overdose and poor absorption after ingestion, coupled with their high-water solubility and degradation resistance. However, the systemic chronic effects of exposure to low environmental concentrations of antibiotics (LECAs) and legal aquaculture doses of antibiotics (LADAs) in fish and their human health risk are currently unknown. To investigate the in vivo chronic effects of exposure to LECAs and LADAs using oxytetracycline (OTC) and sulfamethoxazole (SMZ) in Nile tilapia (Oreochromis niloticus) and their human health risk. Twenty O. niloticus weighing 27.73 ± 0.81 g were exposed to water containing LECAs (OTC at 420 ng/L and SMZ at 260 ng/L) and diets supplemented with LADAs (OTC 80 mg/kg/day and SMZ 100 mg/kg/day) for twelve weeks. General physiological functions, metabolic activities, intestinal and hepatic health were systemically evaluated. The possible human health risks of the consumption of the experimental Nile tilapia fillets in adults and children were assessed by using risk quotient. After exposure, we observed retarded growth performance accompanied by reduced nutrients digestibility, feed efficiency, organ indices, and lipid body composition in treated fish. Antibiotics distorted intestinal morphological features subsequently induced microbiota dysbiosis and suppressed intestinal tight junction proteins. Exposure of fish to LECAs and LADAs induced oxidative stress, suppressed innate immunity, stimulated inflammatory and detoxification responses, concomitantly inhibited antioxidant capacity and caused lipid peroxidation in intestine and liver organs. Both LECAs and LADAs enhanced gluconeogenesis, inhibited lipogenesis and fatty acid beta oxidation in intestine and liver organs. The exposure of fish to LECAs and LADAs induced anaerobic glycolytic pathway and affected intestinal fat catabolism in intestine while halted aerobic glycolysis, increased hepatic fat catabolism, and induced DNA damage in liver. The hazard risk quotient in children for fish treated with OTCD was >1 indicating human health risk. Overall, both LECAs and LADAs impair general physiological functions, nutritional metabolism, and compromise fish immune system. Consumption of fish fed with legal OTC provokes health risk in children. Global stringent prohibition policy for use of antibiotics in aquaculture production and strategies to limit their release into the environment are urgently required to protect human health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neuroendocrine mediated effects of electromagnetic-field exposure: Possible role of the pineal gland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, W.B.; Stevens, R.G.; Anderson, L.E.

Reports from recent epidemiological studies have suggested a possible association between extremely low frequently (ELF; including 50- or 60-Hz) electric- and magnetic-field exposure, and increased risk of certain cancers, depression, and miscarriage. ELF field-induced pineal gland dysfunction is a possible etiological factor in these effects. Work in our laboratory and elsewhere has shown that ELF electromagnetic-field exposure can alter the normal circadian rhythm of melatonin synthesis and release in the pineal gland. Consequences of reduced or inappropriately timed melatonin release on the endocrine, neuronal, and immune systems are discussed. Laboratory data linking ELF field exposure to changes in pineal circadianmore » rhythms in both animal and humans are reviewed. The authors suggest that the pineal gland, in addition to being a convenient locus for measuring dyschronogenic effects of ELF field exposure, may play a central role in biological response to these fields via alterations in the melatonin signal.« less

Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products

PubMed Central

England, Lucinda J.; Aagaard, Kjersti; Bloch, Michele; Conway, Kevin; Cosgrove, Kelly; Grana, Rachel; Gould, Thomas J.; Hatsukami, Dorothy; Jensen, Frances; Kandel, Denise; Lanphear, Bruce; Leslie, Frances; Pauly, James R.; Neiderhiser, Jenae; Rubinstein, Mark; Slotkin, Theodore A.; Spindel, Eliot; Stroud, Laura; Wakschlag, Lauren

2018-01-01

While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during adolescence is associated with deficits in working memory, attention, and auditory processing, as well as increased impulsivity and anxiety. Finally, recent animal studies suggest that nicotine has a priming effect that increases addiction liability for other drugs. The evidence that nicotine adversely affects fetal and adolescent development is sufficient to warrant public health measures to protect pregnant women, children, and adolescents from nicotine exposure. PMID:27890689

Impact of stressor exposure on the interplay between commensal microbiota and host inflammation.

