Modeling approaches for characterizing and evaluating environmental exposure to engineered nanomaterials in support of risk-based decision making.

PubMed

Hendren, Christine Ogilvie; Lowry, Michael; Grieger, Khara D; Money, Eric S; Johnston, John M; Wiesner, Mark R; Beaulieu, Stephen M

2013-02-05

As the use of engineered nanomaterials becomes more prevalent, the likelihood of unintended exposure to these materials also increases. Given the current scarcity of experimental data regarding fate, transport, and bioavailability, determining potential environmental exposure to these materials requires an in depth analysis of modeling techniques that can be used in both the near- and long-term. Here, we provide a critical review of traditional and emerging exposure modeling approaches to highlight the challenges that scientists and decision-makers face when developing environmental exposure and risk assessments for nanomaterials. We find that accounting for nanospecific properties, overcoming data gaps, realizing model limitations, and handling uncertainty are key to developing informative and reliable environmental exposure and risk assessments for engineered nanomaterials. We find methods suited to recognizing and addressing significant uncertainty to be most appropriate for near-term environmental exposure modeling, given the current state of information and the current insufficiency of established deterministic models to address environmental exposure to engineered nanomaterials.

A COMPARATIVE INVESTIGATION OF THE INFLUENCE OF DERMAL APPENDAGES (HAIR FOLLICLES) ON THE PERCUTANEOUS ABSORPTION OF ORGANOPHOSPHORUS (OP) INSECTICIDES USING QSAR AND PBPK/PD MODELS FOR HUMAN RISK ASSESSMENT

EPA Science Inventory

The successful use of the Exposure Related Dose Estimating Model (ERDEM) for assessment of dermal exposure of humans to OP pesticides requires the input of representative and comparable input parameters. In the specific case of dermal exposure, regional anatomical variation in...

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 ...

Exposure information in environmental health research: Current opportunities and future directions for particulate matter, ozone, and toxic air pollutants

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

McKone, Thomas E.; Ryan, P. Barry; Ozkaynak, Haluk

2007-02-01

Understanding and quantifying outdoor and indoor sources of human exposure are essential but often not adequately addressed in health-effects studies for air pollution. Air pollution epidemiology, risk assessment, health tracking and accountability assessments are examples of health-effects studies that require but often lack adequate exposure information. Recent advances in exposure modeling along with better information on time-activity and exposure factors data provide us with unique opportunities to improve the assignment of exposures for both future and ongoing studies linking air pollution to health impacts. In September 2006, scientists from the US Environmental Protection Agency (EPA) and the Centers for Diseasemore » Control and Prevention (CDC) along with scientists from the academic community and state health departments convened a symposium on air pollution exposure and health in order to identify, evaluate, and improve current approaches for linking air pollution exposures to disease. This manuscript presents the key issues, challenges and recommendations identified by the exposure working group, who used cases studies of particulate matter, ozone, and toxic air pollutant exposure to evaluate health-effects for air pollution. One of the over-arching lessons of this workshop is that obtaining better exposure information for these different health-effects studies requires both goal-setting for what is needed and mapping out the transition pathway from current capabilities to meeting these goals. Meeting our long-term goals requires definition of incremental steps that provide useful information for the interim and move us toward our long-term goals. Another over-arching theme among the three different pollutants and the different health study approaches is the need for integration among alternate exposure assessment approaches. For example, different groups may advocate exposure indicators, biomonitoring, mapping methods (GIS), modeling, environmental media monitoring, and/or personal exposure modeling. However, emerging research reveals that the greatest progress comes from integration among two or more of these efforts.« less

MODELING EXPOSURES TO PESTICIDES APPROACHES AND MODELING NEEDS

EPA Science Inventory

Estimation of exposures of children to pesticides requires careful consideration of sources and concentrations of pesticides that may be present in different environmental media and in foods and beverages consumed by children, as well as the different routes and pathways of exp...

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

PubMed Central

Martin, Ciara A.; Barajas, Angel; Lawless, George; Lawal, Hakeem O.; Assani, Khadij; Lumintang, Yosephine P.; Nunez, Vanessa; Krantz, David E.

2014-01-01

The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination. PMID:25160001

20171015 - Predicting Exposure Pathways with Machine Learning (ISES)

EPA Science Inventory

Prioritizing the risk posed to human health from the thousands of chemicals in the environment requires tools that can estimate exposure rates from limited information. High throughput models exist to make predictions of exposure via specific, important pathways such as residenti...

A changing climate: impacts on human exposures to O3 using an integrated modeling methodology

EPA Science Inventory

Predicting the impacts of changing climate on human exposure to air pollution requires future scenarios that account for changes in ambient pollutant concentrations, population sizes and distributions, and housing stocks. An integrated methodology to model changes in human exposu...

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.

MODELING INHALATION AND MULTIMEDIA MULTIPATHWAY HUMAN EXPOSURES TO ENVIRONMENTAL POLLUTANTS

EPA Science Inventory

Estimation of exposures of children and adults to air toxics or multimedia pollutants require careful consideration of sources and concentrations of pollutants that may be present in different media, as well as various routes and pathways of exposures associated with age-specif...

DATA REQUIREMENTS FOR ASSESSING CHILDREN'S EXPOSURE TO PESTICIDES

EPA Science Inventory

Several multimedia, multipathway exposure monitoring studies are currently being planned within EPA/NERL. The overall objectives of these studies are (1) to develop the data and models that can be used to estimate exposure and dose for young children to pesticides and (2) to i...

Swimmer illness associated with marine water exposure and water quality indicators: impact of widely used assumptions

EPA Science Inventory

Studies of health risks associated with recreational water exposure require investigators to make choices about water quality indicator averaging techniques, exposure definitions, follow-up periods, and model specifications; but, investigators seldom describe the impact of these ...

Underwater Sound Propagation Modeling Methods for Predicting Marine Animal Exposure.

PubMed

Hamm, Craig A; McCammon, Diana F; Taillefer, Martin L

2016-01-01

The offshore exploration and production (E&P) industry requires comprehensive and accurate ocean acoustic models for determining the exposure of marine life to the high levels of sound used in seismic surveys and other E&P activities. This paper reviews the types of acoustic models most useful for predicting the propagation of undersea noise sources and describes current exposure models. The severe problems caused by model sensitivity to the uncertainty in the environment are highlighted to support the conclusion that it is vital that risk assessments include transmission loss estimates with statistical measures of confidence.

PREDICTING PARTICULATE (PM-10) FREQUENCY DISTRIBUTIONS FOR URBAN POPULATIONS USING A RANDOM COMPONENT SUPERPOSITION MODEL (RCS) MODEL

EPA Science Inventory

Health risk evaluations usually require the frequency distribution of personal exposures of a given population. For particles, personal exposure field studies have been conducted in only a few urban areas, such as Riverside, CA; Philipsburg, NJ; and Toronto, Ontario. This paper...

HESI EXPOSURE FACTORS DATABASE FOR AGGREGATE AND CUMULATIVE RISK ASSESSMENT

EPA Science Inventory

In recent years, the risk analysis community has broadened its use of complex aggregate and cumulative residential exposure models (e.g., to meet the requirements of the 1996 Food Quality Protection Act). The value of these models is their ability to incorporate a range of inp...

Development of a software based automatic exposure control system for use in image guided radiation therapy

NASA Astrophysics Data System (ADS)

Morton, Daniel R.

Modern image guided radiation therapy involves the use of an isocentrically mounted imaging system to take radiographs of a patient's position before the start of each treatment. Image guidance helps to minimize errors associated with a patients setup, but the radiation dose received by patients from imaging must be managed to ensure no additional risks. The Varian On-Board Imager (OBI) (Varian Medical Systems, Inc., Palo Alto, CA) does not have an automatic exposure control system and therefore requires exposure factors to be manually selected. Without patient specific exposure factors, images may become saturated and require multiple unnecessary exposures. A software based automatic exposure control system has been developed to predict optimal, patient specific exposure factors. The OBI system was modelled in terms of the x-ray tube output and detector response in order to calculate the level of detector saturation for any exposure situation. Digitally reconstructed radiographs are produced via ray-tracing through the patients' volumetric datasets that are acquired for treatment planning. The ray-trace determines the attenuation of the patient and subsequent x-ray spectra incident on the imaging detector. The resulting spectra are used in the detector response model to determine the exposure levels required to minimize detector saturation. Images calculated for various phantoms showed good agreement with the images that were acquired on the OBI. Overall, regions of detector saturation were accurately predicted and the detector response for non-saturated regions in images of an anthropomorphic phantom were calculated to generally be within 5 to 10 % of the measured values. Calculations were performed on patient data and found similar results as the phantom images, with the calculated images being able to determine detector saturation with close agreement to images that were acquired during treatment. Overall, it was shown that the system model and calculation method could potentially be used to predict patients' exposure factors before their treatment begins, thus preventing the need for multiple exposures.

LINKING DERMAL MODELING AND LOADING DATA TO PREDICT LONG-TERM DOSES FROM INTERMITTENT DERMAL CONTACT

EPA Science Inventory

In this paper we assess dermal exposure and dose resulting from intermittent contact with residue-contaminated surfaces. These estimates require an understanding of (1) the quantitative relationship between exposure and absorbed dose; (2) the impact of intermittent exposure on ...

Leveraging Publicly-Available Consumer Product and Chemical Data in Support of Exposure Modeling

EPA Science Inventory

Near-field contact with chemicals in consumer products has been identified as a significant source of human exposure. To predict such exposures, information about chemical occurrence in consumer products is required, but is often not available. The Chemicals and Products Database...

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

Bodkin, J.L.; Udevitz, M.S.

The authors developed an analytical model (intersection model) to estimate the exposure of sea otters (Enhydra lutris), to oil from the Exxon Valdez oil spill. The authors applied estimated and assumed exposure dependent mortality rates to the Kenai Peninsula sea otter population to provide examples of the application of the model in estimating sea otter mortality. The intersection model requires three distinct types of data: (1) distribution, abundance, and movements of oil, (2) abundance and distribution of sea otters, and (3) sea otter mortality rates relative to oil exposure. Initial output of the model is an estimate of exposure ofmore » otters to oil. Exposure is measured in amount and duration of oil near an otter`s observed location (intersections). The authors provide two examples of the model using different assumptions about the relation between exposure and mortality. Because of an apparent non-linear relation between the degree of oiling and survival of otters from rehabilitation, output from the authors` examples are likely biased.« less

Comparison of Modeling Approaches to Prioritize Chemicals Based on Estimates of Exposure and Exposure Potential

EPA Science Inventory

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecologic...

Applicability of western chemical dietary exposure models to the Chinese population.

PubMed

Zhao, Shizhen; Price, Oliver; Liu, Zhengtao; Jones, Kevin C; Sweetman, Andrew J

2015-07-01

A range of exposure models, which have been developed in Europe and North America, are playing an increasingly important role in priority setting and the risk assessment of chemicals. However, the applicability of these tools, which are based on Western dietary exposure pathways, to estimate chemical exposure to the Chinese population to support the development of a risk-based environment and exposure assessment, is unclear. Three frequently used modelling tools, EUSES, RAIDAR and ACC-HUMANsteady, have been evaluated in terms of human dietary exposure estimation by application to a range of chemicals with different physicochemical properties under both model default and Chinese dietary scenarios. Hence, the modelling approaches were assessed by considering dietary pattern differences only. The predicted dietary exposure pathways were compared under both scenarios using a range of hypothetical and current emerging contaminants. Although the differences across models are greater than those between dietary scenarios, model predictions indicated that dietary preference can have a significant impact on human exposure, with the relatively high consumption of vegetables and cereals resulting in higher exposure via plants-based foodstuffs under Chinese consumption patterns compared to Western diets. The selected models demonstrated a good ability to identify key dietary exposure pathways which can be used for screening purposes and an evaluative risk assessment. However, some model adaptations will be required to cover a number of important Chinese exposure pathways, such as freshwater farmed-fish, grains and pork. Copyright © 2015 Elsevier Inc. All rights reserved.

HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE'S EXPOSURE FACTORS DATABASE FOR AGGREGATE AND CUMULATIVE RISK ASSESSMENT

EPA Science Inventory

In recent years, the risk analysis community has broadened its use of complex aggregate and cumulative residential exposure models (e.g., to meet the requirements of the 1996 Food Quality Protection Act). The value of these models is their ability to incorporate a range of input...

Modeling cumulative dose and exposure duration provided insights regarding the associations between benzodiazepines and injuries.

PubMed

Abrahamowicz, Michal; Bartlett, Gillian; Tamblyn, Robyn; du Berger, Roxane

2006-04-01

Accurate assessment of medication impact requires modeling cumulative effects of exposure duration and dose; however, postmarketing studies usually represent medication exposure by baseline or current use only. We propose new methods for modeling various aspects of medication use history and employment of them to assess the adverse effects of selected benzodiazepines. Time-dependent measures of cumulative dose or duration of use, with weighting of past exposures by recency, were proposed. These measures were then included in alternative versions of the multivariable Cox model to analyze the risk of fall related injuries among the elderly new users of three benzodiazepines (nitrazepam, temazepam, and flurazepam) in Quebec. Akaike's information criterion (AIC) was used to select the most predictive model for a given benzodiazepine. The best-fitting model included a combination of cumulative duration and current dose for temazepam, and cumulative dose for flurazepam and nitrazepam, with different weighting functions. The window of clinically relevant exposure was shorter for flurazepam than for the two other products. Careful modeling of the medication exposure history may enhance our understanding of the mechanisms underlying their adverse effects.

A review of air exchange rate models for air pollution exposure assessments.

PubMed

Breen, Michael S; Schultz, Bradley D; Sohn, Michael D; Long, Thomas; Langstaff, John; Williams, Ronald; Isaacs, Kristin; Meng, Qing Yu; Stallings, Casson; Smith, Luther

2014-11-01

A critical aspect of air pollution exposure assessments is estimation of the air exchange rate (AER) for various buildings where people spend their time. The AER, which is the rate of exchange of indoor air with outdoor air, is an important determinant for entry of outdoor air pollutants and for removal of indoor-emitted air pollutants. This paper presents an overview and critical analysis of the scientific literature on empirical and physically based AER models for residential and commercial buildings; the models highlighted here are feasible for exposure assessments as extensive inputs are not required. Models are included for the three types of airflows that can occur across building envelopes: leakage, natural ventilation, and mechanical ventilation. Guidance is provided to select the preferable AER model based on available data, desired temporal resolution, types of airflows, and types of buildings included in the exposure assessment. For exposure assessments with some limited building leakage or AER measurements, strategies are described to reduce AER model uncertainty. This review will facilitate the selection of AER models in support of air pollution exposure assessments.

Inside the black box: starting to uncover the underlying decision rules used in one-by-one expert assessment of occupational exposure in case-control studies

PubMed Central

Wheeler, David C.; Burstyn, Igor; Vermeulen, Roel; Yu, Kai; Shortreed, Susan M.; Pronk, Anjoeka; Stewart, Patricia A.; Colt, Joanne S.; Baris, Dalsu; Karagas, Margaret R.; Schwenn, Molly; Johnson, Alison; Silverman, Debra T.; Friesen, Melissa C.

2014-01-01

Objectives Evaluating occupational exposures in population-based case-control studies often requires exposure assessors to review each study participants' reported occupational information job-by-job to derive exposure estimates. Although such assessments likely have underlying decision rules, they usually lack transparency, are time-consuming and have uncertain reliability and validity. We aimed to identify the underlying rules to enable documentation, review, and future use of these expert-based exposure decisions. Methods Classification and regression trees (CART, predictions from a single tree) and random forests (predictions from many trees) were used to identify the underlying rules from the questionnaire responses and an expert's exposure assignments for occupational diesel exhaust exposure for several metrics: binary exposure probability and ordinal exposure probability, intensity, and frequency. Data were split into training (n=10,488 jobs), testing (n=2,247), and validation (n=2,248) data sets. Results The CART and random forest models' predictions agreed with 92–94% of the expert's binary probability assignments. For ordinal probability, intensity, and frequency metrics, the two models extracted decision rules more successfully for unexposed and highly exposed jobs (86–90% and 57–85%, respectively) than for low or medium exposed jobs (7–71%). Conclusions CART and random forest models extracted decision rules and accurately predicted an expert's exposure decisions for the majority of jobs and identified questionnaire response patterns that would require further expert review if the rules were applied to other jobs in the same or different study. This approach makes the exposure assessment process in case-control studies more transparent and creates a mechanism to efficiently replicate exposure decisions in future studies. PMID:23155187

Environmental Risk Assessment Strategy for Nanomaterials.

PubMed

Scott-Fordsmand, Janeck J; Peijnenburg, Willie J G M; Semenzin, Elena; Nowack, Bernd; Hunt, Neil; Hristozov, Danail; Marcomini, Antonio; Irfan, Muhammad-Adeel; Jiménez, Araceli Sánchez; Landsiedel, Robert; Tran, Lang; Oomen, Agnes G; Bos, Peter M J; Hund-Rinke, Kerstin

2017-10-19

An Environmental Risk Assessment (ERA) for nanomaterials (NMs) is outlined in this paper. Contrary to other recent papers on the subject, the main data requirements, models and advancement within each of the four risk assessment domains are described, i.e., in the: (i) materials, (ii) release, fate and exposure, (iii) hazard and (iv) risk characterisation domains. The material, which is obviously the foundation for any risk assessment, should be described according to the legislatively required characterisation data. Characterisation data will also be used at various levels within the ERA, e.g., exposure modelling. The release, fate and exposure data and models cover the input for environmental distribution models in order to identify the potential (PES) and relevant exposure scenarios (RES) and, subsequently, the possible release routes, both with regard to which compartment(s) NMs are distributed in line with the factors determining the fate within environmental compartment. The initial outcome in the risk characterisation will be a generic Predicted Environmental Concentration (PEC), but a refined PEC can be obtained by applying specific exposure models for relevant media. The hazard information covers a variety of representative, relevant and reliable organisms and/or functions, relevant for the RES and enabling a hazard characterisation. The initial outcome will be hazard characterisation in test systems allowing estimating a Predicted No-Effect concentration (PNEC), either based on uncertainty factors or on a NM adapted version of the Species Sensitivity Distributions approach. The risk characterisation will either be based on a deterministic risk ratio approach (i.e., PEC/PNEC) or an overlay of probability distributions, i.e., exposure and hazard distributions, using the nano relevant models.

Environmental Risk Assessment Strategy for Nanomaterials

PubMed Central

Scott-Fordsmand, Janeck J.; Nowack, Bernd; Hunt, Neil; Hristozov, Danail; Marcomini, Antonio; Irfan, Muhammad-Adeel; Jiménez, Araceli Sánchez; Landsiedel, Robert; Tran, Lang; Oomen, Agnes G.; Bos, Peter M. J.

2017-01-01

An Environmental Risk Assessment (ERA) for nanomaterials (NMs) is outlined in this paper. Contrary to other recent papers on the subject, the main data requirements, models and advancement within each of the four risk assessment domains are described, i.e., in the: (i) materials, (ii) release, fate and exposure, (iii) hazard and (iv) risk characterisation domains. The material, which is obviously the foundation for any risk assessment, should be described according to the legislatively required characterisation data. Characterisation data will also be used at various levels within the ERA, e.g., exposure modelling. The release, fate and exposure data and models cover the input for environmental distribution models in order to identify the potential (PES) and relevant exposure scenarios (RES) and, subsequently, the possible release routes, both with regard to which compartment(s) NMs are distributed in line with the factors determining the fate within environmental compartment. The initial outcome in the risk characterisation will be a generic Predicted Environmental Concentration (PEC), but a refined PEC can be obtained by applying specific exposure models for relevant media. The hazard information covers a variety of representative, relevant and reliable organisms and/or functions, relevant for the RES and enabling a hazard characterisation. The initial outcome will be hazard characterisation in test systems allowing estimating a Predicted No-Effect concentration (PNEC), either based on uncertainty factors or on a NM adapted version of the Species Sensitivity Distributions approach. The risk characterisation will either be based on a deterministic risk ratio approach (i.e., PEC/PNEC) or an overlay of probability distributions, i.e., exposure and hazard distributions, using the nano relevant models. PMID:29048395

EARLY BIOMARKERS OF ACUTE RESPIRATORY ALLERGEN EXPOSURE

EPA Science Inventory

Rationale: Allergic asthma prevalence has been increasing in Western societies for several decades. Identification of potential allergens facilitates reduction in exposure and may reduce the risk of asthma development. Predictive models for recognition of sensitizers require th...

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds.

PubMed

Voorhees, Jaymie R; Rohlman, Diane S; Lein, Pamela J; Pieper, Andrew A

2016-01-01

Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.

Developing ecological scenarios for the prospective aquatic risk assessment of pesticides.

PubMed

Rico, Andreu; Van den Brink, Paul J; Gylstra, Ronald; Focks, Andreas; Brock, Theo Cm

2016-07-01

The prospective aquatic environmental risk assessment (ERA) of pesticides is generally based on the comparison of predicted environmental concentrations in edge-of-field surface waters with regulatory acceptable concentrations derived from laboratory and/or model ecosystem experiments with aquatic organisms. New improvements in mechanistic effect modeling have allowed a better characterization of the ecological risks of pesticides through the incorporation of biological trait information and landscape parameters to assess individual, population and/or community-level effects and recovery. Similarly to exposure models, ecological models require scenarios that describe the environmental context in which they are applied. In this article, we propose a conceptual framework for the development of ecological scenarios that, when merged with exposure scenarios, will constitute environmental scenarios for prospective aquatic ERA. These "unified" environmental scenarios are defined as the combination of the biotic and abiotic parameters that are required to characterize exposure, (direct and indirect) effects, and recovery of aquatic nontarget species under realistic worst-case conditions. Ideally, environmental scenarios aim to avoid a potential mismatch between the parameter values and the spatial-temporal scales currently used in aquatic exposure and effect modeling. This requires a deeper understanding of the ecological entities we intend to protect, which can be preliminarily addressed by the formulation of ecological scenarios. In this article we present a methodological approach for the development of ecological scenarios and illustrate this approach by a case-study for Dutch agricultural ditches and the example focal species Sialis lutaria. Finally, we discuss the applicability of ecological scenarios in ERA and propose research needs and recommendations for their development and integration with exposure scenarios. Integr Environ Assess Manag 2016;12:510-521. © 2015 SETAC. © 2015 SETAC.

A modular Human Exposure Model (HEM) framework to ...

EPA Pesticide Factsheets

Life Cycle Impact Analysis (LCIA) has proven to be a valuable tool for systematically comparing processes and products, and has been proposed for use in Chemical Alternatives Analysis (CAA). The exposure assessment portion of the human health impact scores of LCIA has historically focused on far-field sources (environmentally mediated exposures) while research has shown that use related exposures, (near-field exposures) typically dominate population exposure. Characterizing the human health impacts of chemicals in consumer products over the life cycle of these products requires an evaluation of both near-field as well far-field sources. Assessing the impacts of the near-field exposures requires bridging the scientific and technical gaps that currently prevent the harmonious use of the best available methods and tools from the fields of LCIA and human health exposure and risk assessment. The U.S. EPA’s Chemical Safety and Sustainability LC-HEM project is developing the Human Exposure Model (HEM) to assess near-field exposures to chemicals that occur to various populations over the life cycle of a commercial product. The HEM will be a publically available, web-based, modular system which will allow for the evaluation of chemical/product impacts in a LCIA framework to support CAA. We present here an overview of the framework for the modular HEM system. The framework includes a data flow diagram of in-progress and future planned modules, the definition of each mod

ESTIMATING CONTAMINANT DOSE FOR INTERMITTENT DERMAL CONTACT: MODEL DEVELOPMENT, TESTING, AND APPLICATION

EPA Science Inventory

Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure sc...

Altered exposure-related reshaping of body appreciation in adolescent patients with anorexia nervosa.

PubMed

Mele, Sonia; Cazzato, Valentina; Di Taranto, Francesca; Maestro, Sandra; Fabbro, Franco; Muratori, Filippo; Urgesi, Cosimo

2016-12-01

Several studies suggest a relation between repeated exposure to extremely thin bodies in media and the perceptual and emotional disturbances of body representation in anorexia nervosa (AN). In this study, we utilized an exposure paradigm to investigate how perceptual experience modulates body appreciation in adolescents with AN as compared to healthy adolescents. Twenty AN patients and 20 healthy controls were exposed to pictures of thin or round models and were then required to express liking judgments about bodies of variable weight. Brief exposure to round models increased the liking judgments of round bodies but not those of thin bodies in healthy adolescents. Furthermore, exposure to round models increased the liking judgments of both thin and round bodies in adolescents with AN. Patients did not show any change of liking judgments after exposure to thin models. These results point to weak norm-based reshaping of body appreciation in AN patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aggregate exposure modelling of zinc pyrithione in rinse-off personal cleansing products using a person-orientated approach with market share refinement.

PubMed

Tozer, Sarah A; Kelly, Seamus; O'Mahony, Cian; Daly, E J; Nash, J F

2015-09-01

Realistic estimates of chemical aggregate exposure are needed to ensure consumer safety. As exposure estimates are a critical part of the equation used to calculate acceptable "safe levels" and conduct quantitative risk assessments, methods are needed to produce realistic exposure estimations. To this end, a probabilistic aggregate exposure model was developed to estimate consumer exposure from several rinse off personal cleansing products containing the anti-dandruff preservative zinc pyrithione. The model incorporates large habits and practices surveys, containing data on frequency of use, amount applied, co-use along with market share, and combines these data at the level of the individual based on subject demographics to better estimate exposure. The daily-applied exposure (i.e., amount applied to the skin) was 3.79 mg/kg/day for the 95th percentile consumer. The estimated internal dose for the 95th percentile exposure ranged from 0.01-1.29 μg/kg/day after accounting for retention following rinsing and dermal penetration of ZnPt. This probabilistic aggregate exposure model can be used in the human safety assessment of ingredients in multiple rinse-off technologies (e.g., shampoo, bar soap, body wash, and liquid hand soap). In addition, this model may be used in other situations where refined exposure assessment is required to support a chemical risk assessment. Copyright © 2015 Elsevier Ltd. All rights reserved.

A European model and case studies for aggregate exposure assessment of pesticides.

PubMed

Kennedy, Marc C; Glass, C Richard; Bokkers, Bas; Hart, Andy D M; Hamey, Paul Y; Kruisselbrink, Johannes W; de Boer, Waldo J; van der Voet, Hilko; Garthwaite, David G; van Klaveren, Jacob D

2015-05-01

Exposures to plant protection products (PPPs) are assessed using risk analysis methods to protect public health. Traditionally, single sources, such as food or individual occupational sources, have been addressed. In reality, individuals can be exposed simultaneously to multiple sources. Improved regulation therefore requires the development of new tools for estimating the population distribution of exposures aggregated within an individual. A new aggregate model is described, which allows individual users to include as much, or as little, information as is available or relevant for their particular scenario. Depending on the inputs provided by the user, the outputs can range from simple deterministic values through to probabilistic analyses including characterisations of variability and uncertainty. Exposures can be calculated for multiple compounds, routes and sources of exposure. The aggregate model links to the cumulative dietary exposure model developed in parallel and is implemented in the web-based software tool MCRA. Case studies are presented to illustrate the potential of this model, with inputs drawn from existing European data sources and models. These cover exposures to UK arable spray operators, Italian vineyard spray operators, Netherlands users of a consumer spray and UK bystanders/residents. The model could also be adapted to handle non-PPP compounds. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Modelling the spatial distribution of Fasciola hepatica in dairy cattle in Europe.

PubMed

Ducheyne, Els; Charlier, Johannes; Vercruysse, Jozef; Rinaldi, Laura; Biggeri, Annibale; Demeler, Janina; Brandt, Christina; De Waal, Theo; Selemetas, Nikolaos; Höglund, Johan; Kaba, Jaroslaw; Kowalczyk, Slawomir J; Hendrickx, Guy

2015-03-26

A harmonized sampling approach in combination with spatial modelling is required to update current knowledge of fasciolosis in dairy cattle in Europe. Within the scope of the EU project GLOWORM, samples from 3,359 randomly selected farms in 849 municipalities in Belgium, Germany, Ireland, Poland and Sweden were collected and their infection status assessed using an indirect bulk tank milk (BTM) enzyme-linked immunosorbent assay (ELISA). Dairy farms were considered exposed when the optical density ratio (ODR) exceeded the 0.3 cut-off. Two ensemble-modelling techniques, Random Forests (RF) and Boosted Regression Trees (BRT), were used to obtain the spatial distribution of the probability of exposure to Fasciola hepatica using remotely sensed environmental variables (1-km spatial resolution) and interpolated values from meteorological stations as predictors. The median ODRs amounted to 0.31, 0.12, 0.54, 0.25 and 0.44 for Belgium, Germany, Ireland, Poland and southern Sweden, respectively. Using the 0.3 threshold, 571 municipalities were categorized as positive and 429 as negative. RF was seen as capable of predicting the spatial distribution of exposure with an area under the receiver operation characteristic (ROC) curve (AUC) of 0.83 (0.96 for BRT). Both models identified rainfall and temperature as the most important factors for probability of exposure. Areas of high and low exposure were identified by both models, with BRT better at discriminating between low-probability and high-probability exposure; this model may therefore be more useful in practise. Given a harmonized sampling strategy, it should be possible to generate robust spatial models for fasciolosis in dairy cattle in Europe to be used as input for temporal models and for the detection of deviations in baseline probability. Further research is required for model output in areas outside the eco-climatic range investigated.

Design considerations for case series models with exposure onset measurement error.

PubMed

Mohammed, Sandra M; Dalrymple, Lorien S; Sentürk, Damla; Nguyen, Danh V

2013-02-28

The case series model allows for estimation of the relative incidence of events, such as cardiovascular events, within a pre-specified time window after an exposure, such as an infection. The method requires only cases (individuals with events) and controls for all fixed/time-invariant confounders. The measurement error case series model extends the original case series model to handle imperfect data, where the timing of an infection (exposure) is not known precisely. In this work, we propose a method for power/sample size determination for the measurement error case series model. Extensive simulation studies are used to assess the accuracy of the proposed sample size formulas. We also examine the magnitude of the relative loss of power due to exposure onset measurement error, compared with the ideal situation where the time of exposure is measured precisely. To facilitate the design of case series studies, we provide publicly available web-based tools for determining power/sample size for both the measurement error case series model as well as the standard case series model. Copyright © 2012 John Wiley & Sons, Ltd.

First tier modeling of consumer dermal exposure to substances in consumer articles under REACH: a quantitative evaluation of the ECETOC TRA for consumers tool.

PubMed

Delmaar, J E; Bokkers, B G H; ter Burg, W; van Engelen, J G M

2013-02-01

The demonstration of safe use of chemicals in consumer products, as required under REACH, is proposed to follow a tiered process. In the first tier, simple conservative methods and assumptions should be made to quickly verify whether risks for a particular use are expected. The ECETOC TRA Consumer Exposure Tool was developed to assist in first tier risk assessments for substances in consumer products. The ECETOC TRA is not a prioritization tool, but is meant as a first screening. Therefore, the exposure assessment needs to cover all products/articles in a specific category. For the assessment of the dermal exposure for substances in articles, ECETOC TRA uses the concept of a 'contact layer', a hypothetical layer that limits the exposure to a substance contained in the product. For each product/article category, ECETOC TRA proposes default values for the thickness of this contact layer. As relevant experimental exposure data is currently lacking, default values are based on expert judgment alone. In this paper it is verified whether this concept meets the requirement of being a conservative exposure evaluation method. This is done by confronting the ECETOC TRA expert judgment based predictions with a mechanistic emission model, based on the well established theory of diffusion of substances in materials. Diffusion models have been applied and tested in many applications of emission modeling. Experimentally determined input data for a number of material and substance combinations are available. The estimated emissions provide information on the range of emissions that could occur in reality. First tier tools such as ECETOC TRA tool are required to cover all products/articles in a category and to provide estimates that are at least as high as is expected on the basis of current scientific knowledge. Since this was not the case, it is concluded that the ECETOC TRA does not provide a proper conservative estimation method for the dermal exposure to articles. An alternative method was proposed. Copyright © 2012 Elsevier Inc. All rights reserved.

Low Dose Radiation Cancer Risks: Epidemiological and Toxicological Models

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

David G. Hoel, PhD

2012-04-19

The basic purpose of this one year research grant was to extend the two stage clonal expansion model (TSCE) of carcinogenesis to exposures other than the usual single acute exposure. The two-stage clonal expansion model of carcinogenesis incorporates the biological process of carcinogenesis, which involves two mutations and the clonal proliferation of the intermediate cells, in a stochastic, mathematical way. The current TSCE model serves a general purpose of acute exposure models but requires numerical computation of both the survival and hazard functions. The primary objective of this research project was to develop the analytical expressions for the survival functionmore » and the hazard function of the occurrence of the first cancer cell for acute, continuous and multiple exposure cases within the framework of the piece-wise constant parameter two-stage clonal expansion model of carcinogenesis. For acute exposure and multiple exposures of acute series, it is either only allowed to have the first mutation rate vary with the dose, or to have all the parameters be dose dependent; for multiple exposures of continuous exposures, all the parameters are allowed to vary with the dose. With these analytical functions, it becomes easy to evaluate the risks of cancer and allows one to deal with the various exposure patterns in cancer risk assessment. A second objective was to apply the TSCE model with varing continuous exposures from the cancer studies of inhaled plutonium in beagle dogs. Using step functions to estimate the retention functions of the pulmonary exposure of plutonium the multiple exposure versions of the TSCE model was to be used to estimate the beagle dog lung cancer risks. The mathematical equations of the multiple exposure versions of the TSCE model were developed. A draft manuscript which is attached provides the results of this mathematical work. The application work using the beagle dog data from plutonium exposure has not been completed due to the fact that the research project did not continue beyond its first year.« less

EXPOSURE METHODOLOGIES AND SYSTEMS FOR LONG-TERM CHEMICAL CARCINOGENICITY STUDIES WITH SMALL FISH SPECIES

EPA Science Inventory

Testing waterborne chemical carcinogens in fish models requires accurate, reliable, and reproducible exposures. Because carcinogenesis is a chronic toxicological process and is often associated with prolonged latency periods, systems must accommodate lengthy in-life test periods ...

A Framework for Widespread Replication of a Highly Spatially Resolved Childhood Lead Exposure Risk Model

PubMed Central

Kim, Dohyeong; Galeano, M. Alicia Overstreet; Hull, Andrew; Miranda, Marie Lynn

2008-01-01

Background Preventive approaches to childhood lead poisoning are critical for addressing this longstanding environmental health concern. Moreover, increasing evidence of cognitive effects of blood lead levels < 10 μg/dL highlights the need for improved exposure prevention interventions. Objectives Geographic information system–based childhood lead exposure risk models, especially if executed at highly resolved spatial scales, can help identify children most at risk of lead exposure, as well as prioritize and direct housing and health-protective intervention programs. However, developing highly resolved spatial data requires labor-and time-intensive geocoding and analytical processes. In this study we evaluated the benefit of increased effort spent geocoding in terms of improved performance of lead exposure risk models. Methods We constructed three childhood lead exposure risk models based on established methods but using different levels of geocoded data from blood lead surveillance, county tax assessors, and the 2000 U.S. Census for 18 counties in North Carolina. We used the results to predict lead exposure risk levels mapped at the individual tax parcel unit. Results The models performed well enough to identify high-risk areas for targeted intervention, even with a relatively low level of effort on geocoding. Conclusions This study demonstrates the feasibility of widespread replication of highly spatially resolved childhood lead exposure risk models. The models guide resource-constrained local health and housing departments and community-based organizations on how best to expend their efforts in preventing and mitigating lead exposure risk in their communities. PMID:19079729

Modelling survival: exposure pattern, species sensitivity and uncertainty.

PubMed

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B; Van den Brink, Paul J; Veltman, Karin; Vogel, Sören; Zimmer, Elke I; Preuss, Thomas G

2016-07-06

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

Modelling survival: exposure pattern, species sensitivity and uncertainty

NASA Astrophysics Data System (ADS)

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

2016-07-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

PubMed Central

Voorhees, Jaymie R.; Rohlman, Diane S.; Lein, Pamela J.; Pieper, Andrew A.

2017-01-01

Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally. PMID:28149268

GIS Modeling of Air Toxics Releases from TRI-Reporting and Non-TRI-Reporting Facilities: Impacts for Environmental Justice

PubMed Central

Dolinoy, Dana C.; Miranda, Marie Lynn

2004-01-01

The Toxics Release Inventory (TRI) requires facilities with 10 or more full-time employees that process > 25,000 pounds in aggregate or use > 10,000 pounds of any one TRI chemical to report releases annually. However, little is known about releases from non-TRI-reporting facilities, nor has attention been given to the very localized equity impacts associated with air toxics releases. Using geographic information systems and industrial source complex dispersion modeling, we developed methods for characterizing air releases from TRI-reporting as well as non-TRI-reporting facilities at four levels of geographic resolution. We characterized the spatial distribution and concentration of air releases from one representative industry in Durham County, North Carolina (USA). Inclusive modeling of all facilities rather than modeling of TRI sites alone significantly alters the magnitude and spatial distribution of modeled air concentrations. Modeling exposure receptors at more refined levels of geographic resolution reveals localized, neighborhood-level exposure hot spots that are not apparent at coarser geographic scales. Multivariate analysis indicates that inclusive facility modeling at fine levels of geographic resolution reveals exposure disparities by income and race. These new methods significantly enhance the ability to model air toxics, perform equity analysis, and clarify conflicts in the literature regarding environmental justice findings. This work has substantial implications for how to structure TRI reporting requirements, as well as methods and types of analysis that will successfully elucidate the spatial distribution of exposure potentials across geographic, income, and racial lines. PMID:15579419

BK/TD models for analyzing in vitro impedance data on cytotoxicity.

PubMed

Teng, S; Barcellini-Couget, S; Beaudouin, R; Brochot, C; Desousa, G; Rahmani, R; Pery, A R R

2015-06-01

The ban of animal testing has enhanced the development of new in vitro technologies for cosmetics safety assessment. Impedance metrics is one such technology which enables monitoring of cell viability in real time. However, analyzing real time data requires moving from static to dynamic toxicity assessment. In the present study, we built mechanistic biokinetic/toxicodynamic (BK/TD) models to analyze the time course of cell viability in cytotoxicity assay using impedance. These models account for the fate of the tested compounds during the assay. BK/TD models were applied to analyze HepaRG cell viability, after single (48 h) and repeated (4 weeks) exposures to three hepatotoxic compounds (coumarin, isoeugenol and benzophenone-2). The BK/TD models properly fit the data used for their calibration that was obtained for single or repeated exposure. Only for one out of the three compounds, the models calibrated with a single exposure were able to predict repeated exposure data. We therefore recommend the use of long-term exposure in vitro data in order to adequately account for chronic hepatotoxic effects. The models we propose here are capable of being coupled with human biokinetic models in order to relate dose exposure and human hepatotoxicity. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

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.

Probabilistic modelling to assess exposure to three artificial sweeteners of young Irish patients aged 1-3 years with PKU and CMPA.

PubMed

O'Sullivan, Aaron J; Pigat, Sandrine; O'Mahony, Cian; Gibney, Michael J; McKevitt, Aideen I

2016-11-01

The choice of suitable normal foods is limited for individuals with particular medical conditions, e.g., inborn errors of metabolism (phenylketonuria - PKU) or severe cow's milk protein allergy (CMPA). Patients may have dietary restrictions and exclusive or partial replacement of specific food groups with specially formulated products to meet particular nutrition requirements. Artificial sweeteners are used to improve the appearance and palatability of such food products to avoid food refusal and ensure dietary adherence. Young children have a higher risk of exceeding acceptable daily intakes for additives than adults due to higher food intakes kg -1 body weight. The Budget Method and EFSA's Food Additives Intake Model (FAIM) are not equipped to assess partial dietary replacement with special formulations as they are built on data from dietary surveys of consumers without special medical requirements impacting the diet. The aim of this study was to explore dietary exposure modelling as a means of estimating the intake of artificial sweeteners by young PKU and CMPA patients aged 1-3 years. An adapted validated probabilistic model (FACET) was used to assess patients' exposure to artificial sweeteners. Food consumption data were derived from the food consumption survey data of healthy young children in Ireland from the National Preschool and Nutrition Survey (NPNS, 2010-11). Specially formulated foods for special medical purposes were included in the exposure model to replace restricted foods. Inclusion was based on recommendations for adequate protein intake and dietary adherence data. Exposure assessment results indicated that young children with PKU and CMPA have higher relative average intakes of artificial sweeteners than healthy young children. The reliability and robustness of the model in the estimation of patient additive exposures was further investigated and provides the first exposure estimates for these special populations.

Modeling Joint Exposures and Health Outcomes for Cumulative Risk Assessment: the Case of Radon and Smoking

EPA Science Inventory

Community-based cumulative risk assessment requires characterization of exposures to multiple chemical and non-chemical stressors, with consideration of how the non-chemical stressors may influence risks from chemical stressors. Residential radon provides an interesting case exam...

The Human Exposure Model (HEM): A Tool to Support Rapid ...

EPA Pesticide Factsheets

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 exposure. The use of consumer products often results in near-field exposures (exposures that occur directly from the use of a product) that are larger than environmentally mediated exposures (i.e. far-field sources)1,2. Failure to consider near-field exposures could result in biases in LCIA-based determinations of the relative sustainability of consumer products. HEM is designed to provide this information.Characterizing near-field sources of chemical exposures present a challenge to LCIA practitioners. Unlike far-field sources, where multimedia mass balance models have been used to determine human exposure, near-field sources require product-specific models of human exposure and considerable information on product use and product composition. Such information is difficult and time-consuming to gather and curate. The HEM software will characterize the distribution of doses and product intake fractions2 across populations of product users and bystanders, allowing for differentiation by various demographic characteristics. The tool incorporates a newly developed database of the composition of more than 17,000 products, data on physical and chemical properties for more than 2,000 chemicals, and mo

Life sciences research in space: The requirement for animal models

NASA Technical Reports Server (NTRS)

Fuller, C. A.; Philips, R. W.; Ballard, R. W.

1987-01-01

Use of animals in NASA space programs is reviewed. Animals are needed because life science experimentation frequently requires long-term controlled exposure to environments, statistical validation, invasive instrumentation or biological tissue sampling, tissue destruction, exposure to dangerous or unknown agents, or sacrifice of the subject. The availability and use of human subjects inflight is complicated by the multiple needs and demands upon crew time. Because only living organisms can sense, integrate and respond to the environment around them, the sole use of tissue culture and computer models is insufficient for understanding the influence of the space environment on intact organisms. Equipment for spaceborne experiments with animals is described.

A changing climate: impacts on human exposures to O3 using ...

EPA Pesticide Factsheets

Predicting the impacts of changing climate on human exposure to air pollution requires future scenarios that account for changes in ambient pollutant concentrations, population sizes and distributions, and housing stocks. An integrated methodology to model changes in human exposures due to these impacts was developed by linking climate, air quality, land-use, and human exposure models. This methodology was then applied to characterize changes in predicted human exposures to O3 under multiple future scenarios. Regional climate projections for the U.S. were developed by downscaling global circulation model (GCM) scenarios for three of the Intergovernmental Panel on Climate Change’s (IPCC’s) Representative Concentration Pathways (RCPs) using the Weather Research and Forecasting (WRF) model. The regional climate results were in turn used to generate air quality (concentration) projections using the Community Multiscale Air Quality (CMAQ) model. For each of the climate change scenarios, future U.S. census-tract level population distributions from the Integrated Climate and Land Use Scenarios (ICLUS) model for four future scenarios based on the IPCC’s Special Report on Emissions Scenarios (SRES) storylines were used. These climate, air quality, and population projections were used as inputs to EPA’s Air Pollutants Exposure (APEX) model for 12 U.S. cities. Probability density functions show changes in the population distribution of 8 h maximum daily O3 exposur

Predictive & Prognostic Controller for Wide Band Gap (Silicon Carbide) Power Conversion (Preprint)

DTIC Science & Technology

2006-11-01

that is required for them to achieve their full potential, or other elements that are different from the traditional practice of Power Conditioning...symptoms, medical clinicians rely strongly on family history, individual history, environmental conditions or exposures and lifestyle to ascertain the...the model and possibly related models of the particular converter design. The lifestyle , the stress and the exposure that is considered in human

Incorporating High-Dimensional Exposure Modelling into Studies of Air Pollution and Health.

PubMed

Liu, Yi; Shaddick, Gavin; Zidek, James V

2017-01-01

Performing studies on the risks of environmental hazards on human health requires accurate estimates of exposures that might be experienced by the populations at risk. Often there will be missing data and in many epidemiological studies, the locations and times of exposure measurements and health data do not match. To a large extent this will be due to the health and exposure data having arisen from completely different data sources and not as the result of a carefully designed study, leading to problems of both 'change of support' and 'misaligned data'. In such cases, a direct comparison of the exposure and health outcome is often not possible without an underlying model to align the two in the spatial and temporal domains. The Bayesian approach provides the natural framework for such models; however, the large amounts of data that can arise from environmental networks means that inference using Markov Chain Monte Carlo might not be computationally feasible in this setting. Here we adapt the integrated nested Laplace approximation to implement spatio-temporal exposure models. We also propose methods for the integration of large-scale exposure models and health analyses. It is important that any model structure allows the correct propagation of uncertainty from the predictions of the exposure model through to the estimates of risk and associated confidence intervals. The methods are demonstrated using a case study of the levels of black smoke in the UK, measured over several decades, and respiratory mortality.

MECHANISTIC DOSIMETRY MODELS OF NANOMATERIAL DEPOSITION IN THE RESPIRATORY TRACT

EPA Science Inventory

Accurate health risk assessments of inhalation exposure to nanomaterials will require dosimetry models that account for interspecies differences in dose delivered to the respiratory tract. Mechanistic models offer the advantage to interspecies extrapolation that physicochemica...

PROBABILISTIC AQUATIC EXPOSURE ASSESSMENT FOR PESTICIDES 1: FOUNDATIONS

EPA Science Inventory

Models that capture underlying mechanisms and processes are necessary for reliable extrapolation of laboratory chemical data to field conditions. For validation, these models require a major revision of the conventional model testing paradigm to better recognize the conflict betw...

HYDROCARBON SPILL EXPOSURE ASSESSMENT MODELING

EPA Science Inventory

Hydrocarbon spills impact drinking water supplies at down gradient locations. onventional finite difference and finite element models of multiphase, multicomponent flow have extreme requirements for both computer time and site data. ite data and the intent of the modeling often d...

Explicit Pharmacokinetic Modeling: Tools for Documentation, Verification, and Portability

EPA Science Inventory

Quantitative estimates of tissue dosimetry of environmental chemicals due to multiple exposure pathways require the use of complex mathematical models, such as physiologically-based pharmacokinetic (PBPK) models. The process of translating the abstract mathematics of a PBPK mode...

Application of physiologically based pharmacokinetic (PBPK) model of trichloroethylene in rats for estimation of internal dose

EPA Science Inventory

Potential human health risk from chemical exposure must often be assessed for conditions for which suitable human or animal data are not available, requiring extrapolation across duration and concentration. The default method for exposure-duration adjustment is based on Haber's r...

Modelling survival: exposure pattern, species sensitivity and uncertainty

PubMed Central

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; Van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

2016-01-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans. PMID:27381500

[Physically-based model of pesticide application for risk assessment of agricultural workers].

PubMed

Rubino, F M; Mandic-Rajcevic, S; Vianello, G; Brambilla, G; Colosio, C

2012-01-01

Due to their unavoidable toxicity to non-target organisms, including man, the not of Plant Protection Products requires a thorough risk assessment to rationally advise safe use procedures and protection equipment by farmers. Most information on active substances and formulations, such as dermal absorption rates and exposure limits are available in the large body of regulatory data. Physically-based computational models can be used to forecast risk in real-life conditions (preventive assessment by 'exposure profiles'), to drive the cost-effective use of products and equipment and to understand the sources of unexpected exposure.

The relationship between inadvertent ingestion and dermal exposure pathways: a new integrated conceptual model and a database of dermal and oral transfer efficiencies.

PubMed

Gorman Ng, Melanie; Semple, Sean; Cherrie, John W; Christopher, Yvette; Northage, Christine; Tielemans, Erik; Veroughstraete, Violaine; Van Tongeren, Martie

2012-11-01

Occupational inadvertent ingestion exposure is ingestion exposure due to contact between the mouth and contaminated hands or objects. Although individuals are typically oblivious to their exposure by this route, it is a potentially significant source of occupational exposure for some substances. Due to the continual flux of saliva through the oral cavity and the non-specificity of biological monitoring to routes of exposure, direct measurement of exposure by the inadvertent ingestion route is challenging; predictive models may be required to assess exposure. The work described in this manuscript has been carried out as part of a project to develop a predictive model for estimating inadvertent ingestion exposure in the workplace. As inadvertent ingestion exposure mainly arises from hand-to-mouth contact, it is closely linked to dermal exposure. We present a new integrated conceptual model for dermal and inadvertent ingestion exposure that should help to increase our understanding of ingestion exposure and our ability to simultaneously estimate exposure by the dermal and ingestion routes. The conceptual model consists of eight compartments (source, air, surface contaminant layer, outer clothing contaminant layer, inner clothing contaminant layer, hands and arms layer, perioral layer, and oral cavity) and nine mass transport processes (emission, deposition, resuspension or evaporation, transfer, removal, redistribution, decontamination, penetration and/or permeation, and swallowing) that describe event-based movement of substances between compartments (e.g. emission, deposition, etc.). This conceptual model is intended to guide the development of predictive exposure models that estimate exposure from both the dermal and the inadvertent ingestion pathways. For exposure by these pathways the efficiency of transfer of materials between compartments (for example from surfaces to hands, or from hands to the mouth) are important determinants of exposure. A database of transfer efficiency data relevant for dermal and inadvertent ingestion exposure was developed, containing 534 empirically measured transfer efficiencies measured between 1980 and 2010 and reported in the peer-reviewed and grey literature. The majority of the reported transfer efficiencies (84%) relate to transfer between surfaces and hands, but the database also includes efficiencies for other transfer scenarios, including surface-to-glove, hand-to-mouth, and skin-to-skin. While the conceptual model can provide a framework for a predictive exposure assessment model, the database provides detailed information on transfer efficiencies between the various compartments. Together, the conceptual model and the database provide a basis for the development of a quantitative tool to estimate inadvertent ingestion exposure in the workplace.

Strengthening the weak link: Built Environment modelling for loss analysis

NASA Astrophysics Data System (ADS)

Millinship, I.

2012-04-01

Methods to analyse insured losses from a range of natural perils, including pricing by primary insurers and catastrophe modelling by reinsurers, typically lack sufficient exposure information. Understanding the hazard intensity in terms of spatial severity and frequency is only the first step towards quantifying the risk of a catastrophic event. For any given event we need to know: Are any structures affected? What type of buildings are they? How much damaged occurred? How much will the repairs cost? To achieve this, detailed exposure information is required to assess the likely damage and to effectively calculate the resultant loss. Modelling exposures in the Built Environment therefore plays as important a role in understanding re/insurance risk as characterising the physical hazard. Across both primary insurance books and aggregated reinsurance portfolios, the location of a property (a risk) and its monetary value is typically known. Exactly what that risk is in terms of detailed property descriptors including structure type and rebuild cost - and therefore its vulnerability to loss - is often omitted. This data deficiency is a primary source of variations between modelled losses and the actual claims value. Built Environment models are therefore required at a high resolution to describe building attributes that relate vulnerability to property damage. However, national-scale household-level datasets are often not computationally practical in catastrophe models and data must be aggregated. In order to provide more accurate risk analysis, we have developed and applied a methodology for Built Environment modelling for incorporation into a range of re/insurance applications, including operational models for different international regions and different perils and covering residential, commercial and industry exposures. Illustrated examples are presented, including exposure modelling suitable for aggregated reinsurance analysis for the UK and bespoke high resolution modelling for industrial sites in Germany. A range of attributes are included following detailed claims analysis and engineering research with property type, age and condition identified as important differentiators of damage from flood, wind and freeze events.

Statistical multi-path exposure method for assessing the whole-body SAR in a heterogeneous human body model in a realistic environment.

PubMed

Vermeeren, Günter; Joseph, Wout; Martens, Luc

2013-04-01

Assessing the whole-body absorption in a human in a realistic environment requires a statistical approach covering all possible exposure situations. This article describes the development of a statistical multi-path exposure method for heterogeneous realistic human body models. The method is applied for the 6-year-old Virtual Family boy (VFB) exposed to the GSM downlink at 950 MHz. It is shown that the whole-body SAR does not differ significantly over the different environments at an operating frequency of 950 MHz. Furthermore, the whole-body SAR in the VFB for multi-path exposure exceeds the whole-body SAR for worst-case single-incident plane wave exposure by 3.6%. Moreover, the ICNIRP reference levels are not conservative with the basic restrictions in 0.3% of the exposure samples for the VFB at the GSM downlink of 950 MHz. The homogeneous spheroid with the dielectric properties of the head suggested by the IEC underestimates the absorption compared to realistic human body models. Moreover, the variation in the whole-body SAR for realistic human body models is larger than for homogeneous spheroid models. This is mainly due to the heterogeneity of the tissues and the irregular shape of the realistic human body model compared to homogeneous spheroid human body models. Copyright © 2012 Wiley Periodicals, Inc.

Toward a Stress Process Model of Children’s Exposure to Physical Family and Community Violence

PubMed Central

Brooks-Gunn, Jeanne

2011-01-01

Theoretically informed models are required to further the comprehensive understanding of children’s ETV. We draw on the stress process paradigm to forward an overall conceptual model of ETV (ETV) in childhood and adolescence. Around this conceptual model, we synthesize research in four dominant areas of the literature which are detailed but often disconnected including: (1) exposure to three forms of physical violence (e.g., child physical maltreatment, interparental violence, and community ETV); (2) the multilevel correlates and causes of ETV (e.g., neighborhood characteristics including concentrated disadvantage; family characteristics including socio-economic status and family stressors); (3) a range of consequences of ETV (e.g., internalizing and externalizing mental health problems, role transitions, and academic outcomes); and (4) multilevel and cross domain mediators and moderators of ETV influences (e.g., school and community factors, family social support, and individual coping resources). We highlight the range of interconnected processes through which violence exposures may influence children and suggest opportunities for prevention and intervention. We further identify needed future research on children’s ETV including coping resources as well as research on cumulative contributions of violence exposure, violence exposure modifications, curvilinearity, and timing of exposure. PMID:19434492

Calibration and validation of toxicokinetic-toxicodynamic models for three neonicotinoids and some aquatic macroinvertebrates.

PubMed

Focks, Andreas; Belgers, Dick; Boerwinkel, Marie-Claire; Buijse, Laura; Roessink, Ivo; Van den Brink, Paul J

2018-05-01

Exposure patterns in ecotoxicological experiments often do not match the exposure profiles for which a risk assessment needs to be performed. This limitation can be overcome by using toxicokinetic-toxicodynamic (TKTD) models for the prediction of effects under time-variable exposure. For the use of TKTD models in the environmental risk assessment of chemicals, it is required to calibrate and validate the model for specific compound-species combinations. In this study, the survival of macroinvertebrates after exposure to the neonicotinoid insecticide was modelled using TKTD models from the General Unified Threshold models of Survival (GUTS) framework. The models were calibrated on existing survival data from acute or chronic tests under static exposure regime. Validation experiments were performed for two sets of species-compound combinations: one set focussed on multiple species sensitivity to a single compound: imidacloprid, and the other set on the effects of multiple compounds for a single species, i.e., the three neonicotinoid compounds imidacloprid, thiacloprid and thiamethoxam, on the survival of the mayfly Cloeon dipterum. The calibrated models were used to predict survival over time, including uncertainty ranges, for the different time-variable exposure profiles used in the validation experiments. From the comparison between observed and predicted survival, it appeared that the accuracy of the model predictions was acceptable for four of five tested species in the multiple species data set. For compounds such as neonicotinoids, which are known to have the potential to show increased toxicity under prolonged exposure, the calibration and validation of TKTD models for survival needs to be performed ideally by considering calibration data from both acute and chronic tests.

Modelling the seasonal variation of vitamin D due to sun exposure.

PubMed

Diffey, B L

2010-06-01

The current interest in vitamin D as a preventive agent in many chronic diseases has led to a reappraisal of adequate sun exposure. Yet just what constitutes adequacy remains to be clearly defined and validated. To do this requires an understanding of how behaviour outdoors during the year translates into seasonal changes in vitamin D status. To develop a model for estimating the changes in serum 25-hydroxyvitamin D [25(OH)D] levels as a consequence of sun exposure throughout the year. A novel mathematical model is described that incorporates the changes in serum 25(OH)D following a single, whole-body exposure to solar ultraviolet radiation with daily sun exposure in order to estimate the annual variation in serum 25(OH)D. The model yields results that agree closely with measured data from a large population-based study. Application of the model showed that current advice about 10-20 min of daily sun exposure during the summer months does little in the way of boosting overall 25(OH)D levels, while sufficient sun exposure that could achieve a worthwhile benefit would compromise skin health. There is little in the way of public health advice concerning the benefits of sun exposure that can be given as an effective means of maintaining adequate vitamin D levels throughout the year. Instead it would seem safer and more effective to fortify more foods with vitamin D and/or to consider the use of supplements during the winter months. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and should avoid giving specific advice on what might be 'optimal' sun exposure. © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

Comparison of dermal and inhalation routes of entry for organic chemicals

NASA Technical Reports Server (NTRS)

Jepson, Gary W.; Mcdougal, James N.; Clewell, Harvey J., III

1992-01-01

The quantitative comparison of the chemical concentration inside the body as the result of a dermal exposure versus an inhalation exposure is useful for assessing human health risks and deciding on an appropriate protective posture. In order to describe the relationship between dermal and inhalation routes of exposure, a variety of organic chemicals were evaluated. The types of chemicals chosen for the study were halogenated hydrocarbons, aromatic compounds, non-polar hydrocarbons and inhalation anesthetics. Both dermal and inhalation exposures were conducted in rats and the chemicals were in the form of vapors. Prior to the dermal exposure, rat fur was closely clipped and during the exposure rats were provided fresh breathing air through latex masks. Blood samples were taken during 4-hour exposures and analyzed for the chemical of interest. A physiologically based pharmacokinetic model was used to predict permeability constants (cm/hr) consistent with the observed blood concentrations of the chemical. The ratio of dermal exposure to inhalation exposure required to achieve the same internal dose of chemical was calculated for each test chemical. The calculated ratio in humans ranged from 18 for styrene to 1180 for isoflurane. This methodology can be used to estimate the dermal exposure required to reach the internal dose achieved by a specific inhalation exposure. Such extrapolation is important since allowable exposure standards are often set for inhalation exposures, but occupational exposures may be dermal.

Validity of a traffic air pollutant dispersion model to assess exposure to fine particles.

PubMed

Kostrzewa, Aude; Reungoat, Patrice; Raherison, Chantal

2009-08-01

Fine particles (PM(2.5)) are an important component of air pollution. Epidemiological studies have shown health effects due to ambient air particles, particularly allergies in children. Since the main difficulty is to determine exposure to such pollution, traffic air pollutant (TAP) dispersions models have been developed to improve the estimation of individual exposure levels. One such model, the ExTra index, has been validated for nitrogen oxide concentrations but not for other pollutants. The purpose of this study was to assess the validity of the ExTra index to assess PM(2.5) exposure. We compared PM(2.5) concentrations calculated by the ExTra index to reference measures (passive samplers situated under the covered part of the playground), in 15 schools in Bordeaux, in 2000. First, we collected the input data required by the ExTra index: background and local pollution depending on traffic, meteorology and topography. Second, the ExTra index was calculated for each school. Statistical analysis consisted of a graphic description; then, we calculated an intraclass correlation coefficient. Concentrations calculated with the ExTra index and the reference method were similar. The ExTra index underestimated exposure by 2.2 microg m(-3) on average compared to the reference method. The intraclass correlation coefficient was 0.85 and its 95% confidence interval was [0.62; 0.95]. The results suggest that the ExTra index provides an assessment of PM(2.5) exposure similar to that of the reference method. Although caution is required in interpreting these results owing to the small number of sites, the ExTra index could be a useful epidemiological tool for reconstructing individual exposure, an important challenge in epidemiology.

A Pilot Study on Integrating Videography and Environmental Microbial Sampling to Model Fecal Bacterial Exposures in Peri-Urban Tanzania.

PubMed

Julian, Timothy R; Pickering, Amy J

2015-01-01

Diarrheal diseases are a leading cause of under-five mortality and morbidity in sub-Saharan Africa. Quantitative exposure modeling provides opportunities to investigate the relative importance of fecal-oral transmission routes (e.g. hands, water, food) responsible for diarrheal disease. Modeling, however, requires accurate descriptions of individuals' interactions with the environment (i.e., activity data). Such activity data are largely lacking for people in low-income settings. In the present study, we collected activity data and microbiological sampling data to develop a quantitative microbial exposure model for two female caretakers in peri-urban Tanzania. Activity data were combined with microbiological data of contacted surfaces and fomites (e.g. broom handle, soil, clothing) to develop example exposure profiles describing second-by-second estimates of fecal indicator bacteria (E. coli and enterococci) concentrations on the caretaker's hands. The study demonstrates the application and utility of video activity data to quantify exposure factors for people in low-income countries and apply these factors to understand fecal contamination exposure pathways. This study provides both a methodological approach for the design and implementation of larger studies, and preliminary data suggesting contacts with dirt and sand may be important mechanisms of hand contamination. Increasing the scale of activity data collection and modeling to investigate individual-level exposure profiles within target populations for specific exposure scenarios would provide opportunities to identify the relative importance of fecal-oral disease transmission routes.

Spatial Resolution Requirements for Traffic-Related Air Pollutant Exposure Evaluations

PubMed Central

Batterman, Stuart; Chambliss, Sarah; Isakov, Vlad

2014-01-01

Vehicle emissions represent one of the most important air pollution sources in most urban areas, and elevated concentrations of pollutants found near major roads have been associated with many adverse health impacts. To understand these impacts, exposure estimates should reflect the spatial and temporal patterns observed for traffic-related air pollutants. This paper evaluates the spatial resolution and zonal systems required to estimate accurately intraurban and near-road exposures of traffic-related air pollutants. The analyses use the detailed information assembled for a large (800 km2) area centered on Detroit, Michigan, USA. Concentrations of nitrogen oxides (NOx) due to vehicle emissions were estimated using hourly traffic volumes and speeds on 9,700 links representing all but minor roads in the city, the MOVES2010 emission model, the RLINE dispersion model, local meteorological data, a temporal resolution of 1 hr, and spatial resolution as low as 10 m. Model estimates were joined with the corresponding shape files to estimate residential exposures for 700,000 individuals at property parcel, census block, census tract, and ZIP code levels. We evaluate joining methods, the spatial resolution needed to meet specific error criteria, and the extent of exposure misclassification. To portray traffic-related air pollutant exposure, raster or inverse distance-weighted interpolations are superior to nearest neighbor approaches, and interpolations between receptors and points of interest should not exceed about 40 m near major roads, and 100 m at larger distances. For census tracts and ZIP codes, average exposures are overestimated since few individuals live very near major roads, the range of concentrations is compressed, most exposures are misclassified, and high concentrations near roads are entirely omitted. While smaller zones improve performance considerably, even block-level data can misclassify many individuals. To estimate exposures and impacts of traffic-related pollutants accurately, data should be geocoded or estimated at the most-resolved spatial level; census tract and larger zones have little if any ability to represent intraurban variation in traffic-related air pollutant concentrations. These results are based on one of the most comprehensive intraurban modeling studies in the literature and results are robust. Recommendations address the value of dispersion models to portray spatial and temporal variation of air pollutants in epidemiology and other studies; techniques to improve accuracy and reduce the computational burden in urban scale modeling; the necessary spatial resolution for health surveillance, demographic, and pollution data; and the consequences of low resolution data in terms of exposure misclassification. PMID:25132794

ADDRESSING ENVIRONMENTAL ENGINEERING CHALLENGES WITH COMPUTATIONAL FLUID DYNAMICS

EPA Science Inventory

In the field of environmental engineering, modeling tools are playing an ever larger role in addressing air quality issues, including source pollutant emissions, atmospheric dispersion and human exposure risks. More detailed modeling of environmental flows requires tools for c...

EXPOSURE ASSESSMENT MODELING FOR HYDROCARBON SPILLS INTO THE SUBSURFACE

EPA Science Inventory

Hydrocarbons which enter the subsurface through spills or leaks may create serious, long-lived ground-water contamination problems. onventional finite difference and finite element models of multiphase, multicomponent flow often have extreme requirements for both computer time an...

Environmental fate and exposure models: advances and challenges in 21st century chemical risk assessment.

PubMed

Di Guardo, Antonio; Gouin, Todd; MacLeod, Matthew; Scheringer, Martin

2018-01-24

Environmental fate and exposure models are a powerful means to integrate information on chemicals, their partitioning and degradation behaviour, the environmental scenario and the emissions in order to compile a picture of chemical distribution and fluxes in the multimedia environment. A 1995 pioneering book, resulting from a series of workshops among model developers and users, reported the main advantages and identified needs for research in the field of multimedia fate models. Considerable efforts were devoted to their improvement in the past 25 years and many aspects were refined; notably the inclusion of nanomaterials among the modelled substances, the development of models at different spatial and temporal scales, the estimation of chemical properties and emission data, the incorporation of additional environmental media and processes, the integration of sensitivity and uncertainty analysis in the simulations. However, some challenging issues remain and require research efforts and attention: the need of methods to estimate partition coefficients for polar and ionizable chemical in the environment, a better description of bioavailability in different environments as well as the requirement of injecting more ecological realism in exposure predictions to account for the diversity of ecosystem structures and functions in risk assessment. Finally, to transfer new scientific developments into the realm of regulatory risk assessment, we propose the formation of expert groups that compare, discuss and recommend model modifications and updates and help develop practical tools for risk assessment.

Ares I Scale Model Acoustic Test Instrumentation for Acoustic and Pressure Measurements

NASA Technical Reports Server (NTRS)

Vargas, Magda B.; Counter, Douglas

2011-01-01

Ares I Scale Model Acoustic Test (ASMAT) is a 5% scale model test of the Ares I vehicle, launch pad and support structures conducted at MSFC to verify acoustic and ignition environments and evaluate water suppression systems Test design considerations 5% measurements must be scaled to full scale requiring high frequency measurements Users had different frequencies of interest Acoustics: 200 - 2,000 Hz full scale equals 4,000 - 40,000 Hz model scale Ignition Transient: 0 - 100 Hz full scale equals 0 - 2,000 Hz model scale Environment exposure Weather exposure: heat, humidity, thunderstorms, rain, cold and snow Test environments: Plume impingement heat and pressure, and water deluge impingement Several types of sensors were used to measure the environments Different instrument mounts were used according to the location and exposure to the environment This presentation addresses the observed effects of the selected sensors and mount design on the acoustic and pressure measurements

ANALYSIS OF THE MOTOR NEUROTOXICITY INDUCED BY ACUTE ORAL EXPOSURE TO MULTIPLE PYRETHROID COMPOUNDS IN THE RAT USING AN ADDITIVITY MODEL.

EPA Science Inventory

Use of pyrethroids has increased in the last decade, and co-exposure to multiple pyrethroids has been reported in humans. Pyrethroids produce neurotoxicity in mammals at dosages far below those producing lethality. The Food Quality Protection Act requires the EPA to consider cumu...

PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene

PubMed Central

Kim, David; Andersen, Melvin E.; Chao, Yi-Chun E.; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

2007-01-01

Background Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Objective Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. Methods The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. Results The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 × 10−5 cm/hr, b) permeability coefficient for the viable epidermis 3.0 × 10−3 cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers’ exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). Conclusions PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures. PMID:17589597

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.

PubMed

Kim, David; Andersen, Melvin E; Chao, Yi-Chun E; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2007-06-01

Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.

COMMUNITY SCALE AIR TOXICS MODELING WITH CMAQ

EPA Science Inventory

Consideration and movement for an urban air toxics control strategy is toward a community, exposure and risk-based modeling approach, with emphasis on assessments of areas that experience high air toxic concentration levels, the so-called "hot spots". This strategy will requir...

A CONSISTENT APPROACH FOR THE APPLICATION OF PHARMACOKINETIC MODELING IN CANCER RISK ASSESSMENT

EPA Science Inventory

Physiologically based pharmacokinetic (PBPK) modeling provides important capabilities for improving the reliability of the extrapolations across dose, species, and exposure route that are generally required in chemical risk assessment regardless of the toxic endpoint being consid...

PREDICTIVE ORGANOPHOSPHORUS (OP) PESTICIDE QSARS AND PBPK/PD MODELS FOR RISK ASSESSMENT OF SUSCEPTIBLE SUB-POPULATIONS

EPA Science Inventory

Successful use of the Exposure Related Dose Estimating Model (ERDEM) in risk assessment of susceptible human sub-populations, e.g., infants and children, requires input of quality experimental data. In the clear absence of quality data, PBPK models can be developed and possibl...

Exploration of the molecular basis of blast injury in a biofidelic model of traumatic brain injury

NASA Astrophysics Data System (ADS)

Thielen, P.; Mehoke, T.; Gleason, J.; Iwaskiw, A.; Paulson, J.; Merkle, A.; Wester, B.; Dymond, J.

2018-01-01

Biological response to blast overpressure is complex and results in various and potentially non-concomitant acute and long-term deficits to exposed individuals. Clinical links between blast severity and injury outcomes remain elusive and have yet to be fully described, resulting in a critical inability to develop associated protection and mitigation strategies. Further, experimental models frequently fail to reproduce observed physiological phenomena and/or introduce artifacts that confound analysis and reproducibility. New models are required that employ consistent mechanical inputs, scale with biological analogs and known clinical data, and permit high-throughput examination of biological responses for a range of environmental and battlefield- relevant exposures. Here we describe a novel, biofidelic headform capable of integrating complex biological samples for blast exposure studies. We additionally demonstrate its utility in detecting acute transcriptional responses in the model organism Caenorhabditis elegans after exposure to blast overpressure. This approach enables correlation between mechanical exposure and biological outcome, permitting both the enhancement of existing surrogate and computational models and the high-throughput biofidelic testing of current and future protection systems.

Conservative Estimation of Whole-body Average SAR in Infant Model for 0.3-6GHz Far-Field Exposure

NASA Astrophysics Data System (ADS)

Hirata, Akimasa; Nagaya, Yoshio; Ito, Naoki; Fujiwara, Osamu; Nagaoka, Tomoaki; Watanabe, Soichi

From an anatomically-based Japanese model of three-year-old child with a resolution of 1 mm, we developed a nine-month Japanese infant with linear shrink. With these models, we calculated the whole-body average specific absorption rate (WBA-SAR) for plane-wave exposure from 0.1 to 6 GHz. A conservative estimate of the WBA-SAR was also investigated by using three kinds of simple-shaped models: cuboid, ellipsoid and spheroid, whose parameters were determined based on the above three-year-old child model. As a result, the cuboid and ellipsoid were found to provide an overestimate of the WBA-SAR compared to the realistic model, whereas the spheroid does an underestimate. Based on these findings for different body models, we have specified the incident power density required to produce WBA-SAR of 0.08 W/kg, which is the basic restriction for public exposure in the guidelines of International Commission on Non-Ionizing Radiation Protection.

What happens in the skin? Integrating skin permeation kinetics into studies of developmental and reproductive toxicity following topical exposure.

PubMed

Dancik, Yuri; Bigliardi, Paul L; Bigliardi-Qi, Mei

2015-12-01

Animal-based developmental and reproductive toxicological studies involving skin exposure rarely incorporate information on skin permeation kinetics. For practical reasons, animal studies cannot investigate the many factors which can affect human skin permeation and systemic uptake kinetics in real-life scenarios. Traditional route-to-route extrapolation is based on the same types of experiments and requires assumptions regarding route similarity. Pharmacokinetic modeling based on skin physiology and structure is the most efficient way to incorporate the variety of intrinsic skin and exposure-dependent parameters occurring in clinical and occupational settings into one framework. Physiologically-based pharmacokinetic models enable the integration of available in vivo, in vitro and in silico data to quantitatively predict the kinetics of uptake at the site of interest, as needed for 21st century toxicology and risk assessment. As demonstrated herein, proper interpretation and integration of these data is a multidisciplinary endeavor requiring toxicological, risk assessment, mathematical, pharmaceutical, biological and dermatological expertise. Copyright © 2015 Elsevier Inc. All rights reserved.

Exposure calculation code module for reactor core analysis: BURNER

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

Vondy, D.R.; Cunningham, G.W.

1979-02-01

The code module BURNER for nuclear reactor exposure calculations is presented. The computer requirements are shown, as are the reference data and interface data file requirements, and the programmed equations and procedure of calculation are described. The operating history of a reactor is followed over the period between solutions of the space, energy neutronics problem. The end-of-period nuclide concentrations are determined given the necessary information. A steady state, continuous fueling model is treated in addition to the usual fixed fuel model. The control options provide flexibility to select among an unusually wide variety of programmed procedures. The code also providesmore » user option to make a number of auxiliary calculations and print such information as the local gamma source, cumulative exposure, and a fine scale power density distribution in a selected zone. The code is used locally in a system for computation which contains the VENTURE diffusion theory neutronics code and other modules.« less

Acute inhalative exposure assessment: derivation of guideline levels with special regard to sensitive subpopulations and time scaling.

PubMed

Mielke, Hans; Gundert, Anna; Abraham, Klaus; Gundert-Remy, Ursula

2005-10-30

Risk assessment for acute airborne exposure to volatile organic compounds (VOCs), including exposure to chemical warfare agents, requires consideration of local and systemic effects at high concentrations. The operating procedure developed by the US Acute Exposure Guideline Level (AEGL) committee has gained special attention, in part because of the international collaboration in the project. The procedure defines three levels (AEGL-1: discomfort; AEGL-2: irreversible or other serious, long-lasting adverse effects; AEGL-3: life-threatening effects or death) for different exposure times (10 and 30 min, and 1, 4 and 8 h). In this article, the methodology for deriving AEGL values is reported. Extending the areas covered by the existing AEGL methodology, sensitive subpopulations are dealt with in more detail. Sensitive persons are expected to suffer from stronger effects when exposed to a given external concentration. Using a kinetic model with the sample substance dichloromethane (DCM), the higher internal exposure of children is quantified and compared to a healthy, young adult. The difference is shown to depend on age, on dose, and on duration of exposure. Furthermore, several ways are presented to derive AEGL values for exposure times which differ from the exposure duration in animal studies ('time scaling'). In comparison to the conventional procedure, the alternative approaches are based on mechanistic models of the toxicodynamic effect. Use of these models results in AEGL values which are biologically justified.

Evaluating the effect of human activity patterns on air pollution exposure using an integrated field-based and agent-based modelling framework

NASA Astrophysics Data System (ADS)

Schmitz, Oliver; Beelen, Rob M. J.; de Bakker, Merijn P.; Karssenberg, Derek

2015-04-01

Constructing spatio-temporal numerical models to support risk assessment, such as assessing the exposure of humans to air pollution, often requires the integration of field-based and agent-based modelling approaches. Continuous environmental variables such as air pollution are best represented using the field-based approach which considers phenomena as continuous fields having attribute values at all locations. When calculating human exposure to such pollutants it is, however, preferable to consider the population as a set of individuals each with a particular activity pattern. This would allow to account for the spatio-temporal variation in a pollutant along the space-time paths travelled by individuals, determined, for example, by home and work locations, road network, and travel times. Modelling this activity pattern requires an agent-based or individual based modelling approach. In general, field- and agent-based models are constructed with the help of separate software tools, while both approaches should play together in an interacting way and preferably should be combined into one modelling framework, which would allow for efficient and effective implementation of models by domain specialists. To overcome this lack in integrated modelling frameworks, we aim at the development of concepts and software for an integrated field-based and agent-based modelling framework. Concepts merging field- and agent-based modelling were implemented by extending PCRaster (http://www.pcraster.eu), a field-based modelling library implemented in C++, with components for 1) representation of discrete, mobile, agents, 2) spatial networks and algorithms by integrating the NetworkX library (http://networkx.github.io), allowing therefore to calculate e.g. shortest routes or total transport costs between locations, and 3) functions for field-network interactions, allowing to assign field-based attribute values to networks (i.e. as edge weights), such as aggregated or averaged concentration values. We demonstrate the approach by using six land use regression (LUR) models developed in the ESCAPE (European Study of Cohorts for Air Pollution Effects) project. These models calculate several air pollutants (e.g. NO2, NOx, PM2.5) for the entire Netherlands at a high (5 m) resolution. Using these air pollution maps, we compare exposure of individuals calculated at their x, y location of their home, their work place, and aggregated over the close surroundings of these locations. In addition, total exposure is accumulated over daily activity patterns, summing exposure at home, at the work place, and while travelling between home and workplace, by routing individuals over the Dutch road network, using the shortest route. Finally, we illustrate how routes can be calculated with the minimum total exposure (instead of shortest distance).

Modeled occupational exposures to gas-phase medical laser-generated air contaminants.

PubMed

Lippert, Julia F; Lacey, Steven E; Jones, Rachael M

2014-01-01

Exposure monitoring data indicate the potential for substantive exposure to laser-generated air contaminants (LGAC); however the diversity of medical lasers and their applications limit generalization from direct workplace monitoring. Emission rates of seven previously reported gas-phase constituents of medical laser-generated air contaminants (LGAC) were determined experimentally and used in a semi-empirical two-zone model to estimate a range of plausible occupational exposures to health care staff. Single-source emission rates were generated in an emission chamber as a one-compartment mass balance model at steady-state. Clinical facility parameters such as room size and ventilation rate were based on standard ventilation and environmental conditions required for a laser surgical facility in compliance with regulatory agencies. All input variables in the model including point source emission rates were varied over an appropriate distribution in a Monte Carlo simulation to generate a range of time-weighted average (TWA) concentrations in the near and far field zones of the room in a conservative approach inclusive of all contributing factors to inform future predictive models. The concentrations were assessed for risk and the highest values were shown to be at least three orders of magnitude lower than the relevant occupational exposure limits (OELs). Estimated values do not appear to present a significant exposure hazard within the conditions of our emission rate estimates.

Dose conversion factors for radon: recent developments.

PubMed

Marsh, James W; Harrison, John D; Laurier, Dominique; Blanchardon, Eric; Paquet, François; Tirmarche, Margot

2010-10-01

Epidemiological studies of the occupational exposure of miners and domestic exposures of the public have provided strong and complementary evidence of the risks of lung cancer following inhalation of radon progeny. Recent miner epidemiological studies, which include low levels of exposure, long duration of follow-up, and good quality of individual exposure data, suggest higher risks of lung cancer per unit exposure than assumed previously by the International Commission on Radiological Protection (ICRP). Although risks can be managed by controlling exposures, dose estimates are required for the control of occupational exposures and are also useful for comparing sources of public exposure. Currently, ICRP calculates doses from radon and its progeny using dose conversion factors from exposure (WLM) to dose (mSv) based on miner epidemiological studies, referred to as the epidemiological approach. Revision of these dose conversion factors using risk estimates based on the most recent epidemiological data gives values that are in good agreement with the results of calculations using ICRP biokinetic and dosimetric models, the dosimetric approach. ICRP now proposes to treat radon progeny in the same way as other radionuclides and to publish dose coefficients calculated using models, for use within the ICRP system of protection.

Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential

PubMed Central

Mitchell, Jade; Arnot, Jon A.; Jolliet, Olivier; Georgopoulos, Panos G.; Isukapalli, Sastry; Dasgupta, Surajit; Pandian, Muhilan; Wambaugh, John; Egeghy, Peter; Cohen Hubal, Elaine A.; Vallero, Daniel A.

2014-01-01

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA’s need to develop novel approaches and tools for rapidly prioritizing chemicals, a “Challenge” was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA’s effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches. PMID:23707726

Measurement Error Correction for Predicted Spatiotemporal Air Pollution Exposures.

PubMed

Keller, Joshua P; Chang, Howard H; Strickland, Matthew J; Szpiro, Adam A

2017-05-01

Air pollution cohort studies are frequently analyzed in two stages, first modeling exposure then using predicted exposures to estimate health effects in a second regression model. The difference between predicted and unobserved true exposures introduces a form of measurement error in the second stage health model. Recent methods for spatial data correct for measurement error with a bootstrap and by requiring the study design ensure spatial compatibility, that is, monitor and subject locations are drawn from the same spatial distribution. These methods have not previously been applied to spatiotemporal exposure data. We analyzed the association between fine particulate matter (PM2.5) and birth weight in the US state of Georgia using records with estimated date of conception during 2002-2005 (n = 403,881). We predicted trimester-specific PM2.5 exposure using a complex spatiotemporal exposure model. To improve spatial compatibility, we restricted to mothers residing in counties with a PM2.5 monitor (n = 180,440). We accounted for additional measurement error via a nonparametric bootstrap. Third trimester PM2.5 exposure was associated with lower birth weight in the uncorrected (-2.4 g per 1 μg/m difference in exposure; 95% confidence interval [CI]: -3.9, -0.8) and bootstrap-corrected (-2.5 g, 95% CI: -4.2, -0.8) analyses. Results for the unrestricted analysis were attenuated (-0.66 g, 95% CI: -1.7, 0.35). This study presents a novel application of measurement error correction for spatiotemporal air pollution exposures. Our results demonstrate the importance of spatial compatibility between monitor and subject locations and provide evidence of the association between air pollution exposure and birth weight.

Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential.

PubMed

Mitchell, Jade; Arnot, Jon A; Jolliet, Olivier; Georgopoulos, Panos G; Isukapalli, Sastry; Dasgupta, Surajit; Pandian, Muhilan; Wambaugh, John; Egeghy, Peter; Cohen Hubal, Elaine A; Vallero, Daniel A

2013-08-01

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA's need to develop novel approaches and tools for rapidly prioritizing chemicals, a "Challenge" was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA's effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

12 CFR Appendix C to Part 567 - Risk-Based Capital Requirements-Internal-Ratings-Based and Advanced Measurement Approaches

Code of Federal Regulations, 2013 CFR

2013-01-01

... the savings association for one or more exposures is not commensurate with the risks associated with... a provision of this appendix to one or more exposures, provided that: (1) The savings association... sample period not used in model development. In this context, backtesting is one form of out-of-sample...

12 CFR Appendix C to Part 567 - Risk-Based Capital Requirements-Internal-Ratings-Based and Advanced Measurement Approaches

Code of Federal Regulations, 2011 CFR

2011-01-01

... the savings association for one or more exposures is not commensurate with the risks associated with... a provision of this appendix to one or more exposures, provided that: (1) The savings association... sample period not used in model development. In this context, backtesting is one form of out-of-sample...

12 CFR Appendix C to Part 567 - Risk-Based Capital Requirements-Internal-Ratings-Based and Advanced Measurement Approaches

Code of Federal Regulations, 2014 CFR

2014-01-01

... the savings association for one or more exposures is not commensurate with the risks associated with... a provision of this appendix to one or more exposures, provided that: (1) The savings association... sample period not used in model development. In this context, backtesting is one form of out-of-sample...

12 CFR Appendix C to Part 167 - Risk-Based Capital Requirements-Internal-Ratings-Based and Advanced Measurement Approaches

Code of Federal Regulations, 2013 CFR

2013-01-01

... the savings association for one or more exposures is not commensurate with the risks associated with... to apply a provision of this appendix to one or more exposures, provided that: (1) The savings... during a sample period not used in model development. In this context, backtesting is one form of out-of...

12 CFR Appendix C to Part 167 - Risk-Based Capital Requirements-Internal-Ratings-Based and Advanced Measurement Approaches

Code of Federal Regulations, 2012 CFR

2012-01-01

... the savings association for one or more exposures is not commensurate with the risks associated with... to apply a provision of this appendix to one or more exposures, provided that: (1) The savings... during a sample period not used in model development. In this context, backtesting is one form of out-of...

12 CFR Appendix C to Part 567 - Risk-Based Capital Requirements-Internal-Ratings-Based and Advanced Measurement Approaches

Code of Federal Regulations, 2012 CFR

2012-01-01

... the savings association for one or more exposures is not commensurate with the risks associated with... a provision of this appendix to one or more exposures, provided that: (1) The savings association... sample period not used in model development. In this context, backtesting is one form of out-of-sample...

Regulatory-Science: Biphasic Cancer Models or the LNT—Not Just a Matter of Biology!

PubMed Central

Ricci, Paolo F.; Sammis, Ian R.

2012-01-01

There is no doubt that prudence and risk aversion must guide public decisions when the associated adverse outcomes are either serious or irreversible. With any carcinogen, the levels of risk and needed protection before and after an event occurs, are determined by dose-response models. Regulatory law should not crowd out the actual beneficial effects from low dose exposures—when demonstrable—that are inevitably lost when it adopts the linear non-threshold (LNT) as its causal model. Because regulating exposures requires planning and developing protective measures for future acute and chronic exposures, public management decisions should be based on minimizing costs and harmful exposures. We address the direct and indirect effects of causation when the danger consists of exposure to very low levels of carcinogens and toxicants. The societal consequences of a policy can be deleterious when that policy is based on a risk assumed by the LNT, in cases where low exposures are actually beneficial. Our work develops the science and the law of causal risk modeling: both are interwoven. We suggest how their relevant characteristics differ, but do not attempt to keep them separated; as we demonstrate, this union, however unsatisfactory, cannot be severed. PMID:22740778

Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

PubMed Central

Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

2013-01-01

Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

The Effect of Ongoing Exposure Dynamics in Dose Response Relationships

PubMed Central

Pujol, Josep M.; Eisenberg, Joseph E.; Haas, Charles N.; Koopman, James S.

2009-01-01

Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, is a sequence of discrete events where concurrent or prior pathogen arrival affects the capacity of immune effectors to engage and kill newly arriving pathogens. We model immune effector and pathogen interactions during the period before infection becomes established in order to capture the dynamics generating dose timing effects. Model analysis reveals an inverse relationship between the time over which exposures accumulate and the risk of infection. Data from one time dose experiments will thus overestimate per pathogen infection risks of real world exposures. For instance, fitting our model to one time dosing data reveals a risk of 0.66 from 313 Cryptosporidium parvum pathogens. When the temporal exposure window is increased 100-fold using the same parameters fitted by our model to the one time dose data, the risk of infection is reduced to 0.09. Confirmation of this risk prediction requires data from experiments administering doses with different timings. Our model demonstrates that dose timing could markedly alter the risks generated by airborne versus fomite transmitted pathogens. PMID:19503605

Evaluating cardiac risk: exposure response analysis in early clinical drug development.

PubMed

Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

2018-01-01

The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

Vulnerability of Thai rice production to simultaneous climate and socioeconomic changes: a double exposure analysis

NASA Astrophysics Data System (ADS)

Sangpenchan, R.

2011-12-01

This research explores the vulnerability of Thai rice production to simultaneous exposure by climate and socioeconomic change -- so-called "double exposure." Both processes influence Thailand's rice production system, but the vulnerabilities associated with their interactions are unknown. To understand this double exposure, I adopts a mixed-method, qualitative-quantitative analytical approach consisting of three phases of analysis involving a Vulnerability Scoping Diagram, a Principal Component Analysis, and the EPIC crop model using proxy datasets collected from secondary data sources at provincial scales.The first and second phases identify key variables representing each of the three dimensions of vulnerability -- exposure, sensitivity, and adaptive capacity indicating that the greatest vulnerability in the rice production system occurs in households and areas with high exposure to climate change, high sensitivity to climate and socioeconomic stress, and low adaptive capacity. In the third phase, the EPIC crop model simulates rice yields associated with future climate change projected by CSIRO and MIROC climate models. Climate change-only scenarios project the decrease in yields by 10% from the current productivity during 2016-2025 and 30% during 2045-2054. Scenarios applying both climate change and improved technology and management practices show that a 50% increase in rice production is possible, but requires strong collaboration between sectors to advance agricultural research and technology and requires strong adaptive capacity in the rice production system characterized by well-developed social capital, social networks, financial capacity, and infrastructure and household mobility at the local scale. The vulnerability assessment and climate and crop adaptation simulations used here provide useful information to decision makers developing vulnerability reduction plans in the face of concurrent climate and socioeconomic change.

Toward a Stress Process Model of Children's Exposure to Physical Family and Community Violence

ERIC Educational Resources Information Center

Foster, Holly; Brooks-Gunn, Jeanne

2009-01-01

Theoretically informed models are required to further the comprehensive understanding of children's ETV. We draw on the stress process paradigm to forward an overall conceptual model of ETV (ETV) in childhood and adolescence. Around this conceptual model, we synthesize research in four dominant areas of the literature which are detailed but often…

Residential energy use emissions dominate health impacts from exposure to ambient particulate matter in India.

PubMed

Conibear, Luke; Butt, Edward W; Knote, Christoph; Arnold, Stephen R; Spracklen, Dominick V

2018-02-12

Exposure to ambient fine particulate matter (PM 2.5 ) is a leading contributor to diseases in India. Previous studies analysing emission source attributions were restricted by coarse model resolution and limited PM 2.5 observations. We use a regional model informed by new observations to make the first high-resolution study of the sector-specific disease burden from ambient PM 2.5 exposure in India. Observed annual mean PM 2.5 concentrations exceed 100 μg m -3 and are well simulated by the model. We calculate that the emissions from residential energy use dominate (52%) population-weighted annual mean PM 2.5 concentrations, and are attributed to 511,000 (95UI: 340,000-697,000) premature mortalities annually. However, removing residential energy use emissions would avert only 256,000 (95UI: 162,000-340,000), due to the non-linear exposure-response relationship causing health effects to saturate at high PM 2.5 concentrations. Consequently, large reductions in emissions will be required to reduce the health burden from ambient PM 2.5 exposure in India.

Mapping the spatio-temporal risk of lead exposure in apex species for more effective mitigation

PubMed Central

Mateo-Tomás, Patricia; Olea, Pedro P.; Jiménez-Moreno, María; Camarero, Pablo R.; Sánchez-Barbudo, Inés S.; Rodríguez Martín-Doimeadios, Rosa C.; Mateo, Rafael

2016-01-01

Effective mitigation of the risks posed by environmental contaminants for ecosystem integrity and human health requires knowing their sources and spatio-temporal distribution. We analysed the exposure to lead (Pb) in griffon vulture Gyps fulvus—an apex species valuable as biomonitoring sentinel. We determined vultures' lead exposure and its main sources by combining isotope signatures and modelling analyses of 691 bird blood samples collected over 5 years. We made yearlong spatially explicit predictions of the species risk of lead exposure. Our results highlight elevated lead exposure of griffon vultures (i.e. 44.9% of the studied population, approximately 15% of the European, showed lead blood levels more than 200 ng ml−1) partly owing to environmental lead (e.g. geological sources). These exposures to environmental lead of geological sources increased in those vultures exposed to point sources (e.g. lead-based ammunition). These spatial models and pollutant risk maps are powerful tools that identify areas of wildlife exposure to potentially harmful sources of lead that could affect ecosystem and human health. PMID:27466455

Plasma Vehicle Charging Analysis for Orion Flight Test 1

NASA Technical Reports Server (NTRS)

Lallement, L.; McDonald, T.; Norgard, J.; Scully, B.

2014-01-01

In preparation for the upcoming experimental test flight for the Orion crew module, considerable interest was raised over the possibility of exposure to elevated levels of plasma activity and vehicle charging both externally on surfaces and internally on dielectrics during the flight test orbital operations. Initial analysis using NASCAP-2K indicated very high levels of exposure, and this generated additional interest in refining/defining the plasma and spacecraft models used in the analysis. This refinement was pursued, resulting in the use of specific AE8 and AP8 models, rather than SCATHA models, as well as consideration of flight trajectory, time duration, and other parameters possibly affecting the levels of exposure and the magnitude of charge deposition. Analysis using these refined models strongly indicated that, for flight test operations, no special surface coatings were necessary for the thermal protection system, but would definitely be required for future GEO, trans-lunar, and extra-lunar missions...

Plasma Vehicle Charging Analysis for Orion Flight Test 1

NASA Technical Reports Server (NTRS)

Scully, B.; Norgard, J.

2015-01-01

In preparation for the upcoming experimental test flight for the Orion crew module, considerable interest was raised over the possibility of exposure to elevated levels of plasma activity and vehicle charging both externally on surfaces and internally on dielectrics during the flight test orbital operations. Initial analysis using NASCAP-2K indicated very high levels of exposure, and this generated additional interest in refining/defining the plasma and spacecraft models used in the analysis. This refinement was pursued, resulting in the use of specific AE8 and AP8 models, rather than SCATHA models, as well as consideration of flight trajectory, time duration, and other parameters possibly affecting the levels of exposure and the magnitude of charge deposition. Analysis using these refined models strongly indicated that, for flight test operations, no special surface coatings were necessary for the Thermal Protection System (TPS), but would definitely be required for future GEO, trans-lunar, and extra-lunar missions.

Prediction of Chemical Function: Model Development and ...

EPA Pesticide Factsheets

The United States Environmental Protection Agency’s Exposure Forecaster (ExpoCast) project is developing both statistical and mechanism-based computational models for predicting exposures to thousands of chemicals, including those in consumer products. The high-throughput (HT) screening-level exposures developed under ExpoCast can be combined with HT screening (HTS) bioactivity data for the risk-based prioritization of chemicals for further evaluation. The functional role (e.g. solvent, plasticizer, fragrance) that a chemical performs can drive both the types of products in which it is found and the concentration in which it is present and therefore impacting exposure potential. However, critical chemical use information (including functional role) is lacking for the majority of commercial chemicals for which exposure estimates are needed. A suite of machine-learning based models for classifying chemicals in terms of their likely functional roles in products based on structure were developed. This effort required collection, curation, and harmonization of publically-available data sources of chemical functional use information from government and industry bodies. Physicochemical and structure descriptor data were generated for chemicals with function data. Machine-learning classifier models for function were then built in a cross-validated manner from the descriptor/function data using the method of random forests. The models were applied to: 1) predict chemi

A framework for global river flood risk assessment

NASA Astrophysics Data System (ADS)

Winsemius, H. C.; Van Beek, L. P. H.; Bouwman, A.; Ward, P. J.; Jongman, B.

2012-04-01

There is an increasing need for strategic global assessments of flood risks. Such assessments may be required by: (a) International Financing Institutes and Disaster Management Agencies to evaluate where, when, and which investments in flood risk mitigation are most required; (b) (re-)insurers, who need to determine their required coverage capital; and (c) large companies to account for risks of regional investments. In this contribution, we propose a framework for global river flood risk assessment. The framework combines coarse scale resolution hazard probability distributions, derived from global hydrological model runs (typical scale about 0.5 degree resolution) with high resolution estimates of exposure indicators. The high resolution is required because floods typically occur at a much smaller scale than the typical resolution of global hydrological models, and exposure indicators such as population, land use and economic value generally are strongly variable in space and time. The framework therefore estimates hazard at a high resolution ( 1 km2) by using a) global forcing data sets of the current (or in scenario mode, future) climate; b) a global hydrological model; c) a global flood routing model, and d) importantly, a flood spatial downscaling routine. This results in probability distributions of annual flood extremes as an indicator of flood hazard, at the appropriate resolution. A second component of the framework combines the hazard probability distribution with classical flood impact models (e.g. damage, affected GDP, affected population) to establish indicators for flood risk. The framework can be applied with a large number of datasets and models and sensitivities of such choices can be evaluated by the user. The framework is applied using the global hydrological model PCR-GLOBWB, combined with a global flood routing model. Downscaling of the hazard probability distributions to 1 km2 resolution is performed with a new downscaling algorithm, applied on a number of target regions. We demonstrate the use of impact models in these regions based on global GDP, population, and land use maps. In this application, we show sensitivities of the estimated risks with regard to the use of different climate input datasets, decisions made in the downscaling algorithm, and different approaches to establish distributed estimates of GDP and asset exposure to flooding.

Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.

PubMed

Hu, Danqing; Flick, Randall P; Zaccariello, Michael J; Colligan, Robert C; Katusic, Slavica K; Schroeder, Darrell R; Hanson, Andrew C; Buenvenida, Shonie L; Gleich, Stephen J; Wilder, Robert T; Sprung, Juraj; Warner, David O

2017-08-01

Exposure of young animals to general anesthesia causes neurodegeneration and lasting behavioral abnormalities; whether these findings translate to children remains unclear. This study used a population-based birth cohort to test the hypothesis that multiple, but not single, exposures to procedures requiring general anesthesia before age 3 yr are associated with adverse neurodevelopmental outcomes. A retrospective study cohort was assembled from children born in Olmsted County, Minnesota, from 1996 to 2000 (inclusive). Propensity matching selected children exposed and not exposed to general anesthesia before age 3 yr. Outcomes ascertained via medical and school records included learning disabilities, attention-deficit/hyperactivity disorder, and group-administered ability and achievement tests. Analysis methods included proportional hazard regression models and mixed linear models. For the 116 multiply exposed, 457 singly exposed, and 463 unexposed children analyzed, multiple, but not single, exposures were associated with an increased frequency of both learning disabilities and attention-deficit/hyperactivity disorder (hazard ratio for learning disabilities = 2.17 [95% CI, 1.32 to 3.59], unexposed as reference). Multiple exposures were associated with decreases in both cognitive ability and academic achievement. Single exposures were associated with modest decreases in reading and language achievement but not cognitive ability. These findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention. Although a robust association was observed, these data do not determine whether anesthesia per se is causal.

Subcortical amplitude modulation encoding deficits suggest evidence of cochlear synaptopathy in normal-hearing 18-19 year olds with higher lifetime noise exposure.

PubMed

Paul, Brandon T; Waheed, Sajal; Bruce, Ian C; Roberts, Larry E

2017-11-01

Noise exposure and aging can damage cochlear synapses required for suprathreshold listening, even when cochlear structures needed for hearing at threshold remain unaffected. To control for effects of aging, behavioral amplitude modulation (AM) detection and subcortical envelope following responses (EFRs) to AM tones in 25 age-restricted (18-19 years) participants with normal thresholds, but different self-reported noise exposure histories were studied. Participants with more noise exposure had smaller EFRs and tended to have poorer AM detection than less-exposed individuals. Simulations of the EFR using a well-established cochlear model were consistent with more synaptopathy in participants reporting greater noise exposure.

Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

PubMed Central

Weir, Scott M.; Talent, Larry G.; Anderson, Todd A.; Salice, Christopher J.

2014-01-01

Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals. PMID:24941063

Unraveling the relative importance of oral and dermal contaminant exposure in reptiles: insights from studies using the western fence lizard (Sceloporus occidentalis).

PubMed

Weir, Scott M; Talent, Larry G; Anderson, Todd A; Salice, Christopher J

2014-01-01

Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals.

A classical regression framework for mediation analysis: fitting one model to estimate mediation effects.

PubMed

Saunders, Christina T; Blume, Jeffrey D

2017-10-26

Mediation analysis explores the degree to which an exposure's effect on an outcome is diverted through a mediating variable. We describe a classical regression framework for conducting mediation analyses in which estimates of causal mediation effects and their variance are obtained from the fit of a single regression model. The vector of changes in exposure pathway coefficients, which we named the essential mediation components (EMCs), is used to estimate standard causal mediation effects. Because these effects are often simple functions of the EMCs, an analytical expression for their model-based variance follows directly. Given this formula, it is instructive to revisit the performance of routinely used variance approximations (e.g., delta method and resampling methods). Requiring the fit of only one model reduces the computation time required for complex mediation analyses and permits the use of a rich suite of regression tools that are not easily implemented on a system of three equations, as would be required in the Baron-Kenny framework. Using data from the BRAIN-ICU study, we provide examples to illustrate the advantages of this framework and compare it with the existing approaches. © The Author 2017. Published by Oxford University Press.

Operation of the computer model for direct atomic oxygen exposure of Earth satellites

NASA Technical Reports Server (NTRS)

Bourassa, R. J.; Gruenbaum, P. E.; Gillis, J. R.; Hargraves, C. R.

1995-01-01

One of the primary causes of material degradation in low Earth orbit (LEO) is exposure to atomic oxygen. When atomic oxygen molecules collide with an orbiting spacecraft, the relative velocity is 7 to 8 km/sec and the collision energy is 4 to 5 eV per atom. Under these conditions, atomic oxygen may initiate a number of chemical and physical reactions with exposed materials. These reactions contribute to material degradation, surface erosion, and contamination. Interpretation of these effects on materials and the design of space hardware to withstand on-orbit conditions requires quantitative knowledge of the atomic oxygen exposure environment. Atomic oxygen flux is a function of orbit altitude, the orientation of the orbit plan to the Sun, solar and geomagnetic activity, and the angle between exposed surfaces and the spacecraft heading. We have developed a computer model to predict the atomic oxygen exposure of spacecraft in low Earth orbit. The application of this computer model is discussed.

Meeting Vitamin D Requirements in White Caucasians at UK Latitudes: Providing a Choice.

PubMed

Webb, Ann R; Kazantzidis, Andreas; Kift, Richard C; Farrar, Mark D; Wilkinson, Jack; Rhodes, Lesley E

2018-04-17

The body gains vitamin D through both oral intake (diet/supplementation) and synthesis in skin upon exposure to ultraviolet radiation (UVR). Sun exposure is the major source for most people even though sun exposure is complex and limited by climate and culture. We aimed to quantify the sun exposure required to meet vitamin D targets year-round and determine whether this can be safely achieved in a simply defined manner in the UK as an alternative to increasing vitamin D oral intake. Data from observation (sun exposure, diet, and vitamin D status) and UVR intervention studies performed with white Caucasian adults were combined with modeled all-weather UVR climatology. Daily vitamin D effective UVR doses (all-weather) were calculated across the UK based on ten-year climatology for pre-defined lunchtime exposure regimes. Calculations then determined the time necessary to spend outdoors for the body to gain sufficient vitamin D levels for year-round needs without being sunburnt under differing exposure scenarios. Results show that, in specified conditions, white Caucasians across the UK need nine minutes of daily sunlight at lunchtime from March to September for 25(OH)D levels to remain ≥25 nmol/L throughout the winter. This assumes forearms and lower legs are exposed June-August, while in the remaining, cooler months only hands and face need be exposed. Exposing only the hands and face throughout the summer does not meet requirements.

Modeling Physiological Processes That Relate Toxicant Exposure and Bacterial Population Dynamics

PubMed Central

Klanjscek, Tin; Nisbet, Roger M.; Priester, John H.; Holden, Patricia A.

2012-01-01

Quantifying effects of toxicant exposure on metabolic processes is crucial to predicting microbial growth patterns in different environments. Mechanistic models, such as those based on Dynamic Energy Budget (DEB) theory, can link physiological processes to microbial growth. Here we expand the DEB framework to include explicit consideration of the role of reactive oxygen species (ROS). Extensions considered are: (i) additional terms in the equation for the “hazard rate” that quantifies mortality risk; (ii) a variable representing environmental degradation; (iii) a mechanistic description of toxic effects linked to increase in ROS production and aging acceleration, and to non-competitive inhibition of transport channels; (iv) a new representation of the “lag time” based on energy required for acclimation. We estimate model parameters using calibrated Pseudomonas aeruginosa optical density growth data for seven levels of cadmium exposure. The model reproduces growth patterns for all treatments with a single common parameter set, and bacterial growth for treatments of up to 150 mg(Cd)/L can be predicted reasonably well using parameters estimated from cadmium treatments of 20 mg(Cd)/L and lower. Our approach is an important step towards connecting levels of biological organization in ecotoxicology. The presented model reveals possible connections between processes that are not obvious from purely empirical considerations, enables validation and hypothesis testing by creating testable predictions, and identifies research required to further develop the theory. PMID:22328915

Estimating Air-Manganese Exposures in Two Ohio Towns ...

EPA Pesticide Factsheets

Manganese (Mn), a nutrient required for normal metabolic function, is also a persistent air pollutant and a known neurotoxin at high concentrations. Elevated exposures can result in a number of motor and cognitive deficits. Quantifying chronic personal exposures in residential populations studied by environmental epidemiologists can be time-consuming and expensive. We developed an approach for quantifying chronic exposures for two towns (Marietta and East Liverpool, Ohio) with elevated air Mn concentrations (air-Mn) related to ambient emissions from industrial processes. This was accomplished through the use of measured and modeled data in the communities studied. A novel approach was developed because one of the facilities lacked emissions data for the purposes of modeling. A unit emission rate was assumed over the surface area of both source facilities, and offsite concentrations at receptor residences and air monitoring sites were estimated with the American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD). Ratios of all modeled receptor points were created, and a long-running air monitor was identified as a reference location. All ratios were normalized to the reference location. Long-term averages at all residential receptor points were calculated using modeled ratios and data from the reference monitoring location. Modeled five-year average air-Mn exposures ranged from 0.03-1.61 µg/m3 in Marietta and 0.01-6.32 µg/m3 in E

Infants and young children modeling method for numerical dosimetry studies: application to plane wave exposure

NASA Astrophysics Data System (ADS)

Dahdouh, S.; Varsier, N.; Nunez Ochoa, M. A.; Wiart, J.; Peyman, A.; Bloch, I.

2016-02-01

Numerical dosimetry studies require the development of accurate numerical 3D models of the human body. This paper proposes a novel method for building 3D heterogeneous young children models combining results obtained from a semi-automatic multi-organ segmentation algorithm and an anatomy deformation method. The data consist of 3D magnetic resonance images, which are first segmented to obtain a set of initial tissues. A deformation procedure guided by the segmentation results is then developed in order to obtain five young children models ranging from the age of 5 to 37 months. By constraining the deformation of an older child model toward a younger one using segmentation results, we assure the anatomical realism of the models. Using the proposed framework, five models, containing thirteen tissues, are built. Three of these models are used in a prospective dosimetry study to analyze young child exposure to radiofrequency electromagnetic fields. The results lean to show the existence of a relationship between age and whole body exposure. The results also highlight the necessity to specifically study and develop measurements of child tissues dielectric properties.

Sample size calculations for case-control studies

Cancer.gov

This R package can be used to calculate the required samples size for unconditional multivariate analyses of unmatched case-control studies. The sample sizes are for a scalar exposure effect, such as binary, ordinal or continuous exposures. The sample sizes can also be computed for scalar interaction effects. The analyses account for the effects of potential confounder variables that are also included in the multivariate logistic model.

Determinants of wheat antigen and fungal alpha-amylase exposure in bakeries.

PubMed

Burstyn, I; Teschke, K; Bartlett, K; Kennedy, S M

1998-05-01

The study's objectives were to measure flour antigen exposure in bakeries and define the determinants of exposure. Ninety-six bakery workers, employed in seven different bakeries, participated in the study. Two side-by-side full-shift inhalable dust samples were obtained from each study participant on a single occasion. The flour antigen exposure was measured as wheat antigen and fungal alpha-amylase content of the water-soluble fraction of inhalable dust, assayed via enzyme-linked immunosorbent assays. During the entire sampling period bakers were observed and information on 14 different tasks was recorded at 15-minute intervals. Other production characteristics were also recorded for each sampling day and used in statistical modeling to identify significant predictors of exposure. The mean alpha-amylase antigen exposure was 22.0 ng/m3 (ranging from below the limit of detection of 0.1 ng/m3 to 307.1 ng/m3) and the mean wheat antigen exposure was 109 micrograms/m3 (ranging from below the limit of detection of 1 microgram/m3 to 1018 micrograms/m3). Regression models that explained 74% of variability in wheat antigen and alpha-amylase antigen exposures were constructed. The models indicated that tasks such as weighing, pouring, and operating dough-brakers increased flour antigen exposure, while packing and decorating resulted in lower exposures. Croissant, puff-pastry, and bread/bun production lines were associated with increased exposure, while cake production and substitution of dusting with the use of divider oil were associated with decreased exposure. Exposure levels can be reduced by the automation of forming tasks, alteration of tasks requiring pouring of flour, and changes to the types of products manufactured.

Urban gardens: Lead exposure, recontamination mechanisms, and implications for remediation design

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

Clark, Heather F.; Hausladen, Debra M.; Brabander, Daniel J.

2008-07-15

Environmental lead contamination is prevalent in urban areas where soil represents a significant sink and pathway of exposure. This study characterizes the speciation of lead that is relevant to local recontamination and to human exposure in the backyard gardens of Roxbury and Dorchester, MA, USA. One hundred forty-one backyard gardens were tested by X-ray fluorescence, and 81% of gardens have lead levels above the US EPA action limit of 400 {mu}g/g. Raised gardening beds are the in situ exposure reduction method used in the communities to promote urban gardening. Raised beds were tested for lead and the results showed thatmore » the lead concentration increased from an initial range of 150{+-}40 {mu}g/g to an average of 336 {mu}g/g over 4 years. The percent distribution of lead in the fine grain soil (<100 {mu}m) and the trace metal signature of the raised beds support the conclusion that the mechanism of recontamination is wind-transported particles. Scanning electron microscopy and sequential extraction were used to characterize the speciation of lead, and the trace metal signature of the fine grain soil in both gardens and raised gardening beds is characteristic of lead-based paint. This study demonstrates that raised beds are a limited exposure reduction method and require maintenance to achieve exposure reduction goals. An exposure model was developed based on a suite of parameters that combine relevant values from the literature with site-specific quantification of exposure pathways. This model suggests that consumption of homegrown produce accounts for only 3% of children's daily exposure of lead while ingestion of fine grained soil (<100 {mu}m) accounts for 82% of the daily exposure. This study indicates that urban lead remediation on a yard-by-yard scale requires constant maintenance and that remediation may need to occur on a neighborhood-wide scale.« less

Urban gardens: lead exposure, recontamination mechanisms, and implications for remediation design.

PubMed

Clark, Heather F; Hausladen, Debra M; Brabander, Daniel J

2008-07-01

Environmental lead contamination is prevalent in urban areas where soil represents a significant sink and pathway of exposure. This study characterizes the speciation of lead that is relevant to local recontamination and to human exposure in the backyard gardens of Roxbury and Dorchester, MA, USA. One hundred forty-one backyard gardens were tested by X-ray fluorescence, and 81% of gardens have lead levels above the US EPA action limit of 400 microg/g. Raised gardening beds are the in situ exposure reduction method used in the communities to promote urban gardening. Raised beds were tested for lead and the results showed that the lead concentration increased from an initial range of 150+/-40 microg/g to an average of 336 microg/g over 4 years. The percent distribution of lead in the fine grain soil (<100 microm) and the trace metal signature of the raised beds support the conclusion that the mechanism of recontamination is wind-transported particles. Scanning electron microscopy and sequential extraction were used to characterize the speciation of lead, and the trace metal signature of the fine grain soil in both gardens and raised gardening beds is characteristic of lead-based paint. This study demonstrates that raised beds are a limited exposure reduction method and require maintenance to achieve exposure reduction goals. An exposure model was developed based on a suite of parameters that combine relevant values from the literature with site-specific quantification of exposure pathways. This model suggests that consumption of homegrown produce accounts for only 3% of children's daily exposure of lead while ingestion of fine grained soil (<100 microm) accounts for 82% of the daily exposure. This study indicates that urban lead remediation on a yard-by-yard scale requires constant maintenance and that remediation may need to occur on a neighborhood-wide scale.

Exposure Time Distributions reveal Denitrification Rates along Groundwater Flow Path of an Agricultural Unconfined Aquifer

NASA Astrophysics Data System (ADS)

Kolbe, T.; Abbott, B. W.; Thomas, Z.; Labasque, T.; Aquilina, L.; Laverman, A.; Babey, T.; Marçais, J.; Fleckenstein, J. H.; Peiffer, S.; De Dreuzy, J. R.; Pinay, G.

2016-12-01

Groundwater contamination by nitrate is nearly ubiquitous in agricultural regions. Nitrate is highly mobile in groundwater and though it can be denitrified in the aquifer (reduced to inert N2 gas), this process requires the simultaneous occurrence of anoxia, an electron donor (e.g. organic carbon, pyrite), nitrate, and microorganisms capable of denitrification. In addition to this the ratio of the time groundwater spent in a denitrifying environment (exposure time) to the characteristic denitrification reaction time plays an important role, because denitrification can only occur if the exposure time is longer than the characteristic reaction time. Despite a long history of field studies and numerical models, it remains exceedingly difficult to measure or model exposure times in the subsurface at the catchment scale. To approach this problem, we developed a unified modelling approach combining measured environmental proxies with an exposure time based reactive transport model. We measured groundwater age, nitrogen and sulfur isotopes, and water chemistry from agricultural wells in an unconfined aquifer in Brittany, France, to quantify changes in nitrate concentration due to dilution and denitrification. Field data showed large differences in nitrate concentrations among wells, associated with differences in the exposure time distributions. By constraining a catchment-scale characteristic reaction time for denitrification with water chemistry proxies and exposure times, we were able to assess rates of denitrification along groundwater flow paths. This unified modeling approach is transferable to other catchments and could be further used to investigate how catchment structure and flow dynamics interact with biogeochemical processes such as denitrification.

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.

Variable population exposure and distributed travel speeds in least-cost tsunami evacuation modelling

NASA Astrophysics Data System (ADS)

Fraser, S. A.; Wood, N. J.; Johnston, D. M.; Leonard, G. S.; Greening, P. D.; Rossetto, T.

2014-11-01

Evacuation of the population from a tsunami hazard zone is vital to reduce life-loss due to inundation. Geospatial least-cost distance modelling provides one approach to assessing tsunami evacuation potential. Previous models have generally used two static exposure scenarios and fixed travel speeds to represent population movement. Some analyses have assumed immediate departure or a common evacuation departure time for all exposed population. Here, a method is proposed to incorporate time-variable exposure, distributed travel speeds, and uncertain evacuation departure time into an existing anisotropic least-cost path distance framework. The method is demonstrated for hypothetical local-source tsunami evacuation in Napier City, Hawke's Bay, New Zealand. There is significant diurnal variation in pedestrian evacuation potential at the suburb level, although the total number of people unable to evacuate is stable across all scenarios. Whilst some fixed travel speeds approximate a distributed speed approach, others may overestimate evacuation potential. The impact of evacuation departure time is a significant contributor to total evacuation time. This method improves least-cost modelling of evacuation dynamics for evacuation planning, casualty modelling, and development of emergency response training scenarios. However, it requires detailed exposure data, which may preclude its use in many situations.

Variable population exposure and distributed travel speeds in least-cost tsunami evacuation modelling

USGS Publications Warehouse

Fraser, Stuart A.; Wood, Nathan J.; Johnston, David A.; Leonard, Graham S.; Greening, Paul D.; Rossetto, Tiziana

2014-01-01

Evacuation of the population from a tsunami hazard zone is vital to reduce life-loss due to inundation. Geospatial least-cost distance modelling provides one approach to assessing tsunami evacuation potential. Previous models have generally used two static exposure scenarios and fixed travel speeds to represent population movement. Some analyses have assumed immediate departure or a common evacuation departure time for all exposed population. Here, a method is proposed to incorporate time-variable exposure, distributed travel speeds, and uncertain evacuation departure time into an existing anisotropic least-cost path distance framework. The method is demonstrated for hypothetical local-source tsunami evacuation in Napier City, Hawke's Bay, New Zealand. There is significant diurnal variation in pedestrian evacuation potential at the suburb level, although the total number of people unable to evacuate is stable across all scenarios. Whilst some fixed travel speeds approximate a distributed speed approach, others may overestimate evacuation potential. The impact of evacuation departure time is a significant contributor to total evacuation time. This method improves least-cost modelling of evacuation dynamics for evacuation planning, casualty modelling, and development of emergency response training scenarios. However, it requires detailed exposure data, which may preclude its use in many situations.

Use-Exposure Relationships of Pesticides for Aquatic Risk Assessment

PubMed Central

Luo, Yuzhou; Spurlock, Frank; Deng, Xin; Gill, Sheryl; Goh, Kean

2011-01-01

Field-scale environmental models have been widely used in aquatic exposure assessments of pesticides. Those models usually require a large set of input parameters and separate simulations for each pesticide in evaluation. In this study, a simple use-exposure relationship is developed based on regression analysis of stochastic simulation results generated from the Pesticide Root-Zone Model (PRZM). The developed mathematical relationship estimates edge-of-field peak concentrations of pesticides from aerobic soil metabolism half-life (AERO), organic carbon-normalized soil sorption coefficient (KOC), and application rate (RATE). In a case study of California crop scenarios, the relationships explained 90–95% of the variances in the peak concentrations of dissolved pesticides as predicted by PRZM simulations for a 30-year period. KOC was identified as the governing parameter in determining the relative magnitudes of pesticide exposures in a given crop scenario. The results of model application also indicated that the effects of chemical fate processes such as partitioning and degradation on pesticide exposure were similar among crop scenarios, while the cross-scenario variations were mainly associated with the landscape characteristics, such as organic carbon contents and curve numbers. With a minimum set of input data, the use-exposure relationships proposed in this study could be used in screening procedures for potential water quality impacts from the off-site movement of pesticides. PMID:21483772

Comparing Data Input Requirements of Statistical vs. Process-based Watershed Models Applied for Prediction of Fecal Indicator and Pathogen Levels in Recreational Beaches

EPA Science Inventory

Same day prediction of fecal indicator bacteria (FIB) concentrations and bather protection from the risk of exposure to pathogens are two important goals of implementing a modeling program at recreational beaches. Sampling efforts for modelling applications can be expensive and t...

Validity of at home model predictions as a proxy for personal exposure to radiofrequency electromagnetic fields from mobile phone base stations.

PubMed

Martens, Astrid L; Bolte, John F B; Beekhuizen, Johan; Kromhout, Hans; Smid, Tjabe; Vermeulen, Roel C H

2015-10-01

Epidemiological studies on the potential health effects of RF-EMF from mobile phone base stations require efficient and accurate exposure assessment methods. Previous studies have demonstrated that the 3D geospatial model NISMap is able to rank locations by indoor and outdoor RF-EMF exposure levels. This study extends on previous work by evaluating the suitability of using NISMap to estimate indoor RF-EMF exposure levels at home as a proxy for personal exposure to RF-EMF from mobile phone base stations. For 93 individuals in the Netherlands we measured personal exposure to RF-EMF from mobile phone base stations during a 24h period using an EME-SPY 121 exposimeter. Each individual kept a diary from which we extracted the time spent at home and in the bedroom. We used NISMap to model exposure at the home address of the participant (at bedroom height). We then compared model predictions with measurements for the 24h period, when at home, and in the bedroom by the Spearman correlation coefficient (rsp) and by calculating specificity and sensitivity using the 90th percentile of the exposure distribution as a cutpoint for high exposure. We found a low to moderate rsp of 0.36 for the 24h period, 0.51 for measurements at home, and 0.41 for measurements in the bedroom. The specificity was high (0.9) but with a low sensitivity (0.3). These results indicate that a meaningful ranking of personal RF-EMF can be achieved, even though the correlation between model predictions and 24h personal RF-EMF measurements is lower than with at home measurements. However, the use of at home RF-EMF field predictions from mobile phone base stations in epidemiological studies leads to significant exposure misclassification that will result in a loss of statistical power to detect health effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Small fish models for identifying carcinogens in the aqueous environment

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

Hawkins, W.E.; Overstreet, R.M.; Walker, W.W.

1988-10-01

Contaminants in water and sediments can be carcinogenic to aquatic wildlife as well as humans. Identifying those carcinogens, however, is difficult because they often occur in low concentrations and exert their effects over a large part of the life span of affected organisms. Furthermore, the carcinogens are often components of complex mixtures. Recent studies suggest that laboratory-reared fish species might be well suited for testing water-associated and other carcinogens. Here, we review the principal carcinogen exposure methods that utilize small fish species or can be adapted to utilize small fish species to detect carcinogens in aqueous environments. Emphasis is placedmore » on methods for which the end-point is tumor induction. The methods discussed are dietary exposures, skin painting, embryo microinjection, early life stage (pulse) exposures, static water exposures, flow-through exposures, and controlled field exposures. Early life stage exposures seem to have the greatest utility with regard to carcinogen sensitivity, ease of administration, disposal of test compounds, and economy of materials and effort. For certain types of carcinogens, however, long-term flow-through exposures are probably required. In summary, small fish carcinogenesis models offer an array of methodologies that can be utilized in a variety of combinations depending on compounds tested, exposure parameters employed, and end point sought.« less

An introduction to the indirect exposure assessment approach: modeling human exposure using microenvironmental measurements and the recent National Human Activity Pattern Survey.

PubMed Central

Klepeis, N E

1999-01-01

Indirect exposure approaches offer a feasible and accurate method for estimating population exposures to indoor pollutants, including environmental tobacco smoke (ETS). In an effort to make the indirect exposure assessment approach more accessible to people in the health and risk assessment fields, this paper provides examples using real data from (italic>a(/italic>) a week-long personal carbon monoxide monitoring survey conducted by the author; and (italic>b(/italic>) the 1992 to 1994 National Human Activity Pattern Survey (NHAPS) for the United States. The indirect approach uses measurements of exposures in specific microenvironments (e.g., homes, bars, offices), validated microenvironmental models (based on the mass balance equation), and human activity pattern data obtained from questionnaires to predict frequency distributions of exposure for entire populations. This approach requires fewer resources than the direct approach to exposure assessment, for which the distribution of monitors to a representative sample of a given population is necessary. In the indirect exposure assessment approach, average microenvironmental concentrations are multiplied by the total time spent in each microenvironment to give total integrated exposure. By assuming that the concentrations encountered in each of 10 location categories are the same for different members of the U.S. population (i.e., the NHAPS respondents), the hypothetical contribution that ETS makes to the average 24-hr respirable suspended particle exposure for Americans working their main job is calculated in this paper to be 18 microg/m3. This article is an illustrative review and does not contain an actual exposure assessment or model validation. Images Figure 3 Figure 4 PMID:10350522

Effective biological dose from occupational exposure during nanoparticle synthesis

NASA Astrophysics Data System (ADS)

Demou, Evangelia; Tran, Lang; Housiadas, Christos

2009-02-01

Nanomaterial and nanotechnology safety require the characterization of occupational exposure levels for completing a risk assessment. However, equally important is the estimation of the effective internal dose via lung deposition, transport and clearance mechanisms. An integrated source-to-biological dose assessment study is presented using real monitoring data collected during nanoparticle synthesis. Experimental monitoring data of airborne exposure levels during nanoparticle synthesis of CaSO4 and BiPO4 nanoparticles in a research laboratory is coupled with a human lung transport and deposition model, which solves in an Eulerian framework the general dynamic equation for polydisperse aerosols using particle specific physical-chemical properties. Subsequently, the lung deposition model is coupled with a mathematical particle clearance model providing the effective biological dose as well as the time course of the biological dose build-up after exposure. The results for the example of BiPO4 demonstrate that even short exposures throughout the day can lead to particle doses of 1.10·E+08#/(kg-bw·8h-shift), with the majority accumulating in the pulmonary region. Clearance of particles is slow and is not completed within a working shift following a 1 hour exposure. It mostly occurs via macrophage activity in the alveolar region, with small amounts transported to the interstitium and less to the lymph nodes.

Biological Response to SPE Exposures

NASA Technical Reports Server (NTRS)

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

2004-01-01

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

Effects of personal air pollution exposure on asthma symptoms, lung function and airway inflammation.

PubMed

Chambers, L; Finch, J; Edwards, K; Jeanjean, A; Leigh, R; Gonem, S

2018-03-11

There is evidence that air pollution increases the risk of asthma hospitalizations and healthcare utilization, but the effects on day-to-day asthma control are not fully understood. We undertook a prospective single-centre panel study to test the hypothesis that personal air pollution exposure is associated with asthma symptoms, lung function and airway inflammation. Thirty-two patients with a clinical diagnosis of asthma were provided with a personal air pollution monitor (Cairclip NO 2 /O 3 ) which was kept on or around their person throughout the 12-week follow-up period. Ambient levels of NO 2 and particulate matter were modelled based upon satellite imaging data. Directly measured ozone, NO 2 and particulate matter levels were obtained from a monitoring station in central Leicester. Participants made daily electronic records of asthma symptoms, peak expiratory flow and exhaled nitric oxide. Spirometry and asthma symptom questionnaires were completed at fortnightly study visits. Data were analysed using linear mixed effects models and cross-correlation. Cairclip exposure data were of good quality with clear evidence of diurnal variability and a missing data rate of approximately 20%. We were unable to detect consistent relationships between personal air pollution exposure and clinical outcomes in the group as a whole. In an exploratory subgroup analysis, total oxidant exposure was associated with increased daytime symptoms in women but not men. We did not find compelling evidence that air pollution exposure impacts on day-to-day clinical control in an unselected asthma population, but further studies are required in larger populations with higher exposure levels. Women may be more susceptible than men to the effects of air pollution, an observation which requires confirmation in future studies. © 2018 John Wiley & Sons Ltd.

Spatial aspects of building and population exposure data and their implications for global earthquake exposure modeling

USGS Publications Warehouse

Dell’Acqua, F.; Gamba, P.; Jaiswal, K.

2012-01-01

This paper discusses spatial aspects of the global exposure dataset and mapping needs for earthquake risk assessment. We discuss this in the context of development of a Global Exposure Database for the Global Earthquake Model (GED4GEM), which requires compilation of a multi-scale inventory of assets at risk, for example, buildings, populations, and economic exposure. After defining the relevant spatial and geographic scales of interest, different procedures are proposed to disaggregate coarse-resolution data, to map them, and if necessary to infer missing data by using proxies. We discuss the advantages and limitations of these methodologies and detail the potentials of utilizing remote-sensing data. The latter is used especially to homogenize an existing coarser dataset and, where possible, replace it with detailed information extracted from remote sensing using the built-up indicators for different environments. Present research shows that the spatial aspects of earthquake risk computation are tightly connected with the availability of datasets of the resolution necessary for producing sufficiently detailed exposure. The global exposure database designed by the GED4GEM project is able to manage datasets and queries of multiple spatial scales.

Scale models: A proven cost-effective tool for outage planning

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

Lee, R.; Segroves, R.

1995-03-01

As generation costs for operating nuclear stations have risen, more nuclear utilities have initiated efforts to improve cost effectiveness. Nuclear plant owners are also being challenged with lower radiation exposure limits and new revised radiation protection related regulations (10 CFR 20), which places further stress on their budgets. As source term reduction activities continue to lower radiation fields, reducing the amount of time spent in radiation fields becomes one of the most cost-effective ways of reducing radiation exposure. An effective approach for minimizing time spent in radiation areas is to use a physical scale model for worker orientation planning andmore » monitoring maintenance, modifications, and outage activities. To meet the challenge of continued reduction in the annual cumulative radiation exposures, new cost-effective tools are required. One field-tested and proven tool is the physical scale model.« less

Current methods of monitoring radiation exposure from CT.

PubMed

Talati, Ronak K; Dunkin, Jared; Parikh, Shrujal; Moore, William H

2013-09-01

Increased public and regulatory scrutiny of imaging-related radiation exposure requires familiarity with current dose-monitoring techniques and best practices. CT-related ionizing radiation exposure has been cited as the largest and fastest growing source of population-wide iatrogenic ionizing radiation exposure. Upcoming federal regulations require imaging centers to familiarize themselves with available dose-monitoring techniques and implement comprehensive strategies to track patient dose, with particular emphasis on CT. Because of institution-specific and vendor-specific technologies, there are significant barriers to adoption and implementation. In this article, the authors outline the core components of a universal dose-monitoring strategy and detail a few of the many available commercial platforms. In addition, the authors introduce a cloud-based hybrid model dose-tracking system with the goal of rapid implementation, multicenter scalability, real-time dose feedback for technologists, cumulative dose monitoring, and optional dose communication to patients and into the record; doing so results in improved patient loyalty, referring physician satisfaction, and opportunity for repeat business. Copyright © 2013 American College of Radiology. All rights reserved.

Progress in Space Weather Modeling and Observations Needed to Improve the Operational NAIRAS Model Aircraft Radiation Exposure Predictions

NASA Astrophysics Data System (ADS)

Mertens, C. J.; Kress, B. T.; Wiltberger, M. J.; Tobiska, W.; Xu, X.

2011-12-01

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a prototype operational model for predicting commercial aircraft radiation exposure from galactic and solar cosmic rays. NAIRAS predictions are currently streaming live from the project's public website, and the exposure rate nowcast is also available on the SpaceWx smartphone app for iPhone, IPad, and Android. Cosmic rays are the primary source of human exposure to high linear energy transfer radiation at aircraft altitudes, which increases the risk of cancer and other adverse health effects. Thus, the NAIRAS model addresses an important national need with broad societal, public health and economic benefits. The processes responsible for the variability in the solar wind, interplanetary magnetic field, solar energetic particle spectrum, and the dynamical response of the magnetosphere to these space environment inputs, strongly influence the composition and energy distribution of the atmospheric ionizing radiation field. During the development of the NAIRAS model, new science questions were identified that must be addressed in order to obtain a more reliable and robust operational model of atmospheric radiation exposure. Addressing these science questions require improvements in both space weather modeling and observations. The focus of this talk is to present these science questions, the proposed methodologies for addressing these science questions, and the anticipated improvements to the operational predictions of atmospheric radiation exposure. The overarching goal of this work is to provide a decision support tool for the aviation industry that will enable an optimal balance to be achieved between minimizing health risks to passengers and aircrew while simultaneously minimizing costs to the airline companies.

Radiation Transport Modeling and Assessment to Better Predict Radiation Exposure, Dose, and Toxicological Effects to Human Organs on Long Duration Space Flights

NASA Technical Reports Server (NTRS)

Denkins, Pamela; Badhwar, Gautam; Obot, Victor

2000-01-01

NASA's long-range plans include possible human exploratory missions to the moon and Mars within the next quarter century. Such missions beyond low Earth orbit will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and the missions long, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. The focus of this study is radiation exposure to the blood-forming organs of the NASA astronauts. NASA/JSC developed the Phantom Torso Experiment for Organ Dose Measurements which housed active and passive dosimeters that would monitor and record absorbed radiation levels at vital organ locations. This experiment was conducted during the STS-9 I mission in May '98 and provided the necessary space radiation data for correlation to results obtained from the current analytical models used to predict exposure to the blood-forming organs. Numerous models (i.e., BRYNTRN and HZETRN) have been developed and used to predict radiation exposure. However, new models are continually being developed and evaluated. The Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronomy, is to be used and evaluated as a part of the research activity. It is the intent of this research effort to compare the modeled data to the findings from the STS-9 I mission; assess the accuracy and efficiency of this model; and to determine its usefulness for predicting radiation exposure and developing better guidelines for shielding requirements for long duration manned missions.

Prenatal cocaine exposure impairs selective attention: evidence from serial reversal and extradimensional shift tasks.

PubMed

Garavan, H; Morgan, R E; Mactutus, C F; Levitsky, D A; Booze, R M; Strupp, B J

2000-08-01

This study assessed the effects of prenatal cocaine exposure on cognitive functioning, using an intravenous (IV) rodent model that closely mimics the pharmacokinetics seen in humans after smoking or IV injection and that avoids maternal stress and undernutrition. Cocaine-exposed males were significantly impaired on a 3-choice, but not 2-choice, olfactory serial reversal learning task. Both male and female cocaine-exposed rats were significantly impaired on extradimensional shift tasks that required shifting from olfactory to spatial cues; however, they showed no impairment when required to shift from spatial to olfactory cues. In-depth analyses of discrete learning phases implicated deficient selective attention as the basis of impairment in both tasks. These data provide clear evidence that prenatal cocaine exposure produces long-lasting cognitive dysfunction, but they also underscore the specificity of the impairment.

Public support for selected e-cigarette regulations and associations with overall information exposure and contradictory information exposure about e-cigarettes: Findings from a national survey of U.S. adults.

PubMed

Tan, Andy S L; Lee, Chul-Joo; Bigman, Cabral A

2015-12-01

We assessed public support for six e-cigarette regulations and examined whether self-reported exposure to e-cigarette information and contradictory e-cigarette information were associated with support. We conducted an online survey among a nationally representative sample of 527 U.S. adults in July 2014. Weighted, fully adjusted multinomial logistic regression models predicted support for banning e-cigarettes in smoke-free areas, prohibiting e-cigarette sales to youth, requiring addiction warnings, banning flavors, requiring labeling nicotine and harmful ingredients, and banning youth-targeted marketing. Between 34% and 72% supported these six policies (disagreed 6-24%; no opinion 18-38%). We found higher support for policies to protect youth (prohibit sales to youth and youth-targeted marketing) and to require labeling e-cigarette constituents (nicotine and harmful ingredients). Banning the use of flavors in e-cigarettes was the least supported. Overall information exposure predicted lower relative risk of support for three policies (prohibit sales to youth, nicotine and harmful ingredient labeling, addiction warnings). In comparison, contradictory information exposure predicted lower relative risk of support for two policies (prohibit sales to youth, nicotine and harmful ingredient labeling). Exposure to overall and conflicting information about e-cigarettes in the public sphere is associated with reduced support for certain proposed e-cigarette policies. These findings are important for policymakers and tobacco control advocates involved in promulgation of e-cigarette policies. The results provide insights on which policies may meet some public resistance and therefore require efforts to first gain public support. Copyright © 2015 Elsevier Inc. All rights reserved.

Incorporating High-Throughput Exposure Predictions with ...

EPA Pesticide Factsheets

We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast™ HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compared against regulatory exposure estimates, providing an activity-to-exposure ratio (AER) useful for a risk-based ranking strategy. As ToxCast™ efforts expand (i.e., Phase II) beyond food-use pesticides towards a wider chemical domain that lacks exposure and toxicity information, prediction tools become increasingly important. In this study, in vitro hepatic clearance and plasma protein binding were measured to estimate OEDs for a subset of Phase II chemicals. OEDs were compared against high-throughput (HT) exposure predictions generated using probabilistic modeling and Bayesian approaches generated by the U.S. EPA ExpoCast™ program. This approach incorporated chemical-specific use and national production volume data with biomonitoring data to inform the exposure predictions. This HT exposure modeling approach provided predictions for all Phase II chemicals assessed in this study whereas estimates from regulatory sources were available for only 7% of chemicals. Of the 163 chemicals assessed in this study, three or 13 chemicals possessed AERs <1 or <100, respectively. Diverse bioactivities y across a range of assays and concentrations was also noted across the wider chemical space su

CKow -- A More Transparent and Reliable Model for Chemical Transfer to Meat and Milk

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

Rosenbaum, Ralph K.; McKone, Thomas E.; Jolliet, Olivier

The objective of this study is to increase the understanding and transparency of chemical biotransfer modeling into meat and milk and explicitly confront the uncertainties in exposure assessments of chemicals that require such estimates. In cumulative exposure assessments that include food pathways, much of the overall uncertainty is attributable to the estimation of transfer into biota and through food webs. Currently, the most commonly used meat and milk-biotransfer models date back two decades and, in spite of their widespread use in multimedia exposure models few attempts have been made to advance or improve the outdated and highly uncertain Kow regressionsmore » used in these models. Furthermore, in the range of Kow where meat and milk become the dominant human exposure pathways, these models often provide unrealistic rates and do not reflect properly the transfer dynamics. To address these issues, we developed a dynamic three-compartment cow model (called CKow), distinguishing lactating and non-lactating cows. For chemicals without available overall removal rates in the cow, a correlation is derived from measured values reported in the literature to predict this parameter from Kow. Results on carry over rates (COR) and biotransfer factors (BTF) demonstrate that a steady-state ratio between animal intake and meat concentrations is almost never reached. For meat, empirical data collected on short term experiments need to be adjusted to provide estimates of average longer term behaviors. The performance of the new model in matching measurements is improved relative to existing models--thus reducing uncertainty. The CKow model is straight forward to apply at steady state for milk and dynamically for realistic exposure durations for meat COR.« less

An empirical analysis of thermal protective performance of fabrics used in protective clothing.

PubMed

Mandal, Sumit; Song, Guowen

2014-10-01

Fabric-based protective clothing is widely used for occupational safety of firefighters/industrial workers. The aim of this paper is to study thermal protective performance provided by fabric systems and to propose an effective model for predicting the thermal protective performance under various thermal exposures. Different fabric systems that are commonly used to manufacture thermal protective clothing were selected. Laboratory simulations of the various thermal exposures were created to evaluate the protective performance of the selected fabric systems in terms of time required to generate second-degree burns. Through the characterization of selected fabric systems in a particular thermal exposure, various factors affecting the performances were statistically analyzed. The key factors for a particular thermal exposure were recognized based on the t-test analysis. Using these key factors, the performance predictive multiple linear regression and artificial neural network (ANN) models were developed and compared. The identified best-fit ANN models provide a basic tool to study thermal protective performance of a fabric. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

The Be-WetSpa-Pest modeling approach to simulate human and environmental exposure from pesticide application

NASA Astrophysics Data System (ADS)

Binder, Claudia; Garcia-Santos, Glenda; Andreoli, Romano; Diaz, Jaime; Feola, Giuseppe; Wittensoeldner, Moritz; Yang, Jing

2016-04-01

This study presents an integrative and spatially explicit modeling approach for analyzing human and environmental exposure from pesticide application of smallholders in the potato producing Andean region in Colombia. The modeling approach fulfills the following criteria: (i) it includes environmental and human compartments; (ii) it contains a behavioral decision-making model for estimating the effect of policies on pesticide flows to humans and the environment; (iii) it is spatially explicit; and (iv) it is modular and easily expandable to include additional modules, crops or technologies. The model was calibrated and validated for the Vereda La Hoya and was used to explore the effect of different policy measures in the region. The model has moderate data requirements and can be adapted relatively easy to other regions in developing countries with similar conditions.

The effects of body exposure on self-body image and esthetic appreciation in anorexia nervosa.

PubMed

Cazzato, Valentina; Mian, Emanuel; Mele, Sonia; Tognana, Giulia; Todisco, Patrizia; Urgesi, Cosimo

2016-03-01

Repeated exposures to thin-idealized body shapes may alter women's perceptions of what normal (e.g., accepted) and ideal (e.g., desired) bodies in a cultural environment look like. The aim of the present study was to investigate whether exposure to thin and round body shapes may change the subsequent esthetic appreciation of others' bodies and the perceptual and cognitive-affective dimensions of self-body image in patients suffering from anorexia nervosa (AN). Thirteen AN patients and 13 matched healthy controls were exposed to pictures of either thin or round unfamiliar body models and, before and after exposure, they were required to either express liking judgments about round and slim figures of unfamiliar bodies (esthetic task) or to adjust distorted pictures of their own body to their perceptual (How do you see yourself?), affective (How do you feel yourself?), metacognitive (How do others see you?) and ideal (How would you like to look like?) body image (self-body adjustment task). Brief exposures to round models increased liking judgments of round figures in both groups. However, only in AN patients, exposure to round models induced an increase in thin figures liking, which positively correlated with their preoccupation with dieting. Furthermore, exposure to round bodies in AN patients, but not in controls, increased the distortion for the perceptual body image and decreased the size of the ideal one. No differences between the two groups were obtained after adaptation to thin models. Our results suggest that AN patients' perception of their own and others' body is more easily malleable by exposure to round figures as compared to controls. Crucially, this mechanism may strongly contribute to the development and maintenance of self-body image disturbances.

Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure.

PubMed

Liu, Lucy Y; Strassner, James P; Refat, Maggi A; Harris, John E; King, Brett A

2017-10-01

Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors. To evaluate the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo. This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation. Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low-dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration. Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group. Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Modelling the effects of pulse exposure of several PSII inhibitors on two algae.

PubMed

Copin, Pierre-Jean; Chèvre, Nathalie

2015-10-01

Subsequent to crop application and during precipitation events, herbicides can reach surface waters in pulses of high concentrations. These pulses can exceed the Annual Average Environmental Quality Standards (AA-EQS), defined in the EU Water Framework Directive, which aims to protect the aquatic environment. A model was developed in a previous study to evaluate the effects of pulse exposure for the herbicide isoproturon on the alga Scenedesmus vacuolatus. In this study, the model was extended to other substances acting as photosystem II inhibitors and to other algae. The measured and predicted effects were equivalent when pulse exposure of atrazine and diuron were tested on S. vacuolatus. The results were consistent for isoproturon on the alga Pseudokirchneriella subcapitata. The model is thus suitable for the effect prediction of phenylureas and triazines and for the algae used: S. vacuolatus and P. subcapitata. The toxicity classification obtained from the dose-response curves (diuron>atrazine>isoproturon) was conserved for the pulse exposure scenarios modelled for S. vacuolatus. Toxicity was identical for isoproturon on the two algae when the dose-response curves were compared and also for the pulse exposure scenarios. Modelling the effects of any pulse scenario of photosystem II inhibitors on algae is therefore feasible and only requires the determination of the dose-response curves of the substance and growth rate of unexposed algae. It is crucial to detect the longest pulses when measurements of herbicide concentrations are performed in streams because the model showed that they principally affect the cell density inhibition of algae. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estimating exposures in the asphalt industry for an international epidemiological cohort study of cancer risk.

PubMed

Burstyn, Igor; Boffetta, Paolo; Kauppinen, Timo; Heikkilä, Pirjo; Svane, Ole; Partanen, Timo; Stücker, Isabelle; Frentzel-Beyme, Rainer; Ahrens, Wolfgang; Merzenich, Hiltrud; Heederik, Dick; Hooiveld, Mariëtte; Langård, Sverre; Randem, Britt G; Järvholm, Bengt; Bergdahl, Ingvar; Shaham, Judith; Ribak, Joseph; Kromhout, Hans

2003-01-01

An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi-quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi-quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi-quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non-monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. We produced a data-driven EM using methodology that can be adapted for other multicenter studies. Copyright 2003 Wiley-Liss, Inc.

Real-Time Aircraft Cosmic Ray Radiation Exposure Predictions from the NAIRAS Model

NASA Astrophysics Data System (ADS)

Mertens, C. J.; Tobiska, W.; Kress, B. T.; Xu, X.

2012-12-01

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a prototype operational model for predicting commercial aircraft radiation exposure from galactic and solar cosmic rays. NAIRAS predictions are currently streaming live from the project's public website, and the exposure rate nowcast is also available on the SpaceWx smartphone app for iPhone, IPad, and Android. Cosmic rays are the primary source of human exposure to high linear energy transfer radiation at aircraft altitudes, which increases the risk of cancer and other adverse health effects. Thus, the NAIRAS model addresses an important national need with broad societal, public health and economic benefits. There is also interest in extending NAIRAS to the LEO environment to address radiation hazard issues for the emerging commercial spaceflight industry. The processes responsible for the variability in the solar wind, interplanetary magnetic field, solar energetic particle spectrum, and the dynamical response of the magnetosphere to these space environment inputs, strongly influence the composition and energy distribution of the atmospheric ionizing radiation field. Real-time observations are required at a variety of locations within the geospace environment. The NAIRAS model is driven by real-time input data from ground-, atmospheric-, and space-based platforms. During the development of the NAIRAS model, new science questions and observational data gaps were identified that must be addressed in order to obtain a more reliable and robust operational model of atmospheric radiation exposure. The focus of this talk is to present the current capabilities of the NAIRAS model, discuss future developments in aviation radiation modeling and instrumentation, and propose strategies and methodologies of bridging known gaps in current modeling and observational capabilities.

CHEMICAL PROCESSES AND MODELING IN ECOSYSTEMS

EPA Science Inventory

Trends in regulatory strategies require EPA to understand better chemical behavior in natural and impacted ecosystems and in biological systems to carry out the increasingly complex array of exposure and risk assessments needed to develop scientifically defensible regulations (GP...

Measurement errors in the assessment of exposure to solar ultraviolet radiation and its impact on risk estimates in epidemiological studies.

PubMed

Dadvand, Payam; Basagaña, Xavier; Barrera-Gómez, Jose; Diffey, Brian; Nieuwenhuijsen, Mark

2011-07-01

To date, many studies addressing long-term effects of ultraviolet radiation (UVR) exposure on human health have relied on a range of surrogates such as the latitude of the city of residence, ambient UVR levels, or time spent outdoors to estimate personal UVR exposure. This study aimed to differentiate the contributions of personal behaviour and ambient UVR levels on facial UVR exposure and to evaluate the impact of using UVR exposure surrogates on detecting exposure-outcome associations. Data on time-activity, holiday behaviour, and ambient UVR levels were obtained for adult (aged 25-55 years old) indoor workers in six European cities: Athens (37°N), Grenoble (45°N), Milan (45°N), Prague (50°N), Oxford (52°N), and Helsinki (60°N). Annual UVR facial exposure levels were simulated for 10,000 subjects for each city, using a behavioural UVR exposure model. Within-city variations of facial UVR exposure were three times larger than the variation between cities, mainly because of time-activity patterns. In univariate models, ambient UVR levels, latitude and time spent outdoors, each accounted for less than one fourth of the variation in facial exposure levels. Use of these surrogates to assess long-term exposure to UVR resulted in requiring more than four times more participants to achieve similar statistical power to the study that applied simulated facial exposure. Our results emphasise the importance of integrating both personal behaviour and ambient UVR levels/latitude in exposure assessment methodologies.

Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease.

PubMed

Paulin, Laura M; Diette, Gregory B; Blanc, Paul D; Putcha, Nirupama; Eisner, Mark D; Kanner, Richard E; Belli, Andrew J; Christenson, Stephanie; Tashkin, Donald P; Han, MeiLan; Barr, R Graham; Hansel, Nadia N

2015-03-01

Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. To determine the impact of occupational exposures on COPD morbidity. A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

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

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

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

1977-05-01

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

Functionalized anatomical models for EM-neuron Interaction modeling

NASA Astrophysics Data System (ADS)

Neufeld, Esra; Cassará, Antonino Mario; Montanaro, Hazael; Kuster, Niels; Kainz, Wolfgang

2016-06-01

The understanding of interactions between electromagnetic (EM) fields and nerves are crucial in contexts ranging from therapeutic neurostimulation to low frequency EM exposure safety. To properly consider the impact of in vivo induced field inhomogeneity on non-linear neuronal dynamics, coupled EM-neuronal dynamics modeling is required. For that purpose, novel functionalized computable human phantoms have been developed. Their implementation and the systematic verification of the integrated anisotropic quasi-static EM solver and neuronal dynamics modeling functionality, based on the method of manufactured solutions and numerical reference data, is described. Electric and magnetic stimulation of the ulnar and sciatic nerve were modeled to help understanding a range of controversial issues related to the magnitude and optimal determination of strength-duration (SD) time constants. The results indicate the importance of considering the stimulation-specific inhomogeneous field distributions (especially at tissue interfaces), realistic models of non-linear neuronal dynamics, very short pulses, and suitable SD extrapolation models. These results and the functionalized computable phantom will influence and support the development of safe and effective neuroprosthetic devices and novel electroceuticals. Furthermore they will assist the evaluation of existing low frequency exposure standards for the entire population under all exposure conditions.

[The assessment of exposure to and the activity of the manual lifting of patients in wards: methods, procedures, the exposure index (MAPO) and classification criteria. Movimientazione e Assistenza Pazienti Ospedalizzati (Lifting and Assistance to Hospitalized Patients)].

PubMed

Menoni, O; Ricci, M G; Panciera, D; Occhipinti, E

1999-01-01

Since a method for quantifying exposure to patient handling in hospital wards is lacking, the authors describe and propose a model for identifying the main risk factors in this type of occupational exposure: presence of disabled patients, staff engaged on manual handling of patients, structure of the working environment, equipment and aids for moving patients, training of workers according to the specific risk. For each factor a procedure for identification and assessment is proposed that is easily applicable in practice. The authors also propose a formula for the calculation of a condensed exposure index (MAPO Index), which brings together the various factors. The exposure index, which requires further, detailed study and validation, makes it possible, in practice, to plan the preventive and health measures according to a specific order of priority, thus complying with the requirements of Chapter V of Law 626/94. From a practical point of view, in the present state of knowledge, it can be stated that for MAPO Index values between 0 and 1.5, risk is deemed negligible, average for values between 1.51 and 5, and high for values exceeding 5.

Calibrating a population-based job-exposure matrix using inspection measurements to estimate historical occupational exposure to lead for a population-based cohort in Shanghai, China

PubMed Central

Koh, Dong-Hee; Bhatti, Parveen; Coble, Joseph B.; Stewart, Patricia A; Lu, Wei; Shu, Xiao-Ou; Ji, Bu-Tian; Xue, Shouzheng; Locke, Sarah J.; Portengen, Lutzen; Yang, Gong; Chow, Wong-Ho; Gao, Yu-Tang; Rothman, Nathaniel; Vermeulen, Roel; Friesen, Melissa C.

2012-01-01

The epidemiologic evidence for the carcinogenicity of lead is inconsistent and requires improved exposure assessment to estimate risk. We evaluated historical occupational lead exposure for a population-based cohort of women (n=74,942) by calibrating a job-exposure matrix (JEM) with lead fume (n=20,084) and lead dust (n=5,383) measurements collected over four decades in Shanghai, China. Using mixed-effect models, we calibrated intensity JEM ratings to the measurements using fixed-effects terms for year and JEM rating. We developed job/industry-specific estimates from the random-effects terms for job and industry. The model estimates were applied to subjects’ jobs when the JEM probability rating was high for either job or industry; remaining jobs were considered unexposed. The models predicted that exposure increased monotonically with JEM intensity rating and decreased 20–50-fold over time. The cumulative calibrated JEM estimates and job/industry-specific estimates were highly correlated (Pearson correlation=0.79–0.84). Overall, 5% of the person-years and 8% of the women were exposed to lead fume; 2% of the person-years and 4% of the women were exposed to lead dust. The most common lead-exposed jobs were manufacturing electronic equipment. These historical lead estimates should enhance our ability to detect associations between lead exposure and cancer risk in future epidemiologic analyses. PMID:22910004

Developing physical exposure-based back injury risk models applicable to manual handling jobs in distribution centers.

PubMed

Lavender, Steven A; Marras, William S; Ferguson, Sue A; Splittstoesser, Riley E; Yang, Gang

2012-01-01

Using our ultrasound-based "Moment Monitor," exposures to biomechanical low back disorder risk factors were quantified in 195 volunteers who worked in 50 different distribution center jobs. Low back injury rates, determined from a retrospective examination of each company's Occupational Safety and Health Administration (OSHA) 300 records over the 3-year period immediately prior to data collection, were used to classify each job's back injury risk level. The analyses focused on the factors differentiating the high-risk jobs (those having had 12 or more back injuries/200,000 hr of exposure) from the low-risk jobs (those defined as having no back injuries in the preceding 3 years). Univariate analyses indicated that measures of load moment exposure and force application could distinguish between high (n = 15) and low (n = 15) back injury risk distribution center jobs. A three-factor multiple logistic regression model capable of predicting high-risk jobs with very good sensitivity (87%) and specificity (73%) indicated that risk could be assessed using the mean across the sampled lifts of the peak forward and or lateral bending dynamic load moments that occurred during each lift, the mean of the peak push/pull forces across the sampled lifts, and the mean duration of the non-load exposure periods. A surrogate model, one that does not require the Moment Monitor equipment to assess a job's back injury risk, was identified although with some compromise in model sensitivity relative to the original model.

FDTD computation of human eye exposure to ultra-wideband electromagnetic pulses.

PubMed

Simicevic, Neven

2008-03-21

With an increase in the application of ultra-wideband (UWB) electromagnetic pulses in the communications industry, radar, biotechnology and medicine, comes an interest in UWB exposure safety standards. Despite an increase of the scientific research on bioeffects of exposure to non-ionizing UWB pulses, characterization of those effects is far from complete. A numerical computational approach, such as a finite-difference time domain (FDTD) method, is required to visualize and understand the complexity of broadband electromagnetic interactions. The FDTD method has almost no limits in the description of the geometrical and dispersive properties of the simulated material, it is numerically robust and appropriate for current computer technology. In this paper, a complete calculation of exposure of the human eye to UWB electromagnetic pulses in the frequency range of 3.1-10.6, 22-29 and 57-64 GHz is performed. Computation in this frequency range required a geometrical resolution of the eye of 0.1 mm and an arbitrary precision in the description of its dielectric properties in terms of the Debye model. New results show that the interaction of UWB pulses with the eye tissues exhibits the same properties as the interaction of the continuous electromagnetic waves (CWs) with the frequencies from the pulse's frequency spectrum. It is also shown that under the same exposure conditions the exposure to UWB pulses is from one to many orders of magnitude safer than the exposure to CW.

Long Duration Exposure Facility (LDEF) structural verification test report

NASA Technical Reports Server (NTRS)

Jones, T. C.; Lucy, M. H.; Shearer, R. L.

1983-01-01

Structural load tests on the Long Duration Exposure Facility's (LDEF) primary structure were conducted. These tests had three purposes: (1) demonstrate structural adequacy of the assembled LDEF primary structure when subjected to anticipated flight loads; (2) verify analytical models and methods used in loads and stress analysis; and (3) perform tests to comply with the Space Transportation System (STS) requirements. Test loads were based on predicted limit loads which consider all flight events. Good agreement is shown between predicted and observed load, strain, and deflection data. Test data show that the LDEF structure was subjected to 1.2 times limit load to meet the STS requirements. The structural adequacy of the LDEF is demonstrated.

40 CFR 158.1050 - Post-application exposure-general requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1050 Post-application exposure... by the Occupational Safety and Health Administration, provide adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants...

40 CFR 158.1050 - Post-application exposure-general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1050 Post-application exposure... by the Occupational Safety and Health Administration, provide adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants...

40 CFR 158.1050 - Post-application exposure-general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1050 Post-application exposure... by the Occupational Safety and Health Administration, provide adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants...

40 CFR 158.1050 - Post-application exposure-general requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1050 Post-application exposure... by the Occupational Safety and Health Administration, provide adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants...

40 CFR 158.1050 - Post-application exposure-general requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1050 Post-application exposure... by the Occupational Safety and Health Administration, provide adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants...

DESIGN OF EXPOSURE MEASUREMENTS FOR EPIDEMIOLOGIC STUDIES

EPA Science Inventory

This presentation will describe the following items: (1) London daily air pollution and deaths that demonstrate how time series epidemiology can indicate that air pollution caused death; (2) Sophisticated statistical models required to establish this relationship for lower pollut...

Raising Better Boys.

ERIC Educational Resources Information Center

Canada, Geoffrey

2000-01-01

The author of "Reaching Up For Manhood" discusses troubling social/environmental conditions confronting boys. Raising better boys requires caring adults, safer risk-taking situations, positive reinforcement, and role models. Parents should monitor boys' media exposure, provide moral education, broaden their cultural and natural-world…

[Measures of occupational exposure to time-varying low frequency magnetic fields of non-uniform spatial distribution in the light of international guidelines and electrodynamic exposure effects in the human body].

PubMed

Karpowicz, Jolanta; Zradziński, Patryk; Gryz, Krzysztof

2012-01-01

The aim of study was to analyze by computer simulations the electrodynamic effects of magnetic field (MF) on workers, to harmonize the principles of occupational hazards assessment with international guidelines. Simulations involved 50 Hz MF of various spatial distributions, representing workers' exposure in enterprises. Homogeneous models of sigma = 0.2 S/m conductivity and dimensions of body parts - palm, head and trunk - were located at 50 cm ("hand-distance") or 5 cm (adjacent) from the source (circle conductor of 20 cm or 200 cm in diameter). Parameters of magnetic flux density (B(i)) affecting the models were the exposure measures, and the induced electric field strength (E(in)) was the measure of MF exposure effects. The ratio E(in)/B(i) in the analyzed cases ranged from 2.59 to 479 (V/m)/T. The strongest correlation (p < 0.001) between B(i) and E(in) was found for parameters characterizing MF at the surface of body models. Parameters characterizing the averaged value of the field affecting models (measures of non-uniform field exposure following ICNIRP guidelines), were less correlated with exposure effects (p < 0.005). E(in)(trunk)/E(in) (palm) estimated from E(in) calculations was 3.81-4.56 but estimated from parameters representing B(i) measurement accounted for 3.96-9.74. It is justified to accept 3.96-9.74 times higher exposure to limb than that to trunk. This supports the regulation of labor law in Poland, which provides that the ceiling value for limb exposure to MF below 800 kHz is fivefold higher than that of the trunk. High uncertainty in assessing the effects of non-uniform fields exposure, resulting from a strong dependence of the E(in)/B(i) ratio on the conditions of exposure and its applied measures, requires special caution when defining the permissible MF levels and the principles of exposure assessment at workplace.

Data-driven nonlinear optimisation of a simple air pollution dispersion model generating high resolution spatiotemporal exposure

NASA Astrophysics Data System (ADS)

Yuval; Bekhor, Shlomo; Broday, David M.

2013-11-01

Spatially detailed estimation of exposure to air pollutants in the urban environment is needed for many air pollution epidemiological studies. To benefit studies of acute effects of air pollution such exposure maps are required at high temporal resolution. This study introduces nonlinear optimisation framework that produces high resolution spatiotemporal exposure maps. An extensive traffic model output, serving as proxy for traffic emissions, is fitted via a nonlinear model embodying basic dispersion properties, to high temporal resolution routine observations of traffic-related air pollutant. An optimisation problem is formulated and solved at each time point to recover the unknown model parameters. These parameters are then used to produce a detailed concentration map of the pollutant for the whole area covered by the traffic model. Repeating the process for multiple time points results in the spatiotemporal concentration field. The exposure at any location and for any span of time can then be computed by temporal integration of the concentration time series at selected receptor locations for the durations of desired periods. The methodology is demonstrated for NO2 exposure using the output of a traffic model for the greater Tel Aviv area, Israel, and the half-hourly monitoring and meteorological data from the local air quality network. A leave-one-out cross-validation resulted in simulated half-hourly concentrations that are almost unbiased compared to the observations, with a mean error (ME) of 5.2 ppb, normalised mean error (NME) of 32%, 78% of the simulated values are within a factor of two (FAC2) of the observations, and the coefficient of determination (R2) is 0.6. The whole study period integrated exposure estimations are also unbiased compared with their corresponding observations, with ME of 2.5 ppb, NME of 18%, FAC2 of 100% and R2 that equals 0.62.

Computational modeling of temperature elevation and thermoregulatory response in the brains of anesthetized rats locally exposed at 1.5 GHz

NASA Astrophysics Data System (ADS)

Hirata, Akimasa; Masuda, Hiroshi; Kanai, Yuya; Asai, Ryuichi; Fujiwara, Osamu; Arima, Takuji; Kawai, Hiroki; Watanabe, Soichi; Lagroye, Isabelle; Veyret, Bernard

2011-12-01

The dominant effect of human exposures to microwaves is caused by temperature elevation ('thermal effect'). In the safety guidelines/standards, the specific absorption rate averaged over a specific volume is used as a metric for human protection from localized exposure. Further investigation on the use of this metric is required, especially in terms of thermophysiology. The World Health Organization (2006 RF research agenda) has given high priority to research into the extent and consequences of microwave-induced temperature elevation in children. In this study, an electromagnetic-thermal computational code was developed to model electromagnetic power absorption and resulting temperature elevation leading to changes in active blood flow in response to localized 1.457 GHz exposure in rat heads. Both juvenile (4 week old) and young adult (8 week old) rats were considered. The computational code was validated against measurements for 4 and 8 week old rats. Our computational results suggest that the blood flow rate depends on both brain and core temperature elevations. No significant difference was observed between thermophysiological responses in 4 and 8 week old rats under these exposure conditions. The computational model developed herein is thus applicable to set exposure conditions for rats in laboratory investigations, as well as in planning treatment protocols in the thermal therapy.

Modeling Flight Attendants’ Exposures to Pesticide in Disinsected Aircraft Cabins

PubMed Central

Zhang, Yong; Isukapalli, Sastry; Georgopoulos, Panos; Weisel, Clifford

2014-01-01

Aircraft cabin disinsection is required by some countries to kill insects that may pose risks to public health and native ecological systems. A probabilistic model has been developed by considering the microenvironmental dynamics of the pesticide in conjunction with the activity patterns of flight attendants, to assess their exposures and risks to pesticide in disinsected aircraft cabins under three scenarios of pesticide application. Main processes considered in the model are microenvironmental transport and deposition, volatilization, and transfer of pesticide when passengers and flight attendants come in contact with the cabin surfaces. The simulated pesticide airborne mass concentration and surface mass loadings captured measured ranges reported in the literature. The medians (means±standard devitions) of daily total exposures intakes were 0.24 (3.8±10.0), 1.4 (4.2±5.7) and 0.15 (2.1±3.2) μg/(day kg BW) for scenarios of Residual Application, Preflight and Top-of-Descent spraying, respectively. Exposure estimates were sensitive to parameters corresponding to pesticide deposition, body surface area and weight, surface-to-body transfer efficiencies, and efficiency of adherence to skin. Preflight spray posed 2.0 and 3.1 times higher pesticide exposure risk levels for flight attendants in disinsected aircraft cabins than Top-of-Descent spray and Residual Application, respectively. PMID:24251734

Modeling of grating formation in photopolymer that does not need scheduling (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shimura, Tsutomu; Takeda, Yuki; Endo, Masao; Umegaki, Shinsuke; Fujimura, Ryushi

2016-09-01

Recently new photopolymers that does not require scheduled exposure in the multiple page writing for the holographic memory was introduced. Its sensitivity does not decrease throughout the multiple page writing process. We will explain why this photopolymer has such a property with our reaction model. The key is the existence of the molecules which make seeds of the polymers. At the first exposure process to record the page data, seeds are produced corresponding to the light intensity distribution. Then after writing the information of all multiplexed pages, the seeds are growing to be polymers under the spatially uniform light illumination.

33 CFR 149.327 - What are the approval requirements for work vests and anti-exposure (deck) suits?

Code of Federal Regulations, 2012 CFR

2012-07-01

... requirements for work vests and anti-exposure (deck) suits? 149.327 Section 149.327 Navigation and Navigable... approval requirements for work vests and anti-exposure (deck) suits? All work vests and anti-exposure (deck... as a work vest; (b) Approval series 160.053 or 160.153 as an anti-exposure suit; or (c) Approval...

33 CFR 149.327 - What are the approval requirements for work vests and anti-exposure (deck) suits?

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements for work vests and anti-exposure (deck) suits? 149.327 Section 149.327 Navigation and Navigable... approval requirements for work vests and anti-exposure (deck) suits? All work vests and anti-exposure (deck... as a work vest; (b) Approval series 160.053 or 160.153 as an anti-exposure suit; or (c) Approval...

33 CFR 149.327 - What are the approval requirements for work vests and anti-exposure (deck) suits?

Code of Federal Regulations, 2010 CFR

2010-07-01

... requirements for work vests and anti-exposure (deck) suits? 149.327 Section 149.327 Navigation and Navigable... approval requirements for work vests and anti-exposure (deck) suits? All work vests and anti-exposure (deck... as a work vest; (b) Approval series 160.053 or 160.153 as an anti-exposure suit; or (c) Approval...

33 CFR 149.327 - What are the approval requirements for work vests and anti-exposure (deck) suits?

Code of Federal Regulations, 2014 CFR

2014-07-01

... requirements for work vests and anti-exposure (deck) suits? 149.327 Section 149.327 Navigation and Navigable... approval requirements for work vests and anti-exposure (deck) suits? All work vests and anti-exposure (deck... as a work vest; (b) Approval series 160.053 or 160.153 as an anti-exposure suit; or (c) Approval...

33 CFR 149.327 - What are the approval requirements for work vests and anti-exposure (deck) suits?

Code of Federal Regulations, 2011 CFR

2011-07-01

... requirements for work vests and anti-exposure (deck) suits? 149.327 Section 149.327 Navigation and Navigable... approval requirements for work vests and anti-exposure (deck) suits? All work vests and anti-exposure (deck... as a work vest; (b) Approval series 160.053 or 160.153 as an anti-exposure suit; or (c) Approval...

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

PubMed Central

Lioy, Paul J.

2010-01-01

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

Examining Exposure Assessment in Shift Work Research: A Study on Depression Among Nurses.

PubMed

Hall, Amy L; Franche, Renée-Louise; Koehoorn, Mieke

2018-02-13

Coarse exposure assessment and assignment is a common issue facing epidemiological studies of shift work. Such measures ignore a number of exposure characteristics that may impact on health, increasing the likelihood of biased effect estimates and masked exposure-response relationships. To demonstrate the impacts of exposure assessment precision in shift work research, this study investigated relationships between work schedule and depression in a large survey of Canadian nurses. The Canadian 2005 National Survey of the Work and Health of Nurses provided the analytic sample (n = 11450). Relationships between work schedule and depression were assessed using logistic regression models with high, moderate, and low-precision exposure groupings. The high-precision grouping described shift timing and rotation frequency, the moderate-precision grouping described shift timing, and the low-precision grouping described the presence/absence of shift work. Final model estimates were adjusted for the potential confounding effects of demographic and work variables, and bootstrap weights were used to generate sampling variances that accounted for the survey sample design. The high-precision exposure grouping model showed the strongest relationships between work schedule and depression, with increased odds ratios [ORs] for rapidly rotating (OR = 1.51, 95% confidence interval [CI] = 0.91-2.51) and undefined rotating (OR = 1.67, 95% CI = 0.92-3.02) shift workers, and a decreased OR for depression in slow rotating (OR = 0.79, 95% CI = 0.57-1.08) shift workers. For the low- and moderate-precision exposure grouping models, weak relationships were observed for all work schedule categories (OR range 0.95 to 0.99). Findings from this study support the need to consider and collect the data required for precise and conceptually driven exposure assessment and assignment in future studies of shift work and health. Further research into the effects of shift rotation frequency on depression is also recommended. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Atmospheric Ionizing Radiation and Human Exposure

NASA Technical Reports Server (NTRS)

Wilson, John W.; Mertens, Christopher J.; Goldhagen, Paul; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

2005-01-01

Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes. especially along the coastal plain and interior low lands, and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

Atmospheric Ionizing Radiation and Human Exposure

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Goldhagen, P.; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

2004-01-01

Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes especially along the coastal plain and interior low lands and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

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...

Human variability in mercury toxicokinetics and steady state biomarker ratios.

PubMed

Bartell, S M; Ponce, R A; Sanga, R N; Faustman, E M

2000-10-01

Regulatory guidelines regarding methylmercury exposure depend on dose-response models relating observed mercury concentrations in maternal blood, cord blood, and maternal hair to developmental neurobehavioral endpoints. Generalized estimates of the maternal blood-to-hair, blood-to-intake, or hair-to-intake ratios are necessary for linking exposure to biomarker-based dose-response models. Most assessments have used point estimates for these ratios; however, significant interindividual and interstudy variability has been reported. For example, a maternal ratio of 250 ppm in hair per mg/L in blood is commonly used in models, but a 1990 WHO review reports mean ratios ranging from 140 to 370 ppm per mg/L. To account for interindividual and interstudy variation in applying these ratios to risk and safety assessment, some researchers have proposed representing the ratios with probability distributions and conducting probabilistic assessments. Such assessments would allow regulators to consider the range and like-lihood of mercury exposures in a population, rather than limiting the evaluation to an estimate of the average exposure or a single conservative exposure estimate. However, no consensus exists on the most appropriate distributions for representing these parameters. We discuss published reviews of blood-to-hair and blood-to-intake steady state ratios for mercury and suggest statistical approaches for combining existing datasets to form generalized probability distributions for mercury distribution ratios. Although generalized distributions may not be applicable to all populations, they allow a more informative assessment than point estimates where individual biokinetic information is unavailable. Whereas development and use of these distributions will improve existing exposure and risk models, additional efforts in data generation and model development are required.

A 4-Week Model of House Dust Mite (HDM) Induced Allergic Airways Inflammation with Airway Remodeling.

PubMed

Woo, L N; Guo, W Y; Wang, X; Young, A; Salehi, S; Hin, A; Zhang, Y; Scott, J A; Chow, C W

2018-05-02

Animal models of allergic airways inflammation are useful tools in studying the pathogenesis of asthma and potential therapeutic interventions. The different allergic airways inflammation models available to date employ varying doses, frequency, duration and types of allergen, which lead to the development of different features of asthma; showing varying degrees of airways inflammation and hyper-responsiveness (AHR) and airways remodeling. Models that also exhibit airway remodeling, a key feature of asthma, in addition to AHR and airway inflammation typically require 5-12 weeks to develop. In this report, we describe a 4-week mouse model of house dust mite (HDM)-induced allergic airways inflammation, and compare the phenotypic features of two different doses of HDM exposures (10 µg and 25 µg) for 5 days/week with a well-characterized 8-week chronic HDM model. We found that 4 weeks of intranasal HDM (25 µg in 35 µl saline; 5 days/week) resulted in AHR, airway inflammation and airway remodeling that were comparable to the 8-week model. We conclude that this new 4-week HDM model is another useful tool in studies of human asthma that offers advantages of shorter duration for development and decreased costs when compared to other models that require longer durations of exposure (5-12 weeks) to develop.

Release of nanomaterials from solid nanocomposites and consumer exposure assessment - a forward-looking review.

PubMed

Mackevica, Aiga; Foss Hansen, Steffen

2016-08-01

The European chemical legislation requires manufacturers and importers of chemicals to do consumer exposure assessment when the chemical has certain hazards associated to it (e.g. explosive, carcinogenicity, and hazardous to the aquatic environment), but the question is how this obligation can be met in light of the scientific uncertainty and technical challenges related to exposure assessment of nanomaterials. In this paper, we investigate to what extent the information and data in the literature can be used to perform consumer exposure assessment according to the REACH requirements and we identify and discuss the key data needs and provide recommendations for consumer exposure assessment of nanomaterials. In total, we identified 76 studies of relevance. Most studies have analyzed the release of Ag and TiO2 from textiles and paints, and CNT and SiO2 from nanocomposites. Less than half of the studies report their findings in a format that can be used for exposure assessment under REACH, and most do not include characterization of the released particles. Although inhalation, dermal, and oral exposures can be derived using the guidelines on how to complete consumer exposure assessments under REACH, it is clear that the equations are not developed to take the unique properties of nanomaterials into consideration. Future research is therefore needed on developing more generalized methods for representing nanomaterial release from different product groups at relevant environmental conditions. This includes improving the analytical methods for determining nanomaterial alteration and transformation, as well as quantification, which could subsequently lead to more nano-specific consumer exposure assessment models.

Using Gaming To Help Nursing Students Understand Ethics.

ERIC Educational Resources Information Center

Metcalf, Barbara L.; Yankou, Dawn

2003-01-01

An ethics game involves nursing students in defending actions in ethics-based scenarios. Benefits include increased confidence, ability to see multiple perspectives, values clarification, and exposure to decision-making models, professional responsibilities, ethical principles, social expectations, and legal requirements. Difficulties include…

Intended and Unintended Effects of State-Mandated High School Science and Mathematics Course Graduation Requirements on Educational Attainment

ERIC Educational Resources Information Center

Plunk, Andrew D.; Tate, William F.; Bierut, Laura J.; Grucza, Richard A.

2014-01-01

Mathematics and science course graduation requirement (CGR) increases in the 1980s and 1990s might have had both intended and unintended consequences. Using logistic regression with Census and American Community Survey (ACS) data (n = 2,892,444), we modeled CGR exposure on (a) high school dropout, (b) beginning college, and (c) obtaining any…

Estimating associations of mobile phone use and brain tumours taking into account laterality: a comparison and theoretical evaluation of applied methods.

PubMed

Frederiksen, Kirsten; Deltour, Isabelle; Schüz, Joachim

2012-12-10

Estimating exposure-outcome associations using laterality information on exposure and on outcome is an issue, when estimating associations of mobile phone use and brain tumour risk. The exposure is localized; therefore, a potential risk is expected to exist primarily on the side of the head, where the phone is usually held (ipsilateral exposure), and to a lesser extent at the opposite side of the head (contralateral exposure). Several measures of the associations with ipsilateral and contralateral exposure, dealing with different sampling designs, have been presented in the literature. This paper presents a general framework for the analysis of such studies using a likelihood-based approach in a competing risks model setting. The approach clarifies the implicit assumptions required for the validity of the presented estimators, particularly that in some approaches the risk with contralateral exposure is assumed to be zero. The performance of the estimators is illustrated in a simulation study showing for instance that while in some scenarios there is a loss of statistical power, others - in case of a positive ipsilateral exposure-outcome association - would result in a negatively biased estimate of the contralateral exposure parameter, irrespective of any additional recall bias. In conclusion, our theoretical evaluations and results from the simulation study emphasize the importance of setting up a formal model, which furthermore allows for estimation in more complicated and perhaps more realistic exposure settings, such as taking into account exposure to both sides of the head. Copyright © 2012 John Wiley & Sons, Ltd.

Who, What, When, Where? Determining the Health Implications of Wildfire Smoke Exposure

NASA Astrophysics Data System (ADS)

Ford, B.; Lassman, W.; Gan, R.; Burke, M.; Pfister, G.; Magzamen, S.; Fischer, E. V.; Volckens, J.; Pierce, J. R.

2016-12-01

Exposure to poor air quality is associated with negative impacts on human health. A large natural source of PM in the western U.S. is from wildland fires. Accurately attributing health endpoints to wildland-fire smoke requires a determination of the exposed population. This is a difficult endeavor because most current methods for monitoring air quality are not at high temporal and spatial resolutions. Therefore, there is a growing effort to include multiple datasets and create blended products of smoke exposure that can exploit the strengths of each dataset. In this work, we combine model (WRF-Chem) simulations, NASA satellite (MODIS) observations, and in-situ surface monitors to improve exposure estimates. We will also introduce a social-media dataset of self-reported smoke/haze/pollution to improve population-level exposure estimates for the summer of 2015. Finally, we use these detailed exposure estimates in different epidemiologic study designs to provide an in-depth understanding of the role wildfire exposure plays on health outcomes.

Merging Remote Sensing and Socioeconomic Data to Improve Disaster Risk Assessment

NASA Astrophysics Data System (ADS)

Yetman, G.; Chen, R. S.; Huyck, C. K.

2015-12-01

Natural disasters disproportionately impact developing country economies while also impacting business operations for multi-national corporations that rely on supplies and manufacturing in affected areas. Understanding natural hazard risk is only a first step towards preparedness and mitigation—data on facilities, transportation, critical infrastructure, and populations that may be exposed to disasters is required to plan for events and properly assess risks. Detailed exposure data can be used in models to predict casualty rates, aggregate estimates of building damage or destruction, impacts on business operations, and the scale of recovery efforts required. These model outputs are useful for disaster preparedness planning by national and international organizations, as well as for corporations and the reinsurance industry seeking to better understand their risk exposure. Many of these data are lacking for developing countries. Rapid assessment in areas with minimal data for disaster modeling is possible by combing remote sensing data, sample data on construction methods, facility and critical infrastructure data, and economic and demographic census information. This presentation focuses on the methods used to fuse the physical and socioeconomic data by presenting the results from two projects. The first project seeks to improve earthquake risk assessments in Asia using for the reinsurance industry, while the second project builds an integrated exposure database across five countries in Africa for use by international development organizations.

Life-Stage Physiologically-Based Pharmacokinetic (PBPK) ...

EPA Pesticide Factsheets

This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. Adverse outcome pathways (AOPs), in this case endocrine disruption during development, provide a biologically-based framework for linking molecular initiating events triggered by chemical exposures to key events leading to adverse outcomes. The application of AOPs to human health risk assessment requires extrapolation of in vitro HTS toxicity data to in vivo exposures (IVIVE) in humans, which can be achieved through the use of a PBPK/PD model. Exposure scenarios for chemicals in the PBPK/PD model will consider both placental and lactational transfer of chemicals, with a focus on age dependent dosimetry during fetal development and after birth for a nursing infant. This talk proposes a universal life-stage computational model that incorporates changing physiological parameters to link environmental exposures to in vitro levels of HTS assays related to a developmental toxicological AOP for vascular disruption. In vitro toxicity endpoints discussed are based on two mechanisms: 1) Fetal vascular disruption, and 2) Neurodevelopmental toxicity induced by altering thyroid hormone levels in neonates via inhibition of thyroperoxidase in the thyroid gland. Application of our Life-stage computati

Risk assessment of consuming agricultural products irrigated with reclaimed wastewater: An exposure model

NASA Astrophysics Data System (ADS)

van Ginneken, Meike; Oron, Gideon

2000-09-01

This study assesses health risks to consumers due to the use of agricultural products irrigated with reclaimed wastewater. The analysis is based on a definition of an exposure model which takes into account several parameters: (1) the quality of the applied wastewater, (2) the irrigation method, (3) the elapsed times between irrigation, harvest, and product consumption, and (4) the consumers' habits. The exposure model is used for numerical simulation of human consumers' risks using the Monte Carlo simulation method. The results of the numerical simulation show large deviations, probably caused by uncertainty (impreciseness in quality of input data) and variability due to diversity among populations. There is a 10-orders of magnitude difference in the risk of infection between the different exposure scenarios with the same water quality. This variation indicates the need for setting risk-based criteria for wastewater reclamation rather than single water quality guidelines. Extra data are required to decrease uncertainty in the risk assessment. Future research needs to include definition of acceptable risk criteria, more accurate dose-response modeling, information regarding pathogen survival in treated wastewater, additional data related to the passage of pathogens into and in the plants during irrigation, and information regarding the behavior patterns of the community of human consumers.

Predicting exposure-response associations of ambient particulate matter with mortality in 73 Chinese cities.

PubMed

Madaniyazi, Lina; Guo, Yuming; Chen, Renjie; Kan, Haidong; Tong, Shilu

2016-01-01

Estimating the burden of mortality associated with particulates requires knowledge of exposure-response associations. However, the evidence on exposure-response associations is limited in many cities, especially in developing countries. In this study, we predicted associations of particulates smaller than 10 μm in aerodynamic diameter (PM10) with mortality in 73 Chinese cities. The meta-regression model was used to test and quantify which city-specific characteristics contributed significantly to the heterogeneity of PM10-mortality associations for 16 Chinese cities. Then, those city-specific characteristics with statistically significant regression coefficients were treated as independent variables to build multivariate meta-regression models. The model with the best fitness was used to predict PM10-mortality associations in 73 Chinese cities in 2010. Mean temperature, PM10 concentration and green space per capita could best explain the heterogeneity in PM10-mortality associations. Based on city-specific characteristics, we were able to develop multivariate meta-regression models to predict associations between air pollutants and health outcomes reasonably well. Copyright © 2015 Elsevier Ltd. All rights reserved.

Field Measurements of Inadvertent Ingestion Exposure to Metals.

PubMed

Gorman Ng, Melanie; MacCalman, Laura; Semple, Sean; van Tongeren, Martie

2017-11-10

The determinants of inadvertent occupational ingestion exposure are poorly understood, largely due to a lack of available exposure measurement data. In this study, perioral exposure wipes were used as a surrogate for inadvertent ingestion exposure to measure exposure to eight metals (chromium, nickel, aluminium, cobalt, lead, arsenic, manganese, and tin) among 38 workers at 5 work sites in the UK. This work was done alongside a previously reported observational study of hand/object-to-mouth contact frequency. Systematic wipes of the perioral area, and of both hands were taken with proprietary cellulose wipes pre-moistened with deionized water. Measurements were taken at the beginning, middle and end of the shift. Mixed-effect models of exposure measurements were built with area of skin sampled, time during shift, and job group entered as fixed effects and worker identification as a random effect. Linear regression modelling was used to study the effect of hand/object-to-mouth contact frequency on perioral exposure, adjusting for the measured exposure on the hand and observed respirator use. Hand and perioral exposure measurements were correlated with one another (r = 0.79) but mass per unit area exposure was significantly higher on the perioral area than on the hands for seven of the metals (at P < 0.05). There were no significant differences between measurements taken at the middle or the end of the shift for five of the metals suggesting that dermal loading may remain relatively constant for much of the workday. This applies to both hand and perioral measurements. In linear regression modelling there was no relationship between hand/object-to-mouth contact frequency and perioral exposure, but hand exposure was significantly positively related to perioral exposure and workers who used respirators had significantly higher perioral exposure than those who did not. The results suggest the levels of exposure on the hand and respirator use are important determinants of potential inadvertent ingestion exposure. The results did not demonstrate a relationship between perioral exposure and hand-to-mouth contact frequency. Perioral wipe sampling may be a useful surrogate measure for exposure by the inadvertent ingestion route, but further research is required to confirm the link between perioral levels and actual exposure, measured using biological monitoring. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Determination of shielding requirements for mammography.

PubMed

Okunade, Akintunde Akangbe; Ademoroti, Olalekan Albert

2004-05-01

Shielding requirements for mammography when considerations are to be given to attenuation by compression paddle, breast tissue, grid and image receptor (intervening materials) has been investigated. By matching of the attenuation and hardening properties, comparisons are made between shielding afforded by breast tissue materials (water, Lucite and 50%-50% adipose-glandular tissue) and some materials considered for shielding diagnostic x-ray beams, namely lead, steel and gypsum wallboard. Results show that significant differences exist between the thickness required to produce equal attenuation and that required to produce equal hardening of a given incident beam. While attenuation equivalent thickness produces equal exposure, it does not produce equal hardening. For shielding purposes, equivalence in exposure reduction without equivalence in penetrating power of an emerging beam does not amount to equivalence in shielding affordable by two different materials. Presented are models and results of sample calculations of additional shielding requirements apart from that provided by intervening materials. The shielding requirements for the integrated beam emerging from intervening materials are different from those for the integrated beam emerging from materials (lead/steel/gypsum wallboard) with attenuation equivalent thicknesses of these intervening materials.

Lead exposure potentiates predatory attack behavior in the cat.

PubMed

Li, Wenjie; Han, Shenggao; Gregg, Thomas R; Kemp, Francis W; Davidow, Amy L; Louria, Donald B; Siegel, Allan; Bogden, John D

2003-07-01

Epidemiologic studies have demonstrated that environmental lead exposure is associated with aggressive behavior in children; however, numerous confounding variables limit the ability of these studies to establish a causal relationship. The study of aggressive behavior using a validated animal model was used to test the hypothesis that there is a causal relationship between lead exposure and aggression in the absence of confounding variables. We studied the effects of lead exposure on a feline model of aggression: predatory (quiet biting) attack of an anesthetized rat. Five cats were stimulated with a precisely controlled electrical current via electrodes inserted into the lateral hypothalamus. The response measure was the predatory attack threshold current (i.e., the current required to elicit an attack response on 50% of the trials). Blocks of trials were administered in which predatory attack threshold currents were measured three times a week for a total of 6-10 weeks, including before, during, and after lead exposure. Lead was incorporated into cat food "treats" at doses of 50-150 mg/kg/day. Two of the five cats received a second period of lead exposure. Blood lead concentrations were measured twice a week and were <1, 21-77, and <20 micro g/dL prior to, during, and after lead exposure, respectively. The predatory attack threshold decreased significantly during initial lead exposure in three of five cats and increased after the cessation of lead exposure in four of the five cats (P<0.01). The predatory attack thresholds and blood lead concentrations for each cat were inversely correlated (r=-0.35 to -0.74). A random-effects mixed model demonstrated a significant (P=0.0019) negative association between threshold current and blood lead concentration. The data of this study demonstrate that lead exposure enhances predatory aggression in the cat and provide experimental support for a causal relationship between lead exposure and aggressive behavior in humans.

A tissue dose-based comparative exposure assessment of manganese using physiologically based pharmacokinetic modeling—The importance of homeostatic control for an essential metal

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

Gentry, P. Robinan, E-mail: rgentry@ramboll.com

A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates. Mn exposure was determined based on measured ambient air Mn concentrations and dietary data in Canada and the United States (US). Incorporating dietary and inhalation exposuresmore » into the models indicated that increases in target tissue concentrations above endogenous levels only begin to occur when humans are exposed to levels of Mn in ambient air (i.e. > 10 μg/m{sup 3}) that are far higher than those currently measured in Canada or the US. A MOS greater than three orders of magnitude was observed, indicating that current Mn air concentrations are far below concentrations that would be required to produce the target tissue Mn concentrations associated with subclinical neurological effects. This application of PBPK modeling for an essential element clearly demonstrates that the conventional application of default factors to “convert” an occupational exposure to an equivalent continuous environmental exposure, followed by the application of safety factors, is not appropriate in the case of Mn. PBPK modeling demonstrates that the relationship between ambient Mn exposures and dose-to-target tissue is not linear due to normal tissue background levels and homeostatic controls. - Highlights: • Manganese is an essential nutrient, adding complexity to its risk assessment. • Nonlinearities in biological processes are important for manganese risk assessment. • A PBPK model was used to estimate target tissue concentrations of manganese. • An MOS approach also considered target tissue concentrations for ambient exposures. • Relationships between ambient Mn exposures and dose-to-target tissue are not linear.« less

Application of in Vitro Biotransformation Data and ...

EPA Pesticide Factsheets

The adverse biological effects of toxic substances are dependent upon the exposure concentration and the duration of exposure. Pharmacokinetic models can quantitatively relate the external concentration of a toxicant in the environment to the internal dose of the toxicant in the target tissues of an exposed organism. The exposure concentration of a toxic substance is usually not the same as the concentration of the active form of the toxicant that reaches the target tissues following absorption, distribution, and biotransformation of the parent toxicant. Biotransformation modulates the biological activity of chemicals through bioactivation and detoxication pathways. Many toxicants require biotransformation to exert their adverse biological effects. Considerable species differences in biotransformation and other pharmacokinetic processes can make extrapolation of toxicity data from laboratory animals to humans problematic. Additionally, interindividual differences in biotransformation among human populations with diverse genetics and lifestyles can lead to considerable variability in the bioactivation of toxic chemicals. Compartmental pharmacokinetic models of animals and humans are needed to understand the quantitative relationships between chemical exposure and target tissue dose as well as animal to human differences and interindividual differences in human populations. The data-based compartmental pharmacokinetic models widely used in clinical pharmacology ha

Assessment of long-term spatio-temporal radiofrequency electromagnetic field exposure.

PubMed

Aerts, Sam; Wiart, Joe; Martens, Luc; Joseph, Wout

2018-02-01

As both the environment and telecommunications networks are inherently dynamic, our exposure to environmental radiofrequency (RF) electromagnetic fields (EMF) at an arbitrary location is not at all constant in time. In this study, more than a year's worth of measurement data collected in a fixed low-cost exposimeter network distributed over an urban environment was analysed and used to build, for the first time, a full spatio-temporal surrogate model of outdoor exposure to downlink Global System for Mobile Communications (GSM) and Universal Mobile Telecommunications System (UMTS) signals. Though no global trend was discovered over the measuring period, the difference in measured exposure between two instances could reach up to 42dB (a factor 12,000 in power density). Furthermore, it was found that, taking into account the hour and day of the measurement, the accuracy of the surrogate model in the area under study was improved by up to 50% compared to models that neglect the daily temporal variability of the RF signals. However, further study is required to assess the extent to which the results obtained in the considered environment can be extrapolated to other geographic locations. Copyright © 2017 Elsevier Inc. All rights reserved.

Incorporating Measurement Error from Modeled Air Pollution Exposures into Epidemiological Analyses.

PubMed

Samoli, Evangelia; Butland, Barbara K

2017-12-01

Outdoor air pollution exposures used in epidemiological studies are commonly predicted from spatiotemporal models incorporating limited measurements, temporal factors, geographic information system variables, and/or satellite data. Measurement error in these exposure estimates leads to imprecise estimation of health effects and their standard errors. We reviewed methods for measurement error correction that have been applied in epidemiological studies that use model-derived air pollution data. We identified seven cohort studies and one panel study that have employed measurement error correction methods. These methods included regression calibration, risk set regression calibration, regression calibration with instrumental variables, the simulation extrapolation approach (SIMEX), and methods under the non-parametric or parameter bootstrap. Corrections resulted in small increases in the absolute magnitude of the health effect estimate and its standard error under most scenarios. Limited application of measurement error correction methods in air pollution studies may be attributed to the absence of exposure validation data and the methodological complexity of the proposed methods. Future epidemiological studies should consider in their design phase the requirements for the measurement error correction method to be later applied, while methodological advances are needed under the multi-pollutants setting.

Cytogenetic damages in peripheral blood of monkey lymphocytes under simulation of cosmonauts irradiation.

NASA Astrophysics Data System (ADS)

Petrov, Vladislav; Ivanov, Alexandr; Barteneva, Svetlana; Snigiryeva, Galina; Shafirkin, Alexandr

Earth modeling of crewmember exposure should be performed for correct estimating radiation hazard during the flight. Such modeling was planned in a monkey experiment for investigating consequences of exposure to a man during an interplanetary flight. It should reflect a chronic impact of galactic cosmic rays and acute and fractional irradiation specified for solar cosmic rays and radiation belts respectively. Due to the difficulty of modeling a chronic impact with the help of a charged particles accelerator it can be used the gamma source. While irradiating big animal groups during a long-term period of time it is preferably to replace chronic irradiation by an equal fractional one. In this case the chosen characteristics of fractional irradiation should ensure the appearances of radiobiological consequences equal to the ones caused by the modeled chronic exposure. So for developing an exposure scheme in the monkey experiment (with Macaca -Rhesus) the model of the acting residual dose, that takes into account repair and recovery processes in the exposed body was used. The total dose value was in the limits from 2.32 Gy up to 3.5 Gy depending on the exposure character. The acting residual dose in all versions of exposure was 2.0 Gy for every monkey. While performing the experiment all the requirements of bioethics for the work with animals were observed. The objects of interest were genomic damages in lymphocytes of monkey's peripheral blood. The data about the CAF during the exposure and at various time moments after exposure particularly directly after the completion of chronicle and fractional irradiation were analyzed. CAF -dose of acute single gamma-irradiation in the range 0 -1.5Gy relationship (calibration curve) was defined in vitro. In addition the rate of the aberrant cells elimination within three months after the irradiation completion was estimated. On the basis of the obtained CAF data we performed verification of applicability of cytogenetic analysis for estimating the monkey gamma -dose exposure in the experiment It was obtained that this method permits to estimate the acting residual dose with accuracy of 30

The impact of urban open space and 'lift-up' building design on building intake fraction and daily pollutant exposure in idealized urban models.

PubMed

Sha, Chenyuan; Wang, Xuemei; Lin, Yuanyuan; Fan, Yifan; Chen, Xi; Hang, Jian

2018-08-15

Sustainable urban design is an effective way to improve urban ventilation and reduce vehicular pollutant exposure to urban residents. This paper investigated the impacts of urban open space and 'lift-up' building design on vehicular CO (carbon monoxide) exposure in typical three-dimensional (3D) urban canopy layer (UCL) models under neutral atmospheric conditions. The building intake fraction (IF) represents the fraction of total vehicular pollutant emissions inhaled by residents when they stay at home. The building daily CO exposure (E t ) means the extent of human beings' contact with CO within one day indoor at home. Computational fluid dynamics (CFD) simulations integrating with these two concepts were performed to solve turbulent flow and assess vehicular CO exposure to urban residents. CFD technique with the standard k-ε model was successfully validated by wind tunnel data. The initial numerical UCL model consists of 5-row and 5-column (5×5) cubic buildings (building height H=street width W=30m) with four approaching wind directions (θ=0°, 15°, 30°, 45°). In Group I, one of the 25 building models is removed to attain urban open space settings. In Group II, the first floor (Lift-up1), or second floor (Lift-up2), or third floor (Lift-up3) of all buildings is elevated respectively to create wind pathways through buildings. Compared to the initial case, urban open space can slightly or significantly reduce pollutant exposure for urban residents. As θ=30° and 45°, open space settings are more effective to reduce pollutant exposure than θ=0° and 15°.The pollutant dilution near or surrounding open space and in its adjacent downstream regions is usually enhanced. Lift-up1 and Lift-up2 experience much greater pollutant exposure reduction in all wind directions than Lift-up3 and open space. Although further investigations are still required to provide practical guidelines, this study is one of the first attempts for reducing urban pollutant exposure by improving urban design. Copyright © 2018. Published by Elsevier B.V.

Outside-In Systems Pharmacology Combines Innovative Computational Methods With High-Throughput Whole Vertebrate Studies.

PubMed

Schulthess, Pascal; van Wijk, Rob C; Krekels, Elke H J; Yates, James W T; Spaink, Herman P; van der Graaf, Piet H

2018-04-25

To advance the systems approach in pharmacology, experimental models and computational methods need to be integrated from early drug discovery onward. Here, we propose outside-in model development, a model identification technique to understand and predict the dynamics of a system without requiring prior biological and/or pharmacological knowledge. The advanced data required could be obtained by whole vertebrate, high-throughput, low-resource dose-exposure-effect experimentation with the zebrafish larva. Combinations of these innovative techniques could improve early drug discovery. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Causal mediation analysis for longitudinal data with exogenous exposure

PubMed Central

Bind, M.-A. C.; Vanderweele, T. J.; Coull, B. A.; Schwartz, J. D.

2016-01-01

Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM-1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. PMID:26272993

49 CFR 227.121 - Recordkeeping.

Code of Federal Regulations, 2010 CFR

2010-10-01

... exposure measurement records for specific locations available to regional or national labor representatives... ceases to do business, it shall transfer to the successor employer all records required to be maintained... measurements of the background sound pressure levels in audiometric test rooms; (vi) The model and serial...

Best practice assessment of disease modelling for infectious disease outbreaks.

PubMed

Dembek, Z F; Chekol, T; Wu, A

2018-05-08

During emerging disease outbreaks, public health, emergency management officials and decision-makers increasingly rely on epidemiological models to forecast outbreak progression and determine the best response to health crisis needs. Outbreak response strategies derived from such modelling may include pharmaceutical distribution, immunisation campaigns, social distancing, prophylactic pharmaceuticals, medical care, bed surge, security and other requirements. Infectious disease modelling estimates are unavoidably subject to multiple interpretations, and full understanding of a model's limitations may be lost when provided from the disease modeller to public health practitioner to government policymaker. We review epidemiological models created for diseases which are of greatest concern for public health protection. Such diseases, whether transmitted from person-to-person (Ebola, influenza, smallpox), via direct exposure (anthrax), or food and waterborne exposure (cholera, typhoid) may cause severe illness and death in a large population. We examine disease-specific models to determine best practices characterising infectious disease outbreaks and facilitating emergency response and implementation of public health policy and disease control measures.

Understanding cancer development processes after HZE-particle exposure: roles of ROS, DNA damage repair and inflammation.

PubMed

Sridharan, D M; Asaithamby, A; Bailey, S M; Costes, S V; Doetsch, P W; Dynan, W S; Kronenberg, A; Rithidech, K N; Saha, J; Snijders, A M; Werner, E; Wiese, C; Cucinotta, F A; Pluth, J M

2015-01-01

During space travel astronauts are exposed to a variety of radiations, including galactic cosmic rays composed of high-energy protons and high-energy charged (HZE) nuclei, and solar particle events containing low- to medium-energy protons. Risks from these exposures include carcinogenesis, central nervous system damage and degenerative tissue effects. Currently, career radiation limits are based on estimates of fatal cancer risks calculated using a model that incorporates human epidemiological data from exposed populations, estimates of relative biological effectiveness and dose-response data from relevant mammalian experimental models. A major goal of space radiation risk assessment is to link mechanistic data from biological studies at NASA Space Radiation Laboratory and other particle accelerators with risk models. Early phenotypes of HZE exposure, such as the induction of reactive oxygen species, DNA damage signaling and inflammation, are sensitive to HZE damage complexity. This review summarizes our current understanding of critical areas within the DNA damage and oxidative stress arena and provides insight into their mechanistic interdependence and their usefulness in accurately modeling cancer and other risks in astronauts exposed to space radiation. Our ultimate goals are to examine potential links and crosstalk between early response modules activated by charged particle exposure, to identify critical areas that require further research and to use these data to reduced uncertainties in modeling cancer risk for astronauts. A clearer understanding of the links between early mechanistic aspects of high-LET response and later surrogate cancer end points could reveal key nodes that can be therapeutically targeted to mitigate the health effects from charged particle exposures.

THE EPA NATIONAL EXPOSURE RESEARCH LABORATORY CHILDREN'S PESTICIDE EXPOSURE MEASUREMENT PROGRAM

EPA Science Inventory

The U.S. EPA's National Exposure Research Laboratory (NERL) conducts research in support of the Food Quality Protection Act (FQPA) of 1996. FQPA requires that children's risks to pesticide exposures be considered during the tolerance-setting process. The Act requires exposure...

Misaligned Image Integration With Local Linear Model.

PubMed

Baba, Tatsuya; Matsuoka, Ryo; Shirai, Keiichiro; Okuda, Masahiro

2016-05-01

We present a new image integration technique for a flash and long-exposure image pair to capture a dark scene without incurring blurring or noisy artifacts. Most existing methods require well-aligned images for the integration, which is often a burdensome restriction in practical use. We address this issue by locally transferring the colors of the flash images using a small fraction of the corresponding pixels in the long-exposure images. We formulate the image integration as a convex optimization problem with the local linear model. The proposed method makes it possible to integrate the color of the long-exposure image with the detail of the flash image without causing any harmful effects to its contrast, where we do not need perfect alignment between the images by virtue of our new integration principle. We show that our method successfully outperforms the state of the art in the image integration and reference-based color transfer for challenging misaligned data sets.

Operations planning simulation model extension study. Volume 1: Long duration exposure facility ST-01-A automated payload

NASA Technical Reports Server (NTRS)

Marks, D. A.; Gendiellee, R. E.; Kelly, T. M.; Giovannello, M. A.

1974-01-01

Ground processing and operation activities for selected automated and sortie payloads are evaluated. Functional flow activities are expanded to identify payload launch site facility and support requirements. Payload definitions are analyzed from the launch site ground processing viewpoint and then processed through the expanded functional flow activities. The requirements generated from the evaluation are compared with those contained in the data sheets. The following payloads were included in the evaluation: Long Duration Exposure Facility; Life Sciences Shuttle Laboratory; Biomedical Experiments Scientific Satellite; Dedicated Solar Sortie Mission; Magnetic Spectrometer; and Mariner Jupiter Orbiter. The expanded functional flow activities and descriptions for the automated and sortie payloads at the launch site are presented.

Overview of atmospheric ionizing radiation (AIR) research: SST-present

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Goldhagen, P.; Rafnsson, V.; Clem, J. M.; De Angelis, G.; Friedberg, W.

2003-01-01

The Supersonic Transport (SST) program, proposed in 1961, first raised concern for the exposure of pregnant occupants by solar energetic particles (SEP), and neutrons were suspected to have a main role in particle propagation deep into the atmosphere. An eight-year flight program confirmed the role of SEP as a significant hazard and of the neutrons as contributing over half of the galactic cosmic ray exposures, with the largest contribution from neutrons above 10 MeV. The FAA Advisory Committee on the Radiobiological Aspects of the SST provided operational requirements. The more recent lowering of ICRP-recommended exposure limits (1990) with the classification of aircrew as "radiation workers" renewed interest in GCR background exposures at commercial flight altitudes and stimulated epidemiological studies in Europe, Japan, Canada and the USA. The proposed development of a High Speed Civil Transport (HSCT) required validation of the role of high-energy neutrons, and this resulted in ER-2 flights at solar minimum (June 1997) and studies on effects of aircraft materials on interior exposures. Recent evaluation of health outcomes of DOE nuclear workers resulted in legislation for health compensation in year 2000 and recent European aircrew epidemiological studies of health outcomes bring renewed interest in aircraft radiation exposures. As improved radiation models become available, it is imperative that a corresponding epidemiological program of US aircrew be implemented. Published by Elsevier Ltd on behalf of COSPAR.

Summary of Atmospheric Ionizing AIR Research: SST-Present

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Goldhagen, P.; Rafnsson, V.; deAngelis, G.; Friedberg, W.; Clem, J. M.

2003-01-01

The Supersonic Transport (SST) program, proposed in 1961, first raised concern for the exposure of pregnant occupants by solar energetic particles (SEP), and neutrons were suspected to have a main role in particle propagation deep into the atmosphere. An eight-year flight program confirmed the role of SEP as a significant hazard and of the neutrons as contributing over half of the galactic cosmic ray (GCR) exposures, with the largest contribution from neutrons above 10 MeV. The FAA Advisory Committee on the Radiobiological Aspects of the SST provided operational requirements. The more recent lowering of the radiation exposure limits by the International Commission on Radiological Protection with the classification of aircrew as radiation workers renewed interest in GCR background exposures at commercial flight altitudes and stimulated epidemiological studies in Europe, Japan, Canada and the USA. The proposed development of a High Speed Civil Transport (HSCT) required validation of the role of high-energy neutrons, and this resulted in ER-2 flights at solar minimum (June 1997) and studies on effects of aircraft materials on interior exposures. Recent evaluation of health outcomes of DOE nuclear workers resulted in legislation for health compensation in year 2000 and recent European aircrew epidemiological studies of health outcomes bring renewed interest in aircraft radiation exposures. As improved radiation models become available, it is imperative that a corresponding epidemiological program of US aircrew be implemented.

Overview of Atmospheric Ionizing Radiation (AIR) Research: SST - Present

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Goldhagen, P.; Rafnsson, V.; Clem, J. M.; DeAngelis, G.; Friedberg, W.

2002-01-01

The Supersonic Transport (SST) program, proposed in 1961, first raised concern for the exposure of pregnant occupants by solar energetic particles (SEP), and neutrons were suspected to have a main role in particle propagation deep into the atmosphere. An eight-year flight program confirmed the role of SEP as a significant hazard and of the neutrons as contributing over half of the galactic cosmic ray (GCR) exposures, with the largest contribution from neutrons above 10 MeV. The FAA Advisory Committee on the Radiobiological Aspects of the SST provided operational requirements. The more recent (1990) lowering of recommended exposure limits by the International Commission on Radiological Protection with the classification of aircrew as "radiation workers" renewed interest in GCR background exposures at commercial flight altitudes and stimulated epidemiological studies in Europe, Japan, Canada and the USA. The proposed development of a High Speed Civil Transport (HSCT) required validation of the role of high-energy neutrons, and this resulted in ER-2 flights at solar minimum (June 1997) and studies on effects of aircraft materials on interior exposures. Recent evaluation of health outcomes of DOE nuclear workers resulted in legislation for health compensation in year 2000 and recent European aircrew epidemiological studies of health outcomes bring renewed interest in aircraft radiation exposures. As improved radiation models become available, it is imperative that a corresponding epidemiological program of US aircrew be implemented.

Overview of atmospheric ionizing radiation (AIR) research: SST-present.

PubMed

Wilson, J W; Goldhagen, P; Rafnsson, V; Clem, J M; De Angelis, G; Friedberg, W

2003-01-01

The Supersonic Transport (SST) program, proposed in 1961, first raised concern for the exposure of pregnant occupants by solar energetic particles (SEP), and neutrons were suspected to have a main role in particle propagation deep into the atmosphere. An eight-year flight program confirmed the role of SEP as a significant hazard and of the neutrons as contributing over half of the galactic cosmic ray exposures, with the largest contribution from neutrons above 10 MeV. The FAA Advisory Committee on the Radiobiological Aspects of the SST provided operational requirements. The more recent lowering of ICRP-recommended exposure limits (1990) with the classification of aircrew as "radiation workers" renewed interest in GCR background exposures at commercial flight altitudes and stimulated epidemiological studies in Europe, Japan, Canada and the USA. The proposed development of a High Speed Civil Transport (HSCT) required validation of the role of high-energy neutrons, and this resulted in ER-2 flights at solar minimum (June 1997) and studies on effects of aircraft materials on interior exposures. Recent evaluation of health outcomes of DOE nuclear workers resulted in legislation for health compensation in year 2000 and recent European aircrew epidemiological studies of health outcomes bring renewed interest in aircraft radiation exposures. As improved radiation models become available, it is imperative that a corresponding epidemiological program of US aircrew be implemented. Published by Elsevier Ltd on behalf of COSPAR.

Pharmacodynamics of levofloxacin in a murine pneumonia model of Pseudomonas aeruginosa infection: determination of epithelial lining fluid targets.

PubMed

Louie, Arnold; Fregeau, Christine; Liu, Weiguo; Kulawy, Robert; Drusano, G L

2009-08-01

The dose choice for Pseudomonas aeruginosa remains a matter of debate. The actual exposure targets required for multilog killing of organisms at the primary infection site have not been delineated. We studied Pseudomonas aeruginosa PAO1 using a murine model of pneumonia. We employed a large mathematical model to fit all the concentration-time data in plasma and epithelial lining fluid (ELF) as well as colony counts in lung simultaneously for all drug doses. Penetration into ELF was calculated to be approximately 77.7%, as indexed to the ratio of the area under the concentration-time curve for ELF (AUC(ELF)) to the AUC(plasma). We determined the ELF concentration-time profile required to drive a stasis response as well as 1-, 2-, or 3-log(10)(CFU/g) kill. AUC/MIC ratios of 12.4, 31.2, 62.8, and 127.6 were required to drive these bacterial responses. Emergence of resistance was seen only at the two lowest doses (three of five animals at 50 mg/kg [body weight] and one of five animals at 100 mg/kg). The low exposure targets were likely driven by a low mutational frequency to resistance. Bridging to humans was performed using Monte Carlo simulation. With a 750-mg levofloxacin dose, target attainment rates fell below 90% at 4 mg/liter, 1 mg/liter, and 0.5 mg/liter for 1-, 2-, and 3-log kills, respectively. Given the low exposure targets seen with this strain, we conclude that levofloxacin at a 750-mg dose is not adequate for serious Pseudomonas aeruginosa pneumonia as a single agent. More isolates need to be studied to make these observations more robust.

Pharmacodynamics of Levofloxacin in a Murine Pneumonia Model of Pseudomonas aeruginosa Infection: Determination of Epithelial Lining Fluid Targets▿

PubMed Central

Louie, Arnold; Fregeau, Christine; Liu, Weiguo; Kulawy, Robert; Drusano, G. L.

2009-01-01

The dose choice for Pseudomonas aeruginosa remains a matter of debate. The actual exposure targets required for multilog killing of organisms at the primary infection site have not been delineated. We studied Pseudomonas aeruginosa PAO1 using a murine model of pneumonia. We employed a large mathematical model to fit all the concentration-time data in plasma and epithelial lining fluid (ELF) as well as colony counts in lung simultaneously for all drug doses. Penetration into ELF was calculated to be approximately 77.7%, as indexed to the ratio of the area under the concentration-time curve for ELF (AUCELF) to the AUCplasma. We determined the ELF concentration-time profile required to drive a stasis response as well as 1-, 2-, or 3-log10(CFU/g) kill. AUC/MIC ratios of 12.4, 31.2, 62.8, and 127.6 were required to drive these bacterial responses. Emergence of resistance was seen only at the two lowest doses (three of five animals at 50 mg/kg [body weight] and one of five animals at 100 mg/kg). The low exposure targets were likely driven by a low mutational frequency to resistance. Bridging to humans was performed using Monte Carlo simulation. With a 750-mg levofloxacin dose, target attainment rates fell below 90% at 4 mg/liter, 1 mg/liter, and 0.5 mg/liter for 1-, 2-, and 3-log kills, respectively. Given the low exposure targets seen with this strain, we conclude that levofloxacin at a 750-mg dose is not adequate for serious Pseudomonas aeruginosa pneumonia as a single agent. More isolates need to be studied to make these observations more robust. PMID:19364849

Development of a pH/alkalinity treatment model for applications of the lampricide TFM to streams tributary to the Great Lakes

USGS Publications Warehouse

Bills, Terry D.; Boogaard, Michael A.; Johnson, David A.; Brege, Dorance C.; Scholefield, Ronald J.; Westman, R. Wayne; Stephens, Brian E.

2003-01-01

It has long been known that the toxicity of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) is influenced by chemical and physical properties of water. As the pH, conductivity, and alkalinity of water increase, greater concentrations of TFM are required to kill sea lamprey (Petromyzon marinus) larvae. Consequently, the concentration of TFM required for effective treatment varies among streams. Brown trout (Salmo trutta) and sea lamprey larvae were exposed to a series of TFM concentrations in a continuous-flow diluter for 12 h. Twenty five exposures were conducted at various water alkalinities and pHs that treatment personnel encounter during lampricide treatments. Survival/mortality data were analyzed for lampricide concentrations that produced 50 and 99.9% mortality (LC50 and LC99.9) for sea lamprey larvae and 25 and 50% mortality (LC25 and LC50) for brown trout. Linear regression analyses were performed for each set of tests for each selected alkalinity by comparing the 12-h post exposure LC99.9 sea lamprey data and LC25 brown trout data at each pH. Mortality data from on-site toxicity tests conducted by lampricide control personnel were compared to predicted values from the pH/alkalinity prediction model. Of the 31 tests examined, 27 resulted in the LC100s (lowest TFM concentration where 100% mortality of sea lamprey was observed after 12 h of exposure) falling within 0.2 mg/L of the predicted sea lamprey minimum lethal (LC99.9) range. The pH/alkalinity prediction model provides managers with an operational tool that reduces the amount of TFM required for effective treatment while minimizing the impact on non-target organisms.

Pregnant Women Models Analyzed for RF Exposure and Temperature Increase in 3T RF Shimmed Birdcages

PubMed Central

Murbach, Manuel; Neufeld, Esra; Samaras, Theodoros; Córcoles, Juan; Robb, Fraser J.; Kainz, Wolfgang; Kuster, Niels

2017-01-01

Purpose MRI is increasingly used to scan pregnant patients. We investigated the effect of 3 Tesla (T) two-port radiofrequency (RF) shimming in anatomical pregnant women models. Theory and Methods RF shimming improves B1+ uniformity, but may at the same time significantly alter the induced current distribution and result in large changes in both the level and location of the absorbed RF energy. In this study, we evaluated the electrothermal exposure of pregnant women in the third, seventh, and ninth month of gestation at various imaging landmarks in RF body coils, including modes with RF shimming. Results Although RF shimmed configurations may lower the local RF exposure for the mother, they can increase the thermal load on the fetus. In worst-case configurations, whole-body exposure and local peak temperatures—up to 40.8°C—are equal in fetus and mother. Conclusions Two-port RF shimming can significantly increase the fetal exposure in pregnant women, requiring further research to derive a very robust safety management. For the time being, restriction to the CP mode, which reduces fetal SAR exposure compared with linear-horizontal polarization modes, may be advisable. Results from this study do not support scanning pregnant patients above the normal operating mode. PMID:27174499

A New Method for Partial Correction of Residual Confounding in Time-Series and Other Observational Studies.

PubMed

Flanders, W Dana; Strickland, Matthew J; Klein, Mitchel

2017-05-15

Methods exist to detect residual confounding in epidemiologic studies. One requires a negative control exposure with 2 key properties: 1) conditional independence of the negative control and the outcome (given modeled variables) absent confounding and other model misspecification, and 2) associations of the negative control with uncontrolled confounders and the outcome. We present a new method to partially correct for residual confounding: When confounding is present and our assumptions hold, we argue that estimators from models that include a negative control exposure with these 2 properties tend to be less biased than those from models without it. Using regression theory, we provide theoretical arguments that support our claims. In simulations, we empirically evaluated the approach using a time-series study of ozone effects on asthma emergency department visits. In simulations, effect estimators from models that included the negative control exposure (ozone concentrations 1 day after the emergency department visit) had slightly or modestly less residual confounding than those from models without it. Theory and simulations show that including the negative control can reduce residual confounding, if our assumptions hold. Our method differs from available methods because it uses a regression approach involving an exposure-based indicator rather than a negative control outcome to partially correct for confounding. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chronic toxicity of selected polycyclic aromatic hydrocarbons to algae and crustaceans using passive dosing.

PubMed

Bragin, Gail E; Parkerton, Thomas F; Redman, Aaron D; Letinksi, Daniel J; Butler, Josh D; Paumen, Miriam Leon; Sutherland, Cary A; Knarr, Tricia M; Comber, Mike; den Haan, Klaas

2016-12-01

Because of the large number of possible aromatic hydrocarbon structures, predictive toxicity models are needed to support substance hazard and risk assessments. Calibration and evaluation of such models requires toxicity data with well-defined exposures. The present study has applied a passive dosing method to generate reliable chronic effects data for 8 polycyclic aromatic hydrocarbons (PAHs) on the green algae Pseudokirchneriella subcapitata and the crustacean Ceriodaphnia dubia. The observed toxicity of these substances on algal growth rate and neonate production were then compared with available literature toxicity data for these species, as well as target lipid model and chemical activity-based model predictions. The use of passive dosing provided well-controlled exposures that yielded more consistent data sets than attained by past literature studies. Results from the present study, which were designed to exclude the complicating influence of ultraviolet light, were found to be well described by both target lipid model and chemical activity effect models. The present study also found that the lack of chronic effects for high molecular weight PAHs was consistent with the limited chemical activity that could be achieved for these compounds in the aqueous test media. Findings from this analysis highlight that variability in past literature toxicity data for PAHs may be complicated by both poorly controlled exposures and photochemical processes that can modulate both exposure and toxicity. Environ Toxicol Chem 2016;35:2948-2957. © 2016 SETAC. © 2016 SETAC.

Monitoring, modelling and environmental exposure assessment of industrial chemicals in the aquatic environment.

PubMed

Holt, M S; Fox, K; Griessbach, E; Johnsen, S; Kinnunen, J; Lecloux, A; Murray-Smith, R; Peterson, D R; Schröder, R; Silvani, M; ten Berge, W F; Toy, R J; Feijtel, T C

2000-12-01

Monitoring and laboratory data play integral roles alongside fate and exposure models in comprehensive risk assessments. The principle in the European Union Technical Guidance Documents for risk assessment is that measured data may take precedence over model results but only after they are judged to be of adequate reliability and to be representative of the particular environmental compartments to which they are applied. In practice, laboratory and field data are used to provide parameters for the models, while monitoring data are used to validate the models' predictions. Thus, comprehensive risk assessments require the integration of laboratory and monitoring data with the model predictions. However, this interplay is often overlooked. Discrepancies between the results of models and monitoring should be investigated in terms of the representativeness of both. Certainly, in the context of the EU risk assessment of existing chemicals, the specific requirements for monitoring data have not been adequately addressed. The resources required for environmental monitoring, both in terms of manpower and equipment, can be very significant. The design of monitoring programmes to optimise the use of resources and the use of models as a cost-effective alternative are increasing in importance. Generic considerations and criteria for the design of new monitoring programmes to generate representative quality data for the aquatic compartment are outlined and the criteria for the use of existing data are discussed. In particular, there is a need to improve the accessibility to data sets, to standardise the data sets, to promote communication and harmonisation of programmes and to incorporate the flexibility to change monitoring protocols to amend the chemicals under investigation in line with changing needs and priorities.

Shelter and indoor air in the twenty-first century--radon, smoking, and lung cancer risks.

PubMed Central

Fabrikant, J I

1990-01-01

Recognition that radon and its daughter products may accumulate to high levels in homes and in the workplace has led to concern about the potential lung cancer risk resulting from indoor domestic exposure. While such risks can be estimated with current dosimetric and epidemiological models for excess relative risks, it must be recognized that these models are based on data from occupational exposure and from underground miners' mortality experience. Several assumptions are required to apply risk estimates from an occupational setting to the indoor domestic environment. Analyses of the relevant data do not lead to a conclusive description of the interaction between radon daughters and cigarette smoking for the induction of lung cancer. The evidence compels the conclusion that indoor radon daughter exposure in homes represents a potential life-threatening public health hazard, particularly in males, and in cigarette smokers. Resolution of complex societal interactions will require public policy decisions involving the governmental, scientific, financial, and industrial sectors. These decisions impact the home, the workplace, and the marketplace, and they extend beyond the constraints of science. Risk identification, assessment, and management require scientific and engineering approaches to guide policy decisions to protect the public health. Mitigation and control procedures are only beginning to receive attention. Full acceptance for protection against what could prove to be a significant public health hazard in the twenty-first century will certainly involve policy decisions, not by scientists, but rather by men and women of government and law. PMID:2401265

Assessing the potency and immunogenicity of inactivated poliovirus vaccine after exposure to freezing temperatures.

PubMed

White, Jessica A; Estrada, Marcus; Weldon, William C; Chumakov, Konstantin; Kouiavskaia, Diana; Fournier-Caruana, Jacqueline; Stevens, Eric; Gary, Howard E; Maes, Edmond F; Oberste, M Steven; Snider, Cynthia J; Anand, Abhijeet; Chen, Dexiang

2018-05-01

According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2°C and 8°C, whereas oral poliovirus vaccine requires storage at -20 °C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better understand the effect of freezing IPVs, samples of single-dose vaccine vials from Statens Serum Institut (VeroPol) and multi-dose vaccine vials from Sanofi Pasteur (IPOL) were exposed to freezing temperatures mimicking what a vaccine vial might encounter in the field. D-antigen content was measured to determine the in vitro potency by ELISA. Immunogenicity testing was conducted for a subset of exposed IPVs using the rat model. Freezing VeroPol had no detectable effect on in vitro potency (D-antigen content) in all exposures tested. Freezing of the IPOL vaccine for 7 days at -20 °C showed statistically significant decreases in D-antigen content by ELISA in poliovirus type 1 (p < 0.0001) and type 3 (p = 0.048). Reduction of poliovirus type 2 potency also approached significance (p = 0.062). The observed loss in D-antigen content did not affect immunogenicity in the rat model. Further work is required to determine the significance of the loss observed and the implications for vaccine handling policies and practices. Copyright © 2018. Published by Elsevier Ltd.

In vivo effects of bisphenol A in laboratory rodent studies

USGS Publications Warehouse

Richter, Catherine A.; Birnbaum, Linda S.; Farabollini, Francesca; Newbold, Retha R.; Rubin, Beverly S.; Talsness, Chris E.; Vandenbergh, John G.; Walser-Kuntz, Debby R.; vom Saal, Frederick S.

2007-01-01

Concern is mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical used in synthesis of plastics. We have reviewed the growing literature on effects of low doses of BPA, below 50 mg/(kg day), in laboratory exposures with mammalian model organisms. Many, but not all, effects of BPA are similar to effects seen in response to the model estrogens diethylstilbestrol and ethinylestradiol. For most effects, the potency of BPA is approximately 10–1000-fold less than that of diethylstilbestrol or ethinylestradiol. Based on our review of the literature, a consensus was reached regarding our level of confidence that particular outcomes occur in response to low dose BPA exposure. We are confident that adult exposure to BPA affects the male reproductive tract, and that long lasting, organizational effects in response to developmental exposure to BPA occur in the brain, the male reproductive system, and metabolic processes. We consider it likely, but requiring further confirmation, that adult exposure to BPA affects the brain, the female reproductive system, and the immune system, and that developmental effects occur in the female reproductive system.

Interim methods for development of inhalation reference concentrations. Draft report

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

Blackburn, K.; Dourson, M.; Erdreich, L.

1990-08-01

An inhalation reference concentration (RfC) is an estimate of continuous inhalation exposure over a human lifetime that is unlikely to pose significant risk of adverse noncancer health effects and serves as a benchmark value for assisting in risk management decisions. Derivation of an RfC involves dose-response assessment of animal data to determine the exposure levels at which no significant increase in the frequency or severity of adverse effects between the exposed population and its appropriate control exists. The assessment requires an interspecies dose extrapolation from a no-observed-adverse-effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL(HBC)).more » The RfC is derived from the NOAEL(HBC) by the application of generally order-of-magnitude uncertainty factors. Intermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. Relationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorption, distribution, metabolism, storage, detoxification, and elimination. To estimate NOAEL(HBC)s when chemical-specific physiologically-based pharmacokinetic models are not available, a dosimetric extrapolation procedure based on anatomical and physiological parameters of the exposed human and animal and the physical parameters of the toxic chemical has been developed which gives equivalent or more conservative exposure concentrations values than those that would be obtained with a PB-PK model.« less

Optimization of camera exposure durations for multi-exposure speckle imaging of the microcirculation

PubMed Central

Kazmi, S. M. Shams; Balial, Satyajit; Dunn, Andrew K.

2014-01-01

Improved Laser Speckle Contrast Imaging (LSCI) blood flow analyses that incorporate inverse models of the underlying laser-tissue interaction have been used to develop more quantitative implementations of speckle flowmetry such as Multi-Exposure Speckle Imaging (MESI). In this paper, we determine the optimal camera exposure durations required for obtaining flow information with comparable accuracy with the prevailing MESI implementation utilized in recent in vivo rodent studies. A looping leave-one-out (LOO) algorithm was used to identify exposure subsets which were analyzed for accuracy against flows obtained from analysis with the original full exposure set over 9 animals comprising n = 314 regional flow measurements. From the 15 original exposures, 6 exposures were found using the LOO process to provide comparable accuracy, defined as being no more than 10% deviant, with the original flow measurements. The optimal subset of exposures provides a basis set of camera durations for speckle flowmetry studies of the microcirculation and confers a two-fold faster acquisition rate and a 28% reduction in processing time without sacrificing accuracy. Additionally, the optimization process can be used to identify further reductions in the exposure subsets for tailoring imaging over less expansive flow distributions to enable even faster imaging. PMID:25071956

TMEM16F is required for phosphatidylserine exposure and microparticle release in activated mouse platelets.

PubMed

Fujii, Toshihiro; Sakata, Asuka; Nishimura, Satoshi; Eto, Koji; Nagata, Shigekazu

2015-10-13

Phosphatidylserine (PtdSer) exposure on the surface of activated platelets requires the action of a phospholipid scramblase(s), and serves as a scaffold for the assembly of the tenase and prothrombinase complexes involved in blood coagulation. Here, we found that the activation of mouse platelets with thrombin/collagen or Ca(2+) ionophore at 20 °C induces PtdSer exposure without compromising plasma membrane integrity. Among five transmembrane protein 16 (TMEM16) members that support Ca(2+)-dependent phospholipid scrambling, TMEM16F was the only one that showed high expression in mouse platelets. Platelets from platelet-specific TMEM16F-deficient mice exhibited defects in activation-induced PtdSer exposure and microparticle shedding, although α-granule and dense granule release remained intact. The rate of tissue factor-induced thrombin generation by TMEM16F-deficient platelets was severely reduced, whereas thrombin-induced clot retraction was unaffected. The imaging of laser-induced thrombus formation in whole animals showed that PtdSer exposure on aggregated platelets was TMEM16F-dependent in vivo. The phenotypes of the platelet-specific TMEM16F-null mice resemble those of patients with Scott syndrome, a mild bleeding disorder, indicating that these mice may provide a useful model for human Scott syndrome.

CORRECTING ENERGY EXPENDITURES FOR FATIGUE AND EXCESS POST-EXERCISE OXYGEN CONSUMPTION

EPA Science Inventory

The EPA's human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the individual's current level of physical activity (PA), which is determined from activity diaries selected from the Conso...

Experimental Validation Plan for the Xolotl Plasma-Facing Component Simulator Using Tokamak Sample Exposures

NASA Astrophysics Data System (ADS)

Chan, V. S.; Wong, C. P. C.; McLean, A. G.; Luo, G. N.; Wirth, B. D.

2013-10-01

The Xolotl code under development by PSI-SciDAC will enhance predictive modeling capability of plasma-facing materials under burning plasma conditions. The availability and application of experimental data to compare to code-calculated observables are key requirements to validate the breadth and content of physics included in the model and ultimately gain confidence in its results. A dedicated effort has been in progress to collect and organize a) a database of relevant experiments and their publications as previously carried out at sample exposure facilities in US and Asian tokamaks (e.g., DIII-D DiMES, and EAST MAPES), b) diagnostic and surface analysis capabilities available at each device, and c) requirements for future experiments with code validation in mind. The content of this evolving database will serve as a significant resource for the plasma-material interaction (PMI) community. Work supported in part by the US Department of Energy under GA-DE-SC0008698, DE-AC52-07NA27344 and DE-AC05-00OR22725.

Do fungi need to be included within environmental radiation protection assessment models?

PubMed

Guillén, J; Baeza, A; Beresford, N A; Wood, M D

2017-09-01

Fungi are used as biomonitors of forest ecosystems, having comparatively high uptakes of anthropogenic and naturally occurring radionuclides. However, whilst they are known to accumulate radionuclides they are not typically considered in radiological assessment tools for environmental (non-human biota) assessment. In this paper the total dose rate to fungi is estimated using the ERICA Tool, assuming different fruiting body geometries, a single ellipsoid and more complex geometries considering the different components of the fruit body and their differing radionuclide contents based upon measurement data. Anthropogenic and naturally occurring radionuclide concentrations from the Mediterranean ecosystem (Spain) were used in this assessment. The total estimated weighted dose rate was in the range 0.31-3.4 μGy/h (5 th -95 th percentile), similar to natural exposure rates reported for other wild groups. The total estimated dose was dominated by internal exposure, especially from 226 Ra and 210 Po. Differences in dose rate between complex geometries and a simple ellipsoid model were negligible. Therefore, the simple ellipsoid model is recommended to assess dose rates to fungal fruiting bodies. Fungal mycelium was also modelled assuming a long filament. Using these geometries, assessments for fungal fruiting bodies and mycelium under different scenarios (post-accident, planned release and existing exposure) were conducted, each being based on available monitoring data. The estimated total dose rate in each case was below the ERICA screening benchmark dose, except for the example post-accident existing exposure scenario (the Chernobyl Exclusion Zone) for which a dose rate in excess of 35 μGy/h was estimated for the fruiting body. Estimated mycelium dose rate in this post-accident existing exposure scenario was close to the 400 μGy/h benchmark for plants, although fungi are generally considered to be less radiosensitive than plants. Further research on appropriate mycelium geometries and their radionuclide content is required. Based on the assessments presented in this paper, there is no need to recommend that fungi should be added to the existing assessment tools and frameworks; if required some tools allow a geometry representing fungi to be created and used within a dose assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parameter and model uncertainty in a life-table model for fine particles (PM2.5): a statistical modeling study

PubMed Central

Tainio, Marko; Tuomisto, Jouni T; Hänninen, Otto; Ruuskanen, Juhani; Jantunen, Matti J; Pekkanen, Juha

2007-01-01

Background The estimation of health impacts involves often uncertain input variables and assumptions which have to be incorporated into the model structure. These uncertainties may have significant effects on the results obtained with model, and, thus, on decision making. Fine particles (PM2.5) are believed to cause major health impacts, and, consequently, uncertainties in their health impact assessment have clear relevance to policy-making. We studied the effects of various uncertain input variables by building a life-table model for fine particles. Methods Life-expectancy of the Helsinki metropolitan area population and the change in life-expectancy due to fine particle exposures were predicted using a life-table model. A number of parameter and model uncertainties were estimated. Sensitivity analysis for input variables was performed by calculating rank-order correlations between input and output variables. The studied model uncertainties were (i) plausibility of mortality outcomes and (ii) lag, and parameter uncertainties (iii) exposure-response coefficients for different mortality outcomes, and (iv) exposure estimates for different age groups. The monetary value of the years-of-life-lost and the relative importance of the uncertainties related to monetary valuation were predicted to compare the relative importance of the monetary valuation on the health effect uncertainties. Results The magnitude of the health effects costs depended mostly on discount rate, exposure-response coefficient, and plausibility of the cardiopulmonary mortality. Other mortality outcomes (lung cancer, other non-accidental and infant mortality) and lag had only minor impact on the output. The results highlight the importance of the uncertainties associated with cardiopulmonary mortality in the fine particle impact assessment when compared with other uncertainties. Conclusion When estimating life-expectancy, the estimates used for cardiopulmonary exposure-response coefficient, discount rate, and plausibility require careful assessment, while complicated lag estimates can be omitted without this having any major effect on the results. PMID:17714598

Parameter and model uncertainty in a life-table model for fine particles (PM2.5): a statistical modeling study.

PubMed

Tainio, Marko; Tuomisto, Jouni T; Hänninen, Otto; Ruuskanen, Juhani; Jantunen, Matti J; Pekkanen, Juha

2007-08-23

The estimation of health impacts involves often uncertain input variables and assumptions which have to be incorporated into the model structure. These uncertainties may have significant effects on the results obtained with model, and, thus, on decision making. Fine particles (PM2.5) are believed to cause major health impacts, and, consequently, uncertainties in their health impact assessment have clear relevance to policy-making. We studied the effects of various uncertain input variables by building a life-table model for fine particles. Life-expectancy of the Helsinki metropolitan area population and the change in life-expectancy due to fine particle exposures were predicted using a life-table model. A number of parameter and model uncertainties were estimated. Sensitivity analysis for input variables was performed by calculating rank-order correlations between input and output variables. The studied model uncertainties were (i) plausibility of mortality outcomes and (ii) lag, and parameter uncertainties (iii) exposure-response coefficients for different mortality outcomes, and (iv) exposure estimates for different age groups. The monetary value of the years-of-life-lost and the relative importance of the uncertainties related to monetary valuation were predicted to compare the relative importance of the monetary valuation on the health effect uncertainties. The magnitude of the health effects costs depended mostly on discount rate, exposure-response coefficient, and plausibility of the cardiopulmonary mortality. Other mortality outcomes (lung cancer, other non-accidental and infant mortality) and lag had only minor impact on the output. The results highlight the importance of the uncertainties associated with cardiopulmonary mortality in the fine particle impact assessment when compared with other uncertainties. When estimating life-expectancy, the estimates used for cardiopulmonary exposure-response coefficient, discount rate, and plausibility require careful assessment, while complicated lag estimates can be omitted without this having any major effect on the results.

Modeling of Army Research Laboratory EMP simulators

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

Miletta, J.R.; Chase, R.J.; Luu, B.B.

1993-12-01

Models are required that permit the estimation of emitted field signatures from EMP simulators to design the simulator antenna structure, to establish the usable test volumes, and to estimate human exposure risk. This paper presents the capabilities and limitations of a variety of EMP simulator models useful to the Army's EMP survivability programs. Comparisons among frequency and time-domain models are provided for two powerful US Army Research Laboratory EMP simulators: AESOP (Army EMP Simulator Operations) and VEMPS II (Vertical EMP Simulator II).

Wait, are you sad or angry? Large exposure time differences required for the categorization of facial expressions of emotion

PubMed Central

Du, Shichuan; Martinez, Aleix M.

2013-01-01

Abstract Facial expressions of emotion are essential components of human behavior, yet little is known about the hierarchical organization of their cognitive analysis. We study the minimum exposure time needed to successfully classify the six classical facial expressions of emotion (joy, surprise, sadness, anger, disgust, fear) plus neutral as seen at different image resolutions (240 × 160 to 15 × 10 pixels). Our results suggest a consistent hierarchical analysis of these facial expressions regardless of the resolution of the stimuli. Happiness and surprise can be recognized after very short exposure times (10–20 ms), even at low resolutions. Fear and anger are recognized the slowest (100–250 ms), even in high-resolution images, suggesting a later computation. Sadness and disgust are recognized in between (70–200 ms). The minimum exposure time required for successful classification of each facial expression correlates with the ability of a human subject to identify it correctly at low resolutions. These results suggest a fast, early computation of expressions represented mostly by low spatial frequencies or global configural cues and a later, slower process for those categories requiring a more fine-grained analysis of the image. We also demonstrate that those expressions that are mostly visible in higher-resolution images are not recognized as accurately. We summarize implications for current computational models. PMID:23509409

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

PubMed

Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

2017-01-01

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

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.

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

PubMed Central

Miller, Steven L.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Prager, Eric M.; Almeida-Suhett, Camila P.; Apland, James P.; Braga, Maria F.M.

2015-01-01

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD50 of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2XLD50), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. PMID:25689173

Reconstruction of Internal Doses for the Alpha-Risk Case-Control Study of Lung Cancer and Leukaemia Among European Nuclear Workers.

PubMed

Bingham, Derek; Bérard, Philippe; Birchall, Alan; Bull, Richard; Cardis, Elisabeth; Challeton-de Vathaire, Cécile; Grellier, James; Hurtgen, Christian; Puncher, Matthew; Riddell, Anthony; Thierry-Chef, Isabelle

2017-05-01

The Alpha-Risk study required the reconstruction of doses to lung and red bone marrow for lung cancer and leukaemia cases and their matched controls from cohorts of nuclear workers in the UK, France and Belgium. The dosimetrists and epidemiologists agreed requirements regarding the bioassay data, biokinetic and dosimetric models and dose assessment software to be used and doses to be reported. The best values to use for uncertainties on the monitoring data, setting of exposure regimes and characteristics of the exposure material, including lung solubility, were the responsibility of the dosimetrist responsible for each cohort. Among 1721 subjects, the median absorbed dose to the lung from alpha radiations was 2.1 mGy, with a maximum dose of 316 mGy. The lung doses calculated reflect the higher levels of exposure seen among workers in the early years of the nuclear industry compared to today. © Crown copyright 2016.

EPA CHILDREN'S PESTICIDE EXPOSURE MEASUREMENT PROGRAM

EPA Science Inventory

The U.S. EPA's National Exposure Research Laboratory conducts research in support of the Food Quality Protection Act (FQPA) of 1996. FQPA requires that children's risks to pesticide exposures be considered during the tolerance-setting process. FQPA requires exposure assessme...

THE EPA CHILDREN'S PESTICIDE EXPOSURE MEASUREMENT PROGRAM

EPA Science Inventory

The U.S. EPA's National Exposure Research Laboratory conducts research in support of the Food Quality Protection Act (FQPA)) of 1996. FQPA requires that children's risks to pesticide exposures be considered during the tolerance-setting process. FQPA requires exposure assessme...

Exposure assessment of process-related contaminants in food by biomarker monitoring.

PubMed

Rietjens, Ivonne M C M; Dussort, P; Günther, Helmut; Hanlon, Paul; Honda, Hiroshi; Mally, Angela; O'Hagan, Sue; Scholz, Gabriele; Seidel, Albrecht; Swenberg, James; Teeguarden, Justin; Eisenbrand, Gerhard

2018-01-01

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario's and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.

Computer program for diagnostic X-ray exposure conversion.

PubMed

Lewis, S

1984-01-01

Presented is a computer program designed to convert any given set of exposure factors sequentially into another, yielding either an equivalent photographic density or one increased or decreased by a specifiable proportion. In addition to containing the wherewithal with which to manipulate a set of exposure factors, the facility to print hard (paper) copy is included enabling the results to be pasted into a notebook and used at any time. This program was originally written as an investigative exercise into examining the potential use of computers for practical radiographic purposes as conventionally encountered. At the same time, its possible use as an educational tool was borne in mind. To these ends, the current version of this program may be used as a means whereby exposure factors used in a diagnostic department may be altered to suit a particular requirement or may be used in the school as a mathematical model to describe the behaviour of exposure factors under manipulation without patient exposure.

Therapeutic Effects of Extinction Learning as a Model of Exposure Therapy in Rats.

PubMed

Fucich, Elizabeth A; Paredes, Denisse; Morