APPROACHES TO ECOSYSTEM AND HUMAN EXPOSURE TO MERCURY FOR SENSITIVE POPULATIONS

EPA Science Inventory

Both human and ecosystem exposure studies evaluate exposure of sensitive and vulnerable populations. We will discuss how ecosystem exposure modeling studies completed for input into the US Clean Air Mercury Rule (CAMR) to evaluate the response of aquatic ecosystems to changes in ...

EPIDEMIOLOGIC CONCEPTS FOR INTERPRETING FINDINGS IN STUDIES OF DRINKING WATER EXPOSURES

EPA Science Inventory

To the inexperienced, environmental epidemiology may appear to be an uncomplicated, straightforward approach to studying exposure-disease associations in human populations. The studies can provide useful information about the risks of environmental exposures that human populatio...

National Human Exposure Assessment Survey (NHEXAS) Data Analysis Work Group

EPA Science Inventory

Three field studies were under conducted the National Human Exposure Assessment Survey. These studies measured exposures in three study regions - Arizona, the six EPA Region V States (Ohio, Indiana, Michigan, Illinois, Wisconsin, Minnesota), and Baltimore and four surrounding cou...

PM ACTIVITY PATTERN RESEARCH

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...

Temporal Profile of Gene Expression Alterations in Primary Human Bronchial Epithelial Cells Following In Vivo Exposure to Ozone

EPA Science Inventory

RATIONALE: Ozone (Os) isa ubiquitous air pollutant that has been shown to have a detrimental effect on human health. Controlled exposure studies in humans have demonstrated that acute exposure to 03 results in reversible reduction in lung function immediately post-exposure, incre...

MANAGEMENT AND DISSEMINATION OF HUMAN EXPOSURE DATABASES AND OTHER DATABASES NEEDED FOR HUMAN EXPOSURE MODELING AND ANALYSIS

EPA Science Inventory

Researchers in the National Exposure Research Laboratory (NERL) have performed a number of large human exposure measurement studies during the past decade. It is the goal of the NERL to make the data available to other researchers for analysis in order to further the scientific ...

Ochratoxin A and human health risk: a review of the evidence.

PubMed

Bui-Klimke, Travis R; Wu, Felicia

2015-01-01

Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including Aspergillus ochraceus, A. carbonarius, A. niger, and Penicillium verrucosum. OTA causes nephrotoxicity and renal tumors in a variety of animal species; however, human health effects are less well-characterized. Various studies have linked OTA exposure with the human diseases Balkan endemic nephropathy (BEN) and chronic interstitial nephropathy (CIN), as well as other renal diseases. This study reviews the epidemiological literature on OTA exposure and adverse health effects in different populations worldwide, and assesses the potential human health risks of OTA exposure. Epidemiological studies identified in a systematic review were used to calculate unadjusted odds ratios for OTA associated with various health endpoints. With one exception, there appears to be no statistically significant evidence for human health risks associated with OTA exposure. One Egyptian study showed a significantly higher risk of nephritic syndrome in those with very high urinary OTA levels compared with relatively unexposed individuals; however, other potential risk factors were not controlled for in the study. Larger cohort or case-control studies are needed in the future to better establish potential OTA-related human health effects, and further duplicate-diet studies are needed to validate biomarkers of OTA exposure in humans.

Effects of Ambient Air Pollution Exposure on Olfaction: A Review

PubMed Central

Ajmani, Gaurav S.; Suh, Helen H.; Pinto, Jayant M.

2016-01-01

Background: Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. Objectives: To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. Methods: We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. Results: We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Conclusions: Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution–related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. Citation: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683–1693; http://dx.doi.org/10.1289/EHP136 PMID:27285588

Adapting Concepts from Systems Biology to Develop Systems Exposure Event Networks for Exposure Science Research

EPA Science Inventory

Systems exposure science has emerged from the traditional environmental exposure assessment framework and incorporates new concepts that link sources of human exposure to internal dose and metabolic processes. Because many human environmental studies are designed for retrospectiv...

UV-B-Induced Erythema in Human Skin: The Circadian Clock Is Ticking.

PubMed

Sarkar, Soumyadeep; Gaddameedhi, Shobhan

2018-02-01

Acute exposure of skin to UV-B causes DNA damage and sunburn erythema in both mice and humans. Previous studies documented time-of-day-related differences in sunburn responses after UV-B exposure in mice. Because humans are diurnal and mice are nocturnal, the circadian rhythm in human skin was hypothesized to be in opposite phase to the rhythm in mice. A study by Nikkola et al. demonstrates that humans are more prone to sunburn erythema after evening exposure to solar UV-B radiation as compared with morning exposure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of Neonicotinoid Pesticide Exposure on Human Health: A Systematic Review.

PubMed

Cimino, Andria M; Boyles, Abee L; Thayer, Kristina A; Perry, Melissa J

2017-02-01

Numerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species, including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure. In this systematic review, we sought to identify human population studies on the health effects of neonics. Studies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the National Toxicology Program's Office of Health Assessment and Translation. Eight studies investigating the human health effects of exposure to neonics were identified. Four examined acute exposure: Three neonic poisoning studies reported two fatalities (n = 1,280 cases) and an occupational exposure study of 19 forestry workers reported no adverse effects. Four general population studies reported associations between chronic neonic exposure and adverse developmental or neurological outcomes, including tetralogy of Fallot (AOR 2.4, 95% CI: 1.1, 5.4), anencephaly (AOR 2.9, 95% CI: 1.0, 8.2), autism spectrum disorder [AOR 1.3, 95% credible interval (CrI): 0.78, 2.2], and a symptom cluster including memory loss and finger tremor (OR 14, 95% CI: 3.5, 57). Reported odds ratios were based on exposed compared to unexposed groups. The studies conducted to date were limited in number with suggestive but methodologically weak findings related to chronic exposure. Given the wide-scale use of neonics, more studies are needed to fully understand their effects on human health. Citation: Cimino AM, Boyles AL, Thayer KA, Perry MJ. 2017. Effects of neonicotinoid pesticide exposure on human health: a systematic review. Environ Health Perspect 125:155-162; http://dx.doi.org/10.1289/EHP515.

POPULATION EXPOSURE AND DOSE MODEL FOR AIR TOXICS: A BENZENE CASE STUDY

EPA Science Inventory

The EPA's National Exposure Research Laboratory (NERL) is developing a human exposure and dose model called the Stochastic Human Exposure and Dose Simulation model for Air Toxics (SHEDS-AirToxics) to characterize population exposure to air toxics in support of the National Air ...

HUMAN-ECOSYSTEM INTERACTIONS: THE CASE OF MERCURY

EPA Science Inventory

Human and ecosystem exposure studies evaluate exposure of sensitive and vulnerable populations. We will discuss how ecosystem exposure modeling studies completed for input into the US Clean Air Mercury Rule (CAMR) to evaluate the response of aquatic ecosystems to changes in mercu...

Human - Ecosystem Interactions: The Case of Mercury

EPA Science Inventory

Human and ecosystem exposure studies evaluate exposure of sensitive and vulnerable populations. We will discuss how ecosystem exposure modeling studies completed for input into the US Clean Air Mercury Rule (CAMR) to evaluate the response of aquatic ecosystems to changes in mercu...

USE OF EXHALED BREATH CONDENSATE IN A HUMAN EXPOSURE STUDY

EPA Science Inventory

Exhaled breath condensate (EBC) is a noninvasive, repeatable collection technique to sample biomarkers of lung inflammation, oxidative stress, and environmental exposure. It is unclear whether EBC is an effective tool in human environmental exposure studies with multi-day samplin...

Scientific and Ethical Approaches for Observational Exposure ...

EPA Pesticide Factsheets

Researchers conduct observational human exposure studies to understand how and the extent to which people come into contact with chemicals and environmental stressors in their everyday lives, through the air they breathe, the food and liquids they consume, and the things they touch. The U.S. Environmental Protection Agency’s (EPA’s) National Exposure Research Laboratory (NERL) has conducted observational human exposure studies for several decades and uses the information and data from these studies to improve the Agency’s understanding of human exposures to chemicals and other stressors and ultimately to support efforts to improve public health. Because these studies involve people as research participants, they are complex and raise numerous scientific and ethical issues that have to be addressed prior to and during their design and implementation. To ensure that EPA’s research continues to be based on the most up-to-date science and the highest ethical standards, the Agency has developed this document that contains state-of-the-science approaches for conducting observational human exposure studies. This document is not meant to represent an official Agency “guidance document” but, rather, serves as a resource tool and source of information for NERL and other researchers on which to rely as they develop and conduct observational human exposure studies.

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: a review.

PubMed

Abdallah, Mohamed Abou-Elwafa; Pawar, Gopal; Harrad, Stuart

2015-01-01

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Source attribution of human campylobacteriosis at the point of exposure by combining comparative exposure assessment and subtype comparison based on comparative genomic fingerprinting.

PubMed

Ravel, André; Hurst, Matt; Petrica, Nicoleta; David, Julie; Mutschall, Steven K; Pintar, Katarina; Taboada, Eduardo N; Pollari, Frank

2017-01-01

Human campylobacteriosis is a common zoonosis with a significant burden in many countries. Its prevention is difficult because humans can be exposed to Campylobacter through various exposures: foodborne, waterborne or by contact with animals. This study aimed at attributing campylobacteriosis to sources at the point of exposure. It combined comparative exposure assessment and microbial subtype comparison with subtypes defined by comparative genomic fingerprinting (CGF). It used isolates from clinical cases and from eight potential exposure sources (chicken, cattle and pig manure, retail chicken, beef, pork and turkey meat, and surface water) collected within a single sentinel site of an integrated surveillance system for enteric pathogens in Canada. Overall, 1518 non-human isolates and 250 isolates from domestically-acquired human cases were subtyped and their subtype profiles analyzed for source attribution using two attribution models modified to include exposure. Exposure values were obtained from a concurrent comparative exposure assessment study undertaken in the same area. Based on CGF profiles, attribution was possible for 198 (79%) human cases. Both models provide comparable figures: chicken meat was the most important source (65-69% of attributable cases) whereas exposure to cattle (manure) ranked second (14-19% of attributable cases), the other sources being minor (including beef meat). In comparison with other attributions conducted at the point of production, the study highlights the fact that Campylobacter transmission from cattle to humans is rarely meat borne, calling for a closer look at local transmission from cattle to prevent campylobacteriosis, in addition to increasing safety along the chicken supply chain.

Bisphenol A and human health: a review of the literature.

PubMed

Rochester, Johanna R

2013-12-01

There is growing evidence that bisphenol A (BPA) may adversely affect humans. BPA is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between BPA and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking BPA to human health; 53 published within the last year. This review outlines this body of literature, showing associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental BPA exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental BPA exposure can be harmful to humans, especially in regards to behavioral and other effects in children. Copyright © 2013 Elsevier Inc. All rights reserved.

Human Exposures to PAHs: an Eastern United States Pilot Study

EPA Science Inventory

Personal exposure monitoring for select polycyclic aromatic hydrocarbons (PAHs) was performed as part of the National Human Exposure Assessment Survey (NHEXAS) Pilot Study in Baltimore, MD and in four surrounding counties (NHEXAS-Maryland). An objective of this effort was to esta...

MIXED MODELS ANALYSIS OR URBANIZATION LEVEL ON CHLORPYRIFOS EXPOSURE

EPA Science Inventory

The National Human Exposure Assessment Survey (NHEXAS) pilot studies were conducted from 1995 through 1997 to examine human population exposure to a wide range of environmental contaminants. In one of the studies, NHEXAS-Maryland, a longitudinal design was used to repeatedly m...

Assessing Human Health Risk to Endocrine Disrupting Chemicals: a Focus on Prenatal Exposures and Oxidative Stress

PubMed Central

Neier, Kari; Marchlewicz, Elizabeth H.; Dolinoy, Dana C.; Padmanabhan, Vasantha

2016-01-01

Understanding the health risk posed by endocrine disrupting chemicals (EDCs) is a challenge that is receiving intense attention. The following study criteria should be considered to facilitate risk assessment for exposure to EDCs: 1) characterization of target health outcomes and their mediators, 2) study of exposures in the context of critical periods of development, 3) accurate estimates of human exposures and use of human-relevant exposures in animal studies, and 4) cross-species comparisons. In this commentary, we discuss the importance and relevance of each of these criteria in studying the effects of prenatal exposure to EDCs. Our discussion focuses on oxidative stress as a mediator of EDC-related health effects due to its association with both EDC exposure and health outcomes. Our recent study (Veiga-Lopez et al. 2015)1 addressed each of the four outlined criteria and demonstrated that prenatal bisphenol-A exposure is associated with oxidative stress, a risk factor for developing diabetes and cardiovascular diseases in adulthood. PMID:27231701

OUTDOOR VS. HUMAN EXPOSURE: NERL PM EXPOSURE PANEL STUDIES

EPA Science Inventory

An association has been demonstrated between ambient particulate matter (PM 2.5 and PM 10) concentrations and human morbidity/mortality. However, little is known regarding the most important sources of PM exposure, interpersonal and intrapersonal variability in exposure, and the...

Human exposure in low Earth orbit

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F.

1984-01-01

Human exposure to trapped electrons and protons in low Earth orbit (LEO) is evaluated on a basis of a simple approximation of the human geometry for spherical shell shields of varying thickness. A data base is presented that may be used to make preliminary assessment of the impact of radiation exposure constraints on human performance. Detailed shielding studies should be performed before final design considerations. A sample impact assessment is discussed on the basis of presently accepted allowable exposure limits. A brief discussion is given on the anticipated impact of an ongoing reassessment of allowable exposure limits.

Review of genotoxicity biomonitoring studies of glyphosate-based formulations

PubMed Central

Kier, Larry D.

2015-01-01

Abstract Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs. The environmental and most of the human biomonitoring studies were not informative because there was either a very low frequency of GBF exposure or exposure to a large number of pesticides without analysis of specific pesticide effects. One pesticide sprayer biomonitoring study indicated there was not a statistically significant relationship between frequency of GBF exposure reported for the last spraying season and oxidative DNA damage. There were three studies of human populations in regions of GBF aerial spraying. One study found increases for the cytokinesis-block micronucleus endpoint but these increases did not show statistically significant associations with self-reported spray exposure and were not consistent with application rates. A second study found increases for the blood cell comet endpoint at high exposures causing toxicity. However, a follow-up to this study 2 years after spraying did not indicate chromosomal effects. The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures. PMID:25687244

THE NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY (NHEXAS) STUDY IN ARIZONA-INTRODUCTION AND PRELIMINARY RESULTS

EPA Science Inventory

The objective of the National Human Exposure Assessment Survey (NHEXAS) in Arizona is to determine the multimedia distribution of total human exposure to environmental pollutants in the classes of metals, pesticides, and volatile organic compounds (VOCs) for the population of Ari...

Human environmental and occupational exposures to boric acid: reconciliation with experimental reproductive toxicity data.

PubMed

Bolt, Hermann M; Başaran, Nurşen; Duydu, Yalçın

2012-01-01

The reproductive toxicity of boric acid and borates is a matter of current regulatory concern. Based on experimental studies in rats, no-observed-adverse-effect levels (NOAELs) were found to be 17.5 mg boron (B)/kg body weight (b.w.) for male fertility and 9.6 mg B/kg b.w. for developmental toxicity. Recently, occupational human field studies in highly exposed cohorts were reported from China and Turkey, with both studies showing negative results regarding male reproduction. A comparison of the conditions of these studies with the experimental NOAEL conditions are based on reported B blood levels, which is clearly superior to a scaling according to estimated B exposures. A comparison of estimated daily B exposure levels and measured B blood levels confirms the preference of biomonitoring data for a comparison of human field studies. In general, it appears that high environmental exposures to B are lower than possible high occupational exposures. The comparison reveals no contradiction between human and experimental reproductive toxicity data. It clearly appears that human B exposures, even in the highest exposed cohorts, are too low to reach the blood (and target tissue) concentrations that would be required to exert adverse effects on reproductive functions.

POPULATION-BASED EXPOSURE MEASUREMENTS IN ARIZONA: A PHASE FIELD STUDY IN SUPPORT OF THE NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY

EPA Science Inventory

The objectives of this field study are to determine the distributions of total human exposures to multi-media pollutants in the classes of metals, pesticides, and volatile organic compounds (VOCs) by studying a proportionate-based sample of the total population (with a nested des...

Safety assessment for hair-spray resins: risk assessment based on rodent inhalation studies.

PubMed

Carthew, Philip; Griffiths, Heather; Keech, Stephen; Hartop, Peter

2002-04-01

The methods involved in the safety assessment of resins used in hair-spray products have received little peer review, or debate in the published literature, despite their widespread use, in both hairdressing salons and the home. The safety assessment for these resins currently involves determining the type of lung pathology that can be caused in animal inhalation exposure studies, and establishing the no-observable-effect level (NOEL) for these pathologies. The likely human consumer exposure is determined by techniques that model the simulated exposure under "in use" conditions. From these values it is then possible to derive the likely safety factors for human exposure. An important part of this process would be to recognize the intrinsic differences between rodents and humans in terms of the respiratory doses that each species experiences during inhalation exposures, for the purpose of the safety assessment. Interspecies scaling factors become necessary when comparing the exposure doses experienced by rats, compared to humans, because of basic differences between species in lung clearance rates and the alveolar area in the lungs. The rodent inhalation data and modeled human exposure to Resin 6965, a resin polymer that is based on vinyl acetate, has been used to calculate the safety factor for human consumer exposure to this resin, under a range of "in use" exposure conditions. The use of this safety assessment process clearly demonstrates that Resin 6965 is acceptable for human consumer exposure under the conditions considered in this risk assessment.

Human Health Effects of Biphenyl: Key Findings and Scientific Issues.

PubMed

Li, Zheng; Hogan, Karen A; Cai, Christine; Rieth, Susan

2016-06-01

In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. We review key findings and scientific issues regarding expected human health effects of biphenyl. Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703-712; http://dx.doi.org/10.1289/ehp.1509730.

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.

The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

PubMed

Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

2017-12-01

Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

*Combining regional - and local-scale air quality models with exposure models for use in environmental health studies - Title changed from Linking air quality and exposure models for use in environmental health studies

EPA Science Inventory

Population-based human exposure models predict the distribution of personal exposures to pollutants of outdoor origin using a variety of inputs, including air pollution concentrations; human activity patterns, such as the amount of time spent outdoors versus indoors, commuting, w...

Potential human exposures to neonicotinoid insecticides: A review.

PubMed

Zhang, Q; Li, Z; Chang, C H; Lou, J L; Zhao, M R; Lu, C

2018-05-01

Due to their systemic character and high efficacy to insect controls, neonicotinoid insecticides (neonics) have been widely used in global agriculture since its introduction in early 1990. Recent studies have indicated that neonics may be ubiquitous, have longer biological half-lives in the environment once applied, and therefore implicitly suggested the increasing probability for human exposure to neonics. Despite of neonics' persistent characters and widespread uses, scientific literature in regard of pathways in which human exposure could occur is relatively meager. In this review, we summarized results from peer-reviewed articles published prior to 2017 that address potential human exposures through ingestion and inhalation, as well as results from human biomonitoring studies. In addition, we proposed the use of relative potency factor approach in order to facilitate the assessment of concurrent exposure to a mixture of neonics with similar chemical structures and toxicological endpoints. We believe that the scientific information that we presented in this review will aid to future assessment of total neonic exposure and subsequently human health risk characterization. Copyright © 2018 Elsevier Ltd. All rights reserved.

IMMUNOCHEMISTRY AT THE U.S. EPA, NATIONAL EXPOSURE RESEARCH LABORATORY'S HUMAN EXPOSURE RESEARCH BRANCH

EPA Science Inventory

The HERB has developed several immunoassay methods for environmental and human exposure studies. Immunoassays to detect low levels (<10 ng/mL) chlorpyrifos in food, track-in dirt and house dust have been developed for dietary and indoor exposure surveys. An immunoassay for th...

Biochemical, endocrine, and hematological factors in human oxygen tolerance extension: Predictive studies 6

NASA Technical Reports Server (NTRS)

Lambertsen, C. J.; Clark, J. M.

1992-01-01

The Predictive Studies VI (Biochemical, endocrine, and hematological factors in human oxygen tolerance extension) Program consisted of two related areas of research activity, integrated in design and performance, that were each based on an ongoing analysis of human organ oxygen tolerance data obtained for the continuous oxygen exposures of the prior Predictive Studies V Program. The two research areas effectively blended broad investigation of systematically varied intermittent exposure patterns in animals with very selective evaluation of specific exposure patterns in man.

Dynamic resetting of the human circadian pacemaker by intermittent bright light

NASA Technical Reports Server (NTRS)

Rimmer, D. W.; Boivin, D. B.; Shanahan, T. L.; Kronauer, R. E.; Duffy, J. F.; Czeisler, C. A.

2000-01-01

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

Predictive dose-based estimation of systemic exposure multiples in mouse and monkey relative to human for antisense oligonucleotides with 2'-o-(2-methoxyethyl) modifications.

PubMed

Yu, Rosie Z; Grundy, John S; Henry, Scott P; Kim, Tae-Won; Norris, Daniel A; Burkey, Jennifer; Wang, Yanfeng; Vick, Andrew; Geary, Richard S

2015-01-20

Evaluation of species differences and systemic exposure multiples (or ratios) in toxicological animal species versus human is an ongoing exercise during the course of drug development. The systemic exposure ratios are best estimated by directly comparing area under the plasma concentration-time curves (AUCs), and sometimes by comparing the dose administered, with the dose being adjusted either by body surface area (BSA) or body weight (BW). In this study, the association between AUC ratio and the administered dose ratio from animals to human were studied using a retrospective data-driven approach. The dataset included nine antisense oligonucleotides (ASOs) with 2'-O-(2-methoxyethyl) modifications, evaluated in two animal species (mouse and monkey) following single and repeated parenteral administrations. We found that plasma AUCs were similar between ASOs within the same species, and are predictable to human exposure using a single animal species, either mouse or monkey. Between monkey and human, the plasma exposure ratio can be predicted directly based on BW-adjusted dose ratios, whereas between mouse and human, the exposure ratio would be nearly fivefold lower in mouse compared to human based on BW-adjusted dose values. Thus, multiplying a factor of 5 for the mouse BW-adjusted dose would likely provide a reasonable AUC exposure estimate in human at steady-state.

Human Health Effects of Biphenyl: Key Findings and Scientific Issues

PubMed Central

Li, Zheng; Hogan, Karen A.; Cai, Christine; Rieth, Susan

2015-01-01

Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. Objectives: We review key findings and scientific issues regarding expected human health effects of biphenyl. Methods: Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Discussion: Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. Conclusions: The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Citation: Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703–712; http://dx.doi.org/10.1289/ehp.1509730 PMID:26529796

ASSESSING HUMAN EXPOSURE AND GENOTOXIC EFFECTS IN HUMAN EXFOLIATED EPITHELIA FROM INDIVDUALS IVING IN AN ENDEMIC REGION IN INNER MONGOLAI

EPA Science Inventory

A pilot study was conducted to characterize arsenic exposure and genotoxic effects in Ba Men located in West Central Inner Mongolia in an attempt to identify biomarkers useful for assessing health risk resulting from chronic arsenic exposure. The study subjects included 19 high ...

TOWARDS RELIABLE AND COST-EFFECTIVE OZONE EXPOSURE ASSESSMENT: PARAMETER EVALUATION AND MODEL VALIDATION USING THE HARVARD SOUTHERN CALIFORNIA CHRONIC OZONE EXPOSURE STUDY DATA

EPA Science Inventory

Accurate assessment of chronic human exposure to atmospheric criteria pollutants, such as ozone, is critical for understanding human health risks associated with living in environments with elevated ambient pollutant concentrations. In this study, we analyzed a data set from a...

The Adverse Effects of Heavy Metals with and without Noise Exposure on the Human Peripheral and Central Auditory System: A Literature Review.

PubMed

Castellanos, Marie-Josée; Fuente, Adrian

2016-12-09

Exposure to some chemicals in the workplace can lead to occupational chemical-induced hearing loss. Attention has mainly focused on the adverse auditory effects of solvents. However, other chemicals such as heavy metals have been also identified as ototoxic agents. The aim of this work was to review the current scientific knowledge about the adverse auditory effects of heavy metal exposure with and without co-exposure to noise in humans. PubMed and Medline were accessed to find suitable articles. A total of 49 articles met the inclusion criteria. Results from the review showed that no evidence about the ototoxic effects in humans of manganese is available. Contradictory results have been found for arsenic, lead and mercury as well as for the possible interaction between heavy metals and noise. All studies found in this review have found that exposure to cadmium and mixtures of heavy metals induce auditory dysfunction. Most of the studies investigating the adverse auditory effects of heavy metals in humans have investigated human populations exposed to lead. Some of these studies suggest peripheral and central auditory dysfunction induced by lead exposure. It is concluded that further evidence from human studies about the adverse auditory effects of heavy metal exposure is still required. Despite this issue, audiologists and other hearing health care professionals should be aware of the possible auditory effects of heavy metals.

Controlled human exposures to diesel exhaust

EPA Science Inventory

Diesel exhaust (DE) is a complex mixture of gaseous and particulate compounds resulting from an incomplete combustion of diesel fuel. Controlled human exposures to DE and diesel exhaust particles (DEP) have contributed to understanding health effects. Such exposure studies of h...

NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY (NHEXAS): ANALYSIS OF EXPOSURE PATHWAYS AND ROUTES FOR ARSENIC AND LEAD IN EPA REGION 5

EPA Science Inventory

The National Human Exposure Assessment Survey (NHEXAS) Phase I field study conducted in EPA Region 5 (Great Lakes Area) provides extensive exposure data on a representative sample of approximately 250 residents of the region. Associated environmental media and biomarker (blood...

Dietary Acrylamide and Human Cancer: A Systematic Review of Literature

PubMed Central

Nagy, Tim R.; Barnes, Stephen; Groopman, John

2014-01-01

Cancer remains the second leading cause of death in the United States, and the numbers of cases are expected to continue to rise worldwide. Cancer prevention strategies are crucial for reducing the cancer burden. The carcinogenic potential of dietary acrylamide exposure from cooked foods is unknown. Acrylamide is a by-product of the common Maillard reaction where reducing sugars (i.e., fructose and glucose) react with the amino acid, asparagine. Based on the evidence of acrylamide carcinogenicity in animals, the International Agency for Research on Cancer has classified acrylamide as a group 2A carcinogen for humans. Since the discovery of acrylamide in foods in 2002, a number of studies have explored its potential as a human carcinogen. This paper outlines a systematic review of dietary acrylamide and human cancer, acrylamide exposure and internal dose, exposure assessment methods in the epidemiologic studies, existing data gaps, and future directions. A majority of the studies reported no statistically significant association between dietary acrylamide intake and various cancers, and few studies reported increased risk for renal, endometrial, and ovarian cancers; however, the exposure assessment has been inadequate leading to potential misclassification or underestimation of exposure. Future studies with improved dietary acrylamide exposure assessment are encouraged. PMID:24875401

Community Engagement in Observational Human Exposure Studies

EPA Science Inventory

Although observational human exposure studies do not deliberately expose participants to chemicals or environmental conditions, merely involving people as research participants and conducting research inside homes raises ethical issues. Community engagement offers a promising st...

STRATEGIC PLAN FOR THE ANALYSIS OF THE NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY (NHEXAS) PILOT STUDY DATA

EPA Science Inventory

The Office of Research and Development (ORD) of the U.S. Environmental Protection Agency (EPA) initiated the National Human Exposure Assessment Survey (NHEXAS) in the early 1990's. It was a population-based pilot study of the exposure of over 500 people in three areas of the U....

EVALUATION OF A PERSONAL NEPHELOMETER FOR HUMAN EXPOSURE MONITORING

EPA Science Inventory

Current particulate matter (PM) exposure studies are using continuous personal nephelometers (pDR-1000, MIE, Inc.) to measure human exposure to PM. The personal nephelometer is a passive sampler which uses light scattering technology to measure particles ranging in size from 0....

New Exposure Biomarkers as Tools for Breast Cancer Epidemiology, Biomonitoring, and Prevention: A Systematic Approach Based on Animal Evidence

PubMed Central

Ackerman, Janet M.; Attfield, Kathleen R.; Brody, Julia Green

2014-01-01

Background: Exposure to chemicals that cause rodent mammary gland tumors is common, but few studies have evaluated potential breast cancer risks of these chemicals in humans. Objective: The goal of this review was to identify and bring together the needed tools to facilitate the measurement of biomarkers of exposure to potential breast carcinogens in breast cancer studies and biomonitoring. Methods: We conducted a structured literature search to identify measurement methods for exposure biomarkers for 102 chemicals that cause rodent mammary tumors. To evaluate concordance, we compared human and animal evidence for agents identified as plausibly linked to breast cancer in major reviews. To facilitate future application of exposure biomarkers, we compiled information about relevant cohort studies. Results: Exposure biomarkers have been developed for nearly three-quarters of these rodent mammary carcinogens. Analytical methods have been published for 73 of the chemicals. Some of the remaining chemicals could be measured using modified versions of existing methods for related chemicals. In humans, biomarkers of exposure have been measured for 62 chemicals, and for 45 in a nonoccupationally exposed population. The Centers for Disease Control and Prevention has measured 23 in the U.S. population. Seventy-five of the rodent mammary carcinogens fall into 17 groups, based on exposure potential, carcinogenicity, and structural similarity. Carcinogenicity in humans and rodents is generally consistent, although comparisons are limited because few agents have been studied in humans. We identified 44 cohort studies, with a total of > 3.5 million women enrolled, that have recorded breast cancer incidence and stored biological samples. Conclusions: Exposure measurement methods and cohort study resources are available to expand biomonitoring and epidemiology related to breast cancer etiology and prevention. Citation: Rudel RA, Ackerman JM, Attfield KR, Brody JG. 2014. New exposure biomarkers as tools for breast cancer epidemiology, biomonitoring, and prevention: a systematic approach based on animal evidence. Environ Health Perspect 122:881–895; http://dx.doi.org/10.1289/ehp.1307455 PMID:24818537

IDENTIFICATION OF TIME-INTEGRATED SAMPLING AND MEASUREMENT TECHNIQUES TO SUPPORT HUMAN EXPOSURE STUDIES

EPA Science Inventory

Accurate exposure classification tools are required to link exposure with health effects in epidemiological studies. Long-term, time-integrated exposure measures would be desirable to address the problem of developing appropriate residential childhood exposure classifications. ...

40 CFR 158.2230 - Toxicology.

Code of Federal Regulations, 2013 CFR

2013-07-01

... pesticide is likely to result in repeated human exposure over a considerable portion of the human lifespan... exposures and adverse neurological effects in human epidemiological studies. iv. The pesticide evokes a... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS...

Human and Animal Fecal Contamination of Community Water Sources, Stored Drinking Water and Hands in Rural India Measured with Validated Microbial Source Tracking Assays

PubMed Central

Schriewer, Alexander; Odagiri, Mitsunori; Wuertz, Stefan; Misra, Pravas R.; Panigrahi, Pinaki; Clasen, Thomas; Jenkins, Marion W.

2015-01-01

We examined pathways of exposure to fecal contamination of human and animal origin in 24 villages in Odisha, India. In a cross-sectional study during the monsoon season, fecal exposure via community water sources (N = 123) and in the home (N = 137) was assessed using human- and nonhuman-associated Bacteroidales microbial source tracking (MST) markers and fecal coliforms (FCs). Detection rates and marker concentrations were examined to pinpoint pathways of human fecal exposure in the public and domestic domains of disease transmission in study communities. Human fecal markers were detected much more frequently in the domestic domain (45% of households) than in public domain sources (8% of ponds; 4% of groundwater drinking sources). Animal fecal markers were widely detected in both domains (74% of ponds, 96% of households, 10% of groundwater drinking sources), indicating ubiquitous risks of exposure to animal feces and zoonotic pathogens. This study confirms an often suggested contamination link from hands to stored water in the home in developing countries separately for mothers' and children's hands and both human and animal fecal contamination. In contrast to MST markers, FCs provided a poor metric to assess risks of exposure to fecal contamination of human origin in this rural setting. PMID:26149868

40 CFR 159.170 - Human epidemiological and exposure studies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... studies. 159.170 Section 159.170 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns any study that a person described in § 159.158(a) has concluded, or might reasonably conclude, shows...

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.

Rare earth elements in human and animal health: State of art and research priorities

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

Pagano, Giovanni, E-mail: gbpagano@tin.it; Aliberti, Francesco; Guida, Marco

Background: A number of applications have been developed using rare earth elements (REE), implying several human exposures and raising unsolved questions as to REE-associated health effects. Methods: A MedLine survey was retrieved from early reports (1980s) up to June 2015, focused on human and animal exposures to REE. Literature from animal models was selected focusing on REE-associated health effects. Results: Some REE occupational exposures, in jobs such as glass polishers, photoengravers and movie projectionists showed a few case reports on health effects affecting the respiratory system. No case-control or cohort studies of occupational REE exposures were retrieved. Environmental exposures havemore » been biomonitored in populations residing in REE mining areas, showing REE accumulation. The case for a iatrogenic REE exposure was raised by the use of gadolinium-based contrast agents for nuclear magnetic resonance. Animal toxicity studies have shown REE toxicity, affecting a number of endpoints in liver, lungs and blood. On the other hand, the use of REE as feed additives in livestock is referred as a safe and promising device in zootechnical activities, possibly suggesting a hormetic effect both known for REE and for other xenobiotics. Thus, investigations on long-term exposures and observations are warranted. Conclusion: The state of art provides a limited definition of the health effects in occupationally or environmentally REE-exposed human populations. Research priorities should be addressed to case-control or cohort studies of REE-exposed humans and to life-long animal experiments. - Highlights: • An extensive number of activities have been developed utilizing rare earth elements (REE). • The literature of REE-associated health effects in humans, and on animal studies is reviewed. • The main literature gaps are discussed, in epidemiological and in animal studies. • Prospects studies are suggested, aimed at evaluating long-term effects of REE exposures. • The relevance of REE-related hormesis, speciation and acidic pollution are discussed.« less

Bayesian Analysis of Silica Exposure and Lung Cancer Using Human and Animal Studies.

PubMed

Bartell, Scott M; Hamra, Ghassan Badri; Steenland, Kyle

2017-03-01

Bayesian methods can be used to incorporate external information into epidemiologic exposure-response analyses of silica and lung cancer. We used data from a pooled mortality analysis of silica and lung cancer (n = 65,980), using untransformed and log-transformed cumulative exposure. Animal data came from chronic silica inhalation studies using rats. We conducted Bayesian analyses with informative priors based on the animal data and different cross-species extrapolation factors. We also conducted analyses with exposure measurement error corrections in the absence of a gold standard, assuming Berkson-type error that increased with increasing exposure. The pooled animal data exposure-response coefficient was markedly higher (log exposure) or lower (untransformed exposure) than the coefficient for the pooled human data. With 10-fold uncertainty, the animal prior had little effect on results for pooled analyses and only modest effects in some individual studies. One-fold uncertainty produced markedly different results for both pooled and individual studies. Measurement error correction had little effect in pooled analyses using log exposure. Using untransformed exposure, measurement error correction caused a 5% decrease in the exposure-response coefficient for the pooled analysis and marked changes in some individual studies. The animal prior had more impact for smaller human studies and for one-fold versus three- or 10-fold uncertainty. Adjustment for Berkson error using Bayesian methods had little effect on the exposure-response coefficient when exposure was log transformed or when the sample size was large. See video abstract at, http://links.lww.com/EDE/B160.

Considerations for human exposure standards for fast-rise-time high-peak-power electromagnetic pulses.

PubMed

Merritt, J H; Kiel, J L; Hurt, W D

1995-06-01

Development of new emitter systems capable of producing high-peak-power electromagnetic pulses with very fast rise times and narrow pulse widths is continuing. Such directed energy weapons systems will be used in the future to defeat electronically vulnerable targets. Human exposures to these pulses can be expected during testing and operations. Development of these technologies for radar and communications purposes has the potential for wider environmental exposure, as well. Current IEEE C95.1-1991 human exposure guidelines do not specifically address these types of pulses, though limits are stated for pulsed emissions. The process for developing standards includes an evaluation of the relevant bioeffects data base. A recommendation has been made that human exposure to ultrashort electromagnetic pulses that engender electromagnetic transients, called precursor waves, should be avoided. Studies that purport to show the potential for tissue damage induced by such pulses were described. The studies cited in support of the recommendation were not relevant to the issues of tissue damage by propagated pulses. A number of investigations are cited in this review that directly address the biological effects of electromagnetic pulses. These studies have not shown evidence of tissue damage as a result of exposure to high-peak-power pulsed microwaves. It is our opinion that the current guidelines are sufficiently protective for human exposure to these pulses.

FIELD COLLECTION METHODS USED IN THE EPA NATIONAL EXPOSURE RESEARCH LABORATORY HUMAN EXPOSURE MEASUREMENT PROGRAM TO EVALUATE CHILDREN'S AGGREGATE EXPOSURE TO PESTICIDES: A TUTORIAL

EPA Science Inventory

A tutorial on the field sampling equipment used to collect multimedia samples.

We conduct observational human exposure measurement studies in order to understand what chemicals people come into contact with, at what levels, what the sources of those chemicals are, and wher...

Modelling ecological and human exposure to POPs in Venice lagoon - Part II: Quantitative uncertainty and sensitivity analysis in coupled exposure models.

PubMed

Radomyski, Artur; Giubilato, Elisa; Ciffroy, Philippe; Critto, Andrea; Brochot, Céline; Marcomini, Antonio

2016-11-01

The study is focused on applying uncertainty and sensitivity analysis to support the application and evaluation of large exposure models where a significant number of parameters and complex exposure scenarios might be involved. The recently developed MERLIN-Expo exposure modelling tool was applied to probabilistically assess the ecological and human exposure to PCB 126 and 2,3,7,8-TCDD in the Venice lagoon (Italy). The 'Phytoplankton', 'Aquatic Invertebrate', 'Fish', 'Human intake' and PBPK models available in MERLIN-Expo library were integrated to create a specific food web to dynamically simulate bioaccumulation in various aquatic species and in the human body over individual lifetimes from 1932 until 1998. MERLIN-Expo is a high tier exposure modelling tool allowing propagation of uncertainty on the model predictions through Monte Carlo simulation. Uncertainty in model output can be further apportioned between parameters by applying built-in sensitivity analysis tools. In this study, uncertainty has been extensively addressed in the distribution functions to describe the data input and the effect on model results by applying sensitivity analysis techniques (screening Morris method, regression analysis, and variance-based method EFAST). In the exposure scenario developed for the Lagoon of Venice, the concentrations of 2,3,7,8-TCDD and PCB 126 in human blood turned out to be mainly influenced by a combination of parameters (half-lives of the chemicals, body weight variability, lipid fraction, food assimilation efficiency), physiological processes (uptake/elimination rates), environmental exposure concentrations (sediment, water, food) and eating behaviours (amount of food eaten). In conclusion, this case study demonstrated feasibility of MERLIN-Expo to be successfully employed in integrated, high tier exposure assessment. Copyright © 2016 Elsevier B.V. All rights reserved.

LESSONS LEARNED FROM THE NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY (NHEXAS)

EPA Science Inventory

Three NHEXAS Studies were conducted from 1995-1997 to evaluate total human exposure to multiple chemicals on community and regional scales. EPA established cooperative agreements with three Consortia to conduct three interrelated NHEXAS field studies. The University of Arizona...

Indicative and complementary effects of human biological indicators for heavy metal exposure assessment.

PubMed

Xing, Ruiya; Li, Yonghua; Zhang, Biao; Li, Hairong; Liao, Xiaoyong

2017-10-01

Although human biological indicators have been widely utilized for biomonitoring environmental pollutants in health exposure assessment, the relationship between internal and external exposure has not yet been adequately established. In this study, we collected and analyzed 61 rice, 56 pepper, and 58 soil samples, together with 107 hair, 107 blood, and 107 urine samples from residents living in selected intensive mining areas in China. Concentrations of most of the four elements considered (Pb, Cd, Hg, and Se) exceeded national standards, implying high exposure risk in the study areas. Regression analysis also revealed a correlation (0.33, P < 0.001) between the concentration of Pb in soil and that in human hair (as well as in human blood); to some extent, Pb content in hair and blood could therefore be used to characterize external Pb exposure. The correlation between Hg in rice and in human hair (up to 0.5, P < 0.001) further confirmed a significant indicative effect of human hair for Hg exposure. A significant correlation was also noted between concentrations of some elements in different human samples, for example, between Hg in hair and blood (0.641, P < 0.01) and between Cd in urine and blood (0.339, P < 0.01). To some extent, there could thus be mutual reflectance of the same heavy metal in different samples, with the possibility for complementary use in assessing heavy metal exposure.

Personalized Exposure Assessment: Promising Approaches for Human Environmental Health Research

PubMed Central

Weis, Brenda K.; Balshaw, David; Barr, John R.; Brown, David; Ellisman, Mark; Lioy, Paul; Omenn, Gilbert; Potter, John D.; Smith, Martyn T.; Sohn, Lydia; Suk, William A.; Sumner, Susan; Swenberg, James; Walt, David R.; Watkins, Simon; Thompson, Claudia; Wilson, Samuel H.

2005-01-01

New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a “toolbox” of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure–disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs. PMID:16002370

Building associations between markers of environmental stressors and adverse human health impacts using frequent itemset mining

EPA Science Inventory

Building associations between markers of exposure and effect using frequent itemset mining The human-health impact of environmental contaminant exposures is unclear. While some exposure-effect relationships are well studied, health effects are unknown for the vast majority of the...

Cardiovascular impacts and micro-environmental exposure factors associated with continuous personal PM2.5 monitoring

EPA Science Inventory

The US Environmental Protection Agency’s (US EPA) Detroit Exposure and Aerosol Research Study (DEARS) has provided extensive data on human exposures to a wide variety of air pollutants and their impact on human health. Previous analyses in the DEARS revealed select cardiovascul...

Development and Evaluation of a New Air Exchange Rate Algorithm for the Stochastic Human Exposure and Dose Simulation Model (ISES Presentation)

EPA Science Inventory

Previous exposure assessment panel studies have observed considerable seasonal, between-home and between-city variability in residential pollutant infiltration. This is likely a result of differences in home ventilation, or air exchange rates (AER). The Stochastic Human Exposure ...

Combining Regional- and Local-Scale Air Quality Models with Exposure Models for Use in Environmental Health Studies

EPA Science Inventory

Population-based human exposure models predict the distribution of personal exposures to pollutants of outdoor origin using a variety of inputs, including: air pollution concentrations; human activity patterns, such as the amount of time spent outdoors vs. indoors, commuting, wal...

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

[Study of work accidents related to human body fluids exposure among health workers at a university hospital].

PubMed

Balsamo, Ana Cristina; Felli, Vanda Elisa Andres

2006-01-01

This descriptive and exploratory study from a quantitative approach aimed to characterize workers who were victims of work accidents related to human body fluids exposure and to evaluate the accident victim care protocol. The population consisted of 48 workers who were victims of work accidents involving exposure to human body fluids, from July 2000 to June 2001. Data were collected through a form and interviews. Results showed that nursing workers presented higher accident risk levels and that 87.50% involved piercing and cutting material, such as needles and butterflies (70%). As to the accident-related situation/activity, the workers indicated that 25% were due to an "inadequate act during the procedure"; 19.64% mentioned that "it happened" and 29.17% answered that they did not have any suggestion. This study provided important tools to review and elaborate strategies to prevent accidents involving exposure to human body fluids.

Prenatal and postnatal cocaine exposure predict teen cocaine use

PubMed Central

Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

2015-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

Prenatal and postnatal cocaine exposure predict teen cocaine use.

PubMed

Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

2011-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

Differential Response of Human Nasal and Bronchial Epithelial Cells upon Exposure to Size-fractionated Dairy Dust

PubMed Central

Hawley, Brie; Schaeffer, Joshua; Poole, Jill A.; Dooley, Gregory P.; Reynolds, Stephen; Volckens, John

2015-01-01

Exposure to organic dusts is associated with increased respiratory morbidity and mortality in agricultural workers. Organic dusts in dairy farm environments are complex, polydisperse mixtures of toxic and immunogenic compounds. Previous toxicological studies focused primarily on exposures to the respirable size fraction, however, organic dusts in dairy farm environments are known to contain larger particles. Given the size distribution of dusts from dairy farm environments, the nasal and bronchial epithelia represent targets of agricultural dust exposures. In this study, well-differentiated normal human bronchial epithelial cells and human nasal epithelial cells were exposed to two different size fractions (PM10 and PM>10) of dairy parlor dust using a novel aerosol-to-cell exposure system. Levels of pro-inflammatory transcripts (IL-8, IL-6, and TNF-α) were measured two hr after exposure. Lactate dehydrogenase (LDH) release was also measured as an indicator of cytotoxicity. Cell exposure to dust was measured in each size fraction as a function of mass, endotoxin, and muramic acid levels. To our knowledge, this is the first study to evaluate the effects of distinct size fractions of agricultural dust on human airway epithelial cells. Our results suggest that both PM10 and PM>10 size fractions elicit a pro-inflammatory response in airway epithelial cells and that the entire inhalable size fraction needs to be considered when assessing potential risks from exposure to agricultural dusts. Further, data suggest that human bronchial cells respond differently to these dusts than human nasal cells and, therefore, the two cell types need to be considered separately in airway cell models of agricultural dust toxicity. PMID:25965193

THE 1998 BALTIMORE PARTICULATE MATTER EPIDEMIOLOGY-EXPOSURE STUDY: PART 2-PERSONAL EXPOSURE ASSESSMENT ASSOCIATED WITH AN ELDERLY STUDY POPULATION

EPA Science Inventory

An integrated epidemiological-exposure panel study was conducted during the summer of 1998 which focused upon establishing relationships between potential human exposures to particulate matter (PM) and related co-pollutants with detectable health effects. The study design incor...

Fathers Matter: Why It’s Time to Consider the Impact of Paternal Environmental Exposures on Children’s Health

PubMed Central

Braun, Joseph M.; Messerlian, Carmen; Hauser, Russ

2017-01-01

Purpose Despite accumulating evidence from experimental animal studies showing that paternal environmental exposures induce genetic and epigenetic alterations in sperm which in turn increase the risk of adverse health outcomes in offspring, there is limited epidemiological data on the effects of human paternal preconception exposures on children’s health. We summarize animal and human studies showing that paternal preconception environmental exposures influence offspring health. We discuss specific approaches and designs for human studies to investigate the health effects of paternal preconception exposures, the specific challenges these studies may face, and how we might address them. Recent Findings In animal studies, paternal preconception diet, stress, and chemical exposures have been associated with offspring health and these effects are mediated by epigenetic modifications transmitted through sperm DNA, histones, and RNA. Most epidemiological studies have examined paternal preconception occupational exposures and their effect on the risk of birth defects and childhood cancer; few have examined the effects of low-level general population exposure to environmental toxicants. While the design and execution of epidemiological studies of paternal preconception exposures face challenges, particularly with regard to selection bias and recruitment, we believe these are tractable and that preconception studies are feasible. Summary New or augmented prospective cohort studies would be the optimal method to address the critical knowledge gaps on the effect of paternal preconception exposures on prevalent childhood health outcomes. Determining if this period of life represents a window of heightened vulnerability would improve our understanding of modifiable risk factors for children’s health and wellbeing. PMID:28848695

ORD BEST PRACTICES FOR OBSERVATIONAL HUMAN EXPOSURE MEASUREMENT STUDIES

EPA Science Inventory

This abstract describes a presentation for the 2007 Society of Toxicology Annual Meeting in Charlotte, NC on March 27, 2007. It will be included in a special Issues Session titled "Scientific and Ethical Considerations in Human Exposure Studies." The presentation desc...