PubMed

Galley, Jeffrey D; Bailey, Michael T

2014-01-01

Exposure to stressful stimuli results in the activation of multiple physiological processes aimed at maintaining homeostasis within the body. These physiological processes also have the capacity to influence the composition of microbial communities, and research now indicates that exposure to stressful stimuli leads to gut microbiota dysbiosis. While the relative abundance of many different bacterial types can be altered during stressor exposure, findings in nonhuman primates and laboratory rodents, as well as humans, indicate that bacteria in the genus Lactobacillus are consistently reduced in the gut during stress. The gut microbiota, including the lactobacilli, have many functions that enhance the health of the host. This review presents studies involving germfree and antibiotic treated mice, as well as mice given Lactobacillus spp. to prevent stressor-induced reductions in lactobacilli, to provide evidence that the microbiota contribute to stressor-induced immunomodulation, both in gut mucosa as well as in systemic compartments. This review will also discuss the evidence that commensal gut microbes have bidirectional effects on gastrointestinal physiology during stressor exposure.

Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products.

PubMed

England, Lucinda J; Aagaard, Kjersti; Bloch, Michele; Conway, Kevin; Cosgrove, Kelly; Grana, Rachel; Gould, Thomas J; Hatsukami, Dorothy; Jensen, Frances; Kandel, Denise; Lanphear, Bruce; Leslie, Frances; Pauly, James R; Neiderhiser, Jenae; Rubinstein, Mark; Slotkin, Theodore A; Spindel, Eliot; Stroud, Laura; Wakschlag, Lauren

2017-01-01

While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during adolescence is associated with deficits in working memory, attention, and auditory processing, as well as increased impulsivity and anxiety. Finally, recent animal studies suggest that nicotine has a priming effect that increases addiction liability for other drugs. The evidence that nicotine adversely affects fetal and adolescent development is sufficient to warrant public health measures to protect pregnant women, children, and adolescents from nicotine exposure. Published by Elsevier Ltd.

Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen

PubMed Central

Zhao, Yanli; Harmatz, Jerold S; Epstein, Carol R; Nakagawa, Yukako; Kurosaki, Chie; Nakamura, Tetsuro; Kadota, Takumi; Giesing, Dennis; Court, Michael H; Greenblatt, David J

2015-01-01

Aims The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo. Methods The effect of favipivir on the transformation of acetaminophen to its glucuronide and sulfate metabolites was studied using a pooled human hepatic S9 fraction in vitro. The effect of acute and extended adminstration of favipiravir on the pharmacokinetics of acetaminophen and metabolites was evaluated in human volunteers. Results Favipiravir inhibited the in vitro formation of acetaminophen sulfate, but not acetaminophen glucuronide. In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed. AUC for acetaminophen glucuronide was increased by 23 to 35 % above control by favipiravir, while AUC for acetaminophen sulfate was reduced by about 20 % compared to control. Urinary excretion of acetaminophen sulfate was likewise reduced to 44 to 65 % of control values during favipiravir co-administration, while excretion of acetaminophen glucuronide increased to 17 to 32 % above control. Conclusion Favipiravir inhibits acetaminophen sulfate formation in vitro and in vivo. However the increase in systemic exposure to acetaminophen due to favipiravir co-administration, though statistically significant, is small in magnitude and unlikely to be of clinical importance. PMID:25808818

Research on sleep, circadian rhythms and aging - Applications to manned spaceflight

NASA Technical Reports Server (NTRS)

Czeisler, Charles A.; Chiasera, August J.; Duffy, Jeanne F.

1991-01-01

Disorders of sleep and circadian rhythmicity are characteristic of both advancing age and manned spaceflight. Sleep fragmentation, reduced nocturnal sleep tendency and sleep efficiency, reduced daytime alertness, and increased daytime napping are common to both of these conditions. Recent research on the pathophysiology and treatment of disrupted sleep in older people has led to a better understanding of how the human circadian pacemaker regulates the timing of the daily sleep-wake cycle and how it responds to the periodic changes in the light-dark cycle to which we are ordinarily exposed. These findings have led to new treatments for some of the sleep disorders common to older individuals, using carefully timed exposure to bright light and darkness to manipulate the phase and/or amplitude of the circadian timing system. These insights and treatment approaches have direct applications in the design of countermeasures allowing astronauts to overcome some of the challenges which manned spaceflight poses for the human circadian timing system. We have conducted an operational feasibility study on the use of scheduled exposure to bright light and darkness prior to launch in order to facilitate adaptation of the circadian system of a NASA Space Shuttle crew to the altered sleep-wake schedule required for their mission. The results of this study illustrate how an understanding of the properties of the human circadian timing system and the consequences of circadian disruption can be applied to manned spaceflight.

Research on sleep, circadian rhythms and aging: applications to manned spaceflight.

PubMed

Czeisler, C A; Chiasera, A J; Duffy, J F

1991-01-01

Disorders of sleep and circadian rhythmicity are characteristic of both advancing age and manned spaceflight. Sleep fragmentation, reduced nocturnal sleep tendency and sleep efficiency, reduced daytime alertness, and increased daytime napping are common to both of these conditions. Recent research on the pathophysiology and treatment of disrupted sleep in older people has led to a better understanding of how the human circadian pacemaker regulates the timing of the daily sleep-wake cycle and how it responds to the periodic changes in the light-dark cycle to which we are ordinarily exposed. These findings have led to new treatments for some of the sleep disorders common to older individuals, using carefully timed exposure to bright light and darkness to manipulate the phase and/or amplitude of the circadian timing system. These insights and treatment approaches have direct applications in the design of countermeasures allowing astronauts to overcome some of the challenges which manned spaceflight poses for the human circadian timing system. We have conducted an operational feasibility study on the use of scheduled exposure to bright light and darkness prior to launch in order to facilitate adaptation of the circadian system of a NASA space shuttle crew to the altered sleep-wake schedule required for their mission. The results of this study illustrate how an understanding of the properties of the human circadian timing system and the consequences of circadian disruption can be applied to manned spaceflight.

Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells.

PubMed

Chan, Tze Khee; Tan, W S Daniel; Peh, Hong Yong; Wong, W S Fred

2017-07-01

Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2-related factor 2-dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Involvement of lysosomal dysfunction in silver nanoparticle-induced cellular damage in A549 human lung alveolar epithelial cells.

PubMed

Miyayama, Takamitsu; Matsuoka, Masato

2016-01-01

While silver nanoparticles (AgNPs) are widely used in consumer and medical products, the mechanism by which AgNPs cause pulmonary cytotoxicity is not clear. AgNP agglomerates are found in endo-lysosomal structures within the cytoplasm of treated cells. In this study, the functional role of lysosomes in AgNP-induced cellular damage was examined in A549 human lung alveolar epithelial cells. We evaluated the intracellular distribution of AgNPs, lysosomal pH, cellular viability, Ag dissolution, and metallothionein (MT) mRNA levels in AgNP-exposed A549 cells that were treated with bafilomycin A1, the lysosomal acidification inhibitor. Exposure of A549 cells to citrate-coated AgNPs (20 nm diameter) for 24 h induced cellular damage and cell death at 100 and 200 μg Ag/ml, respectively. Confocal laser microscopic examination of LysoTracker-stained cells showed that AgNPs colocalized with lysosomes and their agglomeration increased in a dose-dependent manner (50-200 μg Ag/ml). In addition, the fluorescence signals of LysoTracker were reduced following exposure to AgNPs, suggesting the elevation of lysosomal pH. Treatment of A549 cells with 200 nM bafilomycin A1 and AgNPs (50 μg Ag/ml) further reduced the fluorescence signals of LysoTracker. AgNP-induced cell death was also increased by bafilomycin A1 treatment. Finally, treatment with bafilomycin A1 suppressed the dissolution of Ag and decreased the mRNA expression levels of MT-I and MT-II following exposure to AgNPs. The perturbation of lysosomal pH by AgNP exposure may play a role in AgNP agglomeration and subsequent cellular damage in A549 cells.

Increment of ambient exposure to fine particles and the reduced human fertility rate in China, 2000-2010.

PubMed

Xue, Tao; Zhu, Tong

2018-06-13

Epidemiological and toxicological studies suggest that exposure to ambient fine particles (PM 2.5 ) can reduce human reproductive capacity. We previously reported, based on spatial epidemiology, that higher levels of PM 2.5 exposure were associated with a lower fertility rate (FR) in China. However, that study was limited by a lack of temporal variation. Using first-difference regression, we linked temporal changes in FR and PM 2.5 with adjustment for ecological covariates across 2806 counties in China during 2000-2010. Next, we performed a sensitivity analysis of the variation in the PM 2.5 -FR association according to (1) geographic region, (2) indicators of the level of development, and (3) PM 2.5 concentrations. Also, we quantified the reduction in the FR attributable to ambient PM 2.5 in China for the first time. The FR decreased by 3.3% (1.2%, 5.3%) for each 10 μg/m 3 increment in PM 2.5 . The association varied significantly among the geographic regions, but not with the level of development. Nonlinearity analysis suggested a linear exposure-response function with an effect threshold of ~8 μg/m 3 . We also found that comparing to the 2000 scenario, increment of PM 2.5 in 2010 might result in a reduction of 2.50 (2.44, 2.60) infants per 1000 women aged 15-44 years per year in China. Our results confirm the statistical association between ambient particles and FR and suggest that poor air quality may contribute to childlessness in China. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of the toxicity of graphene oxide exposure to the eye.

PubMed

Wu, Wei; Yan, Liang; Wu, Qian; Li, Yijian; Li, Qiyou; Chen, Siyu; Yang, Yuli; Gu, Zhanjun; Xu, Haiwei; Yin, Zheng Qin

2016-11-01

Graphene and its derivatives are the new carbon nanomaterials with the prospect for great applications in electronics, energy storage, biosensors and medicine. However, little is known about the toxicity of graphene or its derivatives in the case of occasional or repeated ocular exposure. We performed in vitro and in vivo studies to evaluate the toxicity of graphene oxide (GO) exposure to the eye. Primary human corneal epithelium cells (hCorECs) and human conjunctiva epithelium cells (hConECs) were exposed to GO (12.5-100 μg/mL). Acute GO exposure (2 h) did not induce cytotoxicity to hCorECs. However, short-term GO exposure (24 h) exerted significant cytotoxicity to hCorECs and hConECs with increased intracellular reactive oxygen species (ROS). Glutathione (GSH) reduced the GO-induced cytotoxicity. We further performed acute eye irritation tests in albino rabbits according to the Organization for Economic Cooperation and Development (OECD) guidelines, and the rabbits did not exhibit corneal opacity, conjunctival redness, abnormality of the iris, or chemosis at any time point after the instillation of 100 μg/mL of GO. However, 5-day repeated GO exposure (50 and 100 μg/mL) caused reversible mild corneal opacity, conjunctival redness and corneal epithelium damage to Sprague-Dawley rats, which was also alleviated by GSH. Therefore, our study suggests that GO-induced time- and dose-dependent cytotoxicity to hCorECs and hConECs via oxidative stress. Occasional GO exposure did not cause acute eye irritation; short-term repeated GO exposure generally resulted in reversible damage to the eye via oxidative stress, which may be alleviated by the antioxidant GSH.

Biomarkers of Tobacco Exposure: Summary of an FDA-sponsored Public Workshop

PubMed Central

Chang, Cindy M.; Edwards, Selvin H.; Arab, Aarthi; Del Valle-Pinero, Arseima Y.; Yang, Ling; Hatsukami, Dorothy K.

2016-01-01

Since 2009, the United States (U.S.) Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has had the authority to regulate the manufacturing, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers of exposure pertain to actual human exposure to chemicals arising from tobacco use and could play an important role across a number of FDA regulatory activities, including assessing new and modified risk tobacco products and identifying and evaluating potential product standards. On August 3–4, 2015, FDA/CTP hosted a public workshop focused on biomarkers of exposure with participants from government, industry, academia, and other organizations. The workshop was divided into four sessions focused on: 1) approaches to evaluating and selecting biomarkers; 2) biomarkers of exposure and relationship to disease risk; 3) currently-used biomarkers of exposure and biomarkers in development; and 4) biomarkers of exposure and the assessment of smokeless tobacco and electronic nicotine delivery systems (ENDS). This paper synthesizes the main findings from the workshop and highlights research areas that could further strengthen the science around biomarkers of exposure and help determine their application in tobacco product regulation. PMID:28151705

Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

PubMed

Narasimhan, Prakash Babu; Akabas, Leor; Tariq, Sameha; Huda, Naureen; Bennuru, Sasisekhar; Sabzevari, Helen; Hofmeister, Robert; Nutman, Thomas B; Tolouei Semnani, Roshanak

2018-04-01

A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma) or to live microfilariae (mf) of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β), M2-associated (CCL13, CD206), Mreg-associated (IL-10, TGF-β), and angiogenesis associated (MMP9, VEGF) genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution: focus on China.

PubMed

Loomis, Dana; Huang, Wei; Chen, Guosheng

2014-04-01

The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population.

The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution: focus on China

PubMed Central

Loomis, Dana; Huang, Wei; Chen, Guosheng

2014-01-01

The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population. PMID:24694836

Advancing environmental health surveillance in the US through a national human biomonitoring network.

PubMed

Latshaw, Megan Weil; Degeberg, Ruhiyyih; Patel, Surili Sutaria; Rhodes, Blaine; King, Ewa; Chaudhuri, Sanwat; Nassif, Julianne

2017-03-01

The United States lacks a comprehensive, nationally-coordinated, state-based environmental health surveillance system. This lack of infrastructure leads to: • varying levels of understanding of chemical exposures at the state & local levels • often inefficient public health responses to chemical exposure emergencies (such as those that occurred in the Flint drinking water crisis, the Gold King mine spill, the Elk river spill and the Gulf Coast oil spill) • reduced ability to measure the impact of public health interventions or environmental policies • less efficient use of resources for cleaning up environmental contamination Establishing the National Biomonitoring Network serves as a step toward building a national, state-based environmental health surveillance system. The Network builds upon CDC investments in emergency preparedness and environmental public health tracking, which have created advanced chemical analysis and information sharing capabilities in the state public health systems. The short-term goal of the network is to harmonize approaches to human biomonitoring in the US, thus increasing the comparability of human biomonitoring data across states and communities. The long-term goal is to compile baseline data on exposures at the state level, similar to data found in CDC's National Report on Human Exposure to Environmental Chemicals. Barriers to success for this network include: available resources, effective risk communication strategies, data comparability & sharing, and political will. Anticipated benefits include high quality data on which to base public health and environmental decisions, data with which to assess the success of public health interventions, improved risk assessments for chemicals, and new ways to prioritize environmental health research. Copyright © 2016 Elsevier GmbH. All rights reserved.

Report on carcinogens monograph on 1-bromopropane.

PubMed

2013-09-01

The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in experimental animals to humans.

Reduced Silver Nanoparticle Phytotoxicity in Crambe abyssinica with Enhanced Glutathione Production by Overexpressing Bacterial y-Glutamylcysteine Synthase

Treesearch

Chuanxin Ma; Sudesh Chhikara; Rakesh Minocha; Stephanie Long; Craig Musante; Jason C. White; Baoshan Xing; Om Parkash Dhankher

2015-01-01

Silver nanoparticles (Ag NPs) are widely used in consumer products, and their release has raised serious concerns about the risk of their exposure to the environment and to human health. However, biochemical mechanisms by which plants counteract NP toxicity are largely unknown. We have previously engineered Crambe abyssinica plants expressing the...

Genome-wide association studies identify heavy metal ATPase3 as the primary determinant of natural variation in leaf cadmium in Arabidopsis thaliana

USDA-ARS?s Scientific Manuscript database

Understanding the mechanism of cadmium (Cd) accumulation in plants is important to help reduce its potential toxicity to both plants and humans through dietary and environmental exposure. Here, we report a study to uncover the genetic basis underlying natural variation in Cd accumulation in a world-...

Proceedings: ISEA Bioavailability Symposium, Durham, North Carolina Use of InVitro Bioaccessibility/Relative Bioavailability Estimates for Metals in Regulatory Settings: What is Needed?

EPA Science Inventory

Oral ingestion of soil and dust is a key pathway for human exposures to metal and metalloid contaminants. It is widely recognized that the site-specific bioavailability of metals in soil and dust may be reduced relative to the metal bioavailability in media such as water and food...