COMPARISON OF FOUR HUMAN STUDIES OF PERINATAL EXPOSURE TO METHYLMERCURY FOR USE IN RISK ASSESSMENT

EPA Science Inventory

Newer data from human epidemiologic studies of methylmercury (MeHg) poisoning in which perinatal exposure occurred are available from four distinct populations. The results of an Iraqi grain-consuming population are compared to results from studies performed in fish-consuming gro...

THE NATIONAL EXPOSURE RESEARCH LABORATORY'S CONSOLIDATED HUMAN ACTIVITY DATABASE

EPA Science Inventory

EPA's National Exposure Research Laboratory (NERL) has combined data from 12 U.S. studies related to human activities into one comprehensive data system that can be accessed via the Internet. The data system is called the Consolidated Human Activity Database (CHAD), and it is ...

Biomarkers of human cardiopulmonary response after short-term exposures to medical laser generated particulate matter from simulated procedures: a pilot study

PubMed Central

Lopez, Ramon; Farber, Mark O.; Wong, Vincent; Lacey, Steven E.

2016-01-01

Objective We conducted an exposure chamber study in humans using a simulated clinical procedure lasing porcine tissue to demonstrate evidence of effects of exposure to laser generated particulate matter (LGPM). Methods We measured pre- and post-exposure changes in exhaled nitric oxide (eNO), spirometry, heart rate variability (HRV), and blood markers of inflammation in five volunteers. Results Change in pre- and post-exposure measurements of eNO and spirometry were unremarkable. Neutrophil and lymphocyte counts increased and fibrinogen levels decreased in four of the five subjects. Measures of HRV showed decreases in the standard deviation of normal between beat intervals and sequential five-minute intervals. Conclusion These data represent the first evidence of human physiologic response to LGPM exposure. Further exploration of coagulation effects and HRV are warranted. PMID:27465102

Phthalates and other additives in plastics: human exposure and associated health outcomes

PubMed Central

Meeker, John D.; Sathyanarayana, Sheela; Swan, Shanna H.

2009-01-01

Concern exists over whether additives in plastics to which most people are exposed, such as phthalates, bisphenol A or polybrominated diphenyl ethers, may cause harm to human health by altering endocrine function or through other biological mechanisms. Human data are limited compared with the large body of experimental evidence documenting reproductive or developmental toxicity in relation to these compounds. Here, we discuss the current state of human evidence, as well as future research trends and needs. Because exposure assessment is often a major weakness in epidemiological studies, and in utero exposures to reproductive or developmental toxicants are important, we also provide original data on maternal exposure to phthalates during and after pregnancy (n = 242). Phthalate metabolite concentrations in urine showed weak correlations between pre- and post-natal samples, though the strength of the relationship increased when duration between the two samples decreased. Phthalate metabolite levels also tended to be higher in post-natal samples. In conclusion, there is a great need for more human studies of adverse health effects associated with plastic additives. Recent advances in the measurement of exposure biomarkers hold much promise in improving the epidemiological data, but their utility must be understood to facilitate appropriate study design. PMID:19528058

A systematic review on human exposure to organophosphorus pesticides in Iran.

PubMed

Shadboorestan, Amir; Vardanjani, Hossein Molavi; Abdollahi, Mohammad; Goharbari, Mohammad Hadi; Khanjani, Narges

2016-07-02

Human exposure to organophosphorus (OP) pesticides is a serious health challenge. We conducted a systematic review by searching international and national databases for published literature on any human exposure to OPs in Iran from 1990 to March 2015. Qualified papers were in two categories including studies in which biomarkers of exposure were assessed (n = 13; total no. of subjects = 759) and studies that had reported prevalence of OPs-induced poisoning (OPP) and mortality (n = 26; total no. of subjects = 5428). The mean level of activity of acetyl-cholinesterase and butyryl-cholinesterase were 68.65% and 74.2%, respectively. Overall proportion (%) of OPP was estimated (16; 95% CI, 14 to 19).

Human and Animal Fecal Contamination of Community Water Sources, Stored Drinking Water and Hands in Rural India Measured with Validated Microbial Source Tracking Assays.

PubMed

Schriewer, Alexander; Odagiri, Mitsunori; Wuertz, Stefan; Misra, Pravas R; Panigrahi, Pinaki; Clasen, Thomas; Jenkins, Marion W

2015-09-01

We examined pathways of exposure to fecal contamination of human and animal origin in 24 villages in Odisha, India. In a cross-sectional study during the monsoon season, fecal exposure via community water sources (N = 123) and in the home (N = 137) was assessed using human- and nonhuman-associated Bacteroidales microbial source tracking (MST) markers and fecal coliforms (FCs). Detection rates and marker concentrations were examined to pinpoint pathways of human fecal exposure in the public and domestic domains of disease transmission in study communities. Human fecal markers were detected much more frequently in the domestic domain (45% of households) than in public domain sources (8% of ponds; 4% of groundwater drinking sources). Animal fecal markers were widely detected in both domains (74% of ponds, 96% of households, 10% of groundwater drinking sources), indicating ubiquitous risks of exposure to animal feces and zoonotic pathogens. This study confirms an often suggested contamination link from hands to stored water in the home in developing countries separately for mothers' and children's hands and both human and animal fecal contamination. In contrast to MST markers, FCs provided a poor metric to assess risks of exposure to fecal contamination of human origin in this rural setting. © The American Society of Tropical Medicine and Hygiene.

Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure.

PubMed

Gouveia-Figueira, Sandra; Karimpour, Masoumeh; Bosson, Jenny A; Blomberg, Anders; Unosson, Jon; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Nording, Malin L

2017-04-01

The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 μg/m 3 ) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, N-acylethanolamines, and related lipid metabolites in the collected BW and BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE 2 , 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

Effect of endocrine disruptors on male reproduction in humans: why the evidence is still lacking?

PubMed

Bliatka, D; Lymperi, S; Mastorakos, G; Goulis, D G

2017-05-01

The so-called "endocrine disruption hypothesis" suggests that exposures to endocrine disruption (EDs) during fetal, neonatal and adult life may interfere with the development of reproductive organs and alter semen quality and reproductive hormone production. Even though animal studies provide substantial evidence of adverse effects of EDs on male reproductive system, epidemiological studies in humans arrive at conflicting results. The aim of the present study was to systematically review the literature to locate methodological characteristics of the studies that struggle the formation of an association between EDs and human male reproduction. Such characteristics include: (i) definition of the exposed and the non-exposed population, (ii) age, (iii) insufficient control for confounders, (iv) ED assay and threshold, (v) time parameters of ED exposure, and (vi) study outcomes. Additional issues are: (i) the late effect of an early exposure, (ii) the multiple exposure effect, and (iii) the fact the same ED may exhibit different modes of action. Unfortunately, the nature of the field precludes the conduction of randomized-controlled trials, which could result to etiological associations between EDs and human male reproduction. Consequently, there is a great need to conduct well-designed studies of case-control or cohort type to evaluate EDs effects on human male reproductive health, and apply possible measures that could limit dangerous exposures. © 2017 American Society of Andrology and European Academy of Andrology.

Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study.

PubMed

Calafat, Antonia M; McKee, Richard H

2006-11-01

The probability of nonoccupational exposure to phthalates is high given their use in a vast range of consumables, including personal care products (e.g., perfumes, lotions, cosmetics), paints, industrial plastics, and certain medical devices and pharmaceuticals. Phthalates are of high interest because of their potential for human exposure and because animal toxicity studies suggest that some phthalates affect male reproductive development apparently via inhibition of androgen biosynthesis. In humans, phthalates are rapidly metabolized to their monoesters, which can be further transformed to oxidative products, conjugated, and eliminated. Phthalate metabolites have been used as biomarkers of exposure. Using urinary phthalate metabolite concentrations allows accurate assessments of human exposure because these concentrations represent an integrative measure of exposure to phthalates from multiple sources and routes. However, the health significance of this exposure is unknown. To link biomarker measurements to exposure, internal dose, or health outcome, additional information (e.g., toxicokinetics, inter- and intraindividual differences) is needed. We present a case study using diethyl phthalate and di(2-ethylhexyl) phthalate as examples to illustrate scientific approaches and their limitations, identify data gaps, and outline research needs for using biomonitoring data in the context of human health risk assessment, with an emphasis on exposure and dose. Although the vast and growing literature on phthalates research could not be covered comprehensively in this article, we made every attempt to include the most relevant publications as of the end of 2005.

Dietary Intervention to Mitigate the Health Effects of PM Exposure in Humans

EPA Science Inventory

Exposure to ambient air pollution is a major cause of global morbidity and mortality. This presentation will highlight previously published, ongoing and planned studies conducted at the Human Studies Facility that have examined the efficacy of nutritional supplementation in modul...

A REVIEW OF HUMAN STUDIES ON THE REPRODUCTIVE AND DEVELOPMENTAL EFFECTS OF PESTICIDE EXPOSURE

EPA Science Inventory

Many pesticides cxause reproductive or developmental toxicity at high doses in animal models, but effects in humans at environmental exposure levels are difficult to assess. Human data on reproductive and developmental outcomes for currently used pesticides may help to define ris...

THE NATIONAL EXPOSURE RESEARCH LABORATORY'S COMPREHENSIVE HUMAN ACTIVITY DATABASE

EPA Science Inventory

EPA's National Exposure Research Laboratory (NERL) has combined data from nine U.S. studies related to human activities into one comprehensive data system that can be accessed via the world-wide web. The data system is called CHAD-Consolidated Human Activity Database-and it is ...

Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways

PubMed Central

Li, Zijian; Jennings, Aaron A.

2017-01-01

Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health. PMID:29546224

A review of the health impacts of barium from natural and anthropogenic exposure.

PubMed

Kravchenko, Julia; Darrah, Thomas H; Miller, Richard K; Lyerly, H Kim; Vengosh, Avner

2014-08-01

There is an increasing public awareness of the relatively new and expanded industrial barium uses which are potential sources of human exposure (e.g., a shale gas development that causes an increased awareness of environmental exposures to barium). However, absorption of barium in exposed humans and a full spectrum of its health effects, especially among chronically exposed to moderate and low doses of barium populations, remain unclear. We suggest a systematic literature review (from 1875 to 2014) on environmental distribution of barium, its bioaccumulation, and potential and proven health impacts (in animal models and humans) to provide the information that can be used for optimization of future experimental and epidemiological studies and developing of mitigative and preventive strategies to minimize negative health effects in exposed populations. The potential health effects of barium exposure are largely based on animal studies, while epidemiological data for humans, specifically for chronic low-level exposures, are sparse. The reported health effects include cardiovascular and kidney diseases, metabolic, neurological, and mental disorders. Age, race, dietary patterns, behavioral risks (e.g., smoking), use of medications (those that interfere with absorbed barium in human organism), and specific physiological status (e.g., pregnancy) can modify barium effects on human health. Identifying, evaluating, and predicting the health effects of chronic low-level and moderate-level barium exposures in humans is challenging: Future research is needed to develop an understanding of barium bioaccumulation in order to mitigate its potential health impacts in various exposured populations. Further, while occupationally exposed at-risk populations exist, it is also important to identify potentially vulnerable subgroups among non-occupationally exposed populations (e.g., elderly, pregnant women, children) who are at higher risk of barium exposure from drinking water and food.

Rare earth elements in human and animal health: State of art and research priorities.

PubMed

Pagano, Giovanni; Aliberti, Francesco; Guida, Marco; Oral, Rahime; Siciliano, Antonietta; Trifuoggi, Marco; Tommasi, Franca

2015-10-01

A number of applications have been developed using rare earth elements (REE), implying several human exposures and raising unsolved questions as to REE-associated health effects. A MedLine survey was retrieved from early reports (1980s) up to June 2015, focused on human and animal exposures to REE. Literature from animal models was selected focusing on REE-associated health effects. Some REE occupational exposures, in jobs such as glass polishers, photoengravers and movie projectionists showed a few case reports on health effects affecting the respiratory system. No case-control or cohort studies of occupational REE exposures were retrieved. Environmental exposures have been biomonitored in populations residing in REE mining areas, showing REE accumulation. The case for a iatrogenic REE exposure was raised by the use of gadolinium-based contrast agents for nuclear magnetic resonance. Animal toxicity studies have shown REE toxicity, affecting a number of endpoints in liver, lungs and blood. On the other hand, the use of REE as feed additives in livestock is referred as a safe and promising device in zootechnical activities, possibly suggesting a hormetic effect both known for REE and for other xenobiotics. Thus, investigations on long-term exposures and observations are warranted. The state of art provides a limited definition of the health effects in occupationally or environmentally REE-exposed human populations. Research priorities should be addressed to case-control or cohort studies of REE-exposed humans and to life-long animal experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of experimental models for predicting laser-tissue interaction from 3.8-micron lasers

NASA Astrophysics Data System (ADS)

Williams, Piper C. M.; Winston, Golda C. H.; Randolph, Don Q.; Neal, Thomas A.; Eurell, Thomas E.; Johnson, Thomas E.

2004-07-01

The purpose of this study was to evaluate the laser-tissue interactions of engineered human skin and in-vivo pig skin following exposure to a single 3.8 micron laser light pulse. The goal of the study was to determine if these tissues shared common histologic features following laser exposure that might prove useful in developing in-vitro and in-vivo experimental models to predict the bioeffects of human laser exposure. The minimum exposure required to produce gross morphologic changes following a four microsecond, pulsed skin exposure for both models was determined. Histology was used to compare the cellular responses of the experimental models following laser exposure. Eighteen engineered skin equivalents (in-vitro model), were exposed to 3.8 micron laser light and the tissue responses compared to equivalent exposures made on five Yorkshire pigs (in-vivo model). Representative biopsies of pig skin were taken for histologic evaluation from various body locations immediately, one hour, and 24 hours following exposure. The pattern of epithelial changes seen following in-vitro laser exposure of the engineered human skin and in-vivo exposure of pig skin indicated a common histologic response for this particular combination of laser parameters.

Impacts of environment on human diseases: a web service for the human exposome

NASA Astrophysics Data System (ADS)

Karssenberg, Derek; Vaartjes, Ilonca; Kamphuis, Carlijn; Strak, Maciek; Schmitz, Oliver; Soenario, Ivan; de Jong, Kor

2017-04-01

The exposome is the totality of human environmental exposures from conception onwards. Identifying the contribution of the exposome to human diseases and health is a key issue in health research. Examples include the effect of air pollution exposure on cardiovascular diseases, the impact of disease vectors (mosquitos) and surface hydrology exposure on malaria, and the effect of fast food restaurant exposure on obesity. Essential to health research is to disentangle the effects of the exposome and genome on health. Ultimately this requires quantifying the totality of all human exposures, for each individual in the studied human population. This poses a massive challenge to geoscientists, as environmental data are required at a high spatial and temporal resolution, with a large spatial and temporal coverage representing the area inhabited by the population studied and the time span representing several decades. Then, these data need to be combined with space-time paths of individuals to calculate personal exposures for each individual in the population. The Global and Geo Health Data Centre is taking this challenge by providing a web service capable of enriching population data with exposome information. Our web service can generate environmental information either from archived national (up to 5 m spatial and 1 h temporal resolution) and global environmental information or generated on the fly using environmental models running as microservices. On top of these environmental data services runs an individual exposure service enabling health researchers to select different spatial and temporal aggregation methods and to upload space-time paths of individuals. These are then enriched with personal exposures and eventually returned to the user. We illustrate the service in an example of individual exposures to air pollutants calculated from hyper resolution air pollution data and various approaches to estimate space-time paths of individuals.

First Attempt To Validate Human IgG Antibody Response to Nterm-34kDa Salivary Peptide as Biomarker for Evaluating Exposure to Aedes aegypti Bites

PubMed Central

Elanga Ndille, Emmanuel; Doucoure, Souleymane; Damien, Georgia; Mouchet, François; Drame, Papa Makhtar; Cornelie, Sylvie; Noukpo, Herbert; Yamadjako, Sandra; Djenontin, Armel; Moiroux, Nicolas; Misse, Dorothee; Akogbeto, Martin; Corbel, Vincent; Henry, Marie-Claire; Chandre, Fabrice; Baldet, Thierry; Remoue, Franck

2012-01-01

Background Much effort is being devoted for developing new indicators to evaluate the human exposure to Aedes mosquito bites and the risk of arbovirus transmission. Human antibody (Ab) responses to mosquito salivary components could represent a promising tool for evaluating the human-vector contact. Methodology/Principal findings To develop a specific biomarker of human exposure to Aedes aegypti bites, we measured IgG Ab response to Ae. aegypti Nterm-34 kDa salivary peptide in exposed children in 7 villages of Southern Benin (West Africa). Results showed that specific IgG response presented high inter-individual heterogeneity between villages. IgG response was associated with rainfall and IgG level increased from dry (low exposure) to rainy (high exposure) seasons. These findings indicate that IgG Ab to Nterm-34 kDa salivary peptide may represent a reliable biomarker to detect variation in human exposure to Ae. aegypti bites. Conclusion/Significance This preliminary study highlights the potential use of Ab response to this salivary peptide for evaluating human exposure to Ae. aegypti. This biomarker could represent a new promising tool for assessing the risk of arbovirus transmission and for evaluating the efficacy of vector control interventions. PMID:23166852

Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

PubMed

Teixeira, Clarissa; Gomes, Regis; Collin, Nicolas; Reynoso, David; Jochim, Ryan; Oliveira, Fabiano; Seitz, Amy; Elnaiem, Dia-Eldin; Caldas, Arlene; de Souza, Ana Paula; Brodskyn, Cláudia I; de Oliveira, Camila Indiani; Mendonca, Ivete; Costa, Carlos H N; Volf, Petr; Barral, Aldina; Kamhawi, Shaden; Valenzuela, Jesus G

2010-03-23

Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive. We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further tested against additional sand fly species. Recombinant proteins of nine transcripts encoding secreted salivary molecules of Lu. longipalpis were produced, purified, and tested for antigenicity and specificity. Use of recombinant proteins corresponding to immunogenic molecules in Lu. longipalpis saliva identified LJM17 and LJM11 as potential markers of exposure. LJM17 was recognized by human, dog, and fox sera; LJM11 by humans and dogs. Notably, LJM17 and LJM11 were specifically recognized by humans exposed to Lu. longipalpis but not by individuals exposed to Lu. intermedia. Salivary recombinant proteins are of value as markers of vector exposure. In humans, LJM17 and LJM11 emerged as potential markers of specific exposure to Lu. longipalpis, the vector of Leishmania infantum chagasi in Latin America. In dogs, LJM17, LJM11, LJL13, LJL23, and LJL143 emerged as potential markers of sand fly exposure. Testing these recombinant proteins in large scale studies will validate their usefulness as specific markers of Lu. longipalpis exposure in humans and of sand fly exposure in dogs.

Air pollution exposure prediction approaches used in air pollution epidemiology studies.

PubMed

Özkaynak, Halûk; Baxter, Lisa K; Dionisio, Kathie L; Burke, Janet

2013-01-01

Epidemiological studies of the health effects of outdoor air pollution have traditionally relied upon surrogates of personal exposures, most commonly ambient concentration measurements from central-site monitors. However, this approach may introduce exposure prediction errors and misclassification of exposures for pollutants that are spatially heterogeneous, such as those associated with traffic emissions (e.g., carbon monoxide, elemental carbon, nitrogen oxides, and particulate matter). We review alternative air quality and human exposure metrics applied in recent air pollution health effect studies discussed during the International Society of Exposure Science 2011 conference in Baltimore, MD. Symposium presenters considered various alternative exposure metrics, including: central site or interpolated monitoring data, regional pollution levels predicted using the national scale Community Multiscale Air Quality model or from measurements combined with local-scale (AERMOD) air quality models, hybrid models that include satellite data, statistically blended modeling and measurement data, concentrations adjusted by home infiltration rates, and population-based human exposure model (Stochastic Human Exposure and Dose Simulation, and Air Pollutants Exposure models) predictions. These alternative exposure metrics were applied in epidemiological applications to health outcomes, including daily mortality and respiratory hospital admissions, daily hospital emergency department visits, daily myocardial infarctions, and daily adverse birth outcomes. This paper summarizes the research projects presented during the symposium, with full details of the work presented in individual papers in this journal issue.

Cadmium osteotoxicity in experimental animals: Mechanisms and relationship to human exposures

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

Bhattacharyya, Maryka H.

Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure,more » within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.« less

Building-associated neurological damage modeled in human cells: a mechanism of neurotoxic effects by exposure to mycotoxins in the indoor environment.

PubMed

Karunasena, Enusha; Larrañaga, Michael D; Simoni, Jan S; Douglas, David R; Straus, David C

2010-12-01

Damage to human neurological system cells resulting from exposure to mycotoxins confirms a previously controversial public health threat for occupants of water-damaged buildings. Leading scientific organizations disagree about the ability of inhaled mycotoxins in the indoor environment to cause adverse human health effects. Damage to the neurological system can result from exposure to trichothecene mycotoxins in the indoor environment. This study demonstrates that neurological system cell damage can occur from satratoxin H exposure to neurological cells at exposure levels that can be found in water-damaged buildings contaminated with fungal growth. The constant activation of inflammatory and apoptotic pathways at low levels of exposure in human brain capillary endothelial cells, astrocytes, and neural progenitor cells may amplify devastation to neurological tissues and lead to neurological system cell damage from indirect events triggered by the presence of trichothecenes.

Identification of fipronil metabolites by time-of-flight mass spectrometry for application in a human exposure study

PubMed Central

McMahen, Rebecca L.; Strynar, Mark J.; Dagnino, Sonia; Herr, David W.; Moser, Virginia C.; Garantziotis, Stavros; Andersen, Erik M.; Freeborn, Danielle L.; McMillan, Larry; Lindstrom, Andrew B.

2016-01-01

Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10 mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported—M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively. Fipronil sulfone was confirmed to be the primary metabolite in rat serum. The fipronil metabolites identified in the respective matrices were then evaluated in matched human urine (n = 84) and serum (n = 96) samples from volunteers with no known pesticide exposures. Although no fipronil or metabolites were detected in human urine, fipronil sulfone was present in the serum of approximately 25% of the individuals at concentrations ranging from 0.1 to 4 ng/mL. These results indicate that many fipronil metabolites are produced following exposures in rats and that fipronil sulfone is a useful biomarker in human serum. Furthermore, human exposure to fipronil may occur regularly and require more extensive characterization. PMID:25687022

Identification of fipronil metabolites by time-of-flight mass spectrometry for application in a human exposure study.

PubMed

McMahen, Rebecca L; Strynar, Mark J; Dagnino, Sonia; Herr, David W; Moser, Virginia C; Garantziotis, Stavros; Andersen, Erik M; Freeborn, Danielle L; McMillan, Larry; Lindstrom, Andrew B

2015-05-01

Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported-M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively. Fipronil sulfone was confirmed to be the primary metabolite in rat serum. The fipronil metabolites identified in the respective matrices were then evaluated in matched human urine (n=84) and serum (n=96) samples from volunteers with no known pesticide exposures. Although no fipronil or metabolites were detected in human urine, fipronil sulfone was present in the serum of approximately 25% of the individuals at concentrations ranging from 0.1 to 4ng/mL. These results indicate that many fipronil metabolites are produced following exposures in rats and that fipronil sulfone is a useful biomarker in human serum. Furthermore, human exposure to fipronil may occur regularly and require more extensive characterization. Published by Elsevier Ltd.

The die is cast: arsenic exposure in early life and disease susceptibility.

PubMed

Thomas, David J

2013-12-16

Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

HExpoChem: a systems biology resource to explore human exposure to chemicals.

PubMed

Taboureau, Olivier; Jacobsen, Ulrik Plesner; Kalhauge, Christian; Edsgärd, Daniel; Rigina, Olga; Gupta, Ramneek; Audouze, Karine

2013-05-01

Humans are exposed to diverse hazardous chemicals daily. Although an exposure to these chemicals is suspected to have adverse effects on human health, mechanistic insights into how they interact with the human body are still limited. Therefore, acquisition of curated data and development of computational biology approaches are needed to assess the health risks of chemical exposure. Here we present HExpoChem, a tool based on environmental chemicals and their bioactivities on human proteins with the objective of aiding the qualitative exploration of human exposure to chemicals. The chemical-protein interactions have been enriched with a quality-scored human protein-protein interaction network, a protein-protein association network and a chemical-chemical interaction network, thus allowing the study of environmental chemicals through formation of protein complexes and phenotypic outcomes enrichment. HExpoChem is available at http://www.cbs.dtu.dk/services/HExpoChem-1.0/.

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.

COMPARING THE UTILITY OF MULTIMEDIA MODELS FOR HUMAN AND ECOLOGICAL EXPOSURE ANALYSIS: TWO CASES

EPA Science Inventory

A number of models are available for exposure assessment; however, few are used as tools for both human and ecosystem risks. This discussion will consider two modeling frameworks that have recently been used to support human and ecological decision making. The study will compare ...

MULTIPLE SOLVENT EXPOSURE IN HUMANS: CROSS-SPECIES EXTRAPOLATIONS

EPA Science Inventory

Multiple Solvent Exposures in Humans:
Cross-Species Extrapolations
(Future Research Plan)

Vernon A. Benignus1, Philip J. Bushnell2 and William K. Boyes2

A few solvents can be safely studied in acute experiments in human subjects. Data exist in rats f...

A systematic review of the human body burden of e-waste exposure in China.

PubMed

Song, Qingbin; Li, Jinhui

2014-07-01

As China is one of the countries facing the most serious pollution and human exposure effects of e-waste in the world, much of the population there is exposed to potentially hazardous substances due to informal e-waste recycling processes. This report reviews recent studies on human exposure to e-waste in China, with particular focus on exposure routes (e.g. dietary intake, inhalation, and soil/dust ingestion) and human body burden markers (e.g. placenta, umbilical cord blood, breast milk, blood, hair, and urine) and assesses the evidence for the association between such e-waste exposure and the human body burden in China. The results suggest that residents in the e-waste exposure areas, located mainly in the three traditional e-waste recycling sites (Taizhou, Guiyu, and Qingyuan), are faced with a potential higher daily intake of these pollutants than residents in the control areas, especially via food ingestion. Moreover, pollutants (PBBs, PBDEs, PCBs, PCDD/Fs, and heavy metals) from the e-waste recycling processes were all detectable in the tissue samples at high levels, showing that they had entered residents' bodies through the environment and dietary exposure. Children and neonates are the groups most sensitive to the human body effects of e-waste exposure. We also recorded plausible outcomes associated with exposure to e-waste, including 7 types of human body burden. Although the data suggest that exposure to e-waste is harmful to health, better designed epidemiological investigations in vulnerable populations, especially neonates and children, are needed to confirm these associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of proteome response to the mobile phone radiation in two types of human primary endothelial cells.

PubMed

Nylund, Reetta; Kuster, Niels; Leszczynski, Dariusz

2010-10-18

Use of mobile phones has widely increased over the past decade. However, in spite of the extensive research, the question of potential health effects of the mobile phone radiation remains unanswered. We have earlier proposed, and applied, proteomics as a tool to study biological effects of the mobile phone radiation, using as a model human endothelial cell line EA.hy926. Exposure of EA.hy926 cells to 900 MHz GSM radiation has caused statistically significant changes in expression of numerous proteins. However, exposure of EA.hy926 cells to 1800 MHz GSM signal had only very small effect on cell proteome, as compared with 900 MHz GSM exposure. In the present study, using as model human primary endothelial cells, we have examined whether exposure to 1800 MHz GSM mobile phone radiation can affect cell proteome. Primary human umbilical vein endothelial cells and primary human brain microvascular endothelial cells were exposed for 1 hour to 1800 MHz GSM mobile phone radiation at an average specific absorption rate of 2.0 W/kg. The cells were harvested immediately after the exposure and the protein expression patterns of the sham-exposed and radiation-exposed cells were examined using two dimensional difference gel electrophoresis-based proteomics (2DE-DIGE). There were observed numerous differences between the proteomes of human umbilical vein endothelial cells and human brain microvascular endothelial cells (both sham-exposed). These differences are most likely representing physiological differences between endothelia in different vascular beds. However, the exposure of both types of primary endothelial cells to mobile phone radiation did not cause any statistically significant changes in protein expression. Exposure of primary human endothelial cells to the mobile phone radiation, 1800 MHz GSM signal for 1 hour at an average specific absorption rate of 2.0 W/kg, does not affect protein expression, when the proteomes were examined immediately after the end of the exposure and when the false discovery rate correction was applied to analysis. This observation agrees with our earlier study showing that the 1800 MHz GSM radiation exposure had only very limited effect on the proteome of human endothelial cell line EA.hy926, as compared with the effect of 900 MHz GSM radiation.

Implementation of the integrated approach in different types of exposure scenarios.

PubMed

Copplestone, D; Hirth, G; Johansen, M; Lazo, E; Takala, J; Sakai, K; Yankovich, T

2018-01-01

The International Commission on Radiological Protection (ICRP) recognises three types of exposure situations: planned, existing, and emergency. In all three situations, the release of radionuclides into the natural environment leads to exposures of non-human biota, as well as the potential for exposures of the public. This paper describes how the key principles of the ICRP system of radiological protection apply to non-human biota and members of the public in each of these exposure situations. Current work in this area within ICRP Task Group 105 is highlighted. For example, how simplified numeric criteria may be used in planned exposure situations that are protective of both the public and non-human biota. In emergency exposure situations, the initial response will always be focused on human protection; however, understanding the potential impacts of radionuclide releases on non-human biota will likely become important in terms of communication as governments and the public seek to understand the exposures that are occurring. For existing exposure situations, there is a need to better understand the potential impacts of radionuclides on animals and plants, especially when deciding on protective actions. Understanding the comparative impacts from radiological, non-radiological, and physical aspects is often important in managing the remediation of legacy sites. Task Group 105 is making use of case studies of how exposure situations have been managed in the past to provide additional guidance and advice for the protection of non-human biota.

Including exposure variability in the life cycle impact assessment of indoor chemical emissions: the case of metal degreasing.

PubMed

Golsteijn, Laura; Huizer, Daan; Hauck, Mara; van Zelm, Rosalie; Huijbregts, Mark A J

2014-10-01

The present paper describes a method that accounts for variation in indoor chemical exposure settings and accompanying human toxicity in life cycle assessment (LCA). Metal degreasing with dichloromethane was used as a case study to show method in practice. We compared the human toxicity related to the degreasing of 1m(2) of metal surface in different exposure scenarios for industrial workers, professional users outside industrial settings, and home consumers. The fraction of the chemical emission that is taken in by exposed individuals (i.e. the intake fraction) was estimated on the basis of operational conditions (e.g. exposure duration), and protective measures (e.g. local exhaust ventilation). The introduction of a time-dependency and a correction for protective measures resulted in reductions in the intake fraction of up to 1.5 orders of magnitude, compared to application of existing, less advanced models. In every exposure scenario, the life cycle impacts for human toxicity were mainly caused by indoor exposure to metal degreaser (>60%). Emissions released outdoors contributed up to 22% of the life cycle impacts for human toxicity, and the production of metal degreaser contributed up to 19%. These findings illustrate that human toxicity from indoor chemical exposure should not be disregarded in LCA case studies. Particularly when protective measures are taken or in the case of a short duration (1h or less), we recommend the use of our exposure scenario-specific approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biomonitoring - An Exposure Science Tool for Exposure and Risk Assessment

EPA Science Inventory

Biomonitoring studies of environmental stressors are useful for confirming exposures, estimating dose levels, and evaluating human health risks. However, the complexities of exposure-biomarker and biomarker-response relationships have limited the use of biomarkers in exposure sc...

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

PubMed Central

Vandenberg, Laura N.; Chahoud, Ibrahim; Heindel, Jerrold J.; Padmanabhan, Vasantha; Paumgartten, Francisco J.R.; Schoenfelder, Gilbert

2010-01-01

Background Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. Importantly, results from a large number of biomonitoring studies are at odds with the results from two toxicokinetic studies. Objective We examined several possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. Data sources We examined > 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism. Data extraction and synthesis The > 80 biomonitoring studies examined included measurements in thousands of individuals from several different countries, and these studies overwhelmingly detected BPA in individual adults, adolescents, and children. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Some regulatory agencies have relied solely on these toxicokinetic models in their risk assessments. Conclusions Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes. PMID:20338858

Toxicological effects of nanoparticles from photocopiers

NASA Astrophysics Data System (ADS)

Khatri, Madhu

Nanotechnology is expanding rapidly and its fast-track to commercialization offering highly promising products and materials. Various physical, chemical and biological processes also results in unintentional generation of nanoparticles (NPs) leading to much higher concentrations at certain workplaces. Thus, human exposures to NPs from anthropogenic sources have increased dramatically in the past few decades. Recently, concerns have been expressed about the potential risks to human health occurring due to NP exposures in various workplaces. Although, a few recent studies have shown that the workplace exposure to NPs has the potential to cause serious human health problems such as pulmonary and related cardiovascular diseases, yet the evidence to establish their association is still lacking. This is partly due to lack of easily accessible settings with continuous NP exposures and the unavailability of sufficiently large cohorts of exposed workers. High volume photocopy (PC) centers are common and are generally operated by a permanent staff. It is now well known that laser printers and photocopiers emit NPs. We have observed that photocopiers emit significantly more NPs than laser printers and that the copy center environments had more than 20 times elevated NP levels over the background. It is evident that a significant fraction of airborne NPs get deposited in the alveolar and nasal cavity regions. Therefore, photocopy centers not only offer an opportunity to study response pattern in workers who are chronically exposed to NPs, but also to test and develop necessary methodologies to link exposures to engineered NPs and early health effects. In this study, early human health effects associated with acute NP exposure were studied. This was done by exposing a few health subjects to PC center environment for a short duration and measuring inflammatory and oxidative stress biomarkers in their nasal lavage and urine samples in response to such exposure. Additionally, potential in-vitro cytotoxicity and induction of cytokines of the collected NP generated during photocopying was studied. Furthermore, airborne fine PM collected from copy center was evaluated for their capability to induce in-vitro cytotoxicity and induction of cytokines. The research addresses one major knowledge gap between possible adverse effects on human health caused due to NP exposure. Additionally, this would help develop useful biomarkers for such exposures. These biomarkers could then assists in early detection of such effects and can potentially be used to assess human health risk from exposures to such NPs and device effective interventions if needed.

Human health exposure assessment for Rocky Mountain Arsenal study area evaluations. Volume 6-E. Central study area exposure assessment. Version 4. 1(volume 6-E). Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis A introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Human health exposure assessment for Rocky Mountain Arsenal study area evaluations. Volume 6-F. Eastern study area exposure assessment. Version 4. 1(volume 6-F). Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis A introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Human health exposure assessment for Rocky Mountain Arsenal study area evaluations. Volume 6-C. Southern study area exposure assessment version 4. 1. Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis A introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Prolonged particulate chromate exposure does not inhibit homologous recombination repair in North Atlantic right whale (Eubalaena glacialis) lung cells.

PubMed

Browning, Cynthia L; Wise, Catherine F; Wise, John Pierce

2017-09-15

Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability. Thus, the goal of this study was to determine the effect of prolonged Cr(VI) exposure on HR repair and clastogenesis in North Atlantic right whale (Eubalaena glacialis) lung cells. We show particulate Cr(VI) induces HR repair activity after both acute (24h) and prolonged (120h) exposure in North Atlantic right whale cells. Although the RAD51 response was lower following prolonged Cr(VI) exposure compared to acute exposure, the response was sufficient for HR repair to occur. In accordance with active HR repair, no increase in Cr(VI)-induced clastogenesis was observed with increased exposure time. These results suggest prolonged Cr(VI) exposure affects HR repair and genomic stability differently in whale and human lung cells. Future investigation of the differences in how human and whale cells respond to chemical carcinogens may provide valuable insight into mechanisms of preventing chemical carcinogenesis. Copyright © 2017. Published by Elsevier Inc.

Analysis of Coupled Model Uncertainties in Source to Dose Modeling of Human Exposures to Ambient Air Pollution: a PM2.5 Case-Study

EPA Science Inventory

Quantitative assessment of human exposures and health effects due to air pollution involve detailed characterization of impacts of air quality on exposure and dose. A key challenge is to integrate these three components on a consistent spatial and temporal basis taking into acco...

Polybrominated diphenyl ethers (PBDEs) in U.S. meat and poultry: 2012-13 levels, trends, and estimated consumer exposures

USDA-ARS?s Scientific Manuscript database

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants whose use has contaminated foods and caused subsequent human exposures. To address the issue of possible human exposure, samples from a 2012-13 U.S. meat and poultry (beef, pork, chicken, turkey) study were analyzed fo...

CONTROLLED DIESEL EXPOSURES: INTER-PHASING HUMAN AND ANIMAL STUDIES AND THEIR USE IN THE RISK ASSESSMENT

EPA Science Inventory

Controlled diesel exposures: Inter-phasing human and animal studies and their use in the risk assessment process.
Michael C. Madden, US EPA.

Particulate matter (PM) has been reported to be associated with health effects (e.g., premature deaths, hospitalizations, lung ...

Repeated measures of inflammation, blood pressure, and heart rate variability associated with personal traffic exposures in healthy adults

EPA Science Inventory

BACKGROUND: Previous human exposure studies of traffic-related air pollutants have demonstrated adverse health effects in human populations by comparing areas of high and low traffic, but few studies have utilized microenvironmental monitoring of pollutants at multiple traffic lo...

Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

NASA Technical Reports Server (NTRS)

Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

2003-01-01

Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

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

NORMAL MAMMARY GLAND MORPHOLOGY IN PUBERTAL FEMALE MICE FOLLOWING IN UTERO AND LACTATIONAL EXPOSURE TO GENISTEIN AT LEVELS COMPARABLE TO HUMAN DIETARY EXPOSURE. (R827402)

EPA Science Inventory

The objective of the study was to determine the effect of in utero and lactational exposure to genistein (0, 0.1, 0.5, 2.5 and 10 mg/kg/day) on mammary gland morphology in female B6D2F1 mice at levels comparable to or greater than human exposures. The effect of diethylstilbest...

Studying permethrin exposure in flight attendants using a physiologically based pharmacokinetic model

PubMed Central

Wei, Binnian; Isukapalli, Sastry S.; Weisel, Clifford P.

2014-01-01

Assessment of potential health risks to flight attendants from exposure to pyrethroid insecticides, used for aircraft disinsection, is limited because of (a) lack of information on exposures to these insecticides, and (b) lack of tools for linking these exposures to biomarker data. We developed and evaluated a physiologically based pharmacokinetic (PBPK) model to assess the exposure of flight attendants to the pyrethroid insecticide permethrin attributable to aircraft disinsection. The permethrin PBPK model was developed by adapting previous models for pyrethroids, and was parameterized using currently available metabolic parameters for permethrin. The human permethrin model was first evaluated with data from published human studies. Then, it was used to estimate urinary metabolite concentrations of permethrin in flight attendants who worked in aircrafts, which underwent residual and pre-flight spray treatments. The human model was also applied to analyze the toxicokinetics following permethrin exposures attributable to other aircraft disinsection scenarios. Predicted levels of urinary 3-phenoxybenzoic acid (3-PBA), a metabolite of permethrin, following residual disinsection treatment were comparable to the measurements made for flight attendants. Simulations showed that the median contributions of the dermal, oral and inhalation routes to permethrin exposure in flight attendants were 83.5%, 16.1% and 0.4% under residual treatment scenario, respectively, and were 5.3%, 5.0% and 89.7% under pre-flight spray scenario, respectively. The PBPK model provides the capability to simulate the toxicokinetic profiles of permethrin, and can be used in the studies on human exposure to permethrin. PMID:23462847

Effects of exposure to oil spills on human health: Updated review.

PubMed

Laffon, Blanca; Pásaro, Eduardo; Valdiglesias, Vanessa

2016-01-01

Oil spills may involve health risks for people participating in the cleanup operations and coastal inhabitants, given the toxicological properties of the oil components. In spite of this, only after a few major oil spills (crude oil or fuel oil no. 6) have studies on effects of exposure to diverse aspects of human health been performed. Previously, Aguilera et al. (2010) examined all documents published to that date dealing with any type of human health outcome in populations exposed to oil spills. The aim of the present review was to compile all new information available and determine whether evidence reported supports the existence of an association between exposure and adverse human health risks. Studies were classified in three groups according to type of health outcome addressed: (i) effects on mental health, (ii) physical/physiological effects, and (iii) genotoxic, immunotoxic, and endocrine toxicity. New studies published on oil-spill-exposed populations-coastal residents in the vicinity of the spills or participants in cleanup operations-provide additional support to previous evidence on adverse health effects related to exposure regarding different parameters in all three categories considered. Some of the observed effects even indicated that several symptoms may persist for some years after exposure. Hence, (1) health protection in these individuals should be a matter of concern; and (2) health risk assessment needs to be carried out not only at the time of exposure but also for prolong periods following exposure, to enable early detection of any potential exposure-related harmful effects.

Wastewater-based epidemiology to assess human exposure to pyrethroid pesticides.

PubMed

Rousis, Nikolaos I; Zuccato, Ettore; Castiglioni, Sara

2017-02-01

Pesticides are active substances with potentially adverse effects on human health, and therefore great effort is addressed to study the relation between their widespread use and the effects on humans. To track human exposure to pesticides, novel approaches are needed to give additional information on exposure at population level. In this study, a novel application of Wastewater-Based Epidemiology (WBE) was developed to measure the intake of pyrethroid pesticides in a population. Three human urinary metabolites of pyrethroids were selected and validated as biomarkers of exposure by evaluating their sources and stability in wastewater. They were measured by liquid chromatography-tandem mass spectrometry in raw urban wastewater collected from the wastewater treatment plants of six Italian cities. Their concentrations were used as biomarkers to back-calculate the intake of pyrethroid pesticides in the population. WBE results were in line with the urinary biomarker levels of biomonitoring studies considering dilution in wastewater. Significant differences in the metabolites levels were observed among different cities. Seasonal variations in human intake of pyrethroids were also seen, as expected, with higher intakes during spring/summer. Intakes in the six cities were compared with the acceptable daily intake (ADI) and it was concluded that some of the populations examined might face significant health risks. Results confirm that this method can provide supplementary information to biomonitoring studies and can be a valuable tool for obtaining objective, direct information on the real levels of exposure to pyrethroids of different populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human melatonin during continuous magnetic field exposure

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

Graham, C.; Cook, M.R.; Riffle, D.W.

This report describes the third in a series of double-blind, laboratory-based studies that were aimed at determining the effects of nocturnal exposure to power frequency magnetic fields on blood levels of melatonin in human volunteers. The two earlier studies evaluated effects on melatonin of intermittent exposure to 60 Hz circularly polarized magnetic fields at 10 and 200 mG. No overall effects on melatonin levels were found. In the present study, men were exposed continuously rather than intermittently through the night to the same 200 mG magnetic field condition that was used previously; again, no overall effects on melatonin levels weremore » found. The authors conclude that the intermittent and continuous exposure conditions used in the laboratory to date are not effective in altering nocturnal blood levels of melatonin in human volunteers.« less

Development of screening assays for nanoparticle toxicity assessment in human blood: preliminary studies with charged Au nanoparticles.

PubMed

Love, Sara A; Thompson, John W; Haynes, Christy L

2012-09-01

As nanoparticles have found increased use in both consumer and medical applications, corresponding increases in possible exposure to humans necessitate studies examining the impacts of these nanomaterials in biological systems. This article examines the effects of approximately 30-nm-diameter gold nanoparticles, with positively and negatively charged surface coatings in human blood. Here, we study the exposure effects, with up to 72 h of exposure to 5, 15, 25 and 50 µg/ml nanoparticles on hemolysis, reactive oxygen species (ROS) generation and platelet aggregation in subsets of cells from human blood. Assessing viability with hemolysis, results show significant changes in a concentration-dependent fashion. Rates of ROS generation were investigated using the dichlorofluorscein diacetate-based assay as ROS generation is a commonly suspected mechanism of nanoparticle toxicity; herein, ROS was not a significant factor. Optical monitoring of platelet aggregation revealed that none of the examined nanoparticles induced aggregation upon short-term exposure.

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.

Pesticide exposures and respiratory health in general populations.

PubMed

Ye, Ming; Beach, Jeremy; Martin, Jonathan W; Senthilselvan, Ambikaipakan

2017-01-01

Human exposures to pesticides can occur in the workplace, in the household and through the ambient environment. While several articles have reviewed the impact of pesticide exposures on human respiratory health in occupational settings, to the best of our knowledge, this article is the first one to review published studies on the association between pesticide exposures and human respiratory health in the general populations. In this article, we critically reviewed evidences up to date studying the associations between non-occupational pesticide exposures and respiratory health in general populations. This article also highlighted questions arising from these studies, including our recent analyses using the data from the Canadian Health Measures Survey (CHMS), for future research. We found few studies have addressed the impact of environmental pesticide exposures on respiratory health, especially on lung function, in general populations. In the studies using the data from CHMS Cycle 1, exposures to OP insecticides, pyrethroid insecticides, and the organochlorine pesticide DDT were associated with impaired lung function in the Canadian general population, but no significant associations were observed for the herbicide 2,4-D. Future research should focus on the potential age-specific and pesticide-specific effect on respiratory health in the general population, and repeated longitudinal study design is critical for assessing the temporal variations in pesticide exposures. Research findings from current studies of non-occupational pesticide exposures and their health impact in general population will help to improve the role of regulatory policies in mitigating pesticide-related public health problems, and thereafter providing greater benefit to the general population. Copyright © 2016. Published by Elsevier B.V.

The contribution of diet to total Bisphenol A body burden in humans: results of a 48 hour fasting study

EPA Science Inventory

Human biomonitoring studies measuring BPA in urine have shown widespread exposure in the general population. Diet is thought to be a major route of exposure. We studied urinary BPA patterns in five individuals over a 48-hr period of fasting (bottled water only). Personal acti...

Human health exposure assessment for Rocky Mountain Arsenal. Volume 7. Summary exposure assessment version 4. 1. Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis A introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Human health exposure assessment for Rocky Mountain Arsenal. Volume 8. Response to comments on the draft exposure assessment version 4. 1. Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis A introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

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

Fabrikant, J.I.

1981-05-01

The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures. (ACR)

Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.

PubMed

Sifakis, Stavros; Androutsopoulos, Vasilis P; Tsatsakis, Aristeidis M; Spandidos, Demetrios A

2017-04-01

Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system. Copyright © 2017 Elsevier B.V. All rights reserved.

TOWARD GREATER IMPLEMENTATION OF THE EXPOSOME RESEARCH PARADIGM WITHIN ENVIRONMENTAL EPIDEMIOLOGY

PubMed Central

Stingone, Jeanette A.; Buck Louis, Germaine M.; Nakayama, Shoji F.; Vermeulen, Roel C. H.; Kwok, Richard K.; Cui, Yuxia; Balshaw, David M.; Teitelbaum, Susan L.

2017-01-01

Investigating a single environmental exposure in isolation does not reflect the actual human exposure circumstance nor does it capture the multifactorial etiology of health and disease. The exposome, defined as the totality of environmental exposures from conception onward, may advance our understanding of environmental contributors to disease by more fully assessing the multitude of human exposures across the life course. Implementation into studies of human health has been limited, in part owing to theoretical and practical challenges including a lack of infrastructure to support comprehensive exposure assessment, difficulty in differentiating physiologic variation from environmentally induced changes, and the need for study designs and analytic methods that accommodate specific aspects of the exposome, such as high-dimensional exposure data and multiple windows of susceptibility. Recommendations for greater data sharing and coordination, methods development, and acknowledgment and minimization of multiple types of measurement error are offered to encourage researchers to embark on exposome research to promote the environmental health and well-being of all populations. PMID:28125387

Wildfire smoke exposure and human health: Significant gaps in research for a growing public health issue.

PubMed

Black, Carolyn; Tesfaigzi, Yohannes; Bassein, Jed A; Miller, Lisa A

2017-10-01

Understanding the effect of wildfire smoke exposure on human health represents a unique interdisciplinary challenge to the scientific community. Population health studies indicate that wildfire smoke is a risk to human health and increases the healthcare burden of smoke-impacted areas. However, wildfire smoke composition is complex and dynamic, making characterization and modeling difficult. Furthermore, current efforts to study the effect of wildfire smoke are limited by availability of air quality measures and inconsistent air quality reporting among researchers. To help address these issues, we conducted a substantive review of wildfire smoke effects on population health, wildfire smoke exposure in occupational health, and experimental wood smoke exposure. Our goal was to evaluate the current literature on wildfire smoke and highlight important gaps in research. In particular we emphasize long-term health effects of wildfire smoke, recovery following wildfire smoke exposure, and health consequences of exposure in children. Copyright © 2017 Elsevier B.V. All rights reserved.

Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review.

PubMed

Bach, Cathrine Carlsen; Vested, Anne; Jørgensen, Kristian Tore; Bonde, Jens Peter Ellekilde; Henriksen, Tine Brink; Toft, Gunnar

2016-10-01

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Systematic literature searches were initially conducted in MEDLINE and EMBASE and subsequently in references and citations of included papers. Studies were included if they assessed exposure to PFASs in biological samples in relation to reproductive hormones, semen characteristics, or time to pregnancy (TTP). Study characteristics and results were abstracted to predefined forms, and the studies were assessed for the risk of bias and confounding. Sixteen studies investigated the association between PFAS exposure in men and semen parameters, reproductive hormone levels, or TTP. There was a lack of consistent results among the numerous investigated exposure-outcome combinations. However, subtle associations between higher PFOS and lower testosterone or abnormal semen morphology cannot be excluded. Eleven studies assessed the association between PFAS exposure in women and TTP or reproductive hormones levels. Four of eight studies found prolonged TTP with higher PFOS or PFOA, but only one study found an association when restricting to nulliparous women. In men, there is little evidence of an association between PFAS exposure and semen quality or levels of reproductive hormones. For PFOS and PFOA, the literature indicates an association with female fecundability in parous women, which is most likely not causal.

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.

Breathing easier? The known impacts of biodiesel on air quality

PubMed Central

Traviss, Nora

2013-01-01

Substantial scientific evidence exists on the negative health effects of exposure to petroleum diesel exhaust. Many view biodiesel as a ‘green’, more environmentally friendly alternative fuel, especially with respect to measured reductions of particulate matter in tailpipe emissions. Tailpipe emissions data sets from heavy-duty diesel engines comparing diesel and biodiesel fuels provide important information regarding the composition and potential aggregate contribution of particulate matter and other pollutants to regional airsheds. However, exposure – defined in this instance as human contact with tailpipe emissions – is another key link in the chain between emissions and human health effects. Although numerous biodiesel emissions studies exist, biodiesel exposure studies are nearly absent from the literature. This article summarizes the known impacts of biodiesel on air quality and health effects, comparing emissions and exposure research. In light of rapidly changing engine, fuel and exhaust technologies, both emissions and exposure studies are necessary for developing a fuller understanding of the impact of biodiesel on air quality and human health. PMID:23585814

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.

EXPOSURE ANALYSIS FROM PERSONAL AND AMBIENT AIR SAMPLING: RESULTS OF THE 1998 BALTIMORE STUDY

EPA Science Inventory

An integrated epidemiological-exposure panel study was conducted during July-August 1998 which focused upon establishing relationships between potential human exposures to particulate matter (PM) and related co-pollutants with detectable health effects. The study design incorpo...

ALTERNATIVE EXPOSURE MEASUREMENT DESIGNS TO IMPROVE EPIDEMIOLOGICAL STUDY DESIGNS: DETERMINANTS OF TEMPORAL VARIABILITY IN ENVIRONMENTAL CONCENTRATIONS, EXPOSURES, AND BIOMARKERS

EPA Science Inventory

The National Human Exposure Assessment Survey in Maryland (NHEXAS-MD) was a longitudinal study of multimedia exposure to metals, pesticides, and polycyclic aromatic compounds (PAHs). Measurements were made and questionnaires were concurrently administered to identify sources o...

Reconstruction of Exposure to m-Xylene from Human Biomonitoring Data Using PBPK Modelling, Bayesian Inference, and Markov Chain Monte Carlo Simulation

PubMed Central

McNally, Kevin; Cotton, Richard; Cocker, John; Jones, Kate; Bartels, Mike; Rick, David; Price, Paul; Loizou, George

2012-01-01

There are numerous biomonitoring programs, both recent and ongoing, to evaluate environmental exposure of humans to chemicals. Due to the lack of exposure and kinetic data, the correlation of biomarker levels with exposure concentrations leads to difficulty in utilizing biomonitoring data for biological guidance values. Exposure reconstruction or reverse dosimetry is the retrospective interpretation of external exposure consistent with biomonitoring data. We investigated the integration of physiologically based pharmacokinetic modelling, global sensitivity analysis, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of inhalation exposure to m-xylene. We used exhaled breath and venous blood m-xylene and urinary 3-methylhippuric acid measurements from a controlled human volunteer study in order to evaluate the ability of our computational framework to predict known inhalation exposures. We also investigated the importance of model structure and dimensionality with respect to its ability to reconstruct exposure. PMID:22719759

The evaluation of stack metal emissions from hazardous waste incinerators: assessing human exposure through noninhalation pathways.

PubMed Central

Sedman, R M; Polisini, J M; Esparza, J R

1994-01-01

Potential public health effects associated with exposure to metal emissions from hazardous waste incinerators through noninhalation pathways were evaluated. Instead of relying on modeling the movement of toxicants through various environmental media, an approach based on estimating changes from baseline levels of exposure was employed. Changes in soil and water As, Cd, Hg, Pb, Cr, and Be concentrations that result from incinerator emissions were first determined. Estimates of changes in human exposure due to direct contact with shallow soil or the ingestion of surface water were then ascertained. Projected changes in dietary intakes of metals due to incinerator emissions were estimated based on changes from baseline dietary intakes that are monitored in U.S. Food and Drug Administration total diet studies. Changes from baseline intake were deemed to be proportional to the projected changes in soil or surface water metal concentrations. Human exposure to metals emitted from nine hazardous waste incinerators were then evaluated. Metal emissions from certain facilities resulted in tangible human exposure through noninhalation pathways. However, the analysis indicated that the deposition of metals from ambient air would result in substantially greater human exposure through noninhalation pathways than the emissions from most of the facilities. PMID:7925180

The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

PubMed Central

Kundakovic, Marija; Jaric, Ivana

2017-01-01

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

Human Bisphenol A Exposure and the “Diabesity Phenotype”

PubMed Central

Leone, Alessandro; Battezzati, Alberto

2015-01-01

Bisphenol A (BPA), a known endocrine disruptor, is a food contaminant suspected of being a contributing factor to the present-day increase in obesity, diabetes, and cardiovascular disease. This issue is of increasing interest in the field of diabetes research and has become a matter of concern for regulatory agencies and food industries. Recently, the number of studies involving BPA has increased exponentially, but there are still many gaps in the knowledge of the relationship between actual BPA exposure and cardiometabolic risk and of the modalities of food intake exposure, all of which prevents sound judgments concerning the risks to human health. This review focuses on the association between human exposure to BPA and obesity, thyroid function, diabetes, insulin resistance, metabolic syndrome, cardiovascular diseases, and BPA content in food. Many cross-sectional studies support, sometimes contradictorily, an adverse effect of BPA exposure on obesity, diabetes, and cardiovascular diseases. Few prospective studies support an adverse effect of BPA exposure on such pathologies. Moreover, no intervention studies have been conducted to evaluate the causality of such associations. This is mainly due to lack of an appropriate database of BPA content in foods, thus hindering any estimation of the usual dietary BPA intake. PMID:26858585

Human exposure to neonicotinoid insecticides and the evaluation of their potential toxicity: An overview.

PubMed

Han, Wenchao; Tian, Ying; Shen, Xiaoming

2018-02-01

Neonicotinoid insecticides have become the fastest growing class of insecticides over the past few decades. The insecticidal activity of neonicotinoids is attributed to their agonist action on nicotinic acetylcholine receptors (nAChRs). Because of the special selective action on nAChRs in central nervous system of insects, and versatility in application methods, neonicotinoids are used to protect crops and pets from insect attacks globally. Although neonicotinoids are considered low toxicity to mammals and humans in comparison with traditional insecticides, more and more studies show exposure to neonicotinoids pose potential risk to mammals and even humans. In recent years, neonicotinoids and their metabolites have been successfully detected in various human biological samples. Meanwhile, many studies have focused on the health effects of neonicotinoids on humans. Our aims here are to review studies on human neonicotinoid exposure levels, health effect, evaluation of potential toxicity and to suggest possible directions for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exposure to Mexicali PM10 Induces IL-8 Expression Through an Alternative NFKB Mechanism In Human Airway Epithelial Cells

EPA Science Inventory

Studies have shown associations between exposure to ambient air particulate matter (PM) and increased rates of cardio-pulmonary morbidity and mortality. The aim of this study was to examine the signaling events involved in the expression of inflammatory genes in cultured human ai...

Systematic review on the health effects of exposure to radiofrequency electromagnetic fields from mobile phone base stations.

PubMed

Röösli, Martin; Frei, Patrizia; Mohler, Evelyn; Hug, Kerstin

2010-12-01

to review and evaluate the recent literature on the health effects of exposure to mobile phone base station (MPBS) radiation. we performed a systematic review of randomized human trials conducted in laboratory settings and of epidemiological studies that investigated the health effects of MPBS radiation in the everyday environment. we included in the analysis 17 articles that met our basic quality criteria: 5 randomized human laboratory trials and 12 epidemiological studies. The majority of the papers (14) examined self-reported non-specific symptoms of ill-health. Most of the randomized trials did not detect any association between MPBS radiation and the development of acute symptoms during or shortly after exposure. The sporadically observed associations did not show a consistent pattern with regard to symptoms or types of exposure. We also found that the more sophisticated the exposure assessment, the less likely it was that an effect would be reported. Studies on health effects other than non-specific symptoms and studies on MPBS exposure in children were scarce. the evidence for a missing relationship between MPBS exposure up to 10 volts per metre and acute symptom development can be considered strong because it is based on randomized, blinded human laboratory trials. At present, there is insufficient data to draw firm conclusions about health effects from long-term low-level exposure typically occurring in the everyday environment.

Induction of oxidative stress by bisphenol A and its pleiotropic effects

PubMed Central

Gassman, Natalie R.

2016-01-01

Bisphenol A (BPA) has become a target of intense public scrutiny since concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer have emerged. BPA is a highly prevalent chemical in consumer products, and human exposure is thought to be ubiquitous. Numerous studies have demonstrated its endocrine disrupting properties and attributed exposure with cytotoxic, genotoxic, and carcinogenic effects; however, the results of these studies are still highly debated and a consensus about BPA's safety and its role in human disease has not been reached. One of the contributing factors is a lack of molecular mechanisms or modes of action that explain the diverse and pleiotropic effects observed after BPA exposure. The increase in BPA research seen over the last ten years has resulted in more studies that examine molecular mechanisms and revealed links between BPA-induced oxidative stress and human disease. Here, a review of the current literature examining BPA exposure and the induction of reactive oxygen species (ROS) or oxidative stress will be provided to examine the landscape of the current BPA literature and provide a framework for understanding how induction of oxidative stress by BPA may contribute to the pleiotropic effects observed after exposure. PMID:28181297

ALVEOLAR BREATH SAMPLING AND ANALYSIS IN HUMAN EXPOSURE ASSESSMENT STUDIES

EPA Science Inventory

Alveolar breath sampling and analysis can be extremely useful in exposure assessment studies involving volatile organic compounds (VOCs). Over recent years scientists from the EPA's National Exposure Research Laboratory have developed and refined an alveolar breath collection ...

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study

PubMed Central

Cullen, Elizabeth; Evans, David; Griffin, Chris; Burke, Padraig; Mannion, Rory; Burns, Damien; Flanagan, Andrew; Kellegher, Ann; Schoeters, Greet; Govarts, Eva; Biot, Pierre; Casteleyn, Ludwine; Castaño, Argelia; Kolossa-Gehring, Marike; Esteban, Marta; Schwedler, Gerda; Angerer, Jürgen; Knudsen, Lisbeth E.; Joas, Reinhard; Joas, Anke; Dumez, Birgit; Sepai, Ovnair; Exley, Karen; Aerts, Dominique

2017-01-01

Background: Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the ‘Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale’ (DEMOCOPHES) pilot biomonitoring study. Methods: the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results: Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions: The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood. PMID:29186834

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study.

PubMed

Cullen, Elizabeth; Evans, David; Griffin, Chris; Burke, Padraig; Mannion, Rory; Burns, Damien; Flanagan, Andrew; Kellegher, Ann; Schoeters, Greet; Govarts, Eva; Biot, Pierre; Casteleyn, Ludwine; Castaño, Argelia; Kolossa-Gehring, Marike; Esteban, Marta; Schwedler, Gerda; Koch, Holger M; Angerer, Jürgen; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Dumez, Birgit; Sepai, Ovnair; Exley, Karen; Aerts, Dominique

2017-11-25

Background : Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the 'Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale' (DEMOCOPHES) pilot biomonitoring study. Methods : the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results : Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions : The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood.

Role of Light in Breast Cancer

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

Stevens, Richard G.; Anderson, Larry E.; Michael F. Holick

1999-06-14

There is a prima facie reason for studying possible biological effects of light-at-night (LAN) in the laboratory and human health effects in the population at large: LAN from the use of electricity represent exposures in the human environment not previously encountered in human evolution. These LAN exposures are pervasive in industrialized societies, and any adverse health effects from them could result in considerable consequences for the population. In particular, exposures of pregnant women to LAN that might result in increased estrogen exposure in utero to their child may lead to increased tissue mass and increased lifetime risk of breast cancermore » of the child.« less

Controlled human exposures to ambient pollutant particles in susceptible populations

EPA Science Inventory

Epidemiologic studies have established an association between exposures to air pollution particles and human mortality and morbidity at concentrations of particles currently found in major metropolitan areas. The adverse effects of pollution particles are most prominent in suscep...

LESSONS LEARNED FROM FOUR EXPOSURE PANEL STUDIES: THE U.S. EPA'S PARTICULATE MATTER STUDIES INVOLVING ELDERLY COHORTS

EPA Science Inventory

The U.S. Environmental Protection Agency and its collaborators are conducting a series of human exposure panel studies on elderly (65+ years) subpopulations. The primary objectives of these studies are

-To determine personal and indoor exposures to particles and relate...

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.

Local Adaptation of Sun-Exposure-Dependent Gene Expression Regulation in Human Skin.

PubMed

Kita, Ryosuke; Fraser, Hunter B

2016-10-01

Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin. We then tested whether genetic variants may influence each individual's gene expression response to sun-exposure. Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). The allele frequencies of the RASSF9 se-eQTL across diverse populations correlate with the magnitude of solar radiation experienced by these populations, suggesting local adaptation to varying levels of sunlight. These results provide the first examples of sun-exposure-dependent regulatory variation and suggest that this variation has contributed to recent human adaptation.

Weight-of-evidence evaluation of short-term ozone exposure and cardiovascular effects.

PubMed

Goodman, Julie E; Prueitt, Robyn L; Sax, Sonja N; Lynch, Heather N; Zu, Ke; Lemay, Julie C; King, Joseph M; Venditti, Ferdinand J

2014-10-01

There is a relatively large body of research on the potential cardiovascular (CV) effects associated with short-term ozone exposure (defined by EPA as less than 30 days in duration). We conducted a weight-of-evidence (WoE) analysis to assess whether it supports a causal relationship using a novel WoE framework adapted from the US EPA's National Ambient Air Quality Standards causality framework. Specifically, we synthesized and critically evaluated the relevant epidemiology, controlled human exposure, and experimental animal data and made a causal determination using the same categories proposed by the Institute of Medicine report Improving the Presumptive Disability Decision-making Process for Veterans ( IOM 2008). We found that the totality of the data indicates that the results for CV effects are largely null across human and experimental animal studies. The few statistically significant associations reported in epidemiology studies of CV morbidity and mortality are very small in magnitude and likely attributable to confounding, bias, or chance. In experimental animal studies, the reported statistically significant effects at high exposures are not observed at lower exposures and thus not likely relevant to current ambient ozone exposures in humans. The available data also do not support a biologically plausible mechanism for CV effects of ozone. Overall, the current WoE provides no convincing case for a causal relationship between short-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation. Thus, we categorize the strength of evidence for a causal relationship between short-term exposure to ozone and CV effects as "below equipoise."

A POPULATION EXPOSURE MODEL FOR PARTICULATE MATTER: CASE STUDY RESULTS FOR PM 2.5 IN PHILADELPHIA, PA

EPA Science Inventory

A population exposure model for particulate matter (PM), called the Stochastic Human Exposure and Dose Simulation (SHEDS-PM) model, has been developed and applied in a case study of daily PM2.5 exposures for the population living in Philadelphia, PA. SHEDS-PM is a probabilisti...

Using exposure prediction tools to link exposure and dosimetry for risk based decisions: a case study with phthalates

EPA Science Inventory

The Population Life-course Exposure to Health Effects Modeling (PLETHEM) platform being developed provides a tool that links results from emerging toxicity testing tools to exposure estimates for humans as defined by the USEPA. A reverse dosimetry case study using phthalates was ...

A critical review of epidemiologic studies of radiofrequency exposure and human cancers.

PubMed Central

Elwood, J M

1999-01-01

This paper reviews studies that have assessed associations between likely exposure to radiofrequency (RF) transmissions and various types of human cancer. These studies include three cluster investigations and five studies relating to general populations; all of these studies consider place of residence at the time of cancer diagnosis in regard to proximity to radio or television transmitters. There are also five relevant occupational cohort studies and several case-control studies of particular types of cancer. These studies assessed a large number of possible associations. Several positive associations suggesting an increased risk of some types of cancer in those who may have had greater exposure to RF emissions have been reported. However, the results are inconsistent: there is no type of cancer that has been consistently associated with RF exposures. The epidemiologic evidence falls short of the strength and consistency of evidence that is required to come to a reasonable conclusion that RF emissions are a likely cause of one or more types of human cancer. The evidence is weak in regard to its inconsistency, the design of the studies, the lack of detail on actual exposures, and the limitations of the studies in their ability to deal with other likely relevant factors. In some studies there may be biases in the data used PMID:10229715

Inflammatory Cytokines and White Blood Cell Counts ...

EPA Pesticide Factsheets

Epidemiological observations of urban inhalation exposures to diesel exhaust (DE) and ozone (O3) have shown pre-clinical cardiopulmonary responses in humans. Identifying the key biological mechanisms that initiate these health bioindicators is difficult due to variability in environmental exposure in time and from person to person. Previously, environmentally controlled human exposure chambers have been used to study DE and O3 dose-response patterns separately, but investigation of co-exposures has not been performed under controlled conditions. Because a mixture is a more realistic exposure scenario for the general public, in this study we investigate the relationships of urban levels of urban-level DE exposure (300 μg/m3), O3 (0.3 ppm), DE + O3 co-exposure, and innate immune system responses. Fifteen healthy human volunteers were studied for changes in ten inflammatory cytokines (interleukins 1β, 2, 4, 5, 8, 10, 12p70 and 13, IFN-γ, and TNF-α) and counts of three white blood cell types (lymphocytes, monocytes, and neutrophils) following controlled exposures to DE, O3, and DE+O3. The results show subtle cytokines responses to the diesel-only and ozone-only exposures, and that a more complex (possibly synergistic) relationship exists in the combination of these two exposures with suppression of IL-5, IL-12p70, IFN-γ, and TNF-α that persists up to 22-hours for IFN-γ and TNF-α. The white blood cell differential counts showed significant monocyte and lympho

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.

Impacts on prenatal development of the human cerebellum: a systematic review.

PubMed

Koning, Irene V; Tielemans, Myrte J; Hoebeek, Freek E; Ecury-Goossen, Ginette M; Reiss, Irwin K M; Steegers-Theunissen, Regine P M; Dudink, Jeroen

2017-10-01

The cerebellum is essential for normal neurodevelopment and is particularly susceptible for intra-uterine disruptions. Although some causal prenatal exposures have been identified, the origin of neurodevelopmental disorders remains mostly unclear. Therefore, a systematic literature search was conducted to provide an overview of parental environmental exposures and intrinsic factors influencing prenatal cerebellar growth and development in humans. The literature search was limited to human studies in the English language and was conducted in Embase, Medline, Cochrane, Web of Science, Pubmed and GoogleScholar. Eligible studies were selected by three independent reviewers and study quality was scored by two independent reviewers. The search yielded 3872 articles. We found 15 eligible studies reporting associations between cerebellar development and maternal smoking (4), use of alcohol (3), in vitro fertilization mediums (1), mercury (1), mifepristone (2), aminopropionitriles (1), ethnicity (2) and cortisol levels (1). No studies reported on paternal factors. Current literature on associations between parental environmental exposures, intrinsic factors and human cerebellar development is scarce. Yet, this systematic review provided an essential overview of human studies demonstrating the vulnerability of the cerebellum to the intra-uterine environment.

Human Health Effects Associated with Exposure to Cyanobacteria and Cyanotoxins: What Do We Know?

EPA Science Inventory

The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

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...

The properties of human body phantoms used in calculations of electromagnetic fields exposure by wireless communication handsets or hand-operated industrial devices.

PubMed

Zradziński, Patryk

2013-06-01

According to international guidelines, the assessment of biophysical effects of exposure to electromagnetic fields (EMF) generated by hand-operated sources needs the evaluation of induced electric field (E(in)) or specific energy absorption rate (SAR) caused by EMF inside a worker's body and is usually done by the numerical simulations with different protocols applied to these two exposure cases. The crucial element of these simulations is the numerical phantom of the human body. Procedures of E(in) and SAR evaluation due to compliance analysis with exposure limits have been defined in Institute of Electrical and Electronics Engineers standards and International Commission on Non-Ionizing Radiation Protection guidelines, but a detailed specification of human body phantoms has not been described. An analysis of the properties of over 30 human body numerical phantoms was performed which has been used in recently published investigations related to the assessment of EMF exposure by various sources. The differences in applicability of these phantoms in the evaluation of E(in) and SAR while operating industrial devices and SAR while using mobile communication handsets are discussed. The whole human body numerical phantom dimensions, posture, spatial resolution and electric contact with the ground constitute the key parameters in modeling the exposure related to industrial devices, while modeling the exposure from mobile communication handsets, which needs only to represent the exposed part of the human body nearest to the handset, mainly depends on spatial resolution of the phantom. The specification and standardization of these parameters of numerical human body phantoms are key requirements to achieve comparable and reliable results from numerical simulations carried out for compliance analysis against exposure limits or within the exposure assessment in EMF-related epidemiological studies.

IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal

PubMed Central

2012-01-01

Background Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low. Methods One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district. Results Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to Anopheles gambiae bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and Anopheles mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to Anopheles bites between different exposure groups of districts. Conclusions Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to Anopheles bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings. PMID:22424570

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

Autopsy tissues as biological monitors of human exposure to environmental pollutants. A case study: Concentrations of metals and PCDD/Fs in subjects living near a hazardous waste incinerator.

PubMed

Domingo, José L; García, Francisco; Nadal, Martí; Schuhmacher, Marta

2017-04-01

Human biomonitoring is of tremendous importance to prevent potential adverse effects derived from human exposure to chemicals. Blood and urine are among the biological monitors more frequently used. However, biological matrices such as breast milk, hair, nails, saliva, feces, teeth, and expired air are also often used. In addition, and focused mainly on long-term exposure, adipose tissue and other human tissues like bone, liver, brain or kidney, are also used as biological monitors of certain substances, especially for long-term biomonitoring. However, for this kind of tissues sampling is always a limiting factor. In this paper, we have examined the role of autopsy tissues as biological monitors of human exposure to environmental pollutants. For it, we have used a case study conducted near a hazardous waste incinerator (HWI) in Catalonia (Spain), in which the concentrations of metals and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), have been periodically determined in autopsy tissues of subjects living in the area under potential influence of the facility. This case study does not show advantages -in comparison to other appropriate biomonitors such as blood- in using autopsy tissues in the monitoring of long-term exposure to metals and PCDD/Fs. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

HBCD and TBBPA in human scalp hair: Evidence of internal exposure.

PubMed

Barghi, Mandana; Shin, Eun-Su; Choi, Sung-Deuk; Dahmardeh Behrooz, Reza; Chang, Yoon-Seok

2018-09-01

Human biomonitoring is a reliable method for evaluating human exposure to specific contaminants. Although blood is an ideal matrix for monitoring purposes, it is regarded as an invasive matrix. Therefore, current developments in the field of human biomonitoring are based on introducing new methods that use non-invasive matrices, such as hair. In this study, we examined the efficiencies of several extraction methods for the analysis of hexabromocyclododecane (HBCD) and tetrabromobisphenol-A (TBBPA) in human hair. The selected pretreatment method was validated through a general QA/QC process that included spiking experiments, and then, the method was used for the determination of HBCD and TBBPA concentrations in scalp hair samples collected from individuals in Korea (n = 24) and Iran (n = 15). The HBCD and TBBPA concentrations in the collected hair samples ranged from ND to 3.24 ng g -1 and ND to 16.04 ng g -1 , respectively. Significantly higher concentrations of TBBPA were found in hair samples from Korea than those in hair samples from Iran (p < 0.05), which is expected to be the result of the large market and higher exposure of TBBPA in Korea. HBCD was not detected in hair samples from Iran. According to our knowledge this is the first study demonstrating the presence of TBBPA in human hair with nonspecific exposure. Lastly, we investigated the important factors that influence the interpretation of the contributions of endogenous and exogenous contaminations in hair. Based on the information, the HBCD and TBBPA in the collected hair samples were most likely from endogenous exposure. Therefore, our study showed that hair is potentially a suitable indicator for the monitoring of internal exposure to HBCD and TBBPA in different populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

PubMed

Qian, Yong; Ducatman, Alan; Ward, Rebecca; Leonard, Steve; Bukowski, Valerie; Lan Guo, Nancy; Shi, Xianglin; Vallyathan, Val; Castranova, Vincent

2010-01-01

Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally. PFOS is non-biodegradable and is persistent in the human body and environment. In this study, data demonstrated that exposure of human microvascular endothelial cells (HMVEC) to PFOS induced the production of reactive oxygen species (ROS) at both high and low concentrations. Morphologically, it was found that exposure to PFOS induced actin filament remodeling and endothelial permeability changes in HMVEC. Furthermore, data demonstrated that the production of ROS plays a regulatory role in PFOS-induced actin filament remodeling and the increase in endothelial permeability. Our results indicate that the generation of ROS may play a role in PFOS-induced aberrations of the endothelial permeability barrier. The results generated from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans at the cellular level.

Human health risk assessment of triclosan in land-applied biosolids.

PubMed

Verslycke, Tim; Mayfield, David B; Tabony, Jade A; Capdevielle, Marie; Slezak, Brian

2016-09-01

Triclosan (5-chloro-2-[2,4-dichlorophenoxy]-phenol) is an antimicrobial agent found in a variety of pharmaceutical and personal care products. Numerous studies have examined the occurrence and environmental fate of triclosan in wastewater, biosolids, biosolids-amended soils, and plants and organisms exposed to biosolid-amended soils. Triclosan has a propensity to adhere to organic carbon in biosolids and biosolid-amended soils. Land application of biosolids containing triclosan has the potential to contribute to multiple direct and indirect human health exposure pathways. To estimate exposures and human health risks from biosolid-borne triclosan, a risk assessment was conducted in general accordance with the methodology incorporated into the US Environmental Protection Agency's Part 503 biosolids rule. Human health exposures to biosolid-borne triclosan were estimated on the basis of published empirical data or modeled using upper-end environmental partitioning estimates. Similarly, a range of published triclosan human health toxicity values was evaluated. Margins of safety were estimated for 10 direct and indirect exposure pathways, both individually and combined. The present risk assessment found large margins of safety (>1000 to >100 000) for potential exposures to all pathways, even under the most conservative exposure and toxicity assumptions considered. The human health exposures and risks from biosolid-borne triclosan are concluded to be de minimis. Environ Toxicol Chem 2016;35:2358-2367. © 2016 SETAC. © 2016 SETAC.

Benzo[a]pyrene, Aflatoxine B1 and Acetaldehyde Mutational Patterns in TP53 Gene Using a Functional Assay: Relevance to Human Cancer Aetiology

PubMed Central

Paget, Vincent; Lechevrel, Mathilde; André, Véronique; Le Goff, Jérémie; Pottier, Didier; Billet, Sylvain; Garçon, Guillaume; Shirali, Pirouz; Sichel, François

2012-01-01

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B1 exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B1 and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers. PMID:22319594

Analysis of currently available data for characterising the risk of engineered nanomaterials to the environment and human health--lessons learned from four case studies.

PubMed

Aschberger, Karin; Micheletti, Christian; Sokull-Klüttgen, Birgit; Christensen, Frans M

2011-08-01

Production volumes and the use of engineered nanomaterials in many innovative products are continuously increasing, however little is known about their potential risk for the environment and human health. We have reviewed publicly available hazard and exposure data for both, the environment and human health and attempted to carry out a basic risk assessment appraisal for four types of nanomaterials: fullerenes, carbon nanotubes, metals, and metal oxides (ENRHES project 2009(1)). This paper presents a summary of the results of the basic environmental and human health risk assessments of these case studies, highlighting the cross cutting issues and conclusions about fate and behaviour, exposure, hazard and methodological considerations. The risk assessment methodology being the basis for our case studies was that of a regulatory risk assessment under REACH (ECHA, 2008(2)), with modifications to adapt to the limited available data. If possible, environmental no-effect concentrations and human no-effect levels were established from relevant studies by applying assessment factors in line with the REACH guidance and compared to available exposure data to discuss possible risks. When the data did not allow a quantitative assessment, the risk was assessed qualitatively, e.g. for the environment by evaluating the information in the literature to describe the potential to enter the environment and to reach the potential ecological targets. Results indicate that the main risk for the environment is expected from metals and metal oxides, especially for algae and Daphnia, due to exposure to both, particles and ions. The main risks for human health may arise from chronic occupational inhalation exposure, especially during the activities of high particle release and uncontrolled exposure. The information on consumer and environmental exposure of humans is too scarce to attempt a quantitative risk characterisation. It is recognised that the currently available database for both, hazard and exposure is limited and there are high uncertainties in any conclusion on a possible risk. The results should therefore not be used for any regulatory decision making. Likewise, it is recognised that the REACH guidance was developed without considering the specific behaviour and the mode of action of nanomaterials and further work in the generation of data but also in the development of methodologies is required. Copyright © 2011 Elsevier Ltd. All rights reserved.

Linking pesticides and human health: a geographic information system (GIS) and Landsat remote sensing method to estimate agricultural pesticide exposure.

PubMed

VoPham, Trang; Wilson, John P; Ruddell, Darren; Rashed, Tarek; Brooks, Maria M; Yuan, Jian-Min; Talbott, Evelyn O; Chang, Chung-Chou H; Weissfeld, Joel L

2015-08-01

Accurate pesticide exposure estimation is integral to epidemiologic studies elucidating the role of pesticides in human health. Humans can be exposed to pesticides via residential proximity to agricultural pesticide applications (drift). We present an improved geographic information system (GIS) and remote sensing method, the Landsat method, to estimate agricultural pesticide exposure through matching pesticide applications to crops classified from temporally concurrent Landsat satellite remote sensing images in California. The image classification method utilizes Normalized Difference Vegetation Index (NDVI) values in a combined maximum likelihood classification and per-field (using segments) approach. Pesticide exposure is estimated according to pesticide-treated crop fields intersecting 500 m buffers around geocoded locations (e.g., residences) in a GIS. Study results demonstrate that the Landsat method can improve GIS-based pesticide exposure estimation by matching more pesticide applications to crops (especially temporary crops) classified using temporally concurrent Landsat images compared to the standard method that relies on infrequently updated land use survey (LUS) crop data. The Landsat method can be used in epidemiologic studies to reconstruct past individual-level exposure to specific pesticides according to where individuals are located.

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER BRAINSTEM AUDITORY EVOKED RESPONSE (BAERS) IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in auditory structures in the periphery and the brainstem and is altered following chlorpyrifos exposure. This study e...

Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure.

PubMed

Mesaros, Clementina; Worth, Andrew J; Snyder, Nathaniel W; Christofidou-Solomidou, Melpo; Vachani, Anil; Albelda, Steven M; Blair, Ian A

2015-01-01

Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.

Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure

PubMed Central

Mesaros, Clementina; Worth, Andrew J; Snyder, Nathaniel W; Christofidou-Solomidou, Melpo; Vachani, Anil; Albelda, Steven M; Blair, Ian A

2015-01-01

Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses. PMID:26039812

Xenotransplantation as a model for human testicular development.

PubMed

Hutka, Marsida; Smith, Lee B; Mitchell, Rod T

The developing male reproductive system may be sensitive to disruption by a wide range of exogenous 'endocrine disruptors'. In-utero exposure to environmental chemicals and pharmaceuticals have been hypothesized to have an impact in the increasing incidence of male reproductive disorders. The vulnerability to adverse effects as a consequence of such exposures is elevated during a specific 'window of susceptibility' in fetal life referred to as the masculinisation programing window (MPW). Exposures that occur during prepuberty, such as chemotherapy treatment for cancer during childhood, may also affect future fertility. Much of our current knowledge about fetal and early postnatal human testicular development derives from studies conducted in animal models predictive for humans. Therefore, over recent years, testicular transplantation has been employed as a 'direct' approach to understand the development of human fetal and prepubertal testis in health and disease. In this review we describe the potential use of human testis xenotransplantation to study testicular development and its application for (i) assessing the effects of environmental exposures in humans, and (ii) establishing fertility preservation options for prepubertal boys with cancer. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Arsenic is Cytotoxic and Genotoxic to Primary Human Lung Cells

PubMed Central

Xie, Hong; Huang, ShouPing; Martin, Sarah; Wise, John P.

2014-01-01

Arsenic originates from both geochemical and numerous anthropogenic activities. Exposure of the general public to significant levels of arsenic is widespread. Arsenic is a well-documented human carcinogen. Long-term exposure to high levels of arsenic in drinking water have been linked to bladder, lung, kidney, liver, prostate, and skin cancer. Among them, lung cancer is of great public concern. However, little is known about how arsenic causes lung cancer and few studies have considered effects in normal human lung cells. The purpose of this study was to determine the cytotoxicity and genotoxicity of arsenic in human primary bronchial fibroblast and epithelial cells. Our data show that arsenic induces a concentration-dependent decrease in cell survival after short (24 h) or long (120 h) exposures. Arsenic induces concentration-dependent but not time-dependent increases in chromosome damage in fibroblasts. No chromosome damage is induced after either 24 h or 120 h arsenic exposure in epithelial cells. Using neutral comet assay and gamma-H2A.X foci forming assay, we found that 24 h or 120 h exposure to arsenic induces increases in DNA double strand breaks in both cell lines. These data indicate that arsenic is cytotoxic and genotoxic to human lung primary cells but lung fibroblasts are more sensitive to arsenic than epithelial cells. Further research is needed to understand the specific mechanisms involved in arsenic-induced genotoxicity in human lung cells. PMID:24291234

Analgesic use in pregnancy and male reproductive development

PubMed Central

Hurtado-Gonzalez, Pablo; Mitchell, Rod T.

2017-01-01

Purpose of review Male reproductive disorders are common and increasing in incidence in many countries. Environmental factors (including pharmaceuticals) have been implicated in the development of these disorders. This review aims to summarise the emerging epidemiological and experimental evidence for a potential role of in-utero exposure to analgesics in the development of male reproductive disorders. Recent findings A number of epidemiological studies have demonstrated an association between in-utero exposure to analgesics and the development of cryptorchidism, although these findings are not consistent across all studies. Where present, these associations primarily relate to exposure during the second trimester of pregnancy. In-vivo and in-vitro experimental studies have demonstrated variable effects of exposure to analgesics on Leydig cell function in the fetal testis of rodents, particularly in terms of testosterone production. These effects frequently involve exposures that are in excess of those to which humans are exposed. Investigation of the effects of analgesics on human fetal testis have also demonstrated effects on Leydig cell function. Variation in species, model system, dosage and timing of exposure is likely to contribute to differences in the findings between studies. Summary There is increasing evidence for analgesic effects on the developing testis that have the potential to impair reproductive function. However, the importance of these findings in relation to human-relevant exposures and the risk of male reproductive disorders remains unclear. PMID:28277341

Risk assessment of human health from exposure to the discharged ballast water after full-scale electrolysis treatment.

PubMed

Zhang, Nahui; Wang, Yidan; Xue, Junzeng; Yuan, Lin; Wang, Qiong; Liu, Liang; Wu, Huixian; Hu, Kefeng

2016-06-01

The presence of disinfection by-products (DBPs) releasing from ballast water management systems (BWMS) can cause a possible adverse effects on humans. The objectives of this study were to compute the Derived No Effect Levels (DNELs) for different exposure scenarios and to compare these levels with the exposure levels from the measured DBPs in treated ballast water. The risk assessment showed that when using animal toxicity data, all the DNELs values were approximately 10(3)-10(12) times higher than the exposure levels of occupational and general public exposure scenarios, indicating the level of risk was low (risk characterization ratios (RCRs) < 1). However, when using human data, the RCRs were higher than 1 for dichlorobromomethane and trichloromethane, indicating that the risk of adverse effects on human were significant. This implies that there are apparent discrepancies between risk characterization from animal and human data, which may affect the overall results. We therefore recommend that when appropriate, human data should be used in risk assessment as much as possible, although human data are very limited. Moreover, more appropriate assessment factors can be considered to be employed in estimating the DNELs for human when the animal data is selected as the dose descriptors. Copyright © 2016 Elsevier Inc. All rights reserved.

Hair and Nails as Noninvasive Biomarkers of Human Exposure to Brominated and Organophosphate Flame Retardants.

PubMed

Liu, Liang-Ying; He, Ka; Hites, Ronald A; Salamova, Amina

2016-03-15

After the phase-out of polybrominated diphenyl ethers (PBDEs), the use of alternative flame retardants (AFRs), such as FireMaster 550, and of organophosphate esters (OPEs) has increased. However, little is known about human exposure to these chemicals. This lack of biomonitoring studies is partially due to the absence of reliable noninvasive biomarkers of exposure. Human hair and nails can provide integrated exposure measurements, and as such, these matrices can potentially be used as noninvasive biomarkers of exposure to these flame retardants. Paired human hair, fingernail, toenail, and serum samples obtained from 50 adult participants recruited at Indiana University Bloomington campus were analyzed by gas chromatographic mass spectrometry for 36 PBDEs, 9 AFRs, and 12 OPEs. BDE-47, BDE-99, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), di(2-ethylhexyl) tetrabromophthalate (TBPH), tris(1,3-dichloro-2-propyl)phosphate (TDCIPP), and triphenyl phosphate (TPHP) were the most abundant compounds detected in almost all hair, fingernail, and toenail samples. The concentrations followed the order OPEs > TBB+TBPH > Σpenta-BDE. PBDE levels in the hair and nail samples were significantly correlated with their levels in serum (P < 0.05), suggesting that human hair and nails can be used as biomarkers to assess human exposure to PBDEs.

Systematic review on the health effects of exposure to radiofrequency electromagnetic fields from mobile phone base stations

PubMed Central

Frei, Patrizia; Mohler, Evelyn; Hug, Kerstin

2010-01-01

Abstract Objective To review and evaluate the recent literature on the health effects of exposure to mobile phone base station (MPBS) radiation. Methods We performed a systematic review of randomized human trials conducted in laboratory settings and of epidemiological studies that investigated the health effects of MPBS radiation in the everyday environment. Findings We included in the analysis 17 articles that met our basic quality criteria: 5 randomized human laboratory trials and 12 epidemiological studies. The majority of the papers (14) examined self-reported non-specific symptoms of ill-health. Most of the randomized trials did not detect any association between MPBS radiation and the development of acute symptoms during or shortly after exposure. The sporadically observed associations did not show a consistent pattern with regard to symptoms or types of exposure. We also found that the more sophisticated the exposure assessment, the less likely it was that an effect would be reported. Studies on health effects other than non-specific symptoms and studies on MPBS exposure in children were scarce. Conclusion The evidence for a missing relationship between MPBS exposure up to 10 volts per metre and acute symptom development can be considered strong because it is based on randomized, blinded human laboratory trials. At present, there is insufficient data to draw firm conclusions about health effects from long-term low-level exposure typically occurring in the everyday environment. PMID:21124713

Concentrations of environmental organic contaminants in meat and meat products and human dietary exposure: A review.

PubMed

Domingo, José L

2017-09-01

Meat and meat products is one of the most relevant food groups in an important number of human diets. Recently, the IARC, based on results of a number of epidemiological studies, classified the consumptions of red meat and processed meat as "probably carcinogenic to humans" and as "carcinogenic to humans", respectively. It was suggested that the substances responsible of the potential carcinogenicity would be mainly generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures. However, the exposure to environmental pollutants through meat consumption was not discussed. The purpose of the present paper was to review recent studies reporting the concentrations of PCDD/Fs, DL-PCBs and PAHs in meat and meat products, as well as the human exposure to these pollutants through the diet. It is concluded that the health risks derived from exposure to carcinogenic environmental contaminants must be considered in the context of each specific diet, which besides meat and meat products, includes other foodstuffs containing also chemical pollutants, some of them with carcinogenic potential. Anyhow, meat and meat products are not the main food group responsible of the dietary exposure to carcinogenic (or probably carcinogenic) environmental organic pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neurophysiologic measures of auditory function in fish consumers: associations with long chain polyunsaturated fatty acids and methylmercury.

PubMed

Dziorny, Adam C; Orlando, Mark S; Strain, J J; Davidson, Philip W; Myers, Gary J

2013-09-01

Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily be quantified, and might be helpful additions to testing. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants and whether they are associated with children's neurodevelopment. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles.

PubMed

Ji, Jie; Hedelin, Anna; Malmlöf, Maria; Kessler, Vadim; Seisenbaeva, Gulaim; Gerde, Per; Palmberg, Lena

2017-01-01

Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents. In this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI). Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER) measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd) nanoparticles which sized 6-10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system. Exposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM. This combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting.

Modeling spatial patterns of link-based PM2.5 emissions and subsequent human exposure in a large canadian metropolitan area

NASA Astrophysics Data System (ADS)

Requia, Weeberb J.; Dalumpines, Ron; Adams, Matthew D.; Arain, Altaf; Ferguson, Mark; Koutrakis, Petros

2017-06-01

Understanding the relationship between mobile source emissions and subsequent human exposure is crucial for emissions control. Determining this relationship over space is fundamental to improve the accuracy and precision of public policies. In this study, we evaluated the spatial patterns of link-based PM2.5 emissions and subsequent human exposure in a large Canadian metropolitan area - the Greater Toronto and Hamilton Area (GTHA). This study was performed in three stages. First, we estimated vehicle emissions using transportation models and emission simulators. Then we evaluated human exposure to PM2.5 emissions using the Intake fraction (iF) approach. Finally, we applied geostatistical methods to assess spatial patterns of vehicle emissions and subsequent human exposure based on three prospective goals: i) classification of emissions (Global Moran's I test), ii) level of emission exposure (Getis-Ord General G test), and; iii) location of emissions (Anselin Local Moran's I). Our results showed that passenger vehicles accounted for the highest total amount of PM2.5 emissions, representing 57% emissions from all vehicles. Examining only the emissions from passenger vehicles, on average, each person in the GTHA inhales 2.58 × 10-3 ppm per day. Accounting the emissions from buses and trucks, on average each person inhales 0.12 × 10-3 and 1.91 × 10-3 ppm per day, respectively. For both PM2.5 emissions and human exposure using iF approach, our analysis showed Moran's Index greater than 0 for all vehicle categories, suggesting the presence of significant clusters (p-value <0.01) in the region. Our study indicates that air pollution control policy must be developed for the whole region, because of the spatial distribution of housing and businesses centers and inter-connectivity of transportation networks across the region, where a policy cannot simply be based on a municipal or other boundaries.

E-waste environmental contamination and harm to public health in China.

PubMed

Xu, Xijin; Zeng, Xiang; Boezen, H Marike; Huo, Xia

2015-06-01

The adverse effects of electronic waste (e-waste) on the human body have stirred up concern in recent years. China is one of the countries that confront serious pollution and human exposure of e-waste, and the majority of the population is exposed to potentially hazardous substances that are derived from informal e-waste recycling processes. This study reviews recent reports on human exposure to e-waste in China, with particular focus on exposure routes (e.g., inhalation and ingestion) and several toxicities of human (e.g., endocrine system, respiratory system, reproductive system, developmental toxicity, neurotoxicity, and genetic toxicity). Pieces of evidence that associate e-waste exposure with human health effects in China are assessed. The role of toxic heavy metals (e.g., lead, cadmium, chromium, mercury, and nickel) and organic pollutants (e.g., polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyl (PCBs), polycyclic aromatic hydrocarbons (PAHs), polybrominated biphenyls (PBBs), polyhalogenated aromatic hydrocarbons (PHAHs), bisphenol A (BPA)) on human health is also briefly discussed.

Reconstructing Exposures from Biomarkers using Exposure-Pharmacokinetic Modeling - A Case Study with Carbaryl

EPA Science Inventory

Sources of uncertainty involved in exposure reconstruction for a short half-life chemical, carbaryl, were characterized using the Cumulative and Aggregate Risk Evaluation System (CARES), an exposure model, and a human physiologically based pharmacokinetic (PBPK) model. CARES was...

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.

Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

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

Muczynski, V.; CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses; INSERM, Unité 967, F-92265, Fontenay aux Roses

The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation andmore » cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.« less

A combined experimental and numerical study on upper airway dosimetry of inhaled nanoparticles from an electrical discharge machine shop.

PubMed

Tian, Lin; Shang, Yidan; Chen, Rui; Bai, Ru; Chen, Chunying; Inthavong, Kiao; Tu, Jiyuan

2017-07-12

Exposure to nanoparticles in the workplace is a health concern to occupational workers with increased risk of developing respiratory, cardiovascular, and neurological disorders. Based on animal inhalation study and human lung tumor risk extrapolation, current authoritative recommendations on exposure limits are either on total mass or number concentrations. Effects of particle size distribution and the implication to regional airway dosages are not elaborated. Real time production of particle concentration and size distribution in the range from 5.52 to 98.2 nm were recorded in a wire-cut electrical discharge machine shop (WEDM) during a typical working day. Under the realistic exposure condition, human inhalation simulations were performed in a physiologically realistic nasal and upper airway replica. The combined experimental and numerical study is the first to establish a realistic exposure condition, and under which, detailed dose metric studies can be performed. In addition to mass concentration guided exposure limit, inhalation risks to nano-pollutant were reexamined accounting for the actual particle size distribution and deposition statistics. Detailed dosimetries of the inhaled nano-pollutants in human nasal and upper airways with respect to particle number, mass and surface area were discussed, and empirical equations were developed. An astonishing enhancement of human airway dosages were detected by current combined experimental and numerical study in the WEDM machine shop. Up to 33 folds in mass, 27 folds in surface area and 8 folds in number dosages were detected during working hours in comparison to the background dosimetry measured at midnight. The real time particle concentration measurement showed substantial emission of nano-pollutants by WEDM machining activity, and the combined experimental and numerical study provided extraordinary details on human inhalation dosimetry. It was found out that human inhalation dosimetry was extremely sensitive to real time particle concentration and size distribution. Averaged particle concentration over 24-h period will inevitably misrepresent the sensible information critical for realistic inhalation risk assessment. Particle size distribution carries very important information in determining human airway dosimetry. A pure number or mass concentration recommendation on the exposure limit at workplace is insufficient. A particle size distribution, together with the deposition equations, is critical to recognize the actual exposure risks. In addition, human airway dosimetry in number, mass and surface area varies significantly. A complete inhalation risk assessment requires the knowledge of toxicity mechanisms in response to each individual metric. Further improvements in these areas are needed.

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.

A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and immunological health conditions in humans

PubMed Central

Chang, Ellen T.; Adami, Hans-Olov; Boffetta, Paolo; Wedner, H. James; Mandel, Jack S.

2016-01-01

Abstract Whether perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS), two widely used and biopersistent synthetic chemicals, are immunotoxic in humans is unclear. Accordingly, this article systematically and critically reviews the epidemiologic evidence on the association between exposure to PFOA and PFOS and various immune-related health conditions in humans. Twenty-four epidemiologic studies have reported associations of PFOA and/or PFOS with immune-related health conditions, including ten studies of immune biomarker levels or gene expression patterns, ten studies of atopic or allergic disorders, five studies of infectious diseases, four studies of vaccine responses, and five studies of chronic inflammatory or autoimmune conditions (with several studies evaluating multiple endpoints). Asthma, the most commonly studied condition, was evaluated in seven studies. With few, often methodologically limited studies of any particular health condition, generally inconsistent results, and an inability to exclude confounding, bias, or chance as an explanation for observed associations, the available epidemiologic evidence is insufficient to reach a conclusion about a causal relationship between exposure to PFOA and PFOS and any immune-related health condition in humans. When interpreting such studies, an immunodeficiency should not be presumed to exist when there is no evidence of a clinical abnormality. Large, prospective studies with repeated exposure assessment in independent populations are needed to confirm some suggestive associations with certain endpoints. PMID:26761418

Statistical Properties of Longitudinal Time-Activity Data for Use in Human Exposure Modeling

EPA Science Inventory

Understanding the longitudinal properties of the time spent in different locations and activities is important in characterizing human exposure to pollutants. The results of a four-season longitudinal time-activity diary study in eight working adults are presented, with the goal ...

CULTURE CONDITIONS AFFECT HUMAN AIRWAY EPITHELIAL CELL RESPONSE TO DIESEL PARTICLE EXPOSURE IN VITRO

EPA Science Inventory

Diesel exhaust particles (DEP) are a ubiquitous ambient air contaminant that may contribute to the health effects of particulate matter inhalation. In vitro studies have shown that DEP exposure induces pro-inflammatory proteins in human airway epithelial cells (HAEC) with varying...

IDENTIFICATION AND CHARACTERIZATION OF HUMAN AIRWAY EPITHELIAL CELL PROTEINS PHOSPHORYLATED IN RESPONSE TO PARTICULATE MATTER (PM) EXPOSURE.

EPA Science Inventory

Multiple studies conducted by NHEERL scientists in recent years have shown that acute exposure to metals found associated with combustion-derived particulate matter (PM) alters phosphoprotein metabolism in human airway epithelial cells causing intracellular signaling. This disreg...

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.

Spontaneous pregnancy loss in humans and exposure to arsenic in drinking water.

PubMed

Bloom, Michael S; Fitzgerald, Edward F; Kim, Keewan; Neamtiu, Iulia; Gurzau, Eugen S

2010-11-01

Maternal exposure to high concentrations of inorganic arsenic (iAs) in naturally contaminated drinking groundwater sources has been associated with an increased risk for the spontaneous loss of clinically recognized pregnancies in several epidemiologic studies. Whereas a large worldwide population depends on drinking groundwater sources with high levels of iAs contamination, in quantities exceeding 10 parts per billion (ppb), an even larger population is likely to be exposed to mild-moderate drinking groundwater iAs contamination, in quantities <10ppb. Only a single epidemiologic study to date has considered spontaneous pregnancy loss in association with consumption of drinking water with mild-moderate iAs contamination; the vast majority of published studies of spontaneous loss addressed populations with substantial exposure. The aim of this review is to evaluate the published literature to assess the plausibility for a causal association between exposure to iAs-contaminated drinking water and the spontaneous loss of clinically recognized pregnancy. In spite of numerous methodologic limitations resulting from circumstance or design, a consistent pattern of increased risk for loss is suggested by the epidemiologic literature. Moreover, these study results are corroborated by a large number of experimental studies, albeit usually conducted at concentrations exceeding that to which humans are exposed via contaminated drinking water. In this review, we discuss sources of human iAs exposure, highlight several experimental studies pertinent to a possible causal link between iAs and spontaneous pregnancy loss in humans, and provide a critical review of published epidemiologic studies of pregnancy loss and drinking water iAs exposures, and their limitations. Based on a review of the published literature, we recommend the future conduct of a two-stage comprehensive prospective study of low-moderate iAs drinking water exposure and spontaneous pregnancy loss. Copyright © 2010 Elsevier GmbH. All rights reserved.

Arsenic geochemistry and human health in South East Asia

PubMed Central

McCarty, Kathleen M.; Hanh, Hoang Thi; Kim, Kyoung-Woong

2011-01-01

Arsenic occurs naturally in many environmental components and enters the human body through several exposure pathways. Natural enrichment of arsenic may result in considerable contamination of soil, water, and air. Arsenic in groundwater can exceed values hundreds of time higher than the concentration recommended for drinking water. Such exposure levels indicate a serious potential health risk to individuals consuming raw groundwater. Human activities that have an impact on the environment may increase the distribution of inorganic arsenic. Abandoned mines are of great concern due to the extremely high arsenic concentrations detected in mine drainage and tailings. Diet, drinking water, air, soil, and occupational exposures are all sources of inorganic arsenic for humans. Interdisciplinary efforts to better characterize the transport of arsenic and reactants that facilitate their release to the environment are important for human health studies. Multi-disciplinary efforts are needed to study diet, infectious disease, genetics, and cultural practices unique to each region to better understand human health risk and to design public health interventions. PMID:21714384

Prenatal Famine and Adult Health

PubMed Central

Lumey, L.H.; Stein, Aryeh D.; Susser, Ezra

2013-01-01

We review human studies on the relation between acute exposures to prenatal famine and adult physical and mental health. These studies are observational and include exposures to a famine environment by natural or man-made causes or, more commonly, from the interplay between natural and human factors. These natural experiments provide an opportunity to examine long-term outcomes after famine exposures by comparing exposed and nonexposed individuals. The studies show consistent associations between prenatal famine and adult body size, diabetes, and schizophrenia. For other measures of adult health, findings are less robust. A relation between prenatal famine and some reported epigenetic changes may provide a potential mechanism to explain specific associations. Much progress can be made if current separate studies are further analyzed with comparable definitions of exposures and outcomes and using common analytic strategies. PMID:21219171

The human early-life exposome (HELIX): project rationale and design.

PubMed

Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

2014-06-01

Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

PubMed

Winkler-Heil, R; Hussain, M; Hofmann, W

2015-05-01

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

The Detroit Exposure and Aerosol Research Study (DEARS) - Article in National Ambient Air Quality Status and Trends through 2007

EPA Science Inventory

A research study that the U.S. Environmental Protection Agency conducted in Detroit, Michigan, named the Detroit Exposure and Aerosol Research Study (DEARS), will help develop data that improves our understanding of human exposure to various air pollutants in our environment.

EXPOSURE TO PESTICIDES BY MEDIUM AND ROUTE: THE 90TH PERCENTILE AND RELATED UNCERTAINTIES

EPA Science Inventory

This study investigates distributions of exposure to chlorpyrifos and diazinon using the database generated in the state of Arizona by the National Human Exposure Assessment Survey (NHEXAS-AZ). Exposure to pesticide and associated uncertainties are estimated using probabilistic...

ARE ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES ASSOCIATED WITH AN INCREASE IN ADVERSE HUMAN HEALTH EFFECTS?

EPA Science Inventory

Background: Associations between adverse health effects and environmental exposures are difficult to study because exposures may be widespread, low-dose in nature, and common throughout the study population. Individual risk-factor epidemiology may not be able to initially ident...

ASSESSING A COMPUTER MODEL FOR PREDICTING HUMAN EXPOSURE TO PM2.5

EPA Science Inventory

This paper compares outputs of a model for predicting PM2.5 exposure with experimental data obtained from exposure studies of selected subpopulations. The exposure model is built on a WWW platform called pCNEM, "A PC Version of pNEM." Exposure models created by pCNEM are sim...

Upregulation of SQSTM1/p62 contributes to nickel-induced malignant transformation of human bronchial epithelial cells.

PubMed

Huang, Haishan; Zhu, Junlan; Li, Yang; Zhang, Liping; Gu, Jiayan; Xie, Qipeng; Jin, Honglei; Che, Xun; Li, Jingxia; Huang, Chao; Chen, Lung-Chi; Lyu, Jianxin; Gao, Jimin; Huang, Chuanshu

2016-10-02

Chronic lung inflammation is accepted as being associated with the development of lung cancer caused by nickel exposure. Therefore, identifying the molecular mechanisms that lead to a nickel-induced sustained inflammatory microenvironment that causes transformation of human bronchial epithelial cells is of high significance. In the current studies, we identified SQSTM1/p62 as a novel nickel-upregulated protein that is important for nickel-induced inflammatory TNF expression, subsequently resulting in transformation of human bronchial epithelial cells. We found that nickel exposure induced SQSTM1 protein upregulation in human lung epithelial cells in vitro and in mouse lung tissues in vivo. The SQSTM1 upregulation was also observed in human lung squamous cell carcinoma. Further studies revealed that the knockdown of SQSTM1 expression dramatically inhibited transformation of human lung epithelial cells upon chronic nickel exposure, whereas ectopic expression of SQSTM1 promoted such transformation. Mechanistic studies showed that the SQSTM1 upregulation by nickel was the compromised result of upregulating SQSTM1 mRNA transcription and promoting SQSTM1 protein degradation. We demonstrated that nickel-initiated SQSTM1 protein degradation is mediated by macroautophagy/autophagy via an MTOR-ULK1-BECN1 axis, whereas RELA is important for SQSTM1 transcriptional upregulation following nickel exposure. Furthermore, SQSTM1 upregulation exhibited its promotion of nickel-induced cell transformation through exerting an impetus for nickel-induced inflammatory TNF mRNA stability. Consistently, the MTOR-ULK1-BECN1 autophagic cascade acted as an inhibitory effect on nickel-induced TNF expression and cell transformation. Collectively, our results demonstrate a novel SQSTM1 regulatory network that promotes a nickel-induced tumorigenic effect in human bronchial epithelial cells, which is negatively controlled by an autophagic cascade following nickel exposure.

Upregulation of SQSTM1/p62 contributes to nickel-induced malignant transformation of human bronchial epithelial cells

PubMed Central

Huang, Haishan; Zhu, Junlan; Li, Yang; Zhang, Liping; Gu, Jiayan; Xie, Qipeng; Jin, Honglei; Che, Xun; Li, Jingxia; Huang, Chao; Chen, Lung-Chi; Lyu, Jianxin; Gao, Jimin; Huang, Chuanshu

2016-01-01

ABSTRACT Chronic lung inflammation is accepted as being associated with the development of lung cancer caused by nickel exposure. Therefore, identifying the molecular mechanisms that lead to a nickel-induced sustained inflammatory microenvironment that causes transformation of human bronchial epithelial cells is of high significance. In the current studies, we identified SQSTM1/p62 as a novel nickel-upregulated protein that is important for nickel-induced inflammatory TNF expression, subsequently resulting in transformation of human bronchial epithelial cells. We found that nickel exposure induced SQSTM1 protein upregulation in human lung epithelial cells in vitro and in mouse lung tissues in vivo. The SQSTM1 upregulation was also observed in human lung squamous cell carcinoma. Further studies revealed that the knockdown of SQSTM1 expression dramatically inhibited transformation of human lung epithelial cells upon chronic nickel exposure, whereas ectopic expression of SQSTM1 promoted such transformation. Mechanistic studies showed that the SQSTM1 upregulation by nickel was the compromised result of upregulating SQSTM1 mRNA transcription and promoting SQSTM1 protein degradation. We demonstrated that nickel-initiated SQSTM1 protein degradation is mediated by macroautophagy/autophagy via an MTOR-ULK1-BECN1 axis, whereas RELA is important for SQSTM1 transcriptional upregulation following nickel exposure. Furthermore, SQSTM1 upregulation exhibited its promotion of nickel-induced cell transformation through exerting an impetus for nickel-induced inflammatory TNF mRNA stability. Consistently, the MTOR-ULK1-BECN1 autophagic cascade acted as an inhibitory effect on nickel-induced TNF expression and cell transformation. Collectively, our results demonstrate a novel SQSTM1 regulatory network that promotes a nickel-induced tumorigenic effect in human bronchial epithelial cells, which is negatively controlled by an autophagic cascade following nickel exposure. PMID:27467530

Vibration safety limits for magnetic resonance elastography.

PubMed

Ehman, E C; Rossman, P J; Kruse, S A; Sahakian, A V; Glaser, K J

2008-02-21

Magnetic resonance elastography (MRE) has been demonstrated to have potential as a clinical tool for assessing the stiffness of tissue in vivo. An essential step in MRE is the generation of acoustic mechanical waves within a tissue via a coupled mechanical driver. Motivated by an increasing volume of human imaging trials using MRE, the objectives of this study were to audit the vibration amplitude of exposure for our IRB-approved human MRE studies, to compare these values to a conservative regulatory standard for vibrational exposure and to evaluate the applicability and implications of this standard for MRE. MRE displacement data were examined from 29 MRE exams, including the liver, brain, kidney, breast and skeletal muscle. Vibrational acceleration limits from a European Union directive limiting occupational exposure to whole-body and extremity vibrations (EU 2002/44/EC) were adjusted for time and frequency of exposure, converted to maximum displacement values and compared to the measured in vivo displacements. The results indicate that the vibrational amplitudes used in MRE studies are below the EU whole-body vibration limit, and the EU guidelines represent a useful standard that could be readily accepted by Institutional Review Boards to define standards for vibrational exposures for MRE studies in humans.

Vibration safety limits for magnetic resonance elastography

PubMed Central

Ehman, E C; Rossman, P J; Kruse, S A; Sahakian, A V; Glaser, K J

2010-01-01

Magnetic resonance elastography (MRE) has been demonstrated to have potential as a clinical tool for assessing the stiffness of tissue in vivo. An essential step in MRE is the generation of acoustic mechanical waves within tissue via a coupled mechanical driver. Motivated by an increasing volume of human imaging trials using MRE, the objectives of this study were to audit the vibration amplitude of exposure for our IRB-approved human MRE studies, to compare these values to a conservative regulatory standard for vibrational exposure, and to evaluate the applicability and implications of this standard for MRE. MRE displacement data were examined from 29 MRE exams, including the liver, brain, kidney, breast, and skeletal muscle. Vibrational acceleration limits from a European Union directive limiting occupational exposure to whole-body and extremity vibrations (EU 2002/44/EC) were adjusted for time and frequency of exposure, converted to maximum displacement values, and compared to the measured in vivo displacements. The results indicate that the vibrational amplitudes used in MRE studies are below the EU whole-body vibration limit and the EU guidelines represent a useful standard that could be readily accepted by Institutional Review Boards to define standards for vibrational exposures for MRE studies in humans. PMID:18263949

[Exposome: from an intuition to a mandatory research field in occupational and enviromental medicine.

PubMed

Paganelli, Matteo; De Palma, Giuseppe; Apostoli, Pietro

2017-11-01

As Genomics aims at the collective characterization and quantification of genes, exposomics refers to the totality of lifetime environmental exposures, consisting in a novel approach to studying the role of the environment in human disease. The aim is to assess all human environmental and occupational exposures in order to better understand their contribution to human diseases. The "omics" revolution infact mostly regards the underlying method: scientific knowledge is expected to come from the analysis of increasingly extensive databases. The primary focus is on air pollution and water contaminants, but all the determinants of human exposure are conceptually part of the idea of exposome, including physical and psychological factors. Using 'omic' techniques the collected exposure data can be linked to biochemical and molecular changes in our body. Since the first formulation of the idea itself of Exposome many efforts have been made to translate the concept into research, in particular two important studies have been started in Europe. We herein suggest that Occupational Medicine could be a precious contributor to the growth of exposure science also in its omic side thanks to the methods and to the knowledges part of our background. Copyright© by Aracne Editrice, Roma, Italy.

Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.

PubMed

Mathur, Priya; Guo, Su

2011-06-01

Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Long-term impacts of unconventional drilling operations on human and animal health.

PubMed

Bamberger, Michelle; Oswald, Robert E

2015-01-01

Public health concerns related to the expansion of unconventional oil and gas drilling have sparked intense debate. In 2012, we published case reports of animals and humans affected by nearby drilling operations. Because of the potential for long-term effects of even low doses of environmental toxicants and the cumulative impact of exposures of multiple chemicals by multiple routes of exposure, a longitudinal study of these cases is necessary. Twenty-one cases from five states were followed longitudinally; the follow-up period averaged 25 months. In addition to humans, cases involved food animals, companion animals and wildlife. More than half of all exposures were related to drilling and hydraulic fracturing operations; these decreased slightly over time. More than a third of all exposures were associated with wastewater, processing and production operations; these exposures increased slightly over time. Health impacts decreased for families and animals moving from intensively drilled areas or remaining in areas where drilling activity decreased. In cases of families remaining in the same area and for which drilling activity either remained the same or increased, no change in health impacts was observed. Over the course of the study, the distribution of symptoms was unchanged for humans and companion animals, but in food animals, reproductive problems decreased and both respiratory and growth problems increased. This longitudinal case study illustrates the importance of obtaining detailed epidemiological data on the long-term health effects of multiple chemical exposures and multiple routes of exposure that are characteristic of the environmental impacts of unconventional drilling operations.

NATIONAL WWTP EFFLUENT STUDY

EPA Science Inventory

Reports of potential wildlife risk from exposure to environmental estrogens emphasize the need to better understand both estrogenic presence and persistence in treated wastewater effluents. In addition to wildlife exposure, human exposure should also be examined, especially in si...

Human health exposure assessment for Rocky Mountain Arsenal. Volume 2-A. Toxicity assessment. Version 4. 1. Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis a introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Human health exposure assessment for Rocky Mountain Arsenal. Volume 3. Toxicity assessment version 4. 1. Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis A introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Human health exposure assessment for Rocky Mountain Arsenal. Volume 1. Land use and exposed population evaluations version 4. 1. Final report

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

Not Available

The objectives of the Human Health Exposure Assessment include: (1) estimate the type and magnitude of exposures to contaminants; (2) Identify contaminants of concern; (3) Identify sites for remedial action; (4) Recommend sites for the no action remedial alternative; and (5) Provide a basis for detailed characterization of the risk associated with all sites. This document consists of the following: An executive summary. Vol I - Land use and exposed population evaluations. Vol. II III - Toxicity assessment (includes army and shell toxicity profiles). Vol. IV - PPLV Methodology. Vol. V - PPLV Calculations. Vol. VI - Study area exposuremore » analysis A introduction, B Western study ares, C Southern study area, D northern Central study area, E Central study area, F Eastern study area, G South plants study area, and H North plants study area. Vol. VII - Summary exposure assessment.« less

Human Health Exposure Assessment for Rocky Mountain Arsenal. Volume 8. Response to Comments on the Draft Exposure Assessment Version 4.1

DTIC Science & Technology

1990-09-01

ASSESSMENT (INCLUDES ARMY AND SHELL TOXICITY PROFILES). VOL. 41V - PPLV METHODOLOGY. VOL. V - PPLV CALCULATIONS. VOL. VI - STUDY AREA EXPOSURE ANALYSIS (A...INTRODUCTION, B WESTERN STUDY AREA, C SOUTHERN STUDY AREA, D NORTHERN CENTRAL STUDY AREA, E CENTRAL STUDY AREA, F EASTERN STUDY AREA, G SOUTH PLANTS... STUDY AREA, AND H NORTH PLANTS STUDY AREA. VOL. VII - SUMMARY EXPOSURE ASSESSMENT. VOL. VIII - 14. SUBJECT TERMS 15. NUMBER OF PAGES PPLV, LAND USE

Blood transcriptomics: applications in toxicology

PubMed Central

Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

2015-01-01

The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

Examination of cytokines and metals in exhaled breath condensate and lung lavage fluids after diesel exhaust exposure

EPA Science Inventory

Epidemiology studies link human exposure to ambient air pollution with the development and exacerbation of cardiopulmonary disease. Diesel exhaust (DE) is a significant source of ambient air pollution, and thus may contribute to adverse pulmonary health effects. Previous human re...

Dermal uptake of Tetrabromobisphenol A TBBPA by female Wistar Han rat and human skin

EPA Science Inventory

TBBPA, a brominated analog of Bisphenol A, is the highest production volume brominated flame retardant in production and human exposure is ubiquitous. Although the major route of exposure to TBBPA is oral uptake, skin penetration is possible. In the studies presented here, the de...

Tissue distribution of polybrominated diphenyl ethers in rats following oral exposure and the relationship to body burdens

EPA Science Inventory

Polybrominated diphenyl ethers (PBDEs) are a class of widely-used flame retardants which have been found to persist, bioaccumulate, and potentially affect development in animals. Humans are exposed to PBDEs through both their diet and indoor environment. In human exposure studies...

COMPARISON OF PM-INDUCED GENE EXPRESSION PROFILES BETWEEN BRONCHIAL EPITHELIAL CELLS AND NASAL EPITHELIAL CELLS IN HUMAN

EPA Science Inventory

Epidemiologic studies have linked exposures to particulate matter (PM) and increased pulmonary mortality and morbidity. Bronchial epithelial cells (BEC) are the primary target of PM. PM exposure induces a wide array of biological responses in BEC. Primary human BEC, however, need...

The Lunar Environment: Determining the Health Effects of Exposure to Moon Dusts

NASA Technical Reports Server (NTRS)

Khan-Mayberry, Noreen

2007-01-01

The moon's surface is covered with a thin layer of fine, charged, reactive dust capable of layer of fine, charged, reactive dust capable of capable of entering habitats and vehicle compartments, where it can result in crewmember health problems. NASA formed the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to study the effects of exposure to Lunar Dust on human health. To date, no scientifically defensible toxicological studies have been performed on lunar dusts, specifically the determination of exposure limits and their affect on human health. The multi-center LADTAG (Lunar Airborne Dust Toxicology center LADTAG (Lunar Airborne Dust Toxicology Advisory Group) was formed in response to the Office of the Chief Health and Medical Office s (OCHMO) request to develop recommendations for defining risk (OCHMO) request to develop recommendations for defining risk defining risk criteria for human lunar dust exposure.

Newly postulated neurodevelopmental risks of pediatric anesthesia.

PubMed

Hays, Stephen R; Deshpande, Jayant K

2011-04-01

Recent animal and human studies have raised concern that exposure to anesthetic agents in children may cause neuronal damage and be associated with adverse neurodevelopmental outcomes. Exposure of young animals to anesthetic agents above threshold doses and durations during a critical neurodevelopmental window in the absence of concomitant painful stimuli causes widespread neuronal apoptosis and subsequent abnormal behaviors. The relevance of such animal data to humans is unknown. Untreated neonatal pain and stress also are associated with enhanced neuronal death and subsequent maladaptive behaviors, which can be prevented by exposure to these same anesthetic agents. Retrospective observational human studies have suggested a dose-dependent association between multiple anesthetic exposures in early childhood and subsequent learning disability, the causality of which is unknown. Ongoing prospective investigations are underway, the results of which may clarify if and what neurodevelopmental risks are associated with pediatric anesthesia. No change in current practice is yet indicated.

Diesel engine exhaust and lung cancer: an unproven association.

PubMed Central

Muscat, J E; Wynder, E L

1995-01-01

The risk of lung cancer associated with diesel exhaust has been calculated from 14 case-control or cohort studies. We evaluated the findings from these studies to determine whether there is sufficient evidence to implicate diesel exhaust as a human lung carcinogen. Four studies found increased risks associated with long-term exposure, although two of the four studies were based on the same cohort of railroad workers. Six studies were inconclusive due to missing information on smoking habits, internal inconsistencies, or inadequate characterization of diesel exposure. Four studies found no statistically significant associations. It can be concluded that short-term exposure to diesel engine exhaust (< 20 years) does not have a causative role in human lung cancer. There is statistical but not causal evidence that long-term exposure to diesel exhaust (> 20 years) increases the risk of lung cancer for locomotive engineers, brakemen, and diesel engine mechanics. There is inconsistent evidence on the effects of long-term exposure to diesel exhaust in the trucking industry. There is no evidence for a joint effect of diesel exhaust and cigarette smoking on lung cancer risk. Using common criteria for determining causal associations, the epidemiologic evidence is insufficient to establish diesel engine exhaust as a human lung carcinogen. Images p812-a PMID:7498093

Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: a review of rodent and human data.

PubMed

Rasier, G; Toppari, J; Parent, A-S; Bourguignon, J-P

2006-07-25

Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents.

Environmental exposures to agrochemicals in the Sierra Nevada mountain range

USGS Publications Warehouse

LeNoir, J.; Aston, L.; Data, S.; Fellers, G.; McConnell, L.; Sieber, J.

2000-01-01

The release of pesticides into the environment may impact human and environmental health. Despite the need for environmental exposure data, few studies quantify exposures in urban areas and even fewer determine exposures to wildlife in remote areas. Although it is expected that concentrations in remote regions will be low, recent studies suggest that even low concentrations may have deleterious effects on wildlife. Many pesticides are known to interfere with the endocrine systems of humans and wildlife, adversely affecting growth, development, and behavior. This chapter reviews the fate and transport of pesticides applied in the Central Valley of California and quantifies their subsequent deposition into the relatively pristine Sierra Nevada Mountain Range.

Estimating human exposure to PFOS isomers and PFCA homologues: the relative importance of direct and indirect (precursor) exposure.

PubMed

Gebbink, Wouter A; Berger, Urs; Cousins, Ian T

2015-01-01

Contributions of direct and indirect (via precursors) pathways of human exposure to perfluorooctane sulfonic acid (PFOS) isomers and perfluoroalkyl carboxylic acids (PFCAs) are estimated using a Scenario-Based Risk Assessment (SceBRA) modelling approach. Monitoring data published since 2008 (including samples from 2007) are used. The estimated daily exposures (resulting from both direct and precursor intake) for the general adult population are highest for PFOS and perfluorooctanoic acid (PFOA), followed by perfluorohexanoic acid (PFHxA) and perfluorodecanoic acid (PFDA), while lower daily exposures are estimated for perfluorobutanoic acid (PFBA) and perfluorododecanoic acid (PFDoDA). The precursor contributions to the individual perfluoroalkyl acid (PFAA) daily exposures are estimated to be 11-33% for PFOS, 0.1-2.5% for PFBA, 3.7-34% for PFHxA, 13-64% for PFOA, 5.2-66% for PFDA, and 0.7-25% for PFDoDA (ranges represent estimated precursor contributions in a low- and high-exposure scenario). For PFOS, direct intake via diet is the major exposure pathway regardless of exposure scenario. For PFCAs, the dominant exposure pathway is dependent on perfluoroalkyl chain length and exposure scenario. Modelled PFOS and PFOA concentrations in human serum using the estimated intakes from an intermediate-exposure scenario are in agreement with measured concentrations in different populations. The isomer pattern of PFOS resulting from total intakes (direct and via precursors) is estimated to be enriched with linear PFOS (84%) relative to technical PFOS (70% linear). This finding appears to be contradictory to the observed enrichment of branched PFOS isomers in recent human serum monitoring studies and suggests that either external exposure is not fully understood (e.g. there are unknown precursors, missing or poorly quantified exposure pathways) and/or that there is an incomplete understanding of the isomer-specific human pharmacokinetic processes of PFOS, its precursors and intermediates. Copyright © 2014. Published by Elsevier Ltd.

ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES AND ASSOCIATION WITH ADVERSE HUMAN HEALTH EFFECTS: EXAMPLE OF THE NEED FOR BETTER METHODS

EPA Science Inventory

Previous studies have made the following observations: newly emerging global patterns of disease have been observed, and environmental exposures have been implicated. Ecologic studies are fundamental for the identification of public health problems. Some level of exposure in a...

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.

Perfluorooctanoic acid (PFOA), an emerging drinking water contaminant: a critical review of recent literature.

PubMed

Post, Gloria B; Cohn, Perry D; Cooper, Keith R

2012-07-01

Perfluorooctanoic acid (PFOA) is an anthropogenic contaminant that differs in several ways from most other well-studied organic chemicals found in drinking water. PFOA is extremely resistant to environmental degradation processes and thus persists indefinitely. Unlike most other persistent and bioaccumulative organic pollutants, PFOA is water-soluble, does not bind well to soil or sediments, and bioaccumulates in serum rather than in fat. It has been detected in finished drinking water and drinking water sources impacted by releases from industrial facilities and waste water treatment plants, as well as in waters with no known point sources. However, the overall occurrence and population exposure from drinking water is not known. PFOA persists in humans with a half-life of several years and is found in the serum of almost all U.S. residents and in populations worldwide. Exposure sources include food, food packaging, consumer products, house dust, and drinking water. Continued exposure to even relatively low concentrations in drinking water can substantially increase total human exposure, with a serum:drinking water ratio of about 100:1. For example, ongoing exposures to drinking water concentrations of 10 ng/L, 40 ng/L, 100 ng/L, or 400 ng/L are expected to increase mean serum levels by about 25%, 100%, 250%, and 1000%, respectively, from the general population background serum level of about 4 ng/mL. Infants are potentially a sensitive subpopulation for PFOA's developmental effects, and their exposure through breast milk from mothers who use contaminated drinking water and/or from formula prepared with contaminated drinking water is higher than in adults exposed to the same drinking water concentration. Numerous health endpoints are associated with human PFOA exposure in the general population, communities with contaminated drinking water, and workers. As is the case for most such epidemiology studies, causality for these effects is not proven. Unlike most other well-studied drinking water contaminants, the human dose-response curve for several effects appears to be steepest at the lower exposure levels, including the general population range, with no apparent threshold for some endpoints. There is concordance in animals and humans for some effects, while humans and animals appear to react differently for other effects such as lipid metabolism. PFOA was classified as "likely to be carcinogenic in humans" by the USEPA Science Advisory Board. In animal studies, developmental effects have been identified as more sensitive endpoints for toxicity than carcinogenicity or the long-established hepatic effects. Notably, exposure to an environmentally relevant drinking water concentration caused adverse effects on mammary gland development in mice. This paper reviews current information relevant to the assessment of PFOA as an emerging drinking water contaminant. This information suggests that continued human exposure to even relatively low concentrations of PFOA in drinking water results in elevated body burdens that may increase the risk of health effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Weighing serological evidence of human exposure to animal influenza viruses - a literature review.

PubMed

Sikkema, Reina Saapke; Freidl, Gudrun Stephanie; de Bruin, Erwin; Koopmans, Marion

2016-11-03

Assessing influenza A virus strains circulating in animals and their potential to cross the species barrier and cause human infections is important to improve human influenza surveillance and preparedness. We reviewed studies describing serological evidence of human exposure to animal influenza viruses. Comparing serological data is difficult due to a lack of standardisation in study designs and in laboratory methods used in published reports. Therefore, we designed a scoring system to assess and weigh specificity of obtained serology results in the selected articles. Many studies report reliable evidence of antibodies to swine influenza viruses among persons occupationally exposed to pigs. Most avian influenza studies target H5, H7 and H9 subtypes and most serological evidence of human exposure to avian influenza viruses is reported for these subtypes. Avian influenza studies receiving a low grade in this review often reported higher seroprevalences in humans compared with studies with a high grade. Official surveillance systems mainly focus on avian H5 and H7 viruses. Swine influenza viruses and avian subtypes other than H5 and H7 (emphasising H9) should be additionally included in official surveillance systems. Surveillance efforts should also be directed towards understudied geographical areas, such as Africa and South America. This article is copyright of The Authors, 2016.

Weighing serological evidence of human exposure to animal influenza viruses − a literature review

PubMed Central

Sikkema, Reina Saapke; Freidl, Gudrun Stephanie; de Bruin, Erwin; Koopmans, Marion

2016-01-01

Assessing influenza A virus strains circulating in animals and their potential to cross the species barrier and cause human infections is important to improve human influenza surveillance and preparedness. We reviewed studies describing serological evidence of human exposure to animal influenza viruses. Comparing serological data is difficult due to a lack of standardisation in study designs and in laboratory methods used in published reports. Therefore, we designed a scoring system to assess and weigh specificity of obtained serology results in the selected articles. Many studies report reliable evidence of antibodies to swine influenza viruses among persons occupationally exposed to pigs. Most avian influenza studies target H5, H7 and H9 subtypes and most serological evidence of human exposure to avian influenza viruses is reported for these subtypes. Avian influenza studies receiving a low grade in this review often reported higher seroprevalences in humans compared with studies with a high grade. Official surveillance systems mainly focus on avian H5 and H7 viruses. Swine influenza viruses and avian subtypes other than H5 and H7 (emphasising H9) should be additionally included in official surveillance systems. Surveillance efforts should also be directed towards understudied geographical areas, such as Africa and South America. PMID:27874827

Detection of Human Ig G Using Photoluminescent Porous Silicon Interferometer.

PubMed

Cho, Bomin; Kim, Seongwoong; Woo, Hee-Gweon; Kim, Sungsoo; Sohn, Honglae

2015-02-01

Photoluminescent porous silicon (PSi) interferometers having dual optical properties, both Fabry-Pérot fringe and photolumincence (PL), have been developed and used as biosensors for detection of Human Immunoglobin G (Ig G). PSi samples were prepared by electrochemical etching of p-type silicon under white light exposure. The surface of PSi was characterized using a cold field emission scanning electron microscope. The sensor system studied consisted of a single layer of porous silicon modified with Protein A. The system was probed with various fragments of aqueous human immunoglobin G (Ig G) analyte. Both reflectivity and PL were simultaneously measured under the exposure of human Ig G. An increase of optical thickness and decrease of PL were obtained under the exposure of human Ig G. Detection limit of 500 fM was observed for the human Ig G.

Short-term ozone exposure and asthma severity: Weight-of-evidence analysis.

PubMed

Goodman, Julie E; Zu, Ke; Loftus, Christine T; Lynch, Heather N; Prueitt, Robyn L; Mohar, Isaac; Shubin, Sara Pacheco; Sax, Sonja N

2018-01-01

To determine whether evidence indicates that short-term exposure to ambient concentrations of ozone in the United States can affect asthma severity, we systematically reviewed published controlled human exposure, epidemiology, and animal toxicity studies. The strongest evidence for a potential causal relationship came from epidemiology studies reporting increased emergency department visits and hospital admissions for asthma following elevated ambient ozone concentrations. However, while controlled exposure studies reported lung function decrements and increased asthma symptoms following high ozone exposures 160-400 parts per billion [ppb]), epidemiology studies evaluating similar outcomes reported less consistent results. Animal studies showed changes in pulmonary function at high ozone concentrations (> 500ppb), although there is substantial uncertainty regarding the relevance of these animal models to human asthma. Taken together, the weight of evidence indicates that there is at least an equal likelihood that either explanation is true, i.e., the strength of the evidence for a causal relationship between short-term exposure to ambient ozone concentrations and asthma severity is "equipoise and above." Copyright © 2017 Elsevier Inc. All rights reserved.

Exposure to toxic waste sites: an investigative approach.

PubMed

Stehr-Green, P A; Lybarger, J A

1989-01-01

Improper dumping and storage of hazardous substances and whether these practices produce significant human exposure and health effects are growing concerns. A sequential approach has been used by the Centers for Disease Control and the Agency for Toxic Substances and Disease Registry in investigating potential exposure to and health effects resulting from environmental contamination with materials such as heavy metals, volatile organic compounds, and pesticide residues at sites throughout the United States. The strategy consists of four phases: site evaluation, pilot studies of exposure or health effects, analytic epidemiology studies, and public health surveillance. This approach offers a logical, phased strategy to use limited personnel and financial resources of local, State, national, or global health agency jurisdictions optimally in evaluating populations potentially exposed to hazardous materials in waste sites. Primarily, this approach is most helpful in identifying sites for etiologic studies and providing investigative leads to direct and focus these studies. The results of such studies provide information needed for making risk-management decisions to mitigate or eliminate human exposures and for developing interventions to prevent or minimize health problems resulting from exposures that already have occurred.

Effects of metals within ambient air particulate matter (PM) on human health.

PubMed

Chen, Lung Chi; Lippmann, Morton

2009-01-01

We review literature providing insights on health-related effects caused by inhalation of ambient air particulate matter (PM) containing metals, emphasizing effects associated with in vivo exposures at or near contemporary atmospheric concentrations. Inhalation of much higher concentrations, and high-level exposures via intratracheal (IT) instillation that inform mechanistic processes, are also reviewed. The most informative studies of effects at realistic exposure levels, in terms of identifying influential individual PM components or source-related mixtures, have been based on (1) human and laboratory animal exposures to concentrated ambient particles (CAPs), and (2) human population studies for which both health-related effects were observed and PM composition data were available for multipollutant regression analyses or source apportionment. Such studies have implicated residual oil fly ash (ROFA) as the most toxic source-related mixture, and Ni and V, which are characteristic tracers of ROFA, as particularly influential components in terms of acute cardiac function changes and excess short-term mortality. There is evidence that other metals within ambient air PM, such as Pb and Zn, also affect human health. Most evidence now available is based on the use of ambient air PM components concentration data, rather than actual exposures, to determine significant associations and/or effects coefficients. Therefore, considerable uncertainties about causality are associated with exposure misclassification and measurement errors. As more PM speciation data and more refined modeling techniques become available, and as more CAPs studies involving PM component analyses are performed, the roles of specific metals and other components within PM will become clearer.

Construction of vapor chambers used to expose mice to alcohol during the equivalent of all three trimesters of human development.

PubMed

Morton, Russell A; Diaz, Marvin R; Topper, Lauren A; Valenzuela, C Fernando

2014-07-13

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal Alcohol Spectrum Disorders (FASDs). At the most severe end of the spectrum is Fetal Alcohol Syndrome (FAS), characterized by growth retardation, craniofacial dysmorphology, and neurobehavioral deficits. Studies with animal models, including rodents, have elucidated many molecular and cellular mechanisms involved in the pathophysiology of FASDs. Ethanol administration to pregnant rodents has been used to model human exposure during the first and second trimesters of pregnancy. Third trimester ethanol consumption in humans has been modeled using neonatal rodents. However, few rodent studies have characterized the effect of ethanol exposure during the equivalent to all three trimesters of human pregnancy, a pattern of exposure that is common in pregnant women. Here, we show how to build vapor chambers from readily obtainable materials that can each accommodate up to six standard mouse cages. We describe a vapor chamber paradigm that can be used to model exposure to ethanol, with minimal handling, during all three trimesters. Our studies demonstrate that pregnant dams developed significant metabolic tolerance to ethanol. However, neonatal mice did not develop metabolic tolerance and the number of fetuses, fetus weight, placenta weight, number of pups/litter, number of dead pups/litter, and pup weight were not significantly affected by ethanol exposure. An important advantage of this paradigm is its applicability to studies with genetically-modified mice. Additionally, this paradigm minimizes handling of animals, a major confound in fetal alcohol research.

Exposure assessment for trihalomethanes in municipal drinking water and risk reduction strategy.

PubMed

Chowdhury, Shakhawat

2013-10-01

Lifetime exposure to disinfection byproducts (DBPs) in municipal water may pose risks to human health. Current approaches of exposure assessments use DBPs in cold water during showering, while warming of chlorinated water during showering may increase trihalomethane (THM) formation in the presence of free residual chlorine. Further, DBP exposure through dermal contact during showering is estimated using steady-state condition between the DBPs in shower water impacting on human skin and skin exposed to shower water. The lag times to achieve steady-state condition between DBPs in shower water and human skin can vary in the range of 9.8-391.2 min, while shower duration is often less than the lag times. Assessment of exposure without incorporating these factors might have misinterpreted DBP exposure in some previous studies. In this study, exposure to THMs through ingestion was estimated using cold water THMs, while THM exposure through inhalation and dermal contact during showering was estimated using THMs in warm water. Inhalation of THMs was estimated using THM partition into the shower air, while dermal uptake was estimated by incorporating lag times (e.g., unsteady and steady-state phases of exposure) during showering. Probabilistic approach was followed to incorporate uncertainty in the assessment. Inhalation and dermal contact during showering contributed 25-60% of total exposure. Exposure to THMs during showering can be controlled by varying shower stall volume, shower duration and air exchange rate following power law equations. The findings might be useful in understanding exposure to THMs, which can be extended to other volatile compounds in municipal water. © 2013 Elsevier B.V. All rights reserved.

Development of a Protocol for Epidemiologal Studies of Whole-Body Vibration and Musculoskeletal Disorders of the Lower Back

NASA Astrophysics Data System (ADS)

Magnusson, M. L.; Pope, M. H.; Hulshof, C. T. J.; Bovenzi, M.

1998-08-01

It seems evident from a large number of studies that there is a positive relationship between exposure to whole body vibration (WBV) and the occurrence of low back pain. There are existing standards for evaluating the human exposure to WBV, which are based on other factors than the effect of musculoskeletal disorders. Several national and international standards also exist for evaluating human exposure to WBV. The exposure limit values or health guidance caution zones included in some of these standards are not or only to a limited extent based on systematic epidemiological investigations. It has not yet been possible to establish a clear exposure-response relationship. There are many confounding or contributing factors which influence the hazards to workers caused by exposure to WBV. Reliable methods for the detection and prevention of injury due to vibration exposure at work, alone or in combination with other risk factors, need to be implemented. The aim of this paper was to design a protocol and a questionnaire for conducting collaborative studies of WBV and musculoskeletal back disorders. The protocol will be tested in a pilot study before it will be used in multi-center studies.

Digital music exposure reliably induces temporary threshold shift (TTS) in normal hearing human subjects

PubMed Central

Le Prell, C. G.; Dell, S.; Hensley, B.; Hall, J. W.; Campbell, K. C. M.; Antonelli, P. J.; Green, G. E.; Miller, J. M.; Guire, K.

2012-01-01

Objectives One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is availability of an established clinical paradigm with real world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal hearing human subjects. Design Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93–95 (n=10), 98–100 (n=11), or 100–102 (n=12) dBA in-ear exposure level for a period of four hours. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured prior to and after music exposure. Post-music tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and one week later. Results Changes in thresholds after the lowest level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a “notch” configuration, with the largest changes observed at 4 kHz (mean=6.3±3.9dB; range=0–13 dB). Recovery was largely complete within the first 4 hours post-exposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1-week post-exposure. Conclusions These data provide insight into the variability of TTS induced by music player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function following digital music player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values. PMID:22885407

Microplastics as vectors for bioaccumulation of hydrophobic organic chemicals in the marine environment: A state-of-the-science review.

PubMed

Ziccardi, Linda M; Edgington, Aaron; Hentz, Karyn; Kulacki, Konrad J; Kane Driscoll, Susan

2016-07-01

A state-of-the-science review was conducted to examine the potential for microplastics to sorb hydrophobic organic chemicals (HOCs) from the marine environment, for aquatic organisms to take up these HOCs from the microplastics, and for this exposure to result in adverse effects to ecological and human health. Despite concentrations of HOCs associated with microplastics that can be orders of magnitude greater than surrounding seawater, the relative importance of microplastics as a route of exposure is difficult to quantify because aquatic organisms are typically exposed to HOCs from various compartments, including water, sediment, and food. Results of laboratory experiments and modeling studies indicate that HOCs can partition from microplastics to organisms or from organisms to microplastics, depending on experimental conditions. Very little information is available to evaluate ecological or human health effects from this exposure. Most of the available studies measured biomarkers that are more indicative of exposure than effects, and no studies showed effects to ecologically relevant endpoints. Therefore, evidence is weak to support the occurrence of ecologically significant adverse effects on aquatic life as a result of exposure to HOCs sorbed to microplastics or to wildlife populations and humans from secondary exposure via the food chain. More data are needed to fully understand the relative importance of exposure to HOCs from microplastics compared with other exposure pathways. Environ Toxicol Chem 2016;35:1667-1676. © 2016 SETAC. © 2016 SETAC.

Effects of artificial light at night on human health: A literature review of observational and experimental studies applied to exposure assessment.

PubMed

Cho, YongMin; Ryu, Seung-Hun; Lee, Byeo Ri; Kim, Kyung Hee; Lee, Eunil; Choi, Jaewook

2015-01-01

It has frequently been reported that exposure to artificial light at night (ALAN) may cause negative health effects, such as breast cancer, circadian phase disruption and sleep disorders. Here, we reviewed the literature assessing the effects of human exposure to ALAN in order to list the health effects of various aspects of ALAN. Several electronic databases were searched for articles, published through August 2014, related to assessing the effects of exposure to ALAN on human health; these also included the details of experiments on such exposure. A total of 85 articles were included in the review. Several observational studies showed that outdoor ALAN levels are a risk factor for breast cancer and reported that indoor light intensity and individual lighting habits were relevant to this risk. Exposure to artificial bright light during the nighttime suppresses melatonin secretion, increases sleep onset latency (SOL) and increases alertness. Circadian misalignment caused by chronic ALAN exposure may have negative effects on the psychological, cardiovascular and/or metabolic functions. ALAN also causes circadian phase disruption, which increases with longer duration of exposure and with exposure later in the evening. It has also been reported that shorter wavelengths of light preferentially disturb melatonin secretion and cause circadian phase shifts, even if the light is not bright. This literature review may be helpful to understand the health effects of ALAN exposure and suggests that it is necessary to consider various characteristics of artificial light, beyond mere intensity.

Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

PubMed

Le Prell, Colleen G; Dell, Shawna; Hensley, Brittany; Hall, James W; Campbell, Kathleen C M; Antonelli, Patrick J; Green, Glenn E; Miller, James M; Guire, Kenneth

2012-01-01

One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Health effects of oxygenated fuels.

PubMed Central

Costantini, M G

1993-01-01

The use of oxygenated fuels is anticipated to increase over the next decades. This paper reviews the toxicological and exposure information for methyl tertiary-butyl ether (MTBE), a fuel additive, and methanol, a replacement fuel, and discusses the possible health consequences of exposure of the general public to these compounds. For MTBE, the health effects information available is derived almost exclusively from rodent studies, and the exposure data are limited to a few measurements at some service stations. Based on these data, it appears unlikely that the normal population is at high risk of exposure to MTBE vapor. However, in the absence of health and pharmacokinetic data in humans or in nonhuman primates, this conclusion is not strongly supported. Similarly, there are a number of uncertainties to take into consideration in estimating human risk from the use of methanol as a fuel. Although methanol may be toxic to humans at concentrations that overwhelm certain enzymes involved in methanol metabolism, the data available provide little evidence to indicate that exposure to methanol vapors from the use of methanol as a motor vehicle fuel will result in adverse health effects. The uncertainties in this conclusion are based on the lack of information on dose-response relationship at reasonable, projected exposure levels and of studies examining end points of concern in sensitive species. In developing a quantitative risk assessment, more needs to be known about health effects in primates or humans and the range of exposure expected for the general public for both compounds. PMID:8020439

Clearance of chrysotile asbestos from human lung

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

Churg, A.; DePaoli, L.

1988-01-01

In contrast to amphibole asbestos, chrysotile asbestos fails to accumulate in human lungs. The reason for this phenomenon is not known. To examine this problem, we extracted chrysotile and tremolite fibers from the lungs of 11 chrysotile miners and millers whose last exposure was within 2 years of death and 12 chrysotile miners and millers whose last exposure was greater than 12 years (7 with last exposure 12-15 years and 5 with last exposure 22-25 years) before death. Fibers were extracted by bleach digestion, and concentrations, compositions, and sizes were determined by analytical electron microscopy. Native UICC Canadian chrysotile wasmore » used as a composition standard. Compared to the standard, there was minor loss of magnesium at 2 years and additional very slight loss after 12 years. The ratio of chrysotile to tremolite concentration did not change with time. There was also no evidence of increasing fiber length with time from last exposure. These data indicate that accumulation of amphibole compared to chrysotile in human lungs does not reflect either long-term dissolution of chrysotile or long-term preferential clearance of chrysotile compared to amphibole. Contrary to results of animal studies, fiber length in humans does not increase with time since last exposure. These findings imply that the failure of chrysotile to accumulate in human lungs reflects events that occur early after exposure rather than long-term clearance mechanisms.« less

Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles

PubMed Central

Ji, Jie; Hedelin, Anna; Malmlöf, Maria; Kessler, Vadim; Seisenbaeva, Gulaim; Gerde, Per; Palmberg, Lena

2017-01-01

Background Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents. Methods In this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI). Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER) measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd) nanoparticles which sized 6–10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system. Results Exposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM. Conclusion This combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting. PMID:28107509

Characterization of alveolar macrophage eicosanoid production in a non-human primate model of mineral dust exposure.

PubMed

Kuhn, D C; Griffith, J W; Stauffer, J L; Riling, S; Demers, L M

1993-09-01

The relative activation of eicosanoid production which results from the exposure of the alveolar macrophage (AM) to mineral dusts is thought to be a key factor in the pathophysiology of occupational lung disease. We compared in vitro basal and silica-stimulated production of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) by AM from normal humans and non-human primates (Macaca nemestrina). In addition, we instilled mineral dusts directly into one lung of the non-human primate and evaluated AM eicosanoid production at two week intervals following dust instillation. Unstimulated AM from humans produce more PGE2 and TXA2 than do AM from M. nemestrina. However, in vitro exposure of AM from both species to silica dust produced a qualitatively similar increase in TXA2 production accompanied by no change in PGE2 production. Sequential analysis of AM eicosanoid production following a single bolus exposure to bituminous or anthracite coal dusts, titanium dioxide (TiO2) dust or crystalline silica showed marked variability among individual non-human primates in qualitative and quantitative aspects of dust-induced eicosanoid production. However, the rank order of potency of the different dusts (silica > anthracite > bituminous) correlated with epidemiological evidence relating the type of dust mined to the incidence of pneumoconiosis. These studies suggest that the non-human primate may serve as a model for the study of both the role of eicosanoids in the etiology of dust-induced occupational lung disease and the biochemical basis for individual variability in the response of lung cells to mineral dust exposure.

AMBIENT PARTICULATE MATTER EXPOSURES: A COMPARISON OF SHEDS-PM EXPOSURE MODEL PREDICTIONS AND ESTIMATES DERIVED FROM MEASUREMENTS COLLECTED DURING NERL'S RTP PM PANEL STUDY

EPA Science Inventory

The US EPA National Exposure Research Laboratory (NERL) is currently refining and evaluating a population exposure model for particulate matter (PM), called the Stochastic Human Exposure and Dose Simulation (SHEDS-PM) model. The SHEDS-PM model estimates the population distribu...

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 ...

FDTD analysis of temperature elevation in the lens of human and rabbit models due to near-field and far-field exposures at 2.45 GHz.

PubMed

Oizumi, Takuya; Laakso, Ilkka; Hirata, Akimasa; Fujiwara, Osamu; Watanabe, Soichi; Taki, Masao; Kojima, Masami; Sasaki, Hiroshi; Sasaki, Kazuyuki

2013-07-01

The eye is said to be one of the most sensitive organs to microwave heating. According to previous studies, the possibility of microwave-induced cataract formation has been experimentally investigated in rabbit and monkey eyes, but not for the human eye due to ethical reasons. In the present study, the temperature elevation in the lens, the skin around the eye and the core temperature of numerical human and rabbit models for far-field and near-field exposures at 2.45 GHz are investigated. The temperature elevations in the human and rabbit models were compared with the threshold temperatures for inducing cataracts, thermal pain in the skin and reversible health effects such as heat exhaustion or heat stroke. For plane-wave exposure, the core temperature elevation is shown to be essential both in the human and in the rabbit models as suggested in the international guidelines and standards. For localised exposure of the human eye, the temperature elevation of the skin was essential, and the lens temperature did not reach its threshold for thermal pain. On the other hand, the lens temperature elevation was found to be dominant for the rabbit eye.

The Human Bitumen Study: executive summary.

PubMed

Raulf-Heimsoth, Monika; Pesch, Beate; Rühl, Reinhold; Brüning, Thomas

2011-06-01

Bitumen has attracted attention from the scientific community and regulating agencies. The debate on health effects of exposure to vapours and aerosols of bitumen during the hot application of bitumen ranges from respiratory and neurological effects to carcinogenicity. In 2000, the German Hazardous Substances Committee (AGS), in collaboration with the German Bitumen Forum, initiated the examination of a group of mastic asphalt workers and a same number of construction workers without exposure bitumen using a cross-shift design. The study was then extended to the Human Bitumen Study, and the recruitment was finished in 2008 after examination of 500 workers on 80 construction sites. Three hundred and twenty workers exposed to vapours and aerosols of bitumen at high processing temperatures and 118 workers at outdoor construction sites were included. In the Human Bitumen Study external exposure to vapours and aerosols of bitumen, internal exposure to PAH by analysing urinary 1-hydroxypyrene, the sum of hydroxyphenanthrenes and the sum of 1- and 2-hydroxynaphthalenes, irritative effects in the upper and lower airways and genotoxic effects in blood cells were investigated. The study turned out to be one of the largest investigations of workers exposed to vapours and aerosols of bitumen under current exposure conditions. The present paper summarizes its background and main topics.

Epidemiologic studies of glyphosate and cancer: a review.

PubMed

Mink, Pamela J; Mandel, Jack S; Sceurman, Bonnielin K; Lundin, Jessica I

2012-08-01

The United States Environmental Protection Agency and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. Glyphosate is widely considered by regulatory authorities and scientific bodies to have no carcinogenic potential, based primarily on results of carcinogenicity studies of rats and mice. To examine potential cancer risks in humans, we reviewed the epidemiologic literature to evaluate whether exposure to glyphosate is associated causally with cancer risk in humans. We also reviewed relevant methodological and biomonitoring studies of glyphosate. Seven cohort studies and fourteen case-control studies examined the association between glyphosate and one or more cancer outcomes. Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate. Data from biomonitoring studies underscore the importance of exposure assessment in epidemiologic studies, and indicate that studies should incorporate not only duration and frequency of pesticide use, but also type of pesticide formulation. Because generic exposure assessments likely lead to exposure misclassification, it is recommended that exposure algorithms be validated with biomonitoring data. Copyright © 2012 Elsevier Inc. All rights reserved.

CHILDREN'S RESIDENTIAL EXPOSURE TO CHLORPYRIFOS: APPLICATION OF CPPAES FIELD MEASUREMENTS OF CHLORPYRIFOS AND TCPY WITHIN MENTOR/SHEDS PESTICIDES MODEL

EPA Science Inventory

The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, howev...

Antimicrobial Exposure Assessment Task Force II (AEATF II) Volume 5: Governing Document for a Multi-Year Antimicrobial Chemical Exposure Monitoring Program (interim draft document)

EPA Pesticide Factsheets

Describes the overall scope of the AEATF II program, demonstrates the need for additional human exposure monitoring data and explains the proposed methodology for the exposure monitoring studies proposed for conduct by the AEATF II.

THE INFLUENCE OF HUMAN ACTIVITY PATTERNS ON PERSONAL PM EXPOSURE: A COMPARATIVE ANALYSIS OF FILTER-BASED AND CONTINUOUS PARTICLE MEASUREMENTS

EPA Science Inventory

Particulate matter (PM) exposure data from the U.S. Environmental Protection Agency sponsored 1998 Baltimore and 1999 Fresno PM Exposure Studies were analyzed to identify important microenvironments and activities that may lead to increased particle exposure for select elderly ...

ANALYSIS OF CONCORDANCE OF PROBABILISTIC AGGREGATE EXPOSURE PREDICTIONS WITH OBSERVED BIOMONITORING RESULTS: AN EXAMPLE USING CTEPP DATA

EPA Science Inventory

Three key areas of scientific inquiry in the study of human exposure to environmental contaminants are 1) assessment of aggregate (i.e., multi-pathway, multi-route) exposures, 2) application of probabilistic methods to exposure prediction, and 3) the interpretation of biomarker m...

Human Injury Criteria for Underwater Blasts

PubMed Central

Lance, Rachel M.; Capehart, Bruce; Kadro, Omar; Bass, Cameron R.

2015-01-01

Underwater blasts propagate further and injure more readily than equivalent air blasts. Development of effective personal protection and countermeasures, however, requires knowledge of the currently unknown human tolerance to underwater blast. Current guidelines for prevention of underwater blast injury are not based on any organized injury risk assessment, human data or experimental data. The goal of this study was to derive injury risk assessments for underwater blast using well-characterized human underwater blast exposures in the open literature. The human injury dataset was compiled using 34 case reports on underwater blast exposure to 475 personnel, dating as early as 1916. Using severity ratings, computational reconstructions of the blasts, and survival information from a final set of 262 human exposures, injury risk models were developed for both injury severity and risk of fatality as functions of blast impulse and blast peak overpressure. Based on these human data, we found that the 50% risk of fatality from underwater blast occurred at 302±16 kPa-ms impulse. Conservatively, there is a 20% risk of pulmonary injury at a kilometer from a 20 kg charge. From a clinical point of view, this new injury risk model emphasizes the large distances possible for potential pulmonary and gut injuries in water compared with air. This risk value is the first impulse-based fatality risk calculated from human data. The large-scale inconsistency between the blast exposures in the case reports and the guidelines available in the literature prior to this study further underscored the need for this new guideline derived from the unique dataset of actual injuries in this study. PMID:26606655

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

Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund.

PubMed

Johnson, Eric S; Ndetan, Harrison; Lo, Ka-Ming

2010-08-01

The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.

Tracking natural and anthropogenic Pb exposure to its geological source.

PubMed

Evans, Jane; Pashley, Vanessa; Madgwick, Richard; Neil, Samantha; Chenery, Carolyn

2018-01-31

Human Pb exposure comes from two sources: (i) natural uptake through ingestion of soils and typified by populations that predate mining activity and (ii) anthropogenic exposure caused by the exposure to Pb derived from ore deposits. Currently, the measured concentration of Pb within a sample is used to discriminate between these two exposure routes, with the upper limit for natural exposure in skeletal studies given as 0.5 or 0.7 mg/kg in enamel and 0.5/0.7 μg/dL in blood. This threshold approach to categorising Pb exposure does not distinguish between the geological origins of the exposure types. However, Pb isotopes potentially provide a more definitive means of discriminating between sources. Whereas Pb from soil displays a crustal average 238 U/ 204 Pb (μ) value of c 9.7, Pb from ore displays a much wider range of evolution pathways. These characteristics are transferred into tooth enamel, making it possible to characterize human Pb exposure in terms of the primary source of ingested Pb and to relate mining activity to geotectonic domains. We surmise that this ability to discriminate between silicate and sulphide Pb exposure will lead to a better understanding of the evolution of early human mining activity and development of exposure models through the Anthropocene.

Human exposure to mercury in a compact fluorescent lamp manufacturing area: By food (rice and fish) consumption and occupational exposure.

PubMed

Liang, Peng; Feng, Xinbin; Zhang, Chan; Zhang, Jin; Cao, Yucheng; You, Qiongzhi; Leung, Anna Oi Wah; Wong, Ming-Hung; Wu, Sheng-Chun

2015-03-01

To investigate human Hg exposure by food consumption and occupation exposure in a compact fluorescent lamp (CFL) manufacturing area, human hair and rice samples were collected from Gaohong town, Zhejiang Province, China. The mean values of total mercury (THg) and methylmercury (MeHg) concentrations in local cultivated rice samples were significantly higher than in commercial rice samples which indicated that CFL manufacturing activities resulted in Hg accumulation in local rice samples. For all of the study participants, significantly higher THg concentrations in human hair were observed in CFL workers compared with other residents. In comparison, MeHg concentrations in human hair of residents whose diet consisted of local cultivated rice were significantly higher than those who consumed commercial rice. These results demonstrated that CFL manufacturing activities resulted in THg accumulation in the hair of CFL workers. However, MeHg in hair were mainly affected by the sources of rice of the residents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biomolecular Profiling of Jet Fuel Toxicity Using Proteomics

DTIC Science & Technology

2006-02-28

pulmonary alveolar type II cells and macrophages, and human epidermal keratinocytes in various exposure models. Results strongly suggest an injurious effect ...of exposure on all cells studied. In both pulmonary and skin cells, the protein profiles of JP-8 effect corroborates previous histological findings...potential intervention by Substance P (SP) in the pulmonary effects of JP-8 exposure , studies incorporating SP treatment along with JP-8 exposure

Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

PubMed Central

Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

2016-01-01

Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

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.

Evaluation of the adequacy of published studies of low-dose effects of bisphenol A on the rodent prostate for use in human risk assessment.

PubMed

Milman, Harry A; Bosland, Maarten C; Walden, Paul D; Heinze, John E

2002-06-01

Studies conducted in our laboratories and by others found no consistent correlation between prostate size, prostate pathology, or the development of prostate cancer under a variety of experimental conditions. Furthermore, an evaluation of eight published studies that were conducted in mice and rats following in utero exposure by oral treatment of dams with low levels of bisphenol A (BPA) and that focused on the prostate identified several discrepancies that affect their adequacy for use in human risk assessment. For example, there was inadequate reporting of the purity of BPA and the animal supplier used, and housing of offspring was not the same among the studies. In addition, there were differences between studies with mice and rats in exposure regimen, route of exposure, and numbers of dams or pups used per BPA dose group. Poor inter- and intraspecies correlation (i.e., mouse to rat or between mouse or rat strains) further complicates the ability to use results from these studies to predict potential prostate effects in humans. Thus, we conclude that a finding of increased prostate weight in rodent studies with perinatal exposure in the absence of associated pathologic and/or functional changes is meaningless and not indicative of a potential adverse effect in humans. Copyright 2002 Elsevier Science (USA)

Effect of centrifuge test on blood serum lipids index of cadet pilots.

PubMed

Wochyński, Zbigniew; Kowalczuk, Krzysztof; Kłossowski, Marek; Sobiech, Krzysztof A

2016-01-01

This study aimed at investigating the relationship between the lipid index (WS) in the examined cadets and duration of exposure to +Gz in the human centrifuge. The study involved 19 first-year cadets of the Polish Air Force Academy in Dęblin. Tests in the human centrifuge were repeated twice, i.e. prior to (test I) and 45 days after (test II). After exposure to +Gz, the examined cadets were divided into 2 groups. Group I (N=11) included cadets subjected to a shorter total duration of exposure to +Gz, while group II (N=8) included cadets with a longer total duration of exposure to +Gz. Total cholesterol (TC), high density lipoprotein (HDL), triglycerides (TG), and apolipoproteins A1 and B were assayed in blood serum prior to (assay A) and after (assay B) both exposures to +Gz. Low density lipoprotein (LDL) level was estimated from the Friedewald formula. WS is an own mathematical algorithm. WS was higher in group II, assay A - 10.0 and B - 10.08 of test I in the human centrifuge than in group I where the WS values were 6.91 and 6.96, respectively. WS was also higher in group II in assay A - 10.0 and B -10.1 of test II in the human centrifuge than in group I - 6.96 and 6.80, respectively. The higher value of WS in group II, both after the first and second exposure to +Gz in human centrifuge, in comparison with group I, indicated its usefulness for determination of the maximum capability of applying acceleration of the interval type during training in the human centrifuge.

An In Situ and In Silico Evaluation of Biophysical Effects of 27 MHz Electromagnetic Whole Body Humans Exposure Expressed by the Limb Current

PubMed Central

2017-01-01

Objectives The aim was to evaluate correlations between biophysical effects of 27 MHz electromagnetic field exposure in humans (limb induced current (LIC)) and (1) parameters of affecting heterogeneous electric field and (2) body anthropometric properties, in order to improve the evaluation of electromagnetic environmental hazards. Methods Biophysical effects of exposure were studied in situ by measurements of LIC in 24 volunteers (at the ankle) standing near radio communication rod antenna and in silico in 4 numerical body phantoms exposed near a model of antenna. Results Strong, positive, statistically significant correlations were found in all exposure scenarios between LIC and body volume index (body height multiplied by mass) (r > 0.7; p < 0.001). The most informative exposure parameters, with respect to the evaluation of electromagnetic hazards by measurements (i.e., the ones strongest correlated with LIC), were found to be the value of electric field (unperturbed field, in the absence of body) in front of the chest (50 cm from body axis) or the maximum value in space occupied by human. Such parameters were not analysed in previous studies. Conclusions Exposed person's body volume and electric field strength in front of the chest determine LIC in studied exposure scenarios, but their wider applicability needs further studies. PMID:28758119

Human mutagens: evidence from paternal exposure

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

Narod, S.A.; Douglas, G.R.; Nestmann, E.R.

1988-01-01

The importance of inherited mutations as a cause of human disease has been established clearly through examples of well-defined genetic anomalies, such as Down syndrome and retinoblastoma. Furthermore, it is suspected that environmental contaminants induce mutations resulting in increased risk for such defects in subsequent generations of persons exposed. The present lack of direct evidence for induced inherited genetic disorders in human beings hampers the development of risk estimation techniques for extrapolation from animal models. The most extensive prospective epidemiologic studies of inherited genetic effects have involved survivors of atomic bomb detonations and patients treated with cancer chemotherapy. In neithermore » case has a significant elevation in inherited genetic effects or cancer been detected in the offspring of exposed individuals. Epidemiologic studies of subjects receiving chronic exposure may be confounded by the effect of maternal exposure during pregnancy. Consideration of only paternal exposure can minimize the confounding influence of teratogenicity, enhancing the resolving power of studies for inherited effects. Using this approach, retrospective (case-control) studies of childhood cancer patients have provided limited but suggestive evidence for inheritance of induced effects. Endpoints, such as congenital malformations and spontaneous abortion following paternal exposure, can also be considered as indicators of heritable mutagenic effects. For example, there is limited evidence suggesting that paternal exposure to anaesthetic gases may cause miscarriage and congenital abnormalities as a result of induced male germ cell mutations. 104 references.« less

MODELING POPULATION EXPOSURES TO OUTDOOR SOURCES OF HAZARDOUS AIR POLLUTANTS

EPA Science Inventory

Accurate assessment of human exposures is an important part of environmental health effects research. However, most air pollution epidemiology studies rely upon imperfect surrogates of personal exposures, such as information based on available central-site outdoor concentration ...

Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health.

PubMed

Xiang, Ping; Liu, Rong-Yan; Li, Chao; Gao, Peng; Cui, Xin-Yi; Ma, Lena Q

2017-11-01

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC 50 at 202 μg/mL. A concentration-dependent apoptotic sign was observed in HCECs after exposing to ≥2 μg/mL TDCPP. Endoplasmic reticulum stress induction was evidenced by up-regulation of its biomarker genes (ATF-4, CHOP, BiP, and XBP1). Furthermore, alternation of Bcl-2/Bax expression, mitochondrial membrane potential loss, cellular ATP content decrease, and caspase-3 and -9 activity increase were observed after exposing to 2 or 20 μg/mL TDCPP. Taken together, the data implicated the involvement of endoplasmic reticulum stress in TDCPP-induced HCEC apoptosis, probably mediated by mitochondrial apoptotic pathway. Our findings showed TDCPP exposure induced toxicity to human cornea. Due to TDCPP's presence at high levels in indoor dust, further study is warranted to evaluate its health risk on human corneas. Published by Elsevier Ltd.

Identifying Housing and Meteorological Conditions Influencing Residential Air Exchange Rates in the DEARS and RIOPA Studies: Development of Distributions for Human Exposure Modeling

EPA Science Inventory

Appropriate prediction of residential air exchange rate (AER) is important for estimating human exposures in the residential microenvironment, as AER drives the infiltration of outdoor-generated air pollutants indoors. AER differences among homes may result from a number of fact...

Identification of fipronil metabolites in rodents by time-of-flight mass spectrometry for application in a human exposure study

EPA Science Inventory

Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks associated with fipronil, dosed Long Evans rats were evaluated for metabolites to develop a set of biomarkers for use in human exposur...

ASSESSING ASTHMATIC CHILDREN'S EXPOSURES TO TOXIC AIR POLLUTANTS AND THE POTENTIAL INHALED DOSES USING TIME ACTIVITY INFORMATION AND ENERGY EXPENDITURE DATA

EPA Science Inventory

Accurately quantifying human exposures and the potential doses of various populations to environmental pollutants is critical for the U.S. Environmental Protection Agency to assess and manage human health risks. The Tampa Asthmatic Children's Study (TACS) was a pilot research stu...

The Use of Biomonitoring Data in Exposure and Human Health Risk Assessment: BENZENE CASE STUDY.

EPA Science Inventory

HESI Biomonitoring Technical Committee A framework of "Common Criteria" (i.e., a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment (Albertini et al., 2006). The data-rich chemical b...

Elevated ERCC-1 Gene Expression in blood cells associated with exposure to arsenic from drinking water in Inner Mongolia

EPA Science Inventory

Background: Chronic arsenic exposure has been associated with human cancers. The objective of this study was to investigate arsenic effects on a DNA nucleotide excision repair gene, ERCC1, expression in human blood cells. Material and Methods: Water and toe nail samples were coll...

Assessment of human exposure doses received by activation of medical linear accelerator components

NASA Astrophysics Data System (ADS)

Lee, D.-Y.; Kim, J.-H.; Park, E.-T.

2017-08-01

This study analyzes the radiation exposure dose that an operator can receive from radioactive components during maintenance or repair of a linear accelerator. This study further aims to evaluate radiological safety. Simulations are performed on 10 MV and 15 MV photon beams, which are the most frequently used high-energy beams in clinics. The simulation analyzes components in order of activity and the human exposure dose based on the amount of neutrons received. As a result, the neutron dose, radiation dose, and human exposure dose are ranked in order of target, primary collimator, flattening filter, multi-leaf collimator, and secondary collimator, where the minimum dose is 9.34E-07 mSv/h and the maximum is 1.71E-02 mSv/h. When applying the general dose limit (radiation worker 20 mSv/year, pubic 1 mSv/year) in accordance with the Nuclear Safety Act, all components of a linear accelerator are evaluated as below the threshold value. Therefore, the results suggest that there is no serious safety issue for operators in maintaining and repairing a linear accelerator. Nevertheless, if an operator recognizes an exposure from the components of a linear accelerator during operation and considers the operating time and shielding against external exposure, exposure of the operator is expected to be minimized.

Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health.

PubMed

Tapia-Orozco, Natalia; Santiago-Toledo, Gerardo; Barrón, Valeria; Espinosa-García, Ana María; García-García, José Antonio; García-Arrazola, Roeb

2017-04-01

Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Occupational exposure among medical students and house staff at a New York City Medical Center.

PubMed

Resnic, F S; Noerdlinger, M A

1995-01-09

The purpose of the study was to ascertain the prevalence of and reasons for underreporting of occupational exposures to patients' blood and body fluids among students and house staff. A questionnaire surveyed 110 medical students and 275 house staff members regarding the number of reported and unreported exposures to patients' body fluids, and the reasons why the respondents did or did not report their exposures during the previous 6 months. Of 385 surveys returned, representing a response rate of 60%, 122 respondents (32%) experienced 330 occupational exposures during the previous 6 months. Fifty-two percent of surgical house staff, 27% of students, and 20% of medical house staff were exposed. Whereas the exposure risk to surgical house staff increased with training, the risk to medical house staff decreased with training. Only 29% of exposed respondents reported an exposure. Exposures from sources known to be positive or at high risk for human immunodeficiency virus had the highest reporting rates. The most frequent reason for not reporting an exposure was that the patient was thought not to be infectious. Forty-six percent of respondents exposed to sources of unknown human immunodeficiency virus status who did not report chose "patient thought not to be infectious" as the reason. The most common reason for reporting an exposure was "hospital policy." Although limited by recall bias, this study showed that a high proportion of students and house staff experience occupational exposures. The results suggest that populations at high risk for exposures are the more experienced surgical house staff and the junior medical house staff. Exposures from sources known to be positive or at high risk for human immunodeficiency virus were reported more frequently than those from unknown risk sources.

Assessing human exposure to power-frequency electric and magnetic fields.

PubMed Central

Kaune, W T

1993-01-01

This paper reviews published literature and current problems relating to the assessment of occupational and residential human exposures to power-frequency electric and magnetic fields. Available occupational exposure data suggest that the class of job titles known as electrical workers may be an effective surrogate for time-weighted-average (TWA) magnetic-field (but not electric-field) exposure. Current research in occupational-exposure assessment is directed to the construction of job-exposure matrices based on electric- and magnetic-field measurements and estimates of worker exposures to chemicals and other factors of interest. Recent work has identified five principal sources of residential magnetic fields: electric power transmission lines, electric power distribution lines, ground currents, home wiring, and home appliances. Existing residential-exposure assessments have used one or more of the following techniques: questionnaires, wiring configuration coding, theoretical field calculations, spot electric- and magnetic-field measurements, fixed-site magnetic-field recordings, personal- exposure measurements, and geomagnetic-field measurements. Available normal-power magnetic-field data for residences differ substantially between studies. It is not known if these differences are due to geographical differences, differences in measurement protocols, or instrumentation differences. Wiring codes and measured magnetic fields (but not electric fields) are associated weakly. Available data suggest, but are far from proving, that spot measurements may be more effective than wire codes as predictors of long-term historical magnetic-field exposure. Two studies find that away-from-home TWA magnetic-field exposures are less variable than at-home exposures. The importance of home appliances as contributors to total residential magnetic-field exposure is not known at this time. It also is not known what characteristics (if any) of residential electric and magnetic fields are determinants of human health effects. PMID:8206021

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.

Bioavailability of organic solvents in soils: Input into biologically based dose-response models for human risk assessments. 1998 annual progress report

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

Wester, R.C.; Maibach, H.I.

1998-06-01

'The purpose of this study is to determine the bioavailability of organic solvents following dermal exposures to contaminated soil and water. Breath analysis is being used to obtain real-time measurements of volatile organics in expired air following exposure in rats and humans. Rhesus monkeys will be used as surrogates for humans in benzene exposures. The exhaled breath data is being analyzed using physiologically based pharmacokinetic (PBPK) models to determine the dermal bioavailability of organic solvents under realistic exposure conditions. The end product of this research will be a tested framework for the rapid screening of real and potential exposures whilemore » simultaneously developing physiologically based pharmacokinetic (PBPK) models to comprehensively evaluate and compare exposures to organics from either contaminated soil or water. This report summarizes work 7 months into a 3-year project. Method development has produced systems for solvent exposure from soil and water which mimic actual exposure, and for which animals and human volunteers can be safely tested. Soil exposure is generally open to the air (working the soil) while water exposure is generally immersion. For 6--8 hour test exposure, a patch has been developed where soil is contained against the skin by a non-occlusive membrane, while simultaneously allowing volatilization of test solvent to the environment (activated charcoal). The water counterpart is an occlusive glass culture dish, sealed to skin with silicone adhesive. Shorter term exposure is done by one hand immersion in a bucket containing circulating water or soil, the volunteer instructed to move fingers through the water or soil. Human volunteers and animals breathe fresh air via a new breath-inlet system that allows for continuous real-time analysis of undiluted exhaled air. The air supply system is self-contained and separated from the exposure solvent-laden environment. The system uses a Teledyne 3DQ Discovery ion trap mass spectrometer (MS/MS) equipped with an atmospheric sampling glow discharge ionization source (ASGDI). The MS/MS system provides an appraisal of individual chemical components in the breath stream in the single-digit parts-per-billion (ppb) detectable range for each of the compounds proposed for study, while maintaining linearity of response over a wide dynamic range.'« less

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

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 ...

Truncated Lévy flights and agenda-based mobility are useful for the assessment of personal human exposure.

PubMed

Schlink, Uwe; Ragas, Ad M J

2011-01-01

Receptor-oriented approaches can assess the individual-specific exposure to air pollution. In such an individual-based model we analyse the impact of human mobility to the personal exposure that is perceived by individuals simulated in an exemplified urban area. The mobility models comprise random walk (reference point mobility, RPM), truncated Lévy flights (TLF), and agenda-based walk (RPMA). We describe and review the general concepts and provide an inter-comparison of these concepts. Stationary and ergodic behaviour are explained and applied as well as performance criteria for a comparative evaluation of the investigated algorithms. We find that none of the studied algorithm results in purely random trajectories. TLF and RPMA prove to be suitable for human mobility modelling, because they provide conditions for very individual-specific trajectories and exposure. Suggesting these models we demonstrate the plausibility of their results for exposure to air-borne benzene and the combined exposure to benzene and nonane. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exposure to Mexicali PM induces NFkb-Dependent IL-8 Transcriptional Activity in Human Airway Epithelial Cells

EPA Science Inventory

Studies have reported associations between exposure to ambient air particulate matter (PM) and increased rates of cardio-pulmonary morbidity and mortality. The aim of this study was to determine the effect of exposure to PM of varying size fractions collected in urban (U) and se...

AS 2008: Arsenic exposure a nd health effects in Inner Mongolia: studies on cardiac, diabetes and cancer-related effects

EPA Science Inventory

Chronic arsenic exposure via drinking water has been of great public health concern world wide. Arsenic exposure has been associated with human cancers, diabetes and cardiovascular diseases. The objectives of this study were to investigate health effects of arsenic and to asses...

In Vivo Human Time-Exposure Study of Orally Dosed Commercial Silver Nanoparticles

PubMed Central

Munger, Mark A.; Radwanski, Przemyslaw; Hadlock, Greg C.; Stoddard, Greg; Shaaban, Akram; Falconer, Jonathan; Grainger, David W.; Deering-Rice, Cassandra E.

2013-01-01

Background Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receives increasing health assessment. Methods We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content was determined. Results No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. Conclusion In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems is warranted to assert human toxicity thresholds. PMID:23811290

Reproductive and Developmental Toxicity of Formaldehyde: A Systematic Review

PubMed Central

Duong, Anh; Steinmaus, Craig; McHale, Cliona M.; Vaughan, Charles P.; Zhang, Luoping

2011-01-01

Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20–2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27–1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure. PMID:21787879

Systematic review of the association between oil and natural gas extraction processes and human reproduction.

PubMed

Balise, Victoria D; Meng, Chun-Xia; Cornelius-Green, Jennifer N; Kassotis, Christopher D; Kennedy, Rana; Nagel, Susan C

2016-09-15

This systematic review identified 45 original published research articles related to oil and gas extraction activities and human reproductive endpoints. Reproductive outcomes were categorized as [1] birth outcomes associated with maternal exposure, [2] semen quality, fertility, and birth outcomes associated with adult paternal exposure, [3] reproductive cancers, and [4] disruption of human sex steroid hormone receptors. The results indicate there is moderate evidence for an increased risk of preterm birth, miscarriage, birth defects, decreased semen quality, and prostate cancer. The quality of the evidence is low and/or inadequate for stillbirth, sex ratio, and birth outcomes associated with paternal exposure, and testicular cancer, female reproductive tract cancers, and breast cancer, and the evidence is inconsistent for an increased risk of low birth weight; therefore, no conclusions can be drawn for these health effects. There is ample evidence for disruption of the estrogen, androgen, and progesterone receptors by oil and gas chemicals, which provides a mechanistic rationale for how exposure to oil and gas activities may increase the health risks we have outlined. The results from this systematic review suggest there is a negative impact on human reproduction from exposure to oil and gas activities. Many of the 45 studies reviewed identified potential human health effects. Most of these studies focused on conventional oil and gas activities. Few studies have been conducted to evaluate the impact of unconventional oil and gas operations on human health. The impact of unconventional oil and gas activities may be greater than that of conventional activity, given that unconventional activities employ many of the same approaches and use dozens of known endocrine-disrupting chemicals in hydraulic fracturing. Copyright © 2016. Published by Elsevier Inc.

Assessing the bioavailability and risk from metal-contaminated ...

EPA Pesticide Factsheets

Exposure to contaminated soil and dust is an important pathway in human health risk assessment. Physical and chemical characteristics, as well as biological factors, determine the bioaccessibility/bioavailability of soil and dust contaminants. Within a single sample, contamination may arise from multiple sources of toxic elements that may exist as different forms (species) which impact bioavailability. In turn, the bioaccessibility/bioavailability of soil and dust contaminants has a direct impact on human health risk assessment and risk management practices. Novel research efforts focusing on development and application of in vitro and in vivo methods to measure the bioaccessibility/bioavailability of metal contaminated soils have advanced in the past few years. The objective of this workshop was to focus on recent developments in assessing the bioaccessibility/bioavailability of arsenic contaminated soils, metal contamination in urban residences in Canada and potential children’s exposures to toxic elements in house dust, a community-based study known as the West Oakland Residential Lead Assessment , studies of the bioavailability of soil cadmium, chromium, nickel and mercury and human exposures to contaminated Brownfield soils. These presentations covered issues related to human health and bioavailability along with the most recent studies on community participation in assessing metal contamination, studies of exposures to residential contamination, and

The influence of endocrine disruptors on growth and development of children.

PubMed

DiVall, Sara A

2013-02-01

This review describes the most recent data about the effects of endocrine disrupting compounds (EDCs) on infant and early childhood growth and reproductive tract development as well as controversies in the field. EDCs are present in pregnant women, young children and adolescents. Whether the level of exposure contributes to disease is an ongoing debate. Epidemiological studies suggest associations between prenatal EDC exposure and disease outcome, but animal studies using controlled EDC exposure have varying results with underlying mechanisms largely unknown. Human exposure to EDCs is widespread; bisphenol A, phthalates and persistent organic pollutants are detectable in all age groups and geographical locations in the USA. Epidemiological and animal studies suggest that phthalates and bisphenol A have adverse effects on birth weight, promote development of childhood obesity and adversely affect male reproductive tract development. Differences in the interpretation of available studies underlie the disparate conclusions of scientific and regulatory body's panels on potential toxicological effects of EDCs at current levels of human exposure.

Systematic review of community health impacts of mountaintop removal mining.

PubMed

Boyles, Abee L; Blain, Robyn B; Rochester, Johanna R; Avanasi, Raghavendhran; Goldhaber, Susan B; McComb, Sofie; Holmgren, Stephanie D; Masten, Scott A; Thayer, Kristina A

2017-10-01

The objective of this evaluation is to understand the human health impacts of mountaintop removal (MTR) mining, the major method of coal mining in and around Central Appalachia. MTR mining impacts the air, water, and soil and raises concerns about potential adverse health effects in neighboring communities; exposures associated with MTR mining include particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), metals, hydrogen sulfide, and other recognized harmful substances. A systematic review was conducted of published studies of MTR mining and community health, occupational studies of MTR mining, and any available animal and in vitro experimental studies investigating the effects of exposures to MTR-mining-related chemical mixtures. Six databases (Embase, PsycINFO, PubMed, Scopus, Toxline, and Web of Science) were searched with customized terms, and no restrictions on publication year or language, through October 27, 2016. The eligibility criteria included all human population studies and animal models of human health, direct and indirect measures of MTR-mining exposure, any health-related effect or change in physiological response, and any study design type. Risk of bias was assessed for observational and experimental studies using an approach developed by the National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT). To provide context for these health effects, a summary of the exposure literature is included that focuses on describing findings for outdoor air, indoor air, and drinking water. From a literature search capturing 3088 studies, 33 human studies (29 community, four occupational), four experimental studies (two in rat, one in vitro and in mice, one in C. elegans), and 58 MTR mining exposure studies were identified. A number of health findings were reported in observational human studies, including cardiopulmonary effects, mortality, and birth defects. However, concerns for risk of bias were identified, especially with respect to exposure characterization, accounting for confounding variables (such as socioeconomic status), and methods used to assess health outcomes. Typically, exposure was assessed by proximity of residence or hospital to coal mining or production level at the county level. In addition, assessing the consistency of findings was challenging because separate publications likely included overlapping case and comparison groups. For example, 11 studies of mortality were conducted with most reporting higher rates associated with coal mining, but many of these relied on the same national datasets and were unable to consider individual-level contributors to mortality such as poor socioeconomic status or smoking. Two studies of adult rats reported impaired microvascular and cardiac mitochondrial function after intratracheal exposure to PM from MTR-mining sites. Exposures associated with MTR mining included reports of PM levels that sometimes exceeded Environmental Protection Agency (EPA) standards; higher levels of dust, trace metals, hydrogen sulfide gas; and a report of increased public drinking water violations. This systematic review could not reach conclusions on community health effects of MTR mining because of the strong potential for bias in the current body of human literature. Improved characterization of exposures by future community health studies and further study of the effects of MTR mining chemical mixtures in experimental models will be critical to determining health risks of MTR mining to communities. Without such work, uncertainty will remain regarding the impact of these practices on the health of the people who breathe the air and drink the water affected by MTR mining. Published by Elsevier Ltd.

Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan.

PubMed

Johnson, Paula I; Koustas, Erica; Vesterinen, Hanna M; Sutton, Patrice; Atchley, Dylan S; Kim, Allegra N; Campbell, Marlissa; Donald, James M; Sen, Saunak; Bero, Lisa; Zeise, Lauren; Woodruff, Tracey J

2016-01-01

There are reports of developmental and reproductive health effects associated with the widely used biocide triclosan. Apply the Navigation Guide systematic review methodology to answer the question: Does exposure to triclosan have adverse effects on human development or reproduction? We applied the first 3 steps of the Navigation Guide methodology: 1) Specify a study question, 2) Select the evidence, and 3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the number and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-analysis on a subset of suitable data. We found 4282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concentration outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-analysis. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-analysis of the human data. Through meta-analysis of the data for rats, we estimated for prenatal exposure a 0.09% (95% CI: -0.20, 0.02) reduction in thyroxine concentration per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estimated a 0.31% (95% CI: -0.38, -0.23) reduction in thyroxine per mg triclosan/kg-bw, also compared to control. Overall, we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a "moderate/low" quality rating to the body of evidence for human thyroid hormone alterations and a "moderate" quality rating to the body of evidence for non-human thyroid hormone alterations. Based on this application of the Navigation Guide systematic review methodology, we concluded that there was "sufficient" non-human evidence and "inadequate" human evidence of an association between triclosan exposure and thyroxine concentrations, and consequently, triclosan is "possibly toxic" to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Additional endpoints may be identified as being of equal or greater concern as other data are developed or evaluated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Application of the Navigation Guide Systematic Review Methodology to the Evidence for Developmental and Reproductive Toxicity of Triclosan

PubMed Central

Johnson, Paula I.; Koustas, Erica; Vesterinen, Hanna M.; Sutton, Patrice; Atchley, Dylan S.; Kim, Allegra N.; Campbell, Marlissa; Donald, James M.; Sen, Saunak; Bero, Lisa; Zeise, Lauren; Woodruff, Tracey J.

2016-01-01

Background There are reports of developmental and reproductive health effects associated with the widely used biocide triclosan. Objective Apply the Navigation Guide systematic review methodology to answer the question: Does exposure to triclosan have adverse effects on human development or reproduction? Methods We applied the first 3 steps of the Navigation Guide methodology: 1) Specify a study question, 2) Select the evidence, and 3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the number and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-analysis on a subset of suitable data. Results We found 4,282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concentration outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-analysis. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-analysis of the human data. Through meta-analysis of the data for rats, we estimated for prenatal exposure a 0.09% (95% CI: −0.20, 0.02) reduction in thyroxine concentration per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estimated a 0.31% (95% CI: −0.38, −0.23) reduction in thyroxine per mg triclosan/kg-bw, also compared to control. Overall we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a “moderate/low” quality rating to the body of evidence for human thyroid hormone alterations and a “moderate” quality rating to the body of evidence for non-human thyroid hormone alterations. Conclusion Based on this application of the Navigation Guide systematic review methodology, we concluded that there was “sufficient” non-human evidence and “inadequate” human evidence of an association between triclosan exposure and thyroxine concentrations, and consequently, triclosan is “possibly toxic” to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Additional endpoints may be identified as being of equal or greater concern as other data are developed or evaluated. PMID:27156197

Potential Role of Pet Cats As a Sentinel Species for Human Exposure to Flame Retardants

PubMed Central

Henríquez-Hernández, Luis A.; Carretón, Elena; Camacho, María; Montoya-Alonso, José Alberto; Boada, Luis D.; Bernal Martín, Verónica; Falcón Cordón, Yaiza; Falcón Cordón, Soraya; Zumbado, Manuel; Luzardo, Octavio P.

2017-01-01

Flame retardants are a wide group of chemicals used by the industry to avoid combustion of materials. These substances are commonly found in plastics, electronic equipment, fabrics, and in many other everyday articles. Subsequently, ubiquitous environmental contamination by these common chemical is frequently reported. In the present study, we have evaluated the level of exposure to polychlorinated biphenyls (PCBs), brominated diphenyl ethers (BDEs), and organophosphorous flame retardants (OPFRs) in pet cats through the analysis of their serum. We also analyzed the level exposure to such chemicals in a series of 20 cat owners, trying to disclose the role of pet cats as sentinel species of human exposure to FRs. Our results showed that PCBs, banned 40 years ago, showed the lowest levels of exposure, followed by BDEs—banned recently. Congeners PCB-138 and PCB-180 were detected in ≥50% of the series, while BDE-47 was detected in near 90% of the pet cats. On the other hand, the highest levels were that of OPFRs, whose pattern of detection was similar to that observed in humans, thus suggesting a potential role of cats as a sentinel species for human exposure to these currently used FRs. Six out of 11 OPFRs determined [2-ethylhexyldiphenyl phosphate, tributylphosphate, triisobutylphosphate, triphenylphosphate, tris (2-chloroethyl) phosphate, and tris (2-chloroisopropyl) phosphate] were detected in 100% of the samples. It will be interesting to perform future studied aimed to elucidating the potential toxicological effects of these highly detected chemicals both, in cats and humans. PMID:28620612

Foetal exposure to food and environmental carcinogens in human beings.

PubMed

Myöhänen, Kirsi; Vähäkangas, Kirsi

2012-02-01

Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

ZINC-DEFICIENCY ENHANCES PRO-INFLAMMATORY RESPONSES AFTER OZONE EXPOSURE

EPA Science Inventory

Epidemiological and controlled exposure studies have demonstrated that humans are differentially susceptible to adverse health effects induced by exposure to ozone. Serum analysis of vitamins and trace elements have shown that the elderly (people >65 years) are deficient in sever...

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...

Quantification of nerve agent VX-butyrylcholinesterase adduct biomarker from an accidental exposure.

PubMed

Solano, Maria I; Thomas, Jerry D; Taylor, James T; McGuire, Jeffrey M; Jakubowski, Edward M; Thomson, Sandra A; Maggio, Vincent L; Holland, Kerry E; Smith, J Richard; Capacio, Benedict; Woolfitt, Adrian R; Ashley, David L; Barr, John R

2008-01-01

The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80 nM, it can be calculated that inhibition levels of >or= 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.

Exposure to Animal Feces and Human Health: A Systematic Review and Proposed Research Priorities

PubMed Central

2017-01-01

Humans can be exposed to pathogens from poorly managed animal feces, particularly in communities where animals live in close proximity to humans. This systematic review of peer-reviewed and gray literature examines the human health impacts of exposure to poorly managed animal feces transmitted via water, sanitation, and hygiene (WASH)-related pathways in low- and middle-income countries, where household livestock, small-scale animal operations, and free-roaming animals are common. We identify routes of contamination by animal feces, control measures to reduce human exposure, and propose research priorities for further inquiry. Exposure to animal feces has been associated with diarrhea, soil-transmitted helminth infection, trachoma, environmental enteric dysfunction, and growth faltering. Few studies have evaluated control measures, but interventions include reducing cohabitation with animals, provision of animal feces scoops, controlling animal movement, creating safe child spaces, improving veterinary care, and hygiene promotion. Future research should evaluate: behaviors related to points of contact with animal feces; animal fecal contamination of food; cultural behaviors of animal fecal management; acute and chronic health risks associated with exposure to animal feces; and factors influencing concentrations and shedding rates of pathogens originating from animal feces. PMID:28926696

Effects of Low-Level Blast Exposure on the Nervous System: Is There Really a Controversy?

PubMed Central

Elder, Gregory A.; Stone, James R.; Ahlers, Stephen T.

2014-01-01

High-pressure blast waves can cause extensive CNS injury in human beings. However, in combat settings, such as Iraq and Afghanistan, lower level exposures associated with mild traumatic brain injury (mTBI) or subclinical exposure have been much more common. Yet controversy exists concerning what traits can be attributed to low-level blast, in large part due to the difficulty of distinguishing blast-related mTBI from post-traumatic stress disorder (PTSD). We describe how TBI is defined in human beings and the problems posed in using current definitions to recognize blast-related mTBI. We next consider the problem of applying definitions of human mTBI to animal models, in particular that TBI severity in human beings is defined in relation to alteration of consciousness at the time of injury, which typically cannot be assessed in animals. However, based on outcome assessments, a condition of “low-level” blast exposure can be defined in animals that likely approximates human mTBI or subclinical exposure. We review blast injury modeling in animals noting that inconsistencies in experimental approach have contributed to uncertainty over the effects of low-level blast. Yet, animal studies show that low-level blast pressure waves are transmitted to the brain. In brain, low-level blast exposures cause behavioral, biochemical, pathological, and physiological effects on the nervous system including the induction of PTSD-related behavioral traits in the absence of a psychological stressor. We review the relationship of blast exposure to chronic neurodegenerative diseases noting the paradoxical lowering of Abeta by blast, which along with other observations suggest that blast-related TBI is pathophysiologically distinct from non-blast TBI. Human neuroimaging studies show that blast-related mTBI is associated with a variety of chronic effects that are unlikely to be explained by co-morbid PTSD. We conclude that abundant evidence supports low-level blast as having long-term effects on the nervous system. PMID:25566175

Human and animal evidence of potential transgenerational inheritance of health effects: An evidence map and state-of-the-science evaluation.

PubMed

Walker, Vickie R; Boyles, Abee L; Pelch, Katherine E; Holmgren, Stephanie D; Shapiro, Andrew J; Blystone, Chad R; Devito, Michael J; Newbold, Retha R; Blain, Robyn; Hartman, Pamela; Thayer, Kristina A; Rooney, Andrew A

2018-06-01

An increasing number of reports suggest early life exposures result in adverse effects in offspring who were never directly exposed; this phenomenon is termed "transgenerational inheritance." Given concern for public health implications for potential effects of exposures transmitted to subsequent generations, it is critical to determine how widespread and robust this phenomenon is and to identify the range of exposures and possible outcomes. This scoping report examines the evidence for transgenerational inheritance associated with exposure to a wide range of stressors in humans and animals to identify areas of consistency, uncertainty, data gaps, and to evaluate general risk of bias issues for the transgenerational study design. A protocol was developed to collect and categorize the literature into a systematic evidence map for transgenerational inheritance by health effects, exposures, and evidence streams following the Office of Health Assessment and Translation (OHAT) approach for conducting literature-based health assessments. A PubMed search yielded 63,758 unique records from which 257 relevant studies were identified and categorized into a systematic evidence map by evidence streams (46 human and 211 animal), broad health effect categories, and exposures. Data extracted from the individual studies are available in the Health Assessment Workspace Collaborative (HAWC) program. There are relatively few bodies of evidence where multiple studies evaluated the same exposure and the same or similar outcomes. Studies evaluated for risk of bias generally had multiple issues in design or conduct. The evidence mapping illustrated that risk of bias, few studies, and heterogeneity in exposures and endpoints examined present serious limitations to available bodies of evidence for assessing transgenerational effects. Targeted research is suggested to addressed inconsistencies and risk of bias issues identified, and thereby establish more robust bodies of evidence to critically assess transgenerational effects - particularly by adding data on exposure-outcome pairs where there is some evidence (i.e., reproductive, metabolic, and neurological effects). Copyright © 2017. Published by Elsevier Ltd.

Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus

PubMed Central

Parks, Christine G.; De Roos, Anneclaire J.

2013-01-01

Growing evidence suggests exposure to chemicals and industrial pollutants may increase risk of SLE. Here we review research on SLE associations with occupational and industrial exposures, primarily drawing on studies in human populations and summarizing epidemiologic research published in the past decade. The association of occupational silica exposure with SLE is well established, but key questions remain, including the required dose and susceptibility factors, and SLE risk due to other silicate exposures. Research on SLE and other exposures is less well developed, though several potential associations merit further consideration due to the consistency of preliminary human findings, experimental animal research, and biologic plausibility. These include pesticides and solvents, for which experimental findings also support investigation of specific agents, including organochlorines and trichloroethylene. Experimental findings and biologic plausibility suggest research on SLE and occupational exposure to hydrocarbons (i.e., mineral oils) is warranted, especially given the widespread exposures in the population. Experimental and limited human findings support further investigation of SLE related to mercury exposure, especially in dental occupations. Research on environmental risk factors in risk-enriched cohorts (family based) is recommended, as is further investigation of exposures in relation to intermediate markers of effect (e.g., antinuclear antibodies), clinical features (e.g., nephritis) and outcomes. PMID:24763537

Translational toxicology: a developmental focus for integrated research strategies.

PubMed

Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo

2013-09-30

Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.

Antimicrobial Exposure Assessment Task Force II (AEATF II) Volume 5: Governing Document for a Multi-Year Antimicrobial Chemical Exposure Monitoring Program (interim draft document with changes)

EPA Pesticide Factsheets

This document describes the overall scope of the AEATF II program, demonstrates the need for additional human exposure monitoring data and explains the proposed methodology for the exposure monitoring studies proposed for conduct by the AEATF II.

Biological effects and epidemiological consequences of arsenic exposure, and reagents that can ameliorate arsenic damage in vivo

PubMed Central

Rao, Chinthalapally V.; Pal, Sanya; Mohammed, Altaf; Farooqui, Mudassir; Doescher, Mark P.; Asch, Adam S.; Yamada, Hiroshi Y.

2017-01-01

Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide “hot spots” where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis. High arsenic exposure is epidemiologically associated with skin, lung, bladder, liver, kidney and pancreatic cancer, and cardiovascular, neuronal, and other diseases. This review briefly summarizes the biological effects of arsenic exposure and epidemiological cancer studies worldwide, and provides an overview for emerging rodent-based studies of reagents that can ameliorate the effects of arsenic exposure in vivo. These reagents may be translated to human populations for disease prevention. We propose the importance of developing a biomarker-based precision prevention approach for the health issues associated with arsenic exposure that affects millions of people worldwide. PMID:28915699

Impact of nanoparticles on human and environment: review of toxicity factors, exposures, control strategies, and future prospects.

PubMed

Sajid, Muhammad; Ilyas, Muhammad; Basheer, Chanbasha; Tariq, Madiha; Daud, Muhammad; Baig, Nadeem; Shehzad, Farrukh

2015-03-01

Nanotechnology has revolutionized the world through introduction of a unique class of materials and consumer products in many arenas. It has led to production of innovative materials and devices. Despite of their unique advantages and applications in domestic and industrial sectors, use of materials with dimensions in nanometers has raised the issue of safety for workers, consumers, and human environment. Because of their small size and other unique characteristics, nanoparticles have ability to harm human and wildlife by interacting through various mechanisms. We have reviewed the characteristics of nanoparticles which form the basis of their toxicity. This paper also reviews possible routes of exposure of nanoparticles to human body. Dermal contact, inhalation, and ingestion have been discussed in detail. As very limited data is available for long-term human exposures, there is a pressing need to develop the methods which can determine short and long-term effects of nanoparticles on human and environment. We also discuss in brief the strategies which can help to control human exposures to toxic nanoparticles. We have outlined the current status of toxicological studies dealing with nanoparticles, accomplishments, weaknesses, and future challenges.

Implications of global climate change for the assessment and management of human health risks of chemicals in the natural environment.

PubMed

Balbus, John M; Boxall, Alistair B A; Fenske, Richard A; McKone, Thomas E; Zeise, Lauren

2013-01-01

Global climate change (GCC) is likely to alter the degree of human exposure to pollutants and the response of human populations to these exposures, meaning that risks of pollutants could change in the future. The present study, therefore, explores how GCC might affect the different steps in the pathway from a chemical source in the environment through to impacts on human health and evaluates the implications for existing risk-assessment and management practices. In certain parts of the world, GCC is predicted to increase the level of exposure of many environmental pollutants due to direct and indirect effects on the use patterns and transport and fate of chemicals. Changes in human behavior will also affect how humans come into contact with contaminated air, water, and food. Dietary changes, psychosocial stress, and coexposure to stressors such as high temperatures are likely to increase the vulnerability of humans to chemicals. These changes are likely to have significant implications for current practices for chemical assessment. Assumptions used in current exposure-assessment models may no longer apply, and existing monitoring methods may not be robust enough to detect adverse episodic changes in exposures. Organizations responsible for the assessment and management of health risks of chemicals therefore need to be more proactive and consider the implications of GCC for their procedures and processes. Copyright © 2012 SETAC.

Multifactorial analysis of human blood cell responses to clinical total body irradiation

NASA Technical Reports Server (NTRS)

Yuhas, J. M.; Stokes, T. R.; Lushbaugh, C. C.

1972-01-01

Multiple regression analysis techniques are used to study the effects of therapeutic radiation exposure, number of fractions, and time on such quantal responses as tumor control and skin injury. The potential of these methods for the analysis of human blood cell responses is demonstrated and estimates are given of the effects of total amount of exposure and time of protraction in determining the minimum white blood cell concentration observed after exposure of patients from four disease groups.

Exposure to Hedione Increases Reciprocity in Humans

PubMed Central

Berger, Sebastian; Hatt, Hanns; Ockenfels, Axel

2017-01-01

Cooperation among unrelated humans is frequently regarded as a defining feature in the evolutionary success of our species. Whereas, much research has addressed the strategic and cognitive mechanisms that underlie cooperation, investigations into chemosensory processes have received very limited research attention. To bridge that gap, we build on recent research that has identified the chemically synthesized odorant Hedione (HED) as a ligand for the putative human pheromone receptor (VN1R1) expressed in the olfactory mucosa, and hypothesize that exposure to HED may increase reciprocity. Applying behavioral economics paradigms, the present research shows that exposure to the ligand causes differentiated behavioral effects in reciprocal punishments (Study 1) as well as rewards (Study 2), two types of behaviors that are frequently regarded as essential for the development and maintenance of cooperation. PMID:28512400

Exposure of healthy subjects with emissions from a gas metal arc welding process: part 1--exposure technique and external exposure.

PubMed

Brand, P; Havlicek, P; Steiners, M; Holzinger, K; Reisgen, U; Kraus, T; Gube, M

2013-01-01

Studies concerning welding fume-related adverse health effects in welders are hampered by the heterogeneity of workplace situations, resulting in complex and non-standardized exposure conditions. In order to carry out welding fume exposure studies under controlled and standardized conditions, the Aachen Workplace Simulation Laboratory was developed. This laboratory consists of an emission room, in which welding fume is produced, and an exposure room in which human subjects are exposed to these fumes. Both rooms are connected by a ventilation system which allows the welding fume concentration to be regulated. Particle mass concentration was measured with a TEOM microbalance and the particle number-size distribution using a Grimm SMPS device. In a study, which is the subject of this paper, it has been shown that welding fume concentration can easily be regulated between 1 and about 3 mg m(-3). The chosen concentration can be kept constant for more than 8 h. However, transport of the particles from the emission room into the exposure room leads to a change in particle size distribution, which is probably due to coagulation of the fraction of smallest particles. The Aachen Workplace Simulation Laboratory is suitable for controlled exposure studies with human subjects.

Dim light adaptation attenuates acute melatonin suppression in humans.

PubMed

Jasser, Samar A; Hanifin, John P; Rollag, Mark D; Brainard, George C

2006-10-01

Abstract Studies in rodents with retinal degeneration indicated that neither the rod nor the cone photoreceptors obligatorily participate in circadian responses to light, including melatonin suppression and photoperiodic response. Yet there is a residual phase-shifting response in melanopsin knockout mice, which suggests an alternate or redundant means for light input to the SCN of the hypothalamus. The findings of Aggelopoulos and Meissl suggest a complex, dynamic interrelationship between the classic visual photoreceptors and SCN cell sensitivity to light stimuli, relative to various adaptive lighting conditions. These studies raised the possibility that the phototransductive physiology of the retinohypothalamic tract in humans might be modulated by the visual rod and cone photoreceptors. The aim of the following two-part study was to test the hypothesis that dim light adaptation will dampen the subsequent suppression of melatonin by monochromatic light in healthy human subjects. Each experiment included 5 female and 3 male human subjects between the ages of 18 and 30 years, with normal color vision. Dim white light and darkness adaptation exposures occurred between midnight and 0200 h, and a full-field 460-nm light exposure subsequently occurred between 0200 and 0330-h for each adaptation condition, at 2 different intensities. Plasma samples were drawn following the 2-h adaptation, as well as after the 460-nm monochromatic light exposure, and melatonin was measured by radioimmunoassay. Comparison of melatonin suppression responses to monochromatic light in both studies revealed a loss of significant suppression after dim white light adaptation compared with dark adaptation (p < 0.04 and p < 0.01). These findings indicate that the activity of the novel circadian photoreceptive system in humans is subject to subthreshold modulation of its sensitivity to subsequent monochromatic light exposure, varying with the conditions of light adaptation prior to exposure.

Biomonitoring of human exposures to chlorinated derivatives and structural analogs of bisphenol A.

PubMed

Andra, Syam S; Charisiadis, Pantelis; Arora, Manish; van Vliet-Ostaptchouk, Jana V; Makris, Konstantinos C

2015-12-01

The high reactivity of bisphenol A (BPA) with disinfectant chlorine is evident in the instantaneous formation of chlorinated BPA derivatives (ClxBPA) in various environmental media that show increased estrogen-activity when compared with that of BPA. The documented health risks associated with BPA exposures have led to the gradual market entry of BPA structural analogs, such as bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), etc. A suite of exposure sources to ClxBPA and BPA analogs in the domestic environment is anticipated to drive the nature and range of halogenated BPA derivatives that can form when residual BPA comes in contact with disinfectant in tap water and/or consumer products. The primary objective of this review was to survey all available studies reporting biomonitoring protocols of ClxBPA and structural BPA analogs (BPS, BPF, BPB, etc.) in human matrices. Focus was paid on describing the analytical methodologies practiced for the analysis of ClxBPA and BPA analogs using hyphenated chromatography and mass spectrometry techniques, because current methodologies for human matrices are complex. During the last decade, an increasing number of ecotoxicological, cell-culture and animal-based and human studies dealing with ClxBPA exposure sources and routes of exposure, metabolism and toxicity have been published. Up to date findings indicated the association of ClxBPA with metabolic conditions, such as obesity, lipid accumulation, and type 2 diabetes mellitus, particularly in in-vitro and in-vivo studies. We critically discuss the limitations, research needs and future opportunities linked with the inclusion of ClxBPA and BPA analogs into exposure assessment protocols of relevant epidemiological studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Epidemiologic research on the environment and health: some methodologic aspects].

PubMed

Hémon, D

1995-01-01

Research in environmental epidemiology deals with physical, chemical and biological agents whose presence--or relative absence--within the different media coming into contract with human beings (air, water, soil, food, etc...) may be harmful to human health. Some "major" environmental risk factors are well known. In a number of situations, however, environment-disease associations are "weak". This does not rule out the possibility that the exposures involved have a significant impact on human health, considering their prevalence which is frequently high. However, this complicates their study owing to the potential importance of biases as well as that of sampling fluctuations. Although increasing study size is of crucial importance, it is not sufficient to establish a clearcut distinction between "weak" associations and "diluted" ones. To improve our knowledge of health risks which are associated with environmental exposures, the basic methodological principles of epidemiological research--to define and adequately measure exposures, health outcomes, confounders and effect modifiers--may be very valuable to approach the study of "weak" associations: 1) identifying and quantifying the presence of the agents of interest in the environment, studying the distribution of environmental exposures among individuals and its determinants, taking into account the whole history of personal exposures and integrating adequately the short term time variability of exposures, giving special attention to the type and intensity of exposures may help in the definition and measurement of exposures; 2) carefully analyzing the interactions which may exist between the physical, chemical and biological agents of interest and the human body may greatly help in the elaboration, measurement and validation of relevant health outcomes (exposures to the target organs, early lesions and health impairments); 3) this same approach may also greatly contribute to the identification of constitutional or acquired individual characteristics which may interact with environmental agents in the development of diseases. While there is no guarantee that such approaches will successfully discriminate between "weak" and "diluted" associations, it is likely that inconclusive epidemiological evidence will be very difficult to avoid if such approaches are neglected by environmental epidemiologists.

Lack of Exposure in a First-in-Man Study Due to Aldehyde Oxidase Metabolism: Investigated by Use of 14C-microdose, Humanized Mice, Monkey Pharmacokinetics, and In Vitro Methods.

PubMed

Jensen, Klaus Gjervig; Jacobsen, Anne-Marie; Bundgaard, Christoffer; Nilausen, Dorrit Østergaard; Thale, Zia; Chandrasena, Gamini; Jørgensen, Martin

2017-01-01

Inclusion of a microdose of 14 C-labeled drug in the first-in-man study of new investigational drugs and subsequent analysis by accelerator mass spectrometry has become an integrated part of drug development at Lundbeck. It has been found to be highly informative with regard to investigations of the routes and rates of excretion of the drug and the human metabolite profiles according to metabolites in safety testing guidance and also when additional metabolism-related issues needed to be addressed. In the first-in-man study with the NCE Lu AF09535, contrary to anticipated, surprisingly low exposure was observed when measuring the parent compound using conventional bioanalysis. Parallel accelerator mass spectrometry analysis revealed that the low exposure was almost exclusively attributable to extensive metabolism. The metabolism observed in humans was mediated via a human specific metabolic pathway, whereas an equivalent extent of metabolism was not observed in preclinical species. In vitro, incubation studies in human liver cytosol revealed involvement of aldehyde oxidase (AO) in the biotransformation of Lu AF09535. In vivo, substantially lower plasma exposure of Lu AF09535 was observed in chimeric mice with humanized livers compared with control animals. In addition, Lu AF09535 exhibited very low oral bioavailability in monkeys despite relatively low clearance after intravenous administration in contrast to the pharmacokinetics in rats and dogs, both showing low clearance and high bioavailability. The in vitro and in vivo methods applied were proved useful for identifying and evaluating AO-dependent metabolism. Different strategies to integrate these methods for prediction of in vivo human clearance of AO substrates were evaluated. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Methylphenidate effects in the young brain: friend or foe?

PubMed

Loureiro-Vieira, Sara; Costa, Vera Marisa; de Lourdes Bastos, Maria; Carvalho, Félix; Capela, João Paulo

2017-08-01

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH) is a first-line stimulant drug available worldwide for its treatment. Despite the proven therapeutic efficacy, concerns have been raised regarding the possible consequences of chronic MPH exposure during childhood and adolescence. Disturbances in the neurodevelopment at these crucial stages are major concerns given the unknown future life consequences. This review is focused on the long-term adverse effects of MPH to the brain biochemistry. Reports conducted with young and/or adolescent animals and studies with humans are reviewed in the context of long-term consequences after early life-exposure. MPH pharmacokinetics is also reviewed as there are differences among laboratory animals and humans that may be relevant to extrapolate the findings. Studies reveal that exposure to MPH in laboratory animals during young and/or adolescent ages can impact the brain, but the outcomes are dependent on MPH dose, treatment period, and animal's age. Importantly, the female sex is largely overlooked in both animal and human studies. Unfortunately, human reports that evaluate adults following adolescent or child exposure to MPH are very scarce. In general, human data indicates that MPH is generally safe, although it can promote several brain changes in early ages. Even so, there is a lack of long course patient evaluation to clearly establish whether MPH-induced changes are friendly or foe to the brain and more human studies are needed to assess the adult brain changes that arise from early MPH treatment. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

In-Home Toxic Exposures and the Community of Individuals Who Are Developmentally Disabled

ERIC Educational Resources Information Center

Trousdale, Kristie A.; Martin, Joyce; Abulafia, Laura; Del Bene Davis, Allison

2010-01-01

Chemicals are ubiquitous in the environment, and human exposure to them is inevitable. A benchmark investigation of industrial chemicals, pollutants, and pesticides in umbilical cord blood indicated that humans are born with an average of 200 pollutants already present in their bodies. The study found a total of 287 chemicals, of which, 180 are…

Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review.

PubMed

Chen, Da; Kannan, Kurunthachalam; Tan, Hongli; Zheng, Zhengui; Feng, Yong-Lai; Wu, Yan; Widelka, Margaret

2016-06-07

Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity.

Chlorpyrifos PBPK/PD model for multiple routes of exposure.

PubMed

Poet, Torka S; Timchalk, Charles; Hotchkiss, Jon A; Bartels, Michael J

2014-10-01

1. Chlorpyrifos (CPF) is an important pesticide used to control crop insects. Human Exposures to CPF will occur primarily through oral exposure to residues on foods. A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model has been developed that describes the relationship between oral, dermal and inhalation doses of CPF and key events in the pathway for cholinergic effects. The model was built on a prior oral model that addressed age-related changes in metabolism and physiology. This multi-route model was developed in rats and humans to validate all scenarios in a parallelogram design. 2. Critical biological effects from CPF exposure require metabolic activation to CPF oxon, and small amounts of metabolism in tissues will potentially have a great effect on pharmacokinetics and pharmacodynamic outcomes. Metabolism (bioactivation and detoxification) was therefore added in diaphragm, brain, lung and skin compartments. Pharmacokinetic data are available for controlled human exposures via the oral and dermal routes and from oral and inhalation studies in rats. The validated model was then used to determine relative dermal versus inhalation uptake from human volunteers exposed to CPF in an indoor scenario.

GuLF Study: The Gulf Long-Term Follow-Up Study

MedlinePlus

... Environmental Influences on Child Health Outcomes (ECHO) Exposure Biology Global Environmental Health Gulf Oil Spill Response Efforts ... to investigate the interplay between environmental exposures, human biology, genetics, and common diseases to help prevent disease ...

One Health and the Environment: Toxic Cyanobacteria, a Case Study

EPA Science Inventory

The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants in ambient exposure situations. ...

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...

Incorporating twitter-based human activity information in spatial analysis of crashes in urban areas.

PubMed

Bao, Jie; Liu, Pan; Yu, Hao; Xu, Chengcheng

2017-09-01

The primary objective of this study was to investigate how to incorporate human activity information in spatial analysis of crashes in urban areas using Twitter check-in data. This study used the data collected from the City of Los Angeles in the United States to illustrate the procedure. The following five types of data were collected: crash data, human activity data, traditional traffic exposure variables, road network attributes and social-demographic data. A web crawler by Python was developed to collect the venue type information from the Twitter check-in data automatically. The human activities were classified into seven categories by the obtained venue types. The collected data were aggregated into 896 Traffic Analysis Zones (TAZ). Geographically weighted regression (GWR) models were developed to establish a relationship between the crash counts reported in a TAZ and various contributing factors. Comparative analyses were conducted to compare the performance of GWR models which considered traditional traffic exposure variables only, Twitter-based human activity variables only, and both traditional traffic exposure and Twitter-based human activity variables. The model specification results suggested that human activity variables significantly affected the crash counts in a TAZ. The results of comparative analyses suggested that the models which considered both traditional traffic exposure and human activity variables had the best goodness-of-fit in terms of the highest R 2 and lowest AICc values. The finding seems to confirm the benefits of incorporating human activity information in spatial analysis of crashes using Twitter check-in data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toxicological Assessment of Inhaled Nanoparticles: Role of in Vivo, ex Vivo, in Vitro, and in Silico Studies

PubMed Central

Fröhlich, Eleonore; Salar-Behzadi, Sharareh

2014-01-01

The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced in vitro models, not only in vivo, but also cellular studies can be used for toxicological testing. Advanced in vitro studies use combinations of cells cultured in the air-liquid interface. These cultures are useful for particle uptake and mechanistic studies. Whole-body, nose-only, and lung-only exposures of animals could help to determine retention of NPs in the body. Both approaches also have their limitations; cellular studies cannot mimic the entire organism and data obtained by inhalation exposure of rodents have limitations due to differences in the respiratory system from that of humans. Simulation programs for lung deposition in humans could help to determine the relevance of the biological findings. Combination of biological data generated in different biological models and in silico modeling appears suitable for a realistic estimation of potential risks by inhalation exposure to NPs. PMID:24646916

IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

EPA Pesticide Factsheets

The Draft Toxicological Review was developed to evaluate both the cancer and non cancer human health risks from environmental exposure to vinyl chloride. A reference concentration (RfC), and a reference dose (RfD) were developed based upon induction of liver cell polymorphism in a chronic dietary study utilizing Wistar rats. An RfC of 1E-1 mg/m3 and an RfD of 5E-3 mg/kg-d are recommended. On the basis of sufficient evidence for carcinogenicity in human epidemiology studies vinyl chloride is reaffirmed to be a known human carcinogen. Cancer potencies were derived for oral and inhalation exposure. An oral slope factor of 1.3 per (mg/kg-day) for continuous exposure during adulthood and 2.5 per (mg/kg-day) for continuous lifetime exposure from birth, based upon a chronic dietary study in female Wistar rats is recommended; an inhalation unit risk of 4.3 E-6 per (55g/m3) for continuous exposure during adulthood and 8.7 E-6 per (55g/m3) for continuous lifetime exposure from birth is also recommended, based upon exposure of male and female Sprague Dawley rats and Swiss mice, via inhalation, for a lifetime. A PBPK model was used in the derivation of the RfC, RfD, and cancer potency estimates. Its use is based on the assumption that equal tissue concentrations of reactive metabolite, chlorethylene oxide or chloracetaldehyde, at the critical target site will result in equivalent toxicity between species.

Neuromotor effects of acute ethanol inhalation exposure in humans: a preliminary study.

PubMed

Nadeau, Véronique; Lamoureux, Daniel; Beuter, Anne; Charbonneau, Michel; Tardif, Robert

2003-07-01

Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of carbon monoxide from automobiles emissions. Therefore, addition of ETOH in reformulated fuel will most likely increase and the involuntarily human exposure to this chemical will also increase. This preliminary study was undertaken to evaluate the possible neuromotor effects resulting from acute ETOH exposure by inhalation in humans. Five healthy non-smoking adult males, with no history of alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in air) for six hours. Reaction time, body sway, hand tremor and rapid alternating movements were measured before and after each exposure session by using the CATSYS 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood and in alveolar air were also measured. ETOH was not detected in blood nor in alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml and 253.1 ppm, respectively. The neuromotor tests did not show conclusively significant differences between the exposed and non-exposed conditions. In conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or lower or to concentrations that could be encountered upon refueling is not likely to cause any significant neuromotor alterations in healthy males.

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

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

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathingmore » conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.« less

THE DEVELOPMENT AND TESTING OF A DERMAL EXPOSURE SYSTEM FOR PHARMACOKINETIC STUDIES OF ADMINISTERED AND AMBIENT WATER CONTAMINANTS: METHODS AND RESULTS

EPA Science Inventory

INTRODUCTION: In order to investigate the pharmacokinetics of water-borne chemicals while eliminating exposures by other routes, a dermal exposure system was developed to expose the hand and forearm of human subjects. METHODS: The goal was, primarily, to study the dermal phar...

Fine Ambient Particulate and Ozone Co-Exposures in Durham, North Carolina: Influence of Season on Particle Chemistry and Cardiovascular Responses in Rats

EPA Science Inventory

Epidemiological studies have shown that the presence of one air pollutant modifies the cardiovascular health effects of another while controlled exposure studies in humans have documented synergistic effects of co-exposure to ambient particulate matter (PM) and ozone (O3) on bloo...

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...

Animal studies on growth and development.

PubMed

Lerchl, Alexander

2011-12-01

Despite the fact that no plausible biological mechanism has yet been identified how electromagnetic fields below recommended exposure limits could negatively affect health of animals or humans, many experiments have been performed in various animal species, mainly mice and rats, to investigate the possible effects on growth and development. While older studies often suffered from sub-optimal exposure conditions, recent investigations, using sophisticated exposure devices and thus preventing thermal effects, have been performed without these limitations. In principle, two types of studies can be addressed: those which have investigated the carcinogenic or co-carcinogenic effects of exposure in developing animals, and those which have been done in developing animals without the focus on carcinogenic or co-carcinogenic effects. In both areas, the vast majority of publications did not show adverse effects. The largest study so far has been done in normal mice which have been chronically exposed to UMTS signals up to 1.3 W/kg SAR, thus 16 times higher than the whole-body exposure limit for humans. Even after four generations, no systematic or dose-dependent alterations in development or fertility could be found, supporting the view that negative effects on humans are very unlikely. Ongoing experiments in our laboratory investigate the effects of head-only exposure in rats (up to 10 W/kg local SAR) which are exposed from 14 days of age daily for 2 h. A battery of behavioral tests is performed in young, adult, and pre-senile animals. The results will help to clarify possible effects of exposure on brain development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Using exposure bands for rapid decision making in the ...

EPA Pesticide Factsheets

The ILSI Health and Environmental Sciences Institute (HESI) Risk Assessment in the 21st Century (RISK21) project was initiated to address and catalyze improvements in human health risk assessment. RISK21 is a problem formulation-based conceptual roadmap and risk matrix visualization tool, facilitating transparent evaluation of both hazard and exposure components. The RISK21 roadmap is exposure-driven, i.e. exposure is used as the second step (after problem formulation) to define and focus the assessment. This paper describes the exposure tiers of the RISK21 matrix and the approaches to adapt readily available information to more quickly inform exposure at a screening level. In particular, exposure look-up tables were developed from available exposure tools (European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) for worker exposure, ECETOC TRA, European Solvents Industry Group (ESIG) Generic Exposure Scenario (GES) Risk and Exposure Tool (EGRET) for consumer exposure, and USEtox for indirect exposure to humans via the environment) were tested in a hypothetical mosquito bed netting case study. A detailed WHO risk assessment for a similar mosquito net use served as a benchmark for the performance of the RISK21 approach. The case study demonstrated that the screening methodologies provided suitable conservative exposure estimates for risk assessment. The results of this effort showed that the RISK21 approach is useful f

CORRELATING NEUROBEHAVIORAL PERFORMANCE WITH BIOMARKERS OF ORGANOPHOSPHOROUS PESTICIDE EXPOSURE

PubMed Central

Rohlman, Diane S.; Anger, W Kent; Lein, Pamela J

2011-01-01

There is compelling evidence that adverse neurobehavioral effects are associated with occupational organophosphorous pesticide (OP) exposure in humans. Behavioral studies of pesticide applicators, greenhouse workers, agricultural workers and farm residents exposed repeatedly over months or years to low levels of OPs reveal a relatively consistent pattern of neurobehavioral deficits. However, only two studies have demonstrated a link between neurobehavioral performance and current biomarkers of OP exposure including blood cholinesterase (ChE) activity and urinary levels of OP metabolites. A variety of reasons may explain why so few studies have reported such correlations, including differing individual and group exposure histories, differing methodologies for assessing behavior and exposure, and lack of a reliable index of exposure. Alternatively, these data may suggest that current biomarkers (ChE, urine metabolites) are neither predictive nor diagnostic of the neurobehavioral effects of chronic OP pesticide exposures. This review focuses on the evidence that neurobehavioral performance deficits are associated with occupational OP pesticide exposure and concludes that research needs to return to the basics and rigorously test the relationships between neurobehavioral performance and both current (ChE and urine metabolites) and novel (eg, inflammation and oxidative stress) biomarkers using human and animal models. The results of such studies are critically important because OP pesticides are widely and extensively used throughout the world, including situations where exposure controls and personal protective equipment are not routinely used. PMID:21182866

Placental transport and in vitro effects of Bisphenol A.

PubMed

Mørck, Thit J; Sorda, Giuseppina; Bechi, Nicoletta; Rasmussen, Brian S; Nielsen, Jesper B; Ietta, Francesca; Rytting, Erik; Mathiesen, Line; Paulesu, Luana; Knudsen, Lisbeth E

2010-08-01

Bisphenol A (BPA), an estrogen-like chemical, leaches from consumer products potentially causing human exposure. To examine the effects of BPA exposure during pregnancy, we performed studies using the BeWo trophoblast cell line, placental explant cultures, placental perfusions and skin diffusion models, all of human origin. Results showed BPA cytotoxicity in BeWo cells with an apparent EC50 at 100-125 microM. BPA exposure significantly increased beta-hCG secretion and caspase-3 expression in placental explants at an environmentally relevant concentration of 1 nM. In the transport studies, a rapid transfer of BPA was observed across the term placentae and the BeWo cell monolayer. Further, transdermal transport of BPA was observed. These results indicate that fetal BPA exposure through placental exchange occurs with potential adverse implications for placental and fetal development. This battery of test systems within the realm of human implantation and fetal development represents important elements in risk assessment of reproductive toxicity. Copyright 2010 Elsevier Inc. All rights reserved.

Acute Meteorite Dust Exposure and Pulmonary Inflammation - Implications for Human Space Exploration

NASA Technical Reports Server (NTRS)

Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

2017-01-01

The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness [1-3]" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure [4]. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles [1]. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern [5]. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive [2, 6-9], and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz [6]. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative toxicity of six meteorite samples representing either basalt or regolith breccia on the surfaces of the Moon, Mars, and Asteroid 4Vesta (Table 1); three potential candidates for future human exploration or colonization. Terrestrial mid-ocean ridge basalt (MORB) is also used for comparison as a control sample.

Pulmonary Inflammatory Responses To Acute Meteorite Dust Exposures - Implications For Human Space Exploration

NASA Technical Reports Server (NTRS)

Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

2017-01-01

The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive, and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative toxicity of six meteorite samples representing either basalt or regolith breccia on the surfaces of the Moon, Mars, and Asteroid 4Vesta; three potential candidates for future human exploration or colonization. Terrestrial mid-ocean ridge basalt (MORB) is also used for comparison as a control sample.

ARSENIC IN DRINKING WATER: EPIDEMIOOOGIC STUDIES OF LOW EXPOSURE IN THE UNITED STATES

EPA Science Inventory

Because there is no animal model fully adequate to study the mechanisms of arsenic toxicity and carcinogenicity; human epidemiological studies incorporating sensitive biomarkers for assessing exposure, cancer, noncancer effects and susceptibility of arsenic are needed to evalua...

The human circulating miRNome reflects multiple organ disease risks in association with short-term exposure to traffic-related air pollution.

PubMed

Krauskopf, Julian; Caiment, Florian; van Veldhoven, Karin; Chadeau-Hyam, Marc; Sinharay, Rudy; Chung, Kian Fan; Cullinan, Paul; Collins, Peter; Barratt, Benjamin; Kelly, Frank J; Vermeulen, Roel; Vineis, Paolo; de Kok, Theo M; Kleinjans, Jos C

2018-04-01

Traffic-related air pollution is a complex mixture of particulate matter (PM) and gaseous pollutants, such as nitrogen dioxide (NO2). PM exposure contributes to the pathogenesis of many diseases including several types of cancer, as well as pulmonary, cardiovascular and neurodegenerative diseases. Also exposure to NO2 has been related to increased cardiovascular mortality. In search of an early diagnostic biomarker for improved air pollution-associated health risk assessment, recent human studies have shown that certain circulating miRNAs are altered upon exposure to traffic-related air pollutants. Here, we present for the first time a global analysis of the circulating miRNA genome in an experimental cross-over study of a human population exposed to traffic-related air pollution. By utilizing next-generation sequencing technology and detailed real-time exposure measurements we identified 54 circulating miRNAs to be dose- and pollutant species-dependently associated with PM10, PM2.5, black carbon, ultrafine particles and NO2 already after 2 h of exposure. Bioinformatics analysis suggests that these circulating miRNAs actually reflect the adverse consequences of traffic pollution-induced toxicity in target tissues including the lung, heart, kidney and brain. This study shows the strong potential of circulating miRNAs as novel biomarkers for environmental health risk assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dietary exposure estimates of twenty-one trace elements from a Total Diet Study carried out in Pavia, Northern Italy.

PubMed

Turconi, Giovanna; Minoia, Claudio; Ronchi, Anna; Roggi, Carla

2009-04-01

The significant role of trace elements in human health is well documented. Trace elements are those compounds that need to be present in the human diet to maintain normal physiological functions. However, some microelements may become harmful at high levels of exposure, or, on the other hand, may give rise to malnutrition, when their exposure is too low. The aim of the present study was to provide a reliable estimate of the dietary exposure of twenty-one trace elements in a Northern Italian area. For this purpose, trace element analyses were undertaken on total diet samples collected from a university cafeteria in Pavia, Northern Italy. The average daily exposure for the adult people was calculated on the basis of food consumption frequency, portion size and trace element levels in foodstuffs. The mean exposure values satisfy the Italian RDA for all the essential trace elements, except for Fe exposure in females, and are well below the Provisional Tolerable Daily Intake for all the toxic compounds, showing that the probability of dietary exposure to health risks is overall small. As far as Fe exposure is concerned, a potential risk of anaemia in the female adult population should be considered, then studies aimed at evaluating the Fe nutritional status of adult Italian women should be addressed. In conclusion, while not excluding the possibility that the daily exposure determined in the present study may not be representative of the population as a whole, this study provides a good estimate of the Italian adult consumer exposure to twenty-one trace elements.

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.

Estimated human health risks from recreational exposures to stormwater runoff containing animal faecal material

EPA Science Inventory

Scientific evidence supporting recreational water quality benchmarks primarily stems from epidemiological studies conducted at beaches impacted by human fecal sources. Epidemiological studies conducted at locations impacted by non-human faecal sources have provided ambiguous and ...

Risk of brain tumors from wireless phone use.

PubMed

Dubey, Rash Bihari; Hanmandlu, Madasu; Gupta, Suresh Kumar

2010-01-01

The debate regarding the health effects of low-intensity electromagnetic radiation from sources such as power lines, base stations, and cell phones has recently been reignited. Wireless communication has dramatically influenced our lifestyle; its impact on human health has not been completely assessed. Widespread concern continues in the community about the deleterious effects of radiofrequency radiations on human tissues and the subsequent potential threat of carcinogenesis. Exposure to low-frequency electromagnetic field has been linked to a variety of adverse health outcomes. This article surveys the results of early cell phone studies, where exposure duration was too short to expect tumor genesis, and 2 sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Hardell.

Walls talk: Microbial biogeography of homes spanning urbanization

PubMed Central

Ruiz-Calderon, Jean F.; Cavallin, Humberto; Song, Se Jin; Novoselac, Atila; Pericchi, Luis R.; Hernandez, Jean N.; Rios, Rafael; Branch, Oralee H.; Pereira, Henrique; Paulino, Luciana C.; Blaser, Martin J.; Knight, Rob; Dominguez-Bello, Maria G.

2016-01-01

Westernization has propelled changes in urbanization and architecture, altering our exposure to the outdoor environment from that experienced during most of human evolution. These changes might affect the developmental exposure of infants to bacteria, immune development, and human microbiome diversity. Contemporary urban humans spend most of their time indoors, and little is known about the microbes associated with different designs of the built environment and their interaction with the human immune system. This study addresses the associations between architectural design and the microbial biogeography of households across a gradient of urbanization in South America. Urbanization was associated with households’ increased isolation from outdoor environments, with additional indoor space isolation by walls. Microbes from house walls and floors segregate by location, and urban indoor walls contain human bacterial markers of space use. Urbanized spaces uniquely increase the content of human-associated microbes—which could increase transmission of potential pathogens—and decrease exposure to the environmental microbes with which humans have coevolved. PMID:26933683

Exposure science in an age of rapidly changing climate: challenges and opportunities

PubMed Central

LaKind, Judy S; Overpeck, Jonathan; Breysse, Patrick N; Backer, Lorrie; Richardson, Susan D; Sobus, Jon; Sapkota, Amir; Upperman, Crystal R; Jiang, Chengsheng; Beard, C Ben; Brunkard, J M; Bell, Jesse E; Harris, Ryan; Chretien, Jean-Paul; Peltier, Richard E; Chew, Ginger L; Blount, Benjamin C

2016-01-01

Climate change is anticipated to alter the production, use, release, and fate of environmental chemicals, likely leading to increased uncertainty in exposure and human health risk predictions. Exposure science provides a key connection between changes in climate and associated health outcomes. The theme of the 2015 Annual Meeting of the International Society of Exposure Science—Exposures in an Evolving Environment—brought this issue to the fore. By directing attention to questions that may affect society in profound ways, exposure scientists have an opportunity to conduct “consequential science”—doing science that matters, using our tools for the greater good and to answer key policy questions, and identifying causes leading to implementation of solutions. Understanding the implications of changing exposures on public health may be one of the most consequential areas of study in which exposure scientists could currently be engaged. In this paper, we use a series of case studies to identify exposure data gaps and research paths that will enable us to capture the information necessary for understanding climate change-related human exposures and consequent health impacts. We hope that paper will focus attention on under-developed areas of exposure science that will likely have broad implications for public health. PMID:27485992

The developmental neurotoxicity of arsenic: cognitive and behavioral consequences of early life exposure.

PubMed

Tolins, Molly; Ruchirawat, Mathuros; Landrigan, Philip

2014-01-01

More than 200 million people worldwide are chronically exposed to arsenic. Arsenic is a known human carcinogen, and its carcinogenic and systemic toxicity have been extensively studied. By contrast, the developmental neurotoxicity of arsenic has been less well described. The aim of this review was to provide a comprehensive review of the developmental neurotoxicity of arsenic. We reviewed the published epidemiological and toxicological literature on the developmental neurotoxicity of arsenic. Arsenic is able to gain access to the developing brain and cause neurotoxic effects. Animal models link prenatal and early postnatal exposure to reduction in brain weight, reductions in numbers of glia and neurons, and alterations in neurotransmitter systems. Animal and in vitro studies both suggest that oxidative stress may be a mechanism of arsenic neurotoxicity. Fifteen epidemiological studies indicate that early life exposure is associated with deficits in intelligence and memory. These effects may occur at levels of exposure below current safety guidelines, and some neurocognitive consequences may become manifest only later in life. Sex, concomitant exposures, and timing of exposure appear to modify the developmental neurotoxicity of arsenic. Four epidemiological studies failed to show behavioral outcomes of arsenic exposure. The published literature indicates that arsenic is a human developmental neurotoxicant. Ongoing and future prospective birth cohort studies will allow more precise definition of the developmental consequences of arsenic exposure in early life. Copyright © 2014. Published by Elsevier Inc.

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...

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

Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium

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

Cartularo, Laura; Laulicht, Freda; Sun, Hong

Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the Earth's crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24 h; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181more » genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24 h indicated a reduction in global levels of histone methylation and acetylation that persisted 72 h post-treatment. - Highlights: • A common route of human exposure to the carcinogenic metal cadmium is via diet. • HepG2 cells were treated acutely or chronically with varying doses of cadmium. • Gene expression analysis was performed using Affymetrix Human Gene 1.0 Arrays. • Acute and chronic exposures altered the expression of 333 and 181 genes, respectively. • Acute cadmium exposure altered global levels of histone methylation and acetylation.« less

ASSESSING POPULATION EXPOSURES TO MULTIPLE AIR POLLUTANTS USING A MECHANISTIC SOURCE-TO-DOSE MODELING FRAMEWORK

EPA Science Inventory

The Modeling Environment for Total Risks studies (MENTOR) system, combined with an extension of the SHEDS (Stochastic Human Exposure and Dose Simulation) methodology, provide a mechanistically consistent framework for conducting source-to-dose exposure assessments of multiple pol...

PERSONAL EXPOSURES TO POLYCYCLIC AROMATIC HYDROCARBONS ASSOCIATED WITH THE NHEXAS PILOT

EPA Science Inventory

Personal exposure monitoring for select polycyclic aromatic hydrocarbons (PAHs) was performed as part of the National Human Exposure Assessment Survey (NHEXAS) Pilot Study in Baltimore, MD. Twenty-four hour PM10 sample collections (~5.7 m3) were performed using personal envi...

Identification of Surrogate Measures of Diesel Exhaust Exposure in a Controlled Chamber Study

EPA Science Inventory

Exposure to diesel exhaust (DE) has been associated with acute cardiopulmonary and vascular responses, chronic noncancer health effects, and respiratory cancers in humans. To better understand DE exposures and eventually their related health effects, we established a controlled c...

Evaluation of neural reflex activation as a mode of action for the acute respiratory effects of ozone.

PubMed

Prueitt, Robyn L; Goodman, Julie E

2016-09-01

Exposure to elevated levels of ozone has been associated with a variety of respiratory-related health endpoints in both epidemiology and controlled human exposure studies, including lung function decrements and airway inflammation. A mode of action (MoA) for these effects has not been established, but it has been proposed that they may occur through ozone-induced activation of neural reflexes. We critically reviewed experimental studies of ozone exposure and neural reflex activation and applied the International Programme on Chemical Safety (IPCS) mode-of-action/human relevance framework to evaluate the biological plausibility and human relevance of this proposed MoA. Based on the currently available experimental data, we found that the proposed MoA of neural reflex activation is biologically plausible for the endpoint of ozone-induced lung function decrements at high ozone exposures, but further studies are needed to fill important data gaps regarding the relevance of this MoA at lower exposures. A role for the proposed MoA in ozone-induced airway inflammation is less plausible, as the evidence is conflicting and is also of unclear relevance given the lack of studies conducted at lower exposures. The evidence suggests a different MoA for ozone-induced inflammation that may still be linked to the key events in the proposed MoA, such that neural reflex activation may have some degree of involvement in modulating ozone-induced neutrophil influx, even if it is not a direct role.

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

PubMed Central

Hengstler, JG; Foth, H; Gebel, T; Kramer, P-J; Lilienblum, W; Schweinfurth, H; Völkel, W; Wollin, K-M; Gundert-Remy, U

2011-01-01

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies. PMID:21438738

Derivation of an occupational exposure level for manganese in welding fumes.

PubMed

Bailey, Lisa A; Kerper, Laura E; Goodman, Julie E

2018-01-01

Exposure to high levels of manganese (Mn) in occupational settings is known to lead to adverse neurological effects. Since Mn is an essential nutrient, there are mechanisms that maintain its homeostatic control in the body, and there is some level of Mn in air that does not perturb Mn homeostasis. However, the Mn exposure concentrations at which no adverse effects are expected in occupational settings vary considerably across regulatory agencies. We set out to derive a Mn Occupational Exposure Level (OEL) for welders based on a review of studies that evaluated Mn exposure concentrations from welding fumes and: (1) neurological effects in welders; (2) levels of Mn in the brains of welders (via pallidal index [PI] estimated from magnetic resonance imaging [MRI]); (3) other biomarkers of Mn exposure in welders (i.e., blood and urine); and (4) Mn brain concentrations, PI, and corresponding neurological effects in non-human primates. Our analysis suggests uncertainty in quantifying dose-response associations for Mn from many of the occupational welding studies. The few welding studies that adequately estimate exposure suggest a possible OEL of 100-140μg/m 3 for respirable Mn. This range is consistent with other epidemiology studies, studies of biomarkers of Mn exposure in welders, and with studies in non-human primates, though future studies could provide a stronger basis for deriving a Mn occupational guideline for welders. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

PubMed Central

Roussotte, Florence; Soderberg, Lindsay

2010-01-01

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

Occupational Styrene Exposure on Auditory Function Among Adults: A Systematic Review of Selected Workers.

PubMed

Pleban, Francis T; Oketope, Olutosin; Shrestha, Laxmi

2017-12-01

A review study was conducted to examine the adverse effects of styrene, styrene mixtures, or styrene and/or styrene mixtures and noise on the auditory system in humans employed in occupational settings. The search included peer-reviewed articles published in English language involving human volunteers spanning a 25-year period (1990-2015). Studies included peer review journals, case-control studies, and case reports. Animal studies were excluded. An initial search identified 40 studies. After screening for inclusion, 13 studies were retrieved for full journal detail examination and review. As a whole, the results range from no to mild associations between styrene exposure and auditory dysfunction, noting relatively small sample sizes. However, four studies investigating styrene with other organic solvent mixtures and noise suggested combined exposures to both styrene organic solvent mixtures may be more ototoxic than exposure to noise alone. There is little literature examining the effect of styrene on auditory functioning in humans. Nonetheless, findings suggest public health professionals and policy makers should be made aware of the future research needs pertaining to hearing impairment and ototoxicity from styrene. It is recommended that chronic styrene-exposed individuals be routinely evaluated with a comprehensive audiological test battery to detect early signs of auditory dysfunction.

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

Jeong, Sang Hoon; Kim, Jae Hwan; Yi, Sang Min

Quantum dots (QDs) are rapidly emerging as an important class of nanoparticles (NPs) with potential applications in medicine. However, little is known about penetration of QDs through human skin. This study investigated skin penetration of QDs in both in vivo and in vitro human skin. Using the tape stripping method, this study demonstrates for the first time that QDs can actually penetrate through the stratum corneum (SC) of human skin. Transmission electron microscope (TEM) and energy diverse X-ray (EDX) analysis showed accumulation of QDs in the SC of a human skin equivalent model (HSEM) after dermal exposure to QDs. Thesemore » findings suggest possible transdermal absorption of QDs after dermal exposure over a relatively long period of time.« less

Current pesticide profiles in blood serum of adults in Jiangsu Province of China and a comparison with other countries.

PubMed

Chang, Chunxin; Chen, Minjian; Gao, Jiawei; Luo, Jia; Wu, Keqin; Dong, Tianyu; Zhou, Kun; He, Xiaowei; Hu, Weiyue; Wu, Wei; Lu, Chuncheng; Hang, Bo; Meeker, John D; Wang, Xinru; Xia, Yankai

2017-05-01

Although various pesticides were used globally, the pesticides profiles in human blood serum remain largely unknown. We determined pesticide exposure profiles using solid-phase extraction and gas chromatography tandem with triple quadrupole mass spectrometry in 200 human blood serum samples from the adult population in Jiangsu Province, China. A systematic and comprehensive literature review was carried out to identify the articles investigating pesticide exposure and compare exposure data. Of the 88 pesticides, 76 were found in the blood serum of the population in Jiangsu Province. To the best of our knowledge, 58 pesticides were reported in human blood serum for the first time, and among these pesticides, parathion-methyl, pyrimethanil, fluacrypyrim, simazine, cloquintocet-mexyl and barban were debatable in more than half of the samples. By statistical comparison of the blood serum levels of pesticides between this study and other countries, we found the levels of several organochlorine pesticides were significantly higher in the female population of Jiangsu Province. Health risks related to the pesticide profiling were then revealed, which identified higher carcinogenic toxicity and teratogenic toxicity risk in the female adults of Jiangsu Province caused by organochlorine pesticide exposure. This study not only provides a high-throughput pesticide screening method for future studies of the exposome, but also presents the first human data on exposure to a number of pesticides. It may provide a knowledge database for the risk assessment and management of the pesticides. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Body Burden and Dietary Methylmercury Intake: The Relationship in a Rice-Consuming Population.

PubMed

Li, Ping; Feng, Xinbin; Chan, Hing-Man; Zhang, Xiaofeng; Du, Buyun

2015-08-18

Rice can be the main route of methylmercury (MeHg) exposure for rice-consuming populations living in area where mercury (Hg) is mined. However, the current risk assessment paradigm for MeHg exposure is based on epidemiological data collected from fish-consuming populations. This study was designed to evaluate the relationship between dietary MeHg intake and human body burden in a rice -consuming population from the Wanshan Hg mining area in China. Hair MeHg concentrations averaged 2.07 ± 1.79 μg/g, and the average blood MeHg concentration across the study area ranged from 2.20 to 9.36 μg/L. MeHg constituted 52.8 ± 17.5% and 71.7 ± 18.2% of total Hg (THg) on average in blood and hair samples, respectively. Blood and hair MeHg concentrations, rather than THg, can be used as a proxy of human MeHg exposure. Hair MeHg levels showed no significant monthly variation; however, hair THg can be impacted by inorganic Hg exposure. The toxicokinetic model of MeHg exposure based on fish consumption underestimated the human hair MeHg levels, and this may be a consequence of the high hair-to-blood MeHg ratio (361 ± 105) in the studied rice-consuming population. The use of risk assessment models based on fish consumption may not be appropriate for inland mining areas where rice is the staple food.

Human Exposure Pathways of Heavy Metals in a Lead-Zinc Mining Area, Jiangsu Province, China

PubMed Central

Qu, Chang-Sheng; Ma, Zong-Wei; Yang, Jin; Liu, Yang; Bi, Jun; Huang, Lei

2012-01-01

Heavy metal pollution is becoming a serious issue in developing countries such as China, and the public is increasingly aware of its adverse health impacts in recent years. We assessed the potential health risks in a lead-zinc mining area and attempted to identify the key exposure pathways. We evaluated the spatial distributions of personal exposure using indigenous exposure factors and field monitoring results of water, soil, food, and indoor and outdoor air samples. The risks posed by 10 metals and the contribution of inhalation, ingestion and dermal contact pathways to these risks were estimated. Human hair samples were also analyzed to indicate the exposure level in the human body. Our results show that heavy metal pollution may pose high potential health risks to local residents, especially in the village closest to the mine (V1), mainly due to Pb, Cd and Hg. Correspondingly, the residents in V1 had higher Pb (8.14 mg/kg) levels in hair than those in the other two villages. Most of the estimated risks came from soil, the intake of self-produced vegetables and indoor air inhalation. This study highlights the importance of site-specific multipathway health risk assessments in studying heavy-metal exposures in China. PMID:23152752

The Biomonitoring, Environmental Epidemiology, and Short-Lived Chemicals (BEES-C) Instrument for Assessing Study Quality

EPA Science Inventory

Environmental epidemiology studies can be an effective means to assess impacts on human health from exposure to environmental stressors. Exposure scenarios are often extremely complex and proper assessment is critical for interpreting epidemiological study results. Biomarkers are...

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

PubMed Central

Miller, Desinia B.; Ghio, Andrew J.; Karoly, Edward D.; Bell, Lauren N.; Snow, Samantha J.; Madden, Michael C.; Soukup, Joleen; Cascio, Wayne E.; Gilmour, M. Ian

2016-01-01

Rationale: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and glucose intolerance that are associated with global changes in peripheral glucose, lipid, and amino acid metabolism. Objectives: To examine ozone-induced metabolic derangement in humans using serum metabolomic assessment, establish human-to-rodent coherence, and identify novel nonprotein biomarkers. Methods: Serum samples were obtained from a crossover clinical study that included two clinic visits (n = 24 each) where each subject was blindly exposed in the morning to either filtered air or 0.3 parts per million ozone for 2 hours during 15-minute on-off exercise. Serum samples collected within 1 hour after exposure were assessed for changes in metabolites using a metabolomic approach. Measurements and Main Results: Metabolomic analysis revealed that ozone exposure markedly increased serum cortisol and corticosterone together with increases in monoacylglycerol, glycerol, and medium- and long-chain free fatty acids, reflective of lipid mobilization and catabolism. Additionally, ozone exposure increased serum lysolipids, potentially originating from membrane lipid breakdown. Ozone exposure also increased circulating mitochondrial β-oxidation–derived metabolites, such as acylcarnitines, together with increases in the ketone body 3-hydroxybutyrate. These changes suggested saturation of β-oxidation by ozone in exercising humans. Conclusions: As in rodents, acute ozone exposure increased stress hormones and globally altered peripheral lipid metabolism in humans, likely through activation of a neurohormonally mediated stress response pathway. The metabolomic assessment revealed new biomarkers and allowed for establishment of rodent-to-human coherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01492517). PMID:26745856

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.

Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

EPA Science Inventory

Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our...

Ethanol inhibits human bone cell proliferation and function in vitro

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

Friday, K.E.; Howard, G.A.

1991-06-01

The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantlymore » reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol.« less

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.

Mobile phone radiofrequency exposure has no effect on DNA double strand breaks (DSB) in human lymphocytes.

PubMed

Danese, Elisa; Lippi, Giuseppe; Buonocore, Ruggero; Benati, Marco; Bovo, Chiara; Bonaguri, Chiara; Salvagno, Gian Luca; Brocco, Giorgio; Roggenbuck, Dirk; Montagnana, Martina

2017-07-01

The use of mobile phones has been associated with an increased risk of developing certain type of cancer, especially in long term users. Therefore, this study was aimed to investigate the potential genotoxic effect of mobile phone radiofrequency exposure on human peripheral blood mononuclear cells in vitro. The study population consisted in 14 healthy volunteers. After collection of two whole blood samples, the former was placed in a plastic rack, 1 cm from the chassis of a commercial mobile phone (900 MHz carrier frequency), which was activated by a 30-min call. The second blood sample was instead maintained far from mobile phones or other RF sources. The influence of mobile phone RF on DNA integrity was assessed by analyzing γ-H2AX foci in lymphocytes using immunofluorescence staining kit on AKLIDES. No measure of γ-H2AX foci was significantly influenced by mobile phone RF exposure, nor mobile phone exposure was associated with significant risk of genetic damages in vitro (odds ratio comprised between 0.27 and 1.00). The results of this experimental study demonstrate that exposure of human lymphocytes to a conventional 900 MHz RF emitted by a commercial mobile phone for 30 min does not significantly impact DNA integrity.

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

PubMed

Schrempf, Michael; Thuns, Nadine; Lange, Kezia; Seckmeyer, Gunther

2017-08-16

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%.

A MODEL TO EVALUATE PAST EXPOSURE TO 2,3,7,8 ...

EPA Pesticide Factsheets

Data from several studies suggest that concentrations of dioxins rose in the environment from the 1930s to about the 1960s/70s and have been declining over the last decade or two. The most direct evidence of this trend comes from lake core sediments, which can be used to estimate past atmospheric depositions of dioxins. The primary source of human exposure to dioxins is through the food supply. The pathway relating atmospheric depositions to concentrations in food is quite complex, and accordingly, it is not known to what extent the trend in human exposure mirrors the trend in atmospheric depositions. This paper describes an attempt to statistically reconstruct the pattern of past human exposure to the most toxic dioxin congener, 2,3,7,8-TCDD (abbreviated TCDD), through use of a simple pharmacokinetic (PK) model which included a time-varying TCDD exposure dose. This PK model was fit to TCDD body burden data (i.e., TCDD concentrations in lipid) from five U.S. studies dating from 1972 to 1987 and covering a wide age range. A Bayesian statistical approach was used to fit TCDD exposure; model parameters other than exposure were all previously known or estimated from other data sources. The primary results of the analysis are as follows: 1.) use of a time-varying exposure dose provided a far better fit to the TCDD body burden data than did using a dose that was constant over time; this is strong evidence that exposure to TCDD has, in fact, varied during the

Modeling population exposures to silver nanoparticles present in consumer products

NASA Astrophysics Data System (ADS)

Royce, Steven G.; Mukherjee, Dwaipayan; Cai, Ting; Xu, Shu S.; Alexander, Jocelyn A.; Mi, Zhongyuan; Calderon, Leonardo; Mainelis, Gediminas; Lee, KiBum; Lioy, Paul J.; Tetley, Teresa D.; Chung, Kian Fan; Zhang, Junfeng; Georgopoulos, Panos G.

2014-11-01

Exposures of the general population to manufactured nanoparticles (MNPs) are expected to keep rising due to increasing use of MNPs in common consumer products (PEN 2014). The present study focuses on characterizing ambient and indoor population exposures to silver MNPs (nAg). For situations where detailed, case-specific exposure-related data are not available, as in the present study, a novel tiered modeling system, Prioritization/Ranking of Toxic Exposures with GIS (geographic information system) Extension (PRoTEGE), has been developed: it employs a product life cycle analysis (LCA) approach coupled with basic human life stage analysis (LSA) to characterize potential exposures to chemicals of current and emerging concern. The PRoTEGE system has been implemented for ambient and indoor environments, utilizing available MNP production, usage, and properties databases, along with laboratory measurements of potential personal exposures from consumer spray products containing nAg. Modeling of environmental and microenvironmental levels of MNPs employs probabilistic material flow analysis combined with product LCA to account for releases during manufacturing, transport, usage, disposal, etc. Human exposure and dose characterization further employ screening microenvironmental modeling and intake fraction methods combined with LSA for potentially exposed populations, to assess differences associated with gender, age, and demographics. Population distributions of intakes, estimated using the PRoTEGE framework, are consistent with published individual-based intake estimates, demonstrating that PRoTEGE is capable of capturing realistic exposure scenarios for the US population. Distributions of intakes are also used to calculate biologically relevant population distributions of uptakes and target tissue doses through human airway dosimetry modeling that takes into account product MNP size distributions and age-relevant physiological parameters.

Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects.

EPA Science Inventory

The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive developm...

ACETALDEHYDE (CH3CH0) PRODUCTION IN RODENT LUNG AFTER EXPOSURE TO A METAL-RICH PARTICLES

EPA Science Inventory

Epidemiological reports demonstrate an association between increased human morbidity and mortality with exposure to air pollution particulate matter (PM). Metal-catalyzed oxidative stress has been postulated to contribute to lung injury in response to PM exposure. We studied the ...

CHARACTERIZING THE SOURCES OF HUMAN EXPOSURE TO MUTAGENIC AND CARCINOGENIC CHEMICALS IN AIRBORNE FINE PARTICLES

EPA Science Inventory

Personal and ambient exposures to airborne fine particles, polycyclic aromatic hydrocarbons (PAH), and genotoxic activity has been studied in populations in the US, Japan, China, and the Czech Republic. Personal exposure monitors used to collect fine particles were extracted f...

Environment and human exposure to persistent organic pollutants (POPs) in India: a systematic review of recent and historical data.

PubMed

Sharma, Brij Mohan; Bharat, Girija K; Tayal, Shresth; Nizzetto, Luca; Cupr, Pavel; Larssen, Thorjørn

2014-05-01

Persistent organic pollutants (POPs) have been used in a wide range of agricultural and industrial commodities, resulting in vigorous deterioration of environment and human health. A number of studies on the occurrence of POPs confirm their presence in various environmental compartments and human body. In order to deal with this global concern, India has recently prepared the National Implementation Plan (NIP) of the Stockholm Convention. Common beliefs point at India as a hot spot of POP contamination and human exposure; however no systematic analysis was ever performed so far considering all available past data on POP occurrence. This review aims to examine the distribution pattern of POPs in multicompartment environment and human samples, meta-analysis of time trends in exposure levels to environment and humans, and cross country comparison of POP contamination with China. Based on this review, it can be concluded that the Indian environment and human population are highly contaminated by DDTs and HCHs; however scarcity of data on other POPs makes it challenging to assess their nationwide human and environmental exposure. No evidence of a general decline in DDT and HCH residues in the environment and human body come out from the meta-analysis of time trend. While comparing contamination levels between India and China, tendency towards decline in POP contamination is visible in China, unlike India. Copyright © 2014 Elsevier Ltd. All rights reserved.

How familiar are our doctors towards Rabies prophylaxis- A study from coastal south India.

PubMed

Holla, Ramesh; Darshan, Bhagawan; Guliani, Astha; Unnikrishnan, Bhaskaran; Thapar, Rekha; Mithra, Prasanna; Kumar, Nithin; Kulkarni, Vaman; Kumar, Avinash; Anwar, Salman

2017-10-01

Rabies, a 100% fatal disease claims more than 59,000 human lives every year globally. One human life is lost every 15 minutes due to this deadly preventable disease. Timely initiation of post exposure prophylaxis following an animal exposure can result in 100% preventability of this fatal disease. This facility based study was conducted among clinical fraternities of teaching hospitals. A semi structured questionnaire was used for collection of data. Institutional Ethics Committee approval was sought. The study investigators visited the workplace of the participants and distributed the questionnaire. SPSS Ver 16 (Chicago, IL, USA) was used to analyse the data. Most of the participants knew that veterinary groups and zoo-keepers should be given pre-exposure prophylaxis. Many participants knew about the Intra Muscular schedule of anti-rabies vaccine and its site of administration for pre exposure prophylaxis. It was observed that most participants had knowledge regarding correct intramuscular regimen of anti-rabies vaccine for post-exposure prophylaxis but less than half were able to differentiate between the intramuscular and intradermal regimens. Less than half of participants were aware of the fact that local administration of anti-rabies serum is useful. The knowledge regarding WHO categorisation of animal exposure and recommended post exposure prophylaxis according to type of exposure observed to be minimal among clinical fraternity.

In vitro evaluation of genotoxic effects under magnetic resonant coupling wireless power transfer.

PubMed

Mizuno, Kohei; Shinohara, Naoki; Miyakoshi, Junji

2015-04-07

Wireless power transfer (WPT) technology using the resonant coupling phenomenon has been widely studied, but there are very few studies concerning the possible relationship between WPT exposure and human health. In this study, we investigated whether exposure to magnetic resonant coupling WPT has genotoxic effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was performed using a helical coil-based exposure system designed to transfer power with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the positions of the cell culture dishes is approximately twice the reference level for occupational exposure as stated in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate at the positions of the cell culture dishes matches the respective reference levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we studied cell growth, cell cycle distribution, DNA strand breaks using the comet assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation, and did not detect any significant effects between the WPT-exposed cells and control cells. Our results suggest that WPT exposure under the conditions of the ICNIRP guidelines does not cause detectable cellular genotoxicity.

Installation Restoration Program. Phase II Stage I Study McGuire Air Force Base, Burlington County, New Jersey.

DTIC Science & Technology

1984-10-01

risk level.derive human health criteria. Most evaluation and synthesis. Scientific SurmyofteJlrc &2criteria are based solely on exposure judg~~nt was...State drinking water and human health standards, criteria, and guidelines applica- ble in the State of New Jersey. On November 28, 1980, the U.S...established recommended maximum concentrations for acute and chronic exposure to these pollutants by both humans and aquatic life. The derivation of these

IMPLICATIONS OF GLOBAL CLIMATE CHANGE FOR THE ASSESSMENT AND MANAGEMENT OF HUMAN HEALTH RISKS OF CHEMICALS IN THE NATURAL ENVIRONMENT

PubMed Central

Balbus, John M; Boxall, Alistair BA; Fenske, Richard A; McKone, Thomas E; Zeise, Lauren

2013-01-01

Global climate change (GCC) is likely to alter the degree of human exposure to pollutants and the response of human populations to these exposures, meaning that risks of pollutants could change in the future. The present study, therefore, explores how GCC might affect the different steps in the pathway from a chemical source in the environment through to impacts on human health and evaluates the implications for existing risk-assessment and management practices. In certain parts of the world, GCC is predicted to increase the level of exposure of many environmental pollutants due to direct and indirect effects on the use patterns and transport and fate of chemicals. Changes in human behavior will also affect how humans come into contact with contaminated air, water, and food. Dietary changes, psychosocial stress, and coexposure to stressors such as high temperatures are likely to increase the vulnerability of humans to chemicals. These changes are likely to have significant implications for current practices for chemical assessment. Assumptions used in current exposure-assessment models may no longer apply, and existing monitoring methods may not be robust enough to detect adverse episodic changes in exposures. Organizations responsible for the assessment and management of health risks of chemicals therefore need to be more proactive and consider the implications of GCC for their procedures and processes. Environ. Toxicol. Chem. 2013;32:62–78. © 2012 SETAC PMID:23147420

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

Applying Definitions of “Asbestos” to Environmental and “Low-Dose” Exposure Levels and Health Effects, Particularly Malignant Mesothelioma

PubMed Central

Case, B. W.; Abraham, J. L.; Meeker, G.; Pooley, F. D.; Pinkerton, K. E.

2011-01-01

Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review. PMID:21534084

Applying definitions of “asbestos” to environmental and “low-dose” exposure Levels and health effects, particularly malignant mesothelioma

USGS Publications Warehouse

Case, B.W.; Abraham, J.L.; Meeker, G.; Pooley, F.D.; Pinkerton, K.E.

2011-01-01

Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review.

Chemical Risk Assessment: Traditional vs Public Health ...

EPA Pesticide Factsheets

Preventing adverse health impacts from exposures to environmental chemicals is fundamental to protecting individual and public health. When done efficiently and properly, chemical risk assessment enables risk management actions that minimize the incidence and impacts of environmentally-induced diseases related to chemical exposure. However, traditional chemical risk assessment is faced with multiple challenges with respect to predicting and preventing disease in human populations, and epidemiological studies increasingly report observations of adverse health effects at exposure levels predicted from animal studies to be safe for humans. This discordance reinforces concerns about the adequacy of contemporary risk assessment practices (Birnbaum, Burke, & Jones, 2016) for protecting public health. It is becoming clear that to protect public health more effectively, future risk assessments will need to use the full range of available data, draw on innovative methods to integrate diverse data streams, and consider health endpoints that also reflect the range of subtle effects and morbidities observed in human populations. Given these factors, there is a need to reframe chemical risk assessment to be more clearly aligned with the public health goal of minimizing environmental exposures associated with disease. Preventing adverse health impacts from exposures to environmental chemicals is fundamental to protecting individual and public health. Chemical risk assessments

The environment and male reproduction: The effect of cadmium exposure on reproductive function and its implication in fertility.

PubMed

de Angelis, Cristina; Galdiero, Mariano; Pivonello, Claudia; Salzano, Ciro; Gianfrilli, Daniele; Piscitelli, Prisco; Lenzi, Andrea; Colao, Annamaria; Pivonello, Rosario

2017-10-01

Cadmium is an environmental pollutant known as endocrine disruptor. Testis is particularly susceptible to cadmium, and testis injury occurs at high but even low levels of exposure. Cadmium reproductive toxicity is mediated by multiple mechanisms, including structural damage to testis vasculature and blood-testis barrier, inflammation, cytotoxicity on Sertoli and Leydig cells, oxidative stress mainly by means of mimicry and interference with essential ions, apoptosis, interference with selected signaling pathways and epigenetic regulation of genes involved in the regulation of reproductive function, and disturbance of the hypothalamus-pituitary-gonadal axis. The current review outlines epidemiological observational findings from environmental and occupational exposure in humans, and reports experimental studies in humans and animals. Lastly, a focus on the pathogenetic mechanisms of cadmium toxicity and on the specific mechanisms of cadmium sensitivity and resistance, particularly assessed in animal models, is included. Despite convincing experimental findings in animals and supporting evidences in humans identifying cadmium as reproductive toxicant, observational findings are controversial, suffering from heterogeneity of study design and pattern of exposure, and from co-exposure to multiple pollutants. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Repeated or long-duration TASER electronic control device exposures: acidemia and lack of respiration.

PubMed

Jauchem, James R

2010-03-01

Conducted energy weapons (CEWs), such as TASER devices, may be applied to subjects in repeated or long-duration modes. Such applications may result in more potentially harmful effects (as reflected in blood factor changes) than shorter exposures. In this review, results from a number of studies of repeated and long-duration CEW exposures in an animal model are examined. Additionally, a few limited investigations of shorter CEW applications to human subjects are considered. Specifically, in anesthetized swine, increased blood acidity (acidemia) and lack of effective respiration were found to be common during or immediately after CEW exposure. The acidemia could have been due to both metabolic and respiratory acidosis. A relatively rapid recovery toward baseline pH levels occurred. The lack of effective respiration has not been verified in experiments of CEW applications to human subjects; however, in some incidents of human deaths after CEW exposures subjects have been reported to stop breathing immediately after the exposure. It is not known if all human subjects exposed to CEW applications in the field (often "on drugs" or "in excited delirium") would be able to maintain adequate breathing. Since a limited number of short CEW applications would be less likely to cause adverse effects, however, CEWs can still be a valuable tool for law enforcement activities.

Systemic exposure of vinpocetine in pregnant Sprague Dawley rats following repeated oral exposure: An investigation of fetal transfer.

PubMed

Waidyanatha, Suramya; Toy, Heather; South, Natalie; Gibbs, Seth; Mutlu, Esra; Burback, Brian; McIntyre, Barry S; Catlin, Natasha

2018-01-01

Vinpocetine is being used worldwide by people of all ages, including pregnant women, for its purported multiple health benefits. However, limited data is available addressing the safety/toxicity of vinpocetine. The National Toxicology Program conducted studies to examine potential effects of vinpocetine on the developing rat. Disposition data is helpful to put the fetal findings into context and provide information on the potential risk for humans. The current study reports the systemic exposure and toxicokinetic (TK) parameters of vinpocetine and metabolite, apovincaminic acid (AVA), in pregnant Harlan Sprague Dawley rats, fetuses and amniotic fluid following oral gavage exposure of dams to 5 and 20mg/kg vinpocetine from gestational day 6 to 18. Vinpocetine was absorbed rapidly in dams with a maximum plasma concentration (C max ) reaching ≤1.37h. Predicted C max and area under the concentration versus time curve (AUC) increased less than proportionally to the dose. Vinpocetine was rapidly distributed to the peripheral compartment. More importantly, significant transfer of vinpocetine from dam to fetuses was observed with fetal C max and AUC≥55% of dams. Vinpocetine was cleared rapidly from dam plasma with an elimination half-life of ≤4.02h with no apparent dose-related effect. Vinpocetine was rapidly and highly metabolized to AVA with AVA plasma levels in dams ≥2.7-fold higher than vinpocetine, although in the fetuses, AVA levels were much lower than vinpocetine. Comparison of current rat data with literature human data demonstrates that systemic exposure to vinpocetine in rats following repeated exposure to 5mg/kg is similar to that following a single human relevant dose of 10mg suggesting that the findings from the toxicology study may be relevant to humans. Published by Elsevier Inc.

Illustrative assessment of human health issues arising from the potential release of chemotoxic substances from a generic geological disposal facility for radioactive waste.

PubMed

Wilson, James C; Thorne, Michael C; Towler, George; Norris, Simon

2011-12-01

Many countries have a programme for developing an underground geological disposal facility for radioactive waste. A case study is provided herein on the illustrative assessment of human health issues arising from the potential release of chemotoxic and radioactive substances from a generic geological disposal facility (GDF) for radioactive waste. The illustrative assessment uses a source-pathway-receptor methodology and considers a number of human exposure pathways. Estimated exposures are compared with authoritative toxicological assessment criteria. The possibility of additive and synergistic effects resulting from exposures to mixtures of chemical contaminants or a combination of radiotoxic and chemotoxic substances is considered. The case study provides an illustration of how to assess human health issues arising from chemotoxic species released from a GDF for radioactive waste and highlights potential difficulties associated with a lack of data being available with which to assess synergistic effects. It also highlights how such difficulties can be addressed.

Environmental exposure and leptospirosis, Peru.

PubMed

Johnson, Michael A S; Smith, Hannah; Joeph, Priya; Gilman, Robert H; Bautista, Christian T; Campos, Kalina J; Cespedes, Michelle; Klatsky, Peter; Vidal, Carlos; Terry, Hilja; Calderon, Martiza M; Coral, Carlos; Cabrera, Lilia; Parmar, Paminder S; Vinetz, Joseph M

2004-06-01

Human infection by leptospires has highly variable clinical manifestations, which range from subclinical infection to fulminant disease. We conducted a population-based, cross-sectional seroepidemiologic study in Peru to determine potential relationships of environmental context to human exposure to Leptospira and disease associated with seroconversion. Three areas were studied: a flooded, urban slum in the Peruvian Amazon city of Iquitos; rural, peri-Iquitos villages; and a desert shantytown near Lima. Seroprevalence in Belen was 28% (182/650); in rural areas, 17% (52/316); and in a desert shantytown, 0.7% (1/150). Leptospira-infected peridomestic rats were found in all locales. In Belen, 20 (12.4%) of 161 patients seroconverted between dry and wet seasons (an incidence rate of 288/1,000). Seroconversion was associated with history of febrile illness; severe leptospirosis was not seen. Human exposure to Leptospira in the Iquitos region is high, likely related both to the ubiquity of leptospires in the environment and human behavior conducive to transmission from infected zoonotic sources.

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

SUMMARY FINDINGS FROM THE U.S. EPA'S PARTICULATE MATTER PANEL STUDIES

EPA Science Inventory

The U.S. EPA's Particulate Matter Panel Studies were a series of longitudinal human exposure studies used to characterize personal exposures to particulate matter (PM) and related co-pollutants to that of pollutants of ambient origin. Participants were monitored over time (28 d...

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.

Identifying areas of high risk of human exposure to coccidioidomycosis in Texas using serology data from dogs.

PubMed

Gautam, R; Srinath, I; Clavijo, A; Szonyi, B; Bani-Yaghoub, M; Park, S; Ivanek, R

2013-03-01

Coccidioidomycosis or Valley Fever (VF) is an emerging soil-borne fungal zoonosis affecting humans and animals. Most non-human cases of VF are found in dogs, which we hypothesize may serve as sentinels for estimating the human exposure risk. The objective of this study is to use the spatial and temporal distribution and clusters of dogs seropositive for VF to define the geographic area in Texas where VF is endemic, and thus presents a higher risk of exposure to humans. The included specimens were seropositive dogs tested at a major diagnostic laboratory between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical Bayesian estimation to develop an isopleth map of VF seropositive rates using kriging. Clusters of seropositive dogs were identified using the spatial scan test. Both the isopleth map and the scan test identified an area with a high rate of VF-seropositive dogs in the western and southwestern parts of Texas (relative risk = 31). This location overlapped an area that was previously identified as a potential endemic region based on human surveys. Together, these data suggest that dogs may serve as sentinels for estimating the risk of human exposure to VF. © 2012 Blackwell Verlag GmbH.

A Combined Ecological and Epidemiologic Investigation of Metals Exposure amongst Indigenous Peoples Near the Marlin Mine in Western Guatemala

PubMed Central

Basu, Niladri; Abare, Marce; Buchanan, Susan; Cryderman, Diana; Nam, Dong-Ha; Sirkin, Susannah; Schmitt, Stefan; Hu, Howard

2016-01-01

In August 2009 a combined epidemiological and ecological pilot study was conducted to investigate allegations of human rights abuses in the form of exposures to toxic metals experienced by mine workers and Indigenous Mam Mayan near the Marlin Mine in Guatemala. In the human study there were no differences in blood and urine metals when comparing five mine workers with eighteen non-mine workers, and there were no discernible relationships between metals exposures and self-reported health measures in any study group. On the other hand, individuals residing closest to the mine had significantly higher levels of certain metals (urinary mercury, copper, arsenic, zinc) when compared to those living further away. Levels of blood aluminum, manganese, and cobalt were elevated in comparison to established normal ranges in many individuals; however, there was no apparent relationship to proximity to the mine or occupation, and thus are of unclear significance. In the ecological study, several metals (aluminum, manganese, cobalt) were found significantly elevated in the river water and sediment sites directly below the mine when compared to sites elsewhere. When the results of the human and ecological results are combined, they suggest that exposures to certain metals may be elevated in sites near the mine but it is not clear if the current magnitude of these elevations poses a significant threat to health. The authors conclude that more robust studies are needed while parallel efforts to minimize the ecological and human impacts of mining proceed. This is critical particularly as the impact of the exposures found could be greatly magnified by expected increases in mining activity over time, synergistic toxicity between metals, and susceptibility for the young and those with pre-existing disease. PMID:20952048

Chronic Exposure to Zinc Chromate Induces Centrosome Amplification and Spindle Assembly Checkpoint Bypass in Human Lung Fibroblasts

PubMed Central

Holmes, Amie L.; Wise, Sandra S.; Pelsue, Stephen C.; Aboueissa, AbouEl-Makarim; Lingle, Wilma; Salisbury, Jeffery; Gallagher, Jamie; Wise, John Pierce

2010-01-01

Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen, however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no increase in aneuploidy after a 24 hour exposure to zinc chromate, but with more chronic exposures, zinc chromate induced concentration- and time-dependent increases in aneuploidy in the form of hypodiploidy, hyperdiploidy and tetraploidy. Zinc chromate also induced centrosome amplification in a concentration- and time-dependent manner in both interphase and mitotic cells after chronic exposure, producing cells with centriolar defects. Further, chronic exposure to zinc chromate induced concentration- and time-dependent increases in spindle assembly checkpoint bypass with increases in centromere spreading, premature centromere division and premature anaphase. Lastly, we found that chronic exposure to zinc chromate induced a G2 arrest. All together, these data indicate that zinc chromate can induce chromosome instability after prolonged exposures. PMID:20030412

Exposure to non-persistent pesticides and thyroid function: A systematic review of epidemiological evidence.

PubMed

Campos, Élida; Freire, Carmen

2016-08-01

Numerous pesticides are recognized for their endocrine-disrupting properties. Non-persistent pesticides such as organophosphates, dithiocarbamates and pyrethroids may interfere with thyroid function as suggested by animal studies. However, the influence of chronic exposure to these compounds on thyroidal functions in humans remains to be determined. The present study aimed to review epidemiological evidence for an association between exposure to non-persistent pesticides and circulating levels of thyroid hormones (thyroxin [T4] and triiodothyronine [T3]) and thyroid-stimulating hormone (TSH). A systematic review was conducted using MEDLINE, SCOPUS and Virtual Health Library (BVS) databases. Articles were limited to original studies and reports published in English, Portuguese or Spanish. Nineteen epidemiological studies were identified, 17 of which were cross-sectional, 14 were of occupationally exposed workers and 11 used exposure biomarkers. Fungicides and organophosphates (OP) insecticides were the most studied pesticides. Although methodological heterogeneity between studies was noted, particularly regarding study design, exposure assessment, and control of confounding, most of them showed associations with changes in T3 and T4, and/or TSH levels, while results from a few of these are consistent with experimental data supporting the findings that non-persistent pesticide exposure exerts hypothyroid-like effects. However, reporting quality was moderate to poor in 50% of the studies, particularly regarding method of selection of participants and discussion of external validity. Overall, current knowledge regarding the impact of non-persistent pesticides on human thyroid function is still limited. Given the widespread use of pesticides, future research should assess effects of exposure to currently-used pesticides in cohort studies combining comprehensive questionnaire-based assessment and biomarkers. Investigators need to pay particular attention to exposure during critical windows of brain development and exposure in agricultural populations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Human health risk assessment of lead from mining activities at semi-arid locations in the context of total lead exposure.

PubMed

Zheng, Jiajia; Huynh, Trang; Gasparon, Massimo; Ng, Jack; Noller, Barry

2013-12-01

Lead from historical mining and mineral processing activities may pose potential human health risks if materials with high concentrations of bioavailable lead minerals are released to the environment. Since the Joint Expert Committee on Food Additives of Food and Agriculture Organization/World Health Organization withdrew the Provisional Tolerable Weekly Intake of lead in 2011, an alternative method was required for lead exposure assessment. This study evaluated the potential lead hazard to young children (0-7 years) from a historical mining location at a semi-arid area using the U.S. EPA Integrated Exposure Uptake Biokinetic (IEUBK) Model, with selected site-specific input data. This study assessed lead exposure via the inhalation pathway for children living in a location affected by lead mining activities and with specific reference to semi-arid conditions and made comparison with the ingestion pathway by using the physiologically based extraction test for gastro-intestinal simulation. Sensitivity analysis for major IEUBK input parameters was conducted. Three groups of input parameters were classified according to the results of predicted blood concentrations. The modelled lead absorption attributed to the inhalation route was lower than 2 % (mean ± SE, 0.9 % ± 0.1 %) of all lead intake routes and was demonstrated as a less significant exposure pathway to children's blood, compared with ingestion. Whilst dermal exposure was negligible, diet and ingestion of soil and dust were the dominant parameters in terms of children's blood lead prediction. The exposure assessment identified the changing role of dietary intake when house lead loadings varied. Recommendations were also made to conduct comprehensive site-specific human health risk assessment in future studies of lead exposure under a semi-arid climate.

The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

PubMed

Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

2013-10-25

Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust.

PubMed

Gouveia-Figueira, Sandra; Karimpour, Masoumeh; Bosson, Jenny A; Blomberg, Anders; Unosson, Jon; Sehlstedt, Maria; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Nording, Malin L

2018-08-14

Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF 2α , 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute Lung Injury and Persistent Small Airway Disease in a Rabbit Model of Chlorine Inhalation

PubMed Central

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M.; Powell, Karen S.; Roberts, Andrew M.; Hoyle, Gary W.

2016-01-01

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure-volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. PMID:27913141

The effects of post-exposure smallpox vaccination on clinical disease presentation: Addressing the data gaps between historical epidemiology and modern surrogate model data

PubMed Central

Keckler, M. Shannon; Reynolds, Mary G.; Damon, Inger K.; Karem, Kevin L.

2015-01-01

Decades after public health interventions – including pre- and post-exposure vaccination – were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. PMID:23994378

Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate.

PubMed

Boberg, Julie; Johansson, Hanna K L; Hadrup, Niels; Dreisig, Karin; Berthelsen, Line; Almstrup, Kristian; Vinggaard, Anne Marie; Hass, Ulla

2015-02-01

Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk. We examined the influence of perinatal exposure to mixtures of anti-androgenic and estrogenic chemicals on prostate development. Wistar rats were exposed from gestation day 7 to postnatal day 22 to a mixture of 8 anti-androgenic compounds (AAMix), a mixture of four estrogenic compounds (EMix), or paracetamol or a mixture of all 13 compounds (TotalMix) in mixture ratios reflecting human exposure levels. Ventral prostate weights were reduced by the TotalMix and AAMix in pre-pubertal rats. Histological changes in prostate appeared with increasing age and indicated a shift from the normal age-dependent epithelial atrophy towards hyperplasia. These lesions showed similarities to pre-cancerous lesions in humans. Increased proliferation was observed already in pre-puberty and it was hypothesized that this could be associated with reduced ERβ signaling, but no clear conclusions could be made from gene expression studies on ERβ-related pathways. The influences of the estrogenic chemicals and paracetamol on prostate morphology were minor, but in young adulthood the estrogen mixture reduced ventral prostate mRNA levels of Igf1 and paracetamol reduced the mRNA level ofPbpc3. Mixtures of endocrine disrupters relevant for human exposure was found to elicit persistent effects on the rat prostate following perinatal exposure, suggesting that human perinatal exposure to environmental chemicals may increase the risk of prostate cancer later in life. © 2014 Wiley Periodicals, Inc.

NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

EPA Science Inventory

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult rats were maintained on a chlorpyrifos-containing diet to p...

PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population

USDA-ARS?s Scientific Manuscript database

Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight exposure warrant investigation. The purpose of this study was to as...

Associations between summertime ambient pollutants and respiratory morbidity in New York City: Comparison of results using ambient concentrations versus predicted exposures

EPA Science Inventory

Epidemiological analyses of air quality often estimate human exposure from ambient monitoring data, potentially leading to exposure misclassification and subsequent bias in estimated health risks. To investigate this, we conducted a case-crossover study of summertime ambient ozon...

The Influence of Human and Environmental Exposure Factors on Personal NO2 Exposures

EPA Science Inventory

The US Environmental Protection Agency’s (US EPA) Detroit Exposure and Aerosol Research Study (DEARS) deployed a total of over 2000 nitrogen dioxide, NO₂, passive monitors during 3 years of field data collections. These 24-h based personal, residential outdoor and comm...

Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice

EPA Science Inventory

The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes...

EPA STUDIES OF ARSENIC SPECIATION IN SEAFOOD MATRICES WITH AN EMPHASIS ON EXTRACTABILITY AND ARSENOSUGAR INTEGRITY

EPA Science Inventory

The anthropogenic and geological occurrence of arsenic (As) results in human exposure to a potentially carcinogenic element. The two predominant pathways to As exposure are drinking water (DW) and dietary ingestion (DI). DW exposures are almost exclusively toxic inorganic As. ...

Human exposure assessment to antibiotic-resistant Escherichia coli through drinking water.

PubMed

O'Flaherty, E; Borrego, C M; Balcázar, J L; Cummins, E

2018-03-01

Antibiotic-resistant bacteria (ARB) are a potential threat to human health through drinking water with strong evidence of ARB presence in post treated tap water around the world. This study examines potential human exposure to antibiotic-resistant (AR) Escherichia coli (E. coli) through drinking water, the effect of different drinking water treatments on AR E. coli and the concentration of AR E. coli required in the source water for the EU Drinking Water Directive (DWD) (Council Directive 98/83/EC, 0CFU/100ml of E. coli in drinking water) to be exceeded. A number of scenarios were evaluated to examine different water treatment combinations and to reflect site specific conditions at a study site in Europe. A literature search was carried out to collate data on the effect of environmental conditions on AR E. coli, the effect of different water treatments on AR E. coli and typical human consumption levels of tap water. A human exposure assessment model was developed with probability distributions used to characterise uncertainty and variability in the input data. Overall results show the mean adult human exposure to AR E. coli from tap water consumption ranged between 3.44×10 -7 and 2.95×10 -1 cfu/day for the scenarios tested and varied depending on the water treatments used. The level of AR E. coli required in the source water pre-treatment to exceed the DWD varied between 1 and 5logcfu/ml, depending on the water treatments used. This can be used to set possible monitoring criteria in pre-treated water for potential ARB exposure in drinking water. Copyright © 2017 Elsevier B.V. All rights reserved.

A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human.

PubMed

Fennell, T R; Brown, C D

2001-06-15

Ethylene oxide (EO) is widely used as a gaseous sterilant and industrial intermediate and is a direct-acting mutagen and carcinogen. The objective of these studies was to develop physiologically based pharmacokinetic (PB-PK) models for EO to describe the exposure-tissue dose relationship in rodents and humans. We previously reported results describing in vitro and in vivo kinetics of EO metabolism in male and female F344 rats and B6C3F1 mice. These studies were extended by determining the kinetics of EO metabolism in human liver cytosol and microsomes. The results indicate enzymatically catalyzed GSH conjugation via cytosolic glutathione S-transferase (cGST) and hydrolysis via microsomal epoxide hydrolase (mEH) occur in both rodents and humans. The in vitro kinetic constants were scaled to account for cytosolic (cGST) and microsomal (mEH) protein content and incorporated into PB-PK descriptions for mouse, rat, and human. Flow-limited models adequately predicted blood and tissue EO levels, disposition, and elimination kinetics determined experimentally in rats and mice, with the exception of testis concentrations, which were overestimated. Incorporation of a diffusion-limited description for testis improved the ability of the model to describe testis concentrations. The model accounted for nonlinear increases in blood and tissue concentrations that occur in mice on exposure to EO concentrations greater than 200 ppm. Species differences are predicted in the metabolism and exposure-dose relationship, with a nonlinear relationship observed in the mouse as a result of GSH depletion. These models represent an essential step in developing a mechanistically based EO exposure-dose-response description for estimating human risk from exposure to EO. Copyright 2001 Academic Press.

Glycol ethers and semen quality: a cross‐sectional study among male workers in the Paris Municipality

PubMed Central

Multigner, L; Brik, E Ben; Arnaud, I; Haguenoer, J M; Jouannet, P; Auger, J; Eustache, F

2007-01-01

Objectives Apparent increases in human male reproductive disorders, including low sperm production, may have occurred because of increased chemical exposure. Various glycol ether‐based solvents have pronounced adverse effects on sperm production and male fertility in laboratory animals. The authors investigated the effects of past and current exposure to glycol ether‐containing products on semen quality and reproductive hormones among men employed by the Paris Municipality. Methods Between 2000 and 2001 the authors recruited 109 men who gave semen, blood and urine samples and underwent an andrological examination. Information on lifestyle, occupation, exposure and medical history was obtained by interview. According to their job and chemical products used during the period 1990–2000, men were classified as either occupationally exposed or non‐exposed. Current exposure levels to glycol ethers at the time of the study were evaluated by biological monitoring of six urinary metabolites. Results Previous exposure to glycol ethers was associated with an increased risk for sperm concentration, for rapid progressive motility and for morphologically normal sperm below the World Health Organization semen reference values. No effect of previous glycol ether exposure on hormones levels was observed. By contrast, current glycol ether exposure levels were low and not correlated with either seminal quality or hormone levels. Conclusions This study suggests that most glycol ethers currently used do not impact on human semen characteristics. Those that were more prevalent from the 1960s until recently may have long lasting negative effects on human semen quality. PMID:17332140

Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se.

PubMed

Haussmann, Hans-Juergen; Fariss, Marc W

2016-09-01

The effects of long-term use of nicotine per se on cancer risk, in the absence of tobacco extract or smoke, are not clearly understood. This review evaluates the strength of published scientific evidence, in both epidemiological and animal studies, for the potential carcinogenic effects of nicotine per se; that is to act as a complete carcinogen or as a modulator of carcinogenesis. For human studies, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a carcinogenic effect due to the limited information available. In animal studies, limited evidence suggests an association between long-term nicotine exposure and a lack of a complete carcinogenic effect. Conclusive studies using current bioassay guidelines, however, are missing. In studies using chemical/physical carcinogens or transgenic models, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a modulating (stimulating) effect on carcinogenesis. This is primarily due to the large number of conflicting studies. In contrast, a majority of studies provides sufficient evidence for an association between nicotine exposure and enhanced carcinogenesis of cancer cells inoculated in mice. This modulating effect was especially prominent in immunocompromized mice. Overall, taking the human and animal studies into consideration, there appears to be inadequate evidence to conclude that nicotine per se does or does not cause or modulate carcinogenesis in humans. This conclusion is in agreement with the recent US Surgeon General's 2014 report on the health consequences of nicotine exposure.

Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se

PubMed Central

Haussmann, Hans-Juergen; Fariss, Marc W.

2016-01-01

Abstract The effects of long-term use of nicotine per se on cancer risk, in the absence of tobacco extract or smoke, are not clearly understood. This review evaluates the strength of published scientific evidence, in both epidemiological and animal studies, for the potential carcinogenic effects of nicotine per se; that is to act as a complete carcinogen or as a modulator of carcinogenesis. For human studies, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a carcinogenic effect due to the limited information available. In animal studies, limited evidence suggests an association between long-term nicotine exposure and a lack of a complete carcinogenic effect. Conclusive studies using current bioassay guidelines, however, are missing. In studies using chemical/physical carcinogens or transgenic models, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a modulating (stimulating) effect on carcinogenesis. This is primarily due to the large number of conflicting studies. In contrast, a majority of studies provides sufficient evidence for an association between nicotine exposure and enhanced carcinogenesis of cancer cells inoculated in mice. This modulating effect was especially prominent in immunocompromized mice. Overall, taking the human and animal studies into consideration, there appears to be inadequate evidence to conclude that nicotine per se does or does not cause or modulate carcinogenesis in humans. This conclusion is in agreement with the recent US Surgeon General’s 2014 report on the health consequences of nicotine exposure. PMID:27278157

Exposure to Non-Extreme Solar UV Daylight: Spectral Characterization, Effects on Skin and Photoprotection

PubMed Central

Marionnet, Claire; Tricaud, Caroline; Bernerd, Françoise

2014-01-01

The link between chronic sun exposure of human skin and harmful clinical consequences such as photo-aging and skin cancers is now indisputable. These effects are mostly due to ultraviolet (UV) rays (UVA, 320–400 nm and UVB, 280–320 nm). The UVA/UVB ratio can vary with latitude, season, hour, meteorology and ozone layer, leading to different exposure conditions. Zenithal sun exposure (for example on a beach around noon under a clear sky) can rapidly induce visible and well-characterized clinical consequences such as sunburn, predominantly induced by UVB. However, a limited part of the global population is exposed daily to such intense irradiance and until recently little attention has been paid to solar exposure that does not induce any short term clinical impact. This paper will review different studies on non-extreme daily UV exposures with: (1) the characterization and the definition of the standard UV daylight and its simulation in the laboratory; (2) description of the biological and clinical effects of such UV exposure in an in vitro reconstructed human skin model and in human skin in vivo, emphasizing the contribution of UVA rays and (3) analysis of photoprotection approaches dedicated to prevent the harmful impact of such UV exposure. PMID:25546388

Exposure to non-extreme solar UV daylight: spectral characterization, effects on skin and photoprotection.

PubMed

Marionnet, Claire; Tricaud, Caroline; Bernerd, Françoise

2014-12-23

The link between chronic sun exposure of human skin and harmful clinical consequences such as photo-aging and skin cancers is now indisputable. These effects are mostly due to ultraviolet (UV) rays (UVA, 320-400 nm and UVB, 280-320 nm). The UVA/UVB ratio can vary with latitude, season, hour, meteorology and ozone layer, leading to different exposure conditions. Zenithal sun exposure (for example on a beach around noon under a clear sky) can rapidly induce visible and well-characterized clinical consequences such as sunburn, predominantly induced by UVB. However, a limited part of the global population is exposed daily to such intense irradiance and until recently little attention has been paid to solar exposure that does not induce any short term clinical impact. This paper will review different studies on non-extreme daily UV exposures with: (1) the characterization and the definition of the standard UV daylight and its simulation in the laboratory; (2) description of the biological and clinical effects of such UV exposure in an in vitro reconstructed human skin model and in human skin in vivo, emphasizing the contribution of UVA rays and (3) analysis of photoprotection approaches dedicated to prevent the harmful impact of such UV exposure.

The importance of evaluating metal exposure and predicting human health risks in urban-periurban environments influenced by emerging industry.

PubMed

Yousaf, Balal; Amina; Liu, Guijian; Wang, Ruwei; Imtiaz, Muhammad; Rizwan, Muhammad Shahid; Zia-Ur-Rehman, Muhammad; Qadir, Abdul; Si, Youbin

2016-05-01

The human population boom, urbanization and rapid industrialization have either directly or indirectly resulted in the serious environmental toxification of the soil-food web by metal exposure from anthropogenic sources in most of the developing industrialized world. The present study was conducted to analyze concentrations of Cd, Cr, Cu, Mn, Ni, Pb, and Zn in soil and vegetables in the urban-periurban areas influenced by emerging industry. Vegetables and their corresponding soil samples were collected and analyzed for heavy metals contents from six random sites. According to the results, the potential health risks from metals to the local communities were assessed by following the methodology described by the US-EPA. In general, the total non-carcinogenic risks were shown to be less than the limits set by the US-EPA. However, the potential risk of developing carcinogenicity in humans over a lifetime of exposure could be increased through the dietary intake of Cd, Cr and Ni. In some cases, Pb was also marginally higher than the safe level. It was concluded that some effective remedial approaches should be adopted to mitigate the risks of Cd, Cr, Ni and Pb in the study area because these metal levels have exceeded the safe limits for human health. However, new studies on gastrointestinal bioaccessibility in human are required to heighten our understanding about metals exposure and health risk assessment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk assessment of triclosan [Irgasan] in human breast milk.

PubMed

Dayan, A D

2007-01-01

Triclosan is an established bacteriostatic compound widely used in topical and dental preparations. Its pharmacokinetics and toxicology have been extensively studied in humans and animals. It is known to be absorbed from the gastrointestinal tract and across the skin. A recent report noted its occurrence in human breast milk and this has now been further investigated. Sixty two unselected samples of human milk from Breast Milk Banks in California and Texas have been analysed for triclosan; the concentration ranged from 0 to 2100 microg/kg lipid. A risk assessment of triclosan in human milk has been made, based on a conservative calculation of exposure of neonates and experimental toxicity test results. The broad set of reproduction toxicity tests of triclosan includes a 2-generation study in the rat, in which there was considerable exposure of dams and pups to triclosan throughout fetal development and up to sexual maturity in the F2 generation, and a further study in which pups of dosed dams were followed to weaning. They established an oral NOAEL for pups of 50 mg/kg/d. The maximum exposure of babies via breast milk calculated using very conservative additive assumptions is approximately 7.4 microg/kg/d. The 'Margin of Exposure' between the NOAEL and that calculated in breast fed babies is approximately 6760-fold. It is concluded that there is no evidence to indicate that the presence of a miniscule amount of triclosan in breast milk presents a risk to babies.

Effects of A 60 Hz Magnetic Field of Up to 50 milliTesla on Human Tremor and EEG: A Pilot Study.

PubMed

Davarpanah Jazi, Shirin; Modolo, Julien; Baker, Cadence; Villard, Sebastien; Legros, Alexandre

2017-11-24

Humans are surrounded by sources of daily exposure to power-frequency (60 Hz in North America) magnetic fields (MFs). Such time-varying MFs induce electric fields and currents in living structures which possibly lead to biological effects. The present pilot study examined possible extremely low frequency (ELF) MF effects on human neuromotor control in general, and physiological postural tremor and electroencephalography (EEG) in particular. Since the EEG cortical mu-rhythm (8-12 Hz) from the primary motor cortex and physiological tremor are related, it was hypothesized that a 60 Hz MF exposure focused on this cortical region could acutely modulate human physiological tremor. Ten healthy volunteers (age: 23.8 ± 4 SD) were fitted with a MRI-compatible EEG cap while exposed to 11 MF conditions (60 Hz, 0 to 50 mT rms , 5 mT rms increments). Simultaneously, physiological tremor (recorded from the contralateral index finger) and EEG (from associated motor and somatosensory brain regions) were measured. Results showed no significant main effect of MF exposure conditions on any of the analyzed physiological tremor characteristics. In terms of EEG, no significant effects of the MF were observed for C1, C3, C5 and CP1 electrodes. However, a significant main effect was found for CP3 and CP5 electrodes, both suggesting a decreased mu-rhythm spectral power with increasing MF flux density. This is however not confirmed by Bonferroni corrected pairwise comparisons. Considering both EEG and tremor findings, no effect of the MF exposure on human motor control was observed. However, MF exposure had a subtle effect on the mu-rhythm amplitude in the brain region involved in tactile perception. Current findings are to be considered with caution due to the small size of this pilot work, but they provide preliminary insights to international agencies establishing guidelines regarding electromagnetic field exposure with new experimental data acquired in humans exposed to high mT-range MFs.

Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

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

Corley, R.A., E-mail: rick.corley@pnl.gov; Saghir, S.A.; Bartels, M.J.

2011-02-01

A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrationsmore » exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.« less

Electronic cigarettes and indoor air quality: a review of studies using human volunteers.

PubMed

Zainol Abidin, Najihah; Zainal Abidin, Emilia; Zulkifli, Aziemah; Karuppiah, Karmegam; Syed Ismail, Sharifah Norkhadijah; Amer Nordin, Amer Siddiq

2017-09-26

This paper is primarily aimed to review articles on electronic cigarettes (e-cigarettes) focusing on indoor air quality (IAQ) assessment that were conducted using human volunteers under natural settings that mimic actual vaping scenarios. Such studies may give a better representation of the actual potential exposure towards e-cigarettes emissions in indoor settings. A systematic literature search was conducted using PubMed search engine database. Search terms such as "electronic cigarette", "e-cigarette", "electronic nicotine delivery system", and "indoor air quality" were used to identify the relevant articles to be included in this review. Articles that involved human volunteers who were asked to vape in natural settings or settings that mimic the actual vaping scenario were chosen to be reviewed. The search yielded a total of 15 published articles. Eleven articles were excluded due to 1) unavailability of its full-text (n=1), 2) did not involve human volunteers (n=5) and 3) did not involve an IAQ study (n=5). Four articles were critically reviewed in this paper. From the four selected articles, two of the papers focused on the determination of nicotine level released by e-cigarettes whereas the other two covered IAQ parameters namely; particulate matters (PM), propylene glycols, formaldehyde, metals and polycyclic aromatic hydrocarbons (PAHs). Only two of the studies involved determination of biomarkers of exposure. The level of chemical contents released varied between studies. The differences in the brands of e-cigarette used, number of vapers recruited and the sensitivity of the methodologies employed in these studies may be the possible causes for such differences. However, studies using human volunteers conducted in a natural setting are more relevant to portray the actual exposure to vapors among e-cigarettes users and non-users compared to studies using a smoking machine/an exposure chamber. This is because such studies take into account the behavior of consumers and individual retention of nicotine. Such method will therefore avoid the possibility of overestimation in terms of exposures toward e-cigarettes users and non-users. There are limited e-cigarette studies on the impact of IAQ performed using human volunteers in natural settings. The available studies however, provided inconsistent scientific evidence on the actual exposure towards the vapor contents as unstandardized methodology were used in conducting such research. Therefore, there is a need to conduct IAQ studies in natural settings by using a standardized protocol in terms of the number of vapers recruited, the size of the indoor settings, the methods used in detecting and quantifying the contents and levels of emissions and the sensitivity of the equipment used in analyzing the contents. This will help in better utilization of the findings from such studies for the use of risk assessment of the exposures towards e-cigarette emissions. There is also a need to emphasize that it is the onus of the manufacturers in providing and proving scientifically sound safety claims for their products prior to commercializing it in the market.

Scientific and Ethical Approaches for Observational Exposure Studies

EPA Science Inventory

Researchers conduct observational human exposure studies to understand how and the extent to which people come into contact with chemicals and environmental stressors in their everyday lives, through the air they breathe, the food and liquids they consume, and the things they tou...

ENVIRONMENTAL POLLUTANTS AND ADVERSE HUMAN HEALTH EFFECTS: HAZARD IDENTIFICATION USING INTERREGION COMPARISONS

EPA Science Inventory

Background: Associations between adverse health effects and environmental exposures are difficult to study, because exposures may be widespread, low-dose in nature, and common throughout the study population. Therefore, individual risk-factor epidemiology may not be the right to...

Advanced Exposure Metrics For Chemical Risk Analysis: Systems Biology and 'Omic-based Biomarkers for Exposure Reconstruction

EPA Science Inventory

Direct measurement of human exposure to environmental contaminants in real time (when the exposure is actually occurring) is rare and difficult to obtain. This frustrates both exposure assessments and investigations into the linkage between chemical exposure and human disease. ...

Risk Factors for Breast Cancer, Including Occupational Exposures

PubMed Central

Meo, Margrethe; Vainio, Harri

2011-01-01

The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women. PMID:22953181

EDCs Mixtures: A Stealthy Hazard for Human Health?

PubMed

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-02-07

Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed "body burden" of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex "body burden" of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce.

Human behavior and opportunities for parasite transmission in communities surrounding long-tailed macaque populations in Bali, Indonesia.

PubMed

Lane-DeGraaf, Kelly E; Putra, I G A Arta; Wandia, I Nengah; Rompis, Aida; Hollocher, Hope; Fuentes, Agustin

2014-02-01

Spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (Macaca fascicularis), concentrating them in areas in close proximity to humans. In this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestinal parasites to understand if age, education level, or occupation are significant determinants of exposure behaviors. These exposure risk behaviors and attitudes include fear of macaques, direct contact with macaques, owning pet macaques, hunting and eating macaques, and overlapping water uses. We find that willingness to participate in exposure risk behaviors are correlated with an individual's occupation, age, and/or education level. We also found that because the actual risk of infection varies across populations, activities such as direct macaque contact and pet ownership, could be putting individuals at real risk in certain contexts. Thus, we show that human demographics and social structure can influence willingness to participate in behaviors putting them at increased risk for exposure to parasites. © 2013 Wiley Periodicals, Inc.

EDCs Mixtures: A Stealthy Hazard for Human Health?

PubMed Central

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-01-01

Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed “body burden” of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex “body burden” of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce. PMID:29051438

A short review on human exposure to and tissue distribution of per- and polyfluoroalkyl substances (PFASs).

PubMed

Jian, Jun-Meng; Chen, Da; Han, Fu-Juan; Guo, Ying; Zeng, Lixi; Lu, Xingwen; Wang, Fei

2018-09-15

PFASs are widely distributed in natural and living environment and can enter human bodies via different routes. Many studies have reported that PFASs may be associated with human diseases, such as urine acid and thyroid diseases. In this study, we reviewed PFAS levels in human bodies reported in past seven years, including blood, urine, milk, and tissues (hair and nails). Most studies focused on human blood. Blood type, spatiality, human age, and gender were found to have a strong relationship with PFAS levels in blood samples. The PFAS distribution in urine samples was reported to be associated with the chain length of PFASs and human gender. Urinary excretion was found to be an important pathway of PFAS elimination. PFAS levels in human milk might be affected by various factors, such as mothers' age, dietary habit, parity of mothers and the interval of interpregnancy. Data in hair and nails remain very limited, but these matrices offer a non-invasive approach to evaluate human exposure to PFASs. Copyright © 2018 Elsevier B.V. All rights reserved.

How Questionnaires and Multimedia Measurements collected in the U.S. EPA’s Observational Human Exposure Measurement Studies Inform Exposures

EPA Science Inventory

In the last decade, the U.S. EPA has conducted and/or funded numerous observational humanexposure measurement studies where questionnaires were administered to the study participants in addition tothe collection of multimedia measurements. Questionnaire responses provide ancillar...

EFFECTS OF ACTIVATED CHARCOAL FILTRATION AND OZONATION ON HYDROCARBON AND CARBONYL LEVELS OF AMBIENT AIR USED IN CONTROLLED-EXPOSURE CHAMBER STUDIES OF AIR POLLUTANT HUMAN HEALTH EFFECTS

EPA Science Inventory

Air sampling experiments were done in 1985, 1987, and 1993 at the human-exposure chamber facility of the U.S. EPA Health Effects Research Laboratory in Chapel Hill, NC. easurements of VOC's by GC-FID and aldehyde measurements by the DNPH silica gel cartridge method were made, com...

Comparison of human exposure model estimates of PM2.5 exposure variability using fine-scale CMAQ simulations from the Baltimore DISCOVER-AQ evaluation

EPA Science Inventory

Human exposure models estimate population distributions of exposure to air pollutants by combining ambient (outdoor) concentration data with human activity patterns to account for the time people spend in different locations (e.g., outdoors, indoors, in vehicles) and the various ...

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

Occurrence, sources and human exposure assessment of SCCPs in indoor dust of northeast China.

PubMed

Liu, Li-Hua; Ma, Wan-Li; Liu, Li-Yan; Huo, Chun-Yan; Li, Wen-Long; Gao, Chong-Jing; Li, Hai-Ling; Li, Yi-Fan; Chan, Hing Man

2017-06-01

Short-chain chlorinated paraffins (SCCPs) are widely used chemicals in household products and might cause adverse human health effects. However, limited information is available on the occurrence of SCCPs in indoor environments and their exposure risks on humans. In this study the concentrations, profiles and human exposure of SCCPs in indoor dust from five different indoor environments, including commercial stores, residential apartments, dormitories, offices and laboratories were characterized. The SCCPs levels ranged from 10.1 to 173.0 μg/g, with the median and mean concentration of 47.2 and 53.6 μg/g, respectively. No significant difference was found on concentrations among the five microenvironments. The most abundant compounds in indoor dust samples were homologues of C 13 group, Cl 7 group and N 20 (N is the total number of C and Cl) group. In the five microenvironments, commercial stores were more frequently exposed to shorter carbon chained and higher chlorinated homologues. Three potential sources for SCCPs were identified by the multiple linear regression of factor score model and correspondence analysis. The major sources of SCCPs in indoor dust were technical mixtures of CP-42 (42% chlorine, w/w) and CP-52 b (52% chlorine, w/w). The total daily exposure doses and hazard quotients (HQ) were calculated by the human exposure models, and they were all below the reference doses and threshold values, respectively. Monte Carlo simulation was applied to predict the human exposure risk of SCCPs. Infants and toddlers were at risk of SCCPs based on predicted HQ values, which were exceeded the threshold for neoplastic effects in the worst case. Our results on the occurrences, sources and human exposures of SCCPs will be useful to provide a better understanding of SCCPs behaviors in indoor environment in China, and to support environmental risk evaluation and regulation of SCCPs in the world. Copyright © 2017. Published by Elsevier Ltd.

Occupational Electromagnetic Field Exposures Associated with Sleep Quality: A Cross-Sectional Study

PubMed Central

Liu, Hui; Chen, Guangdi; Pan, Yifeng; Chen, Zexin; Jin, Wen; Sun, Chuan; Chen, Chunjing; Dong, Xuanjun; Chen, Kun; Xu, Zhengping; Zhang, Shanchun; Yu, Yunxian

2014-01-01

Background Exposure to electromagnetic field (EMF) emitted by mobile phone and other machineries concerns half the world’s population and raises the problem of their impact on human health. The present study aims to explore the effects of electromagnetic field exposures on sleep quality and sleep duration among workers from electric power plant. Methods A cross-sectional study was conducted in an electric power plant of Zhejiang Province, China. A total of 854 participants were included in the final analysis. The detailed information of participants was obtained by trained investigators using a structured questionnaire, which including socio-demographic characteristics, lifestyle variables, sleep variables and electromagnetic exposures. Physical examination and venous blood collection were also carried out for every study subject. Results After grouping daily occupational electromagnetic exposure into three categories, subjects with long daily exposure time had a significantly higher risk of poor sleep quality in comparison to those with short daily exposure time. The adjusted odds ratios were 1.68 (95%CI: 1.18, 2.39) and 1.57 (95%CI: 1.10, 2.24) across tertiles. Additionally, among the subjects with long-term occupational exposure, the longer daily occupational exposure time apparently increased the risk of poor sleep quality (OR (95%CI): 2.12 (1.23∼3.66) in the second tertile; 1.83 (1.07∼3.15) in the third tertile). There was no significant association of long-term occupational exposure duration, monthly electric fee or years of mobile-phone use with sleep quality or sleep duration. Conclusions The findings showed that daily occupational EMF exposure was positively associated with poor sleep quality. It implies EMF exposure may damage human sleep quality rather than sleep duration. PMID:25340654

Maternal occupational cadmium exposure and nonsyndromic orofacial clefts.

PubMed

Suhl, Jonathan; Romitti, Paul A; Cao, Yanyan; Rocheleau, Carissa M; Burns, Trudy L; Conway, Kristin; Rajaraman, Preetha; Agopian, A J; Stewart, Patricia

2018-04-17

Cigarette smoking is a well-studied risk factor for orofacial clefts (OFCs). Little is known about which constituents in cigarette smoke contribute to this teratogenicity in humans. One constituent, cadmium, has been associated with OFCs in animal studies; in humans, the role of maternal cadmium exposure on OFCs, independent of cigarette smoke, is unclear. In particular, the relation between maternal occupational cadmium exposure and OFCs is largely unexplored. Using data from a large, population-based case-control study, we compared expert rater assessed maternal occupational cadmium exposure from self-reported occupational histories during the period 1 month before through 3 months after conception between OFC cases (n = 1,185) and unaffected controls (n = 2,832). Multivariable logistic regression analyses were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals for any (yes/no) and cumulative (no, low, high exposure) occupational cadmium exposures and all OFCs, cleft lip ± cleft palate (CL/P) and cleft palate (CP). Overall, 45 mothers (cases = 13, controls = 32) were rated as having occupational cadmium exposure. Comparing all OFCs to controls, we observed inverse, nonsignificant aORs for any or low exposure, and positive, nonsignificant aORs for high exposure. Where data were available, aORs for CL/P and CP tended to parallel those for all OFCs. To our knowledge, this is the first study to specifically examine maternal occupational cadmium exposure and OFCs, using expert rater exposure assessment. The small numbers of exposed mothers observed, however, led to imprecise estimates. Continued research using more detailed occupational exposure assessment and increased sample sizes is recommended. © 2018 Wiley Periodicals, Inc.

Human Exposure Modeling - Databases to Support Exposure Modeling

EPA Pesticide Factsheets

Human exposure modeling relates pollutant concentrations in the larger environmental media to pollutant concentrations in the immediate exposure media. The models described here are available on other EPA websites.

Meet EPA Chemist Linda Sheldon, Ph.D.

EPA Pesticide Factsheets

Environmental chemist Linda Sheldon, Ph.D, is the Associate Director for Human Heath in the National Exposure Research Laboratory. She studies environmental exposure, particularly focusing on children's environments and their contact with chemicals.

Environmental Influences on Reproductive Health, the Importance of Chemical Exposures

PubMed Central

Wang, Aolin; Padula, Amy; Sirota, Marina; Woodruff, Tracey J.

2016-01-01

Unstructured Abstract Chemical exposures during pregnancy can have a profound and life-long impact on human health. Due to the omnipresence of chemicals in our daily life, there is continuous contact with chemicals in food, water, air and consumer products. Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chemicals. In this review, we provide a summary of current data on maternal and fetal exposure as well as health consequences from these exposures. We review several chemical classes including polychlorinated biphenyls (PCBs), perfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), phenols, phthalates, pesticides, and metals. Additionally, we discuss environmental disparities and vulnerable populations, and future research directions. We conclude by providing some recommendations for prevention of chemical exposure and its adverse reproductive health consequences. PMID:27513554

Overview of aerosolized Florida red tide toxins: exposures and effects.

PubMed

Fleming, Lora E; Backer, Lorraine C; Baden, Daniel G

2005-05-01

Florida red tide is caused by Karenia brevis, a dinoflagellate that periodically blooms, releasing its potent neurotoxin, brevetoxin, into the surrounding waters and air along the coast of the Gulf of Mexico. Exposure to Florida red tide toxins has been associated with adverse human health effects and massive fish and marine mammal deaths. The articles in this mini-monograph describe the ongoing interdisciplinary and interagency research program that characterizes the exposures and health effects of aerosolized Florida red tide toxins (brevetoxins). The interdisciplinary research program uses animal models and laboratory studies to develop hypotheses and apply these findings to in situ human exposures. Our ultimate goal is to develop appropriate prevention measures and medical interventions to mitigate or prevent adverse health effects from exposure to complex mixtures of aerosolized red tide toxins.

Continual exposure to cigarette smoke extracts induces tumor-like transformation of human nontumor bronchial epithelial cells in a microfluidic chip.

PubMed

Li, Encheng; Xu, Zhiyun; Liu, Fen; Wang, Huiling; Wen, Jiabin; Shao, Shujuan; Zhang, Lichuan; Wang, Lei; Liu, Chong; Lu, Jianxin; Wang, Wenxin; Gao, Zhancheng; Wang, Qi

2014-08-01

Heavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear. In our study, human tumor-adjacent bronchial epithelial cells were obtained from 10 cases with smoking-related chronic obstructive pulmonary disease and lung squamous carcinoma and cultured in an established microfluidic chip for continual exposure to cigarette smoke extracts (CSE) to investigate the potential tumor-like transformation and mechanisms. The integrated microfluidic chip included upstream concentration gradient generator and downstream cell culture chambers supplied by flowing medium containing different concentrations of CSE. Our results showed that continual exposure to low doses of CSE promoted cell proliferation whereas to high doses of CSE triggered cell apoptosis. Continual exposure to CSE promoted reactive oxygen species production in human epithelial cells in a dose-dependent manner. More importantly, continual exposure to low dose of CSE promoted the epithelial-to-mesenchymal transition process and anchorage-independent growth, and increased chromosome instability in bronchial epithelial cells, accompanied by activating the GRP78, NF-κB, and PI3K pathways. The established microfluidic chip is suitable for primary culture of human tumor-adjacent bronchial epithelial cells to investigate the malignant transformation. Continual exposure to low doses of CSE promoted tumor-like transformation of human nontumor bronchial epithelial cells by inducing reactive oxygen species production and activating the relevant signaling.

Effects of Pulsed and CW (Continuous Wave) 2450 MHz Radiation on Transformation and Chromosomes of Human Lymphocytes in vitro

DTIC Science & Technology

1989-12-15

conditions of these experiments. In order to provide reliable quantitative data on exposure, a system with automated dosimetry was developed, and tested...exposure system and dosimetry, and (2) studies on lymphocyte cultures, and (3) conclusions. EXPOSURE SYSTEM AND DOSIMETRY Description of the Exposure... System The experiments planned in this project necessitated the design and assembly of an exposure system that would meet several engineering

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.

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

Gold, nickel and copper mining and processing.

PubMed

Lightfoot, Nancy E; Pacey, Michael A; Darling, Shelley

2010-01-01

Ore mining occurs in all Canadian provinces and territories except Prince Edward Island. Ores include bauxite, copper, gold, iron, lead and zinc. Workers in metal mining and processing are exposed, not only to the metal of interest, but also to various other substances prevalent in the industry, such as diesel emissions, oil mists, blasting agents, silica, radon, and arsenic. This chapter examines cancer risk related to the mining of gold, nickel and copper. The human carcinogenicity of nickel depends upon the species of nickel, its concentration and the route of exposure. Exposure to nickel or nickel compounds via routes other than inhalation has not been shown to increase cancer risk in humans. As such, cancer sites of concern include the lung, and the nasal sinus. Evidence comes from studies of nickel refinery and leaching, calcining, and sintering workers in the early half of the 20th century. There appears to be little or no detectable risk in most sectors of the nickel industry at current exposure levels. The general population risk from the extremely small concentrations detectable in ambient air are negligible. Nevertheless, animal carcinogenesis studies, studies of nickel carcinogenesis mechanisms, and epidemiological studies with quantitative exposure assessment of various nickel species would enhance our understanding of human health risks associated with nickel. Definitive conclusions linking cancer to exposures in gold and copper mining and processing are not possible at this time. The available results appear to demand additional study of a variety of potential occupational and non-occupational risk factors.

Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen.

PubMed

Thompson, Aaron M S; Zanobetti, Antonella; Silverman, Frances; Schwartz, Joel; Coull, Brent; Urch, Bruce; Speck, Mary; Brook, Jeffrey R; Manno, Michael; Gold, Diane R

2010-01-01

Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardio-vascular disease. We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter

Electric and magnetic fields and tumor progression. Final report

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

Keng, P.C.; Grota, L.J.; Michaelson, S.

This laboratory study has rigorously investigated two previously reported biological effects of 60-Hz electric and magnetic fields. The first effect involves nighttime suppression of melatonin synthesis in the pineal glands of rats exposed to high electric fields. The second concerns the increase in colony forming ability of human colon cancer cells exposed to 1.4-G magnetic fields. Neither effect was detected in the present study. A series of published laboratory studies on rats reported that 60-Hz electric fields at various field levels up to 130 kV/m suppress the nighttime synthesis of melatonin, a hormone produced by the pineal gland. Since melatoninmore » is known to modulate the immune system and may inhibit cancer cell activity, changes in physiological levels of melatonin may have significant health consequences. In the repeat experiments, field exposure did not alter nighttime levels of melatonin or enzyme activities in the pineal gland. A small but statistically significant reduction of about 20% in serum melatonin was seen in exposed animals. Pineal melatonin was also unaffected by the presence of red light as a cofactor with field exposure or by time-shifting the daily field exposure period. Another study reported that 60-Hz magnetic fields can affect the colony forming ability of human cancer cells after exposure in a culture medium. In the repeat experiments, field exposure did not alter the colony forming ability of human Colo 205 cells in two different cell concentrations at plating or in two different incubation conditions. Field exposure also did not affect cell cycling in any of the four cell lines tested.« less

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.

A proposed framework for assessing risk from less-than-lifetime exposures to carcinogens.

PubMed

Felter, Susan P; Conolly, Rory B; Bercu, Joel P; Bolger, P Michael; Boobis, Alan R; Bos, Peter M J; Carthew, Philip; Doerrer, Nancy G; Goodman, Jay I; Harrouk, Wafa A; Kirkland, David J; Lau, Serrine S; Llewellyn, G Craig; Preston, R Julian; Schoeny, Rita; Schnatter, A Robert; Tritscher, Angelika; van Velsen, Frans; Williams, Gary M

2011-07-01

Quantitative methods for estimation of cancer risk have been developed for daily, lifetime human exposures. There are a variety of studies or methodologies available to address less-than-lifetime exposures. However, a common framework for evaluating risk from less-than-lifetime exposures (including short-term and/or intermittent exposures) does not exist, which could result in inconsistencies in risk assessment practice. To address this risk assessment need, a committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute conducted a multisector workshop in late 2009 to discuss available literature, different methodologies, and a proposed framework. The proposed framework provides a decision tree and guidance for cancer risk assessments for less-than-lifetime exposures based on current knowledge of mode of action and dose-response. Available data from rodent studies and epidemiological studies involving less-than-lifetime exposures are considered, in addition to statistical approaches described in the literature for evaluating the impact of changing the dose rate and exposure duration for exposure to carcinogens. The decision tree also provides for scenarios in which an assumption of potential carcinogenicity is appropriate (e.g., based on structural alerts or genotoxicity data), but bioassay or other data are lacking from which a chemical-specific cancer potency can be determined. This paper presents an overview of the rationale for the workshop, reviews historical background, describes the proposed framework for assessing less-than-lifetime exposures to potential human carcinogens, and suggests next steps.

American association of poison control centers database characterization of human tilmicosin exposures, 2001-2005.

PubMed

Oakes, Jennifer; Seifert, Steven

2008-12-01

Tilmicosin is a veterinary antibiotic with significant human toxicity at doses commonly used in animals, but the parenteral dose-response relationship has not been well characterized. Human exposures to tilmicosin in the database of the American Association of Poison Control Centers (AAPCC) from 2001 to 2005 were analyzed for demographic associations, exposure dose, clinical effects and outcomes. Over the 5-year period, there were 1,291 single-substance human exposures to tilmicosin. The mean age was 39.1 years, and 80% were male. By route there were 768 (54%) parenteral exposures. Patients with parenteral exposures had a significantly increased likelihood of being seen at a healthcare facility, admission, and admission to an ICU. With nonparenteral exposure, most had no clinical effects or minor effects, and there were no major effects or deaths. With parenteral exposure, moderate effects occurred in 46 (6%), major effects in 2 (0.3%) and there were 4 (0.5%) deaths, two of which were suicides. A dose-response relationship could be demonstrated. Clinical effect durations of up to a week occurred at even the lowest dose range. Over 250 cases of human tilmicosin exposure are reported to poison centers per year and over 150 of those are parenteral. Most exposures produce no or minor effects, but fatalities have occurred with parenteral exposure. The case fatality rate in parenteral exposures is 10 times the case fatality rate for all human exposures in the AAPCC database. Significant adverse and prolonged effects are reported at parenteral doses > 0.5 mL, suggesting that all parenteral exposures should be referred for healthcare facility evaluation.

Human exposures to tilmicosin reported to poison centres, Texas, 1998-2003.

PubMed

Forrester, Mathias B

2005-05-01

Tilmicosin, or 20-deoxo-20-(3,5-dimethylpiperidin-1-yl)-desmycosin, is a macrolide antibiotic primarily utilized in livestock. This study examined 46 human exposure calls involving tilmicosin received by Texas poison centres during 1998-2003. The majority (91%) of the calls were received from northern and central Texas. All of the cases were unintentional exposures. The most frequent route of exposure was parenteral (48%). The majority of the patients were males (80%) and adults (84%). Only 46% of the patients were managed outside of health care facilities. Some sort of adverse medical outcome was reported in 93% of parenteral exposures and 54% of other-route exposures. However, only 21% of parenteral exposures and 15% of other-route exposures involved medical outcomes that were judged to be moderate or worse. No deaths were reported. The most frequently reported clinical effects among parenteral cases were dermal (79%), while only 9% of other-route exposures had dermal effects. Cardiovascular clinical effects were observed in a single case of parenteral exposure and a single case of other-route exposure. Although the majority of cases were managed with the assistance of health care facilities, the medical outcomes were usually not serious. Outcome depended on the route of exposure.

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

Organochlorine pesticides in tree bark and human hair in Yunnan Province, China: Concentrations, distributions and exposure pathway.

PubMed

Yuan, Haodong; Jin, Jun; Bai, Yao; Li, Qiuxu; Wang, Ying; Wang, Qinghua

2017-02-15

The concentrations and distributions of organochlorine pesticides (OCPs) in West China were investigated and internal and external exposure of humans to OCPs were assessed by analyzing samples of human hair and tree bark collected in Kaiyuan, in Yunnan Province, China. Dichlorodiphenyltrichloroethane and its metabolites (collectively called DDTs), hexachlorocyclohexanes (HCHs), and hexachlorobenzene (HCB) were the dominant OCPs in the human hair and tree bark samples. The mean total DDT, total HCH, and HCB concentrations in the tree bark samples were 298pg/g dry weight (dw), 100pg/g dw, and 183pg/g dw, respectively, and the mean total DDT, total HCH, and HCB concentrations in the hair samples were 2850pg/g dw, 348pg/g dw, and 1026pg/g dw, respectively. The results indicated that relatively new DDT and lindane inputs have occurred in the study area. DDT and lindane may have been released in products that are used locally. The HCB in the environment in the study area is mainly supplied by long-range atmospheric transport. External exposure was found to be the main factor controlling the p,p'-DDT, γ-HCH, and HCB concentrations in human hair, whereas p,p'-DDE and β-HCH were found to be mainly controlled by internal exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of maternal steroids during pregnancy.

PubMed

Reynolds, Rebecca M

2016-12-01

Increased fetal exposure to glucocorticoids is a key mechanism thought to underlie the early life programming of later life disease. There is substantial experimental data in animal models in support of this hypothesis. Emerging evidence suggests glucocorticoid programming may also occur in humans with some studies now linking maternal endogenous cortisol levels with size at birth and gestation at delivery. The dramatic changes to the maternal hypothalamic-pituitary-adrenal axis during pregnancy mean that large-scale studies in humans are challenging to conduct. One of the key regulators of fetal glucocorticoid exposure is the activity of placental "barrier" enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) which converts active cortisol to inactive cortisone. In animal models, this enzyme is down-regulated by various influences including maternal malnutrition, inflammation or stress but it is not known whether this is a major factor in regulation of human fetal glucocorticoid exposure. More studies are needed to understand the mechanisms whereby altered fetal glucocorticoid exposure may alter fetal growth trajectories and whether changes in the maternal hypothalamic-pituitary-adrenal axis in pregnancy could be suitable as a biomarker to identify those pregnancies most at risk. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

Tire tread wear particles in ambient air--a previously unknown source of human exposure to the biocide 2-mercaptobenzothiazole.

PubMed

Avagyan, Rozanna; Sadiktsis, Ioannis; Bergvall, Christoffer; Westerholm, Roger

2014-10-01

Urban particulate matter (PM), asphalt, and tire samples were investigated for their content of benzothiazole and benzothiazole derivates. The purpose of this study was to examine whether wear particles, i.e., tire tread wear or road surface wear, could contribute to atmospheric concentrations of benzothiazole derivatives. Airborne particulate matter (PM10) sampled at a busy street in Stockholm, Sweden, contained on average 17 pg/m(3) benzothiazole and 64 pg/m(3) 2-mercaptobenzothiazole, and the total suspended particulate-associated benzothiazole and 2-mercaptobenzothiazole concentrations were 199 and 591 pg/m(3), respectively. This indicates that tire tread wear may be a major source of these benzothiazoles to urban air PM in Stockholm. Furthermore, 2-mercaptobenzothiazole was determined in urban air particulates for the first time in this study, and its presence in inhalable PM10 implies that the human exposure to this biocide is underestimated. This calls for a revision of the risk assessments of 2-mercaptobenzothiazole exposure to humans which currently is limited to occupational exposure.

Chemical Risk Assessment: Traditional vs Public Health Perspectives

PubMed Central

Axelrad, Daniel A.; Bahadori, Tina; Bussard, David; Cascio, Wayne E.; Deener, Kacee; Dix, David; Thomas, Russell S.; Kavlock, Robert J.; Burke, Thomas A.

2017-01-01

Preventing adverse health effects of environmental chemical exposure is fundamental to protecting individual and public health. When done efficiently and properly, chemical risk assessment enables risk management actions that minimize the incidence and effects of environmentally induced diseases related to chemical exposure. However, traditional chemical risk assessment is faced with multiple challenges with respect to predicting and preventing disease in human populations, and epidemiological studies increasingly report observations of adverse health effects at exposure levels predicted from animal studies to be safe for humans. This discordance reinforces concerns about the adequacy of contemporary risk assessment practices for protecting public health. It is becoming clear that to protect public health more effectively, future risk assessments will need to use the full range of available data, draw on innovative methods to integrate diverse data streams, and consider health endpoints that also reflect the range of subtle effects and morbidities observed in human populations. Considering these factors, there is a need to reframe chemical risk assessment to be more clearly aligned with the public health goal of minimizing environmental exposures associated with disease. PMID:28520487

Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs).

PubMed

Sharma, Monita; Nikota, Jake; Halappanavar, Sabina; Castranova, Vincent; Rothen-Rutishauser, Barbara; Clippinger, Amy J

2016-07-01

The increased production and use of multi-walled carbon nanotubes (MWCNTs) in a diverse array of consumer, medical, and industrial applications have raised concerns about potential human exposure to these materials in the workplace and ambient environments. Inhalation is a primary route of exposure to MWCNTs, and the existing data indicate that they are potentially hazardous to human health. While a 90-day rodent inhalation test (e.g., OECD Test No. 413: subchronic inhalation toxicity: 90-day study or EPA Health Effects Test Guidelines OPPTS 870.3465 90-day inhalation toxicity) is recommended by the U.S. Environmental Protection Agency Office of Pollution Prevention and Toxics for MWCNTs (and other CNTs) if they are to be commercially produced (Godwin et al. in ACS Nano 9:3409-3417, 2015), this test is time and cost-intensive and subject to scientific and ethical concerns. As a result, there has been much interest in transitioning away from studies on animals and moving toward human-based in vitro and in silico models. However, given the multiple mechanisms of toxicity associated with subchronic exposure to inhaled MWCNTs, a battery of non-animal tests will likely be needed to evaluate the key endpoints assessed by the 90-day rodent study. Pulmonary fibrosis is an important adverse outcome related to inhalation exposure to MWCNTs and one that the non-animal approach should be able to assess. This review summarizes the state-of-the-science regarding in vivo and in vitro toxicological methods for predicting MWCNT-induced pulmonary fibrosis.

Human responses to bright light of different durations.

PubMed

Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

2012-07-01

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

Developmental Neurotoxicity of Inhaled Ambient Ultrafine Particle Air Pollution: Parallels with Neuropathological and Behavioral Features of Autism and Other Neurodevelopmental Disorders

PubMed Central

Allen, J. L.; Oberdorster, G.; Morris-Schafer, K.; Wong, C.; Klocke, C.; Sobolewski, M.; Conrad, K.; Mayer-Proschel, M.; Cory-Slechta, D. A.

2016-01-01

Accumulating evidence from both human and animal studies show that brain is a target of air pollution. Multiple epidemiological studies have now linked components of air pollution to diagnosis of autism spectrum disorder (ASD), a linkage with plausibility based on the shared mechanisms of inflammation. Additional plausibility appears to be provided by findings from our studies in mice of exposures from postnatal day (PND) 4-7 and 10-13 (human 3rd trimester equivalent), to concentrated ambient ultrafine (UFP) particles, considered the most reactive component of air pollution, at levels consistent with high traffic areas of major U.S. cities and thus highly relevant to human exposures. These exposures, occurring during a period of marked neuro- and gliogenesis, unexpectedly produced a pattern of developmental neurotoxicity notably similar to multiple hypothesized mechanistic underpinnings of ASD, including its greater impact in males. UFP exposures induced inflammation/microglial activation, reductions in size of the corpus callosum (CC) and associated hypomyelination, aberrant white matter development and/or structural integrity with ventriculomegaly (VM), elevated glutamate and excitatory/inhibitory imbalance, increased amygdala astrocytic activation, and repetitive and impulsive behaviors. Collectively, these findings suggest the human 3rd trimester equivalent as a period of potential vulnerability to neurodevelopmental toxicity to UFP, particularly in males, and point to the possibility that UFP air pollution exposure during periods of rapid neuro- and gliogenesis may be a risk factor not only for ASD, but also for other neurodevelopmental disorders that share features with ASD, such as schizophrenia, attention deficit disorder, and periventricular leukomalacia. PMID:26721665

Inland Transport of Aerosolized Florida Red Tide Toxins.

PubMed

Kirkpatrick, Barbara; Pierce, Richard; Cheng, Yung Sung; Henry, Michael S; Blum, Patricia; Osborn, Shannon; Nierenberg, Kate; Pederson, Bradley A; Fleming, Lora E; Reich, Andrew; Naar, Jerome; Kirkpatrick, Gary; Backer, Lorraine C; Baden, Daniel

2010-02-01

Florida red tides, an annual event off the west coast of Florida, are caused by the toxic dinoflagellate, Karenia brevis. K. brevis produces a suite of potent neurotoxins, brevetoxins, which kill fish, sea birds, and marine mammals, as well as sickening humans who consume contaminated shellfish. These toxins become part of the marine aerosol, and can also be inhaled by humans and other animals. Recent studies have demonstrated a significant increase in symptoms and decrease lung function in asthmatics after only one hour of beach exposure during an onshore Florida red tide bloom.This study constructed a transect line placing high volume air samplers to measure brevetoxins at sites beginning at the beach, moving approximately 6.4 km inland. One non-exposure and 2 exposure studies, each of 5 days duration, were conducted. No toxins were measured in the air during the non-exposure period. During the 2 exposure periods, the amount of brevetoxins varied considerably by site and by date. Nevertheless, brevetoxins were measured at least 4.2 kilometers from the beach and/or 1.6 km from the coastal shoreline. Therefore, populations sensitive to brevetoxins (such as asthmatics) need to know that leaving the beach may not discontinue their environmental exposure to brevetoxin aerosols.

Human health risk assessment of chloroxylenol in liquid hand soap and dishwashing soap used by consumers and health-care professionals.

PubMed

Yost, Lisa J; Rodricks, Joseph D; Turnbull, Duncan; DeLeo, Paul C; Nash, J Frank; Quiñones-Rivera, Antonio; Carlson, Pete A

2016-10-01

A quantitative human risk assessment of chloroxylenol was conducted for liquid hand and dishwashing soap products used by consumers and health-care workers. The toxicological data for chloroxylenol indicate lack of genotoxicity, no evidence of carcinogenicity, and minimal systemic toxicity. No observed adverse effect levels (NOAEL) were established from chronic toxicity studies, specifically a carcinogenicity study that found no cancer excess (18 mg/kg-day) and studies of developmental and reproductive toxicity (100 mg/kg-day). Exposure to chloroxylenol for adults and children was estimated for two types of rinse-off cleaning products, one liquid hand soap, and two dishwashing products. The identified NOAELs were used together with exposure estimates to derive margin of exposure (MOE) estimates for chloroxylenol (i.e., estimates of exposure over NOAELs). These estimates were designed with conservative assumptions and likely overestimate exposure and risk (i.e., highest frequency, 100% dermal penetration). The resulting MOEs ranged from 178 to over 100, 000, 000 indicating negligibly small potential for harm related to consumer or health-care worker exposure to chloroxylenol in liquid soaps used in dish washing and hand washing. Copyright © 2016 Elsevier Inc. All rights reserved.

Human biomonitoring of chromium and nickel from an experimental exposure to manual metal arc welding fumes of low and high alloyed steel.

PubMed

Bertram, Jens; Brand, Peter; Schettgen, Thomas; Lenz, Klaus; Purrio, Ellwyn; Reisgen, Uwe; Kraus, Thomas

2015-05-01

The uptake and elimination of metals from welding fumes is currently not fully understood. In the Aachen Workplace Simulation Laboratory (AWSL) it is possible to investigate the impact of welding fumes on human subjects under controlled exposure conditions. In this study, the uptake and elimination of chromium or chromium (VI) respectively as well as nickel was studied in subjects after exposure to the emissions of a manual metal arc welding process using low or high alloyed steel. In this present study 12 healthy male non-smokers, who never worked as welders before, were exposed for 6h to welding fumes of a manual metal arc welding process. In a three-fold crossover study design, subjects were exposed in randomized order to either clean air, emissions from welding low alloyed steel, and emissions from welding high alloyed steel. Particle mass concentration of the exposure aerosol was 2.5mg m(-3). The content of chromium and nickel in the air was determined by analysing air filter samples on a high emission scenario. Urine analysis for chromium and nickel was performed before and after exposure using methods of human biomonitoring. There were significantly elevated chromium levels after exposure to welding fumes from high alloyed steel compared to urinary chromium levels before exposure to high alloyed welding fumes, as well as compared to the other exposure scenarios. The mean values increased from 0.27 µg l(-1) to 18.62 µg l(-1). The results were in good agreement with already existing correlations between external and internal exposure (German exposure equivalent for carcinogenic working materials EKA). The variability of urinary chromium levels was high. For urinary nickel no significant changes could be detected at all. Six-hour exposure to 2.5mg m(-3) high alloyed manual metal arc welding fumes lead to elevated urinary chromium levels far higher (7.11-34.16 µg l(-1)) than the German biological exposure reference value (BAR) of 0.6 µg l(-1) directly after exposure. On the other hand mean urinary nickel concentrations slightly increased, but did not exceed background levels due to lower bioavailability. We could underline with our single exposure experiment that a welding work related chromium exposure can be measured immediately after the work shift, while the same is not possible for nickel exposure due to lower nickel bioavailability. The data provide useful information for real occupational welding work places. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Prioritizing Chemicals and Data Requirements for Screening-Level Exposure and Risk Assessment

PubMed Central

Brown, Trevor N.; Wania, Frank; Breivik, Knut; McLachlan, Michael S.

2012-01-01

Background: Scientists and regulatory agencies strive to identify chemicals that may cause harmful effects to humans and the environment; however, prioritization is challenging because of the large number of chemicals requiring evaluation and limited data and resources. Objectives: We aimed to prioritize chemicals for exposure and exposure potential and obtain a quantitative perspective on research needs to better address uncertainty in screening assessments. Methods: We used a multimedia mass balance model to prioritize > 12,000 organic chemicals using four far-field human exposure metrics. The propagation of variance (uncertainty) in key chemical information used as model input for calculating exposure metrics was quantified. Results: Modeled human concentrations and intake rates span approximately 17 and 15 orders of magnitude, respectively. Estimates of exposure potential using human concentrations and a unit emission rate span approximately 13 orders of magnitude, and intake fractions span 7 orders of magnitude. The actual chemical emission rate contributes the greatest variance (uncertainty) in exposure estimates. The human biotransformation half-life is the second greatest source of uncertainty in estimated concentrations. In general, biotransformation and biodegradation half-lives are greater sources of uncertainty in modeled exposure and exposure potential than chemical partition coefficients. Conclusions: Mechanistic exposure modeling is suitable for screening and prioritizing large numbers of chemicals. By including uncertainty analysis and uncertainty in chemical information in the exposure estimates, these methods can help identify and address the important sources of uncertainty in human exposure and risk assessment in a systematic manner. PMID:23008278

The biology of human psychosexual differentiation.

PubMed

Gooren, Louis

2006-11-01

Most attempts to identify biological underpinnings of gender identity and sexual orientation in humans have investigated effects of sex steroids, so pivotal in the differentiation of the genitalia, showing strong parallels between animals and the human. The information on humans is derived from the so-called 'experiments of nature', clinical entities with a lesser-than-normal androgen exposure in XY subjects and a higher than normal androgen exposure in XX subjects. Prenatal androgenization appears to predispose to a male gender identity development, but apparently not decisively since 40-50% of 46,XY intersexed children with a history of prenatal androgen exposure do not develop a male gender identity. Obviously, male-to-female transsexuals, with a normal androgen exposure prenatally (there is no serious evidence to the contrary) develop a female gender identity, through unknown biological mechanisms apparently overriding the effects of prenatal androgens. The latest studies in 46, XX subjects exposed to prenatal androgens show that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior but does not lead to gender confusion/dysphoria. The example of female-to-male transsexuals, without evidence of prenatal androgen exposure, indicates that a male gender identity can develop without a significant androgen stimulus. So we are far away from any comprehensive understanding of hormonal imprinting on gender identity formation. Brain studies in homosexuals have not held up in replication studies or are in need of replication in transsexuals. Genetic studies and the fraternal birth order hypothesis provide indications of familial clustering of homosexuality but in many homosexuals these genetic patterns cannot be identified. The biological explanations advanced for the birth order hypothesis lack any experimental support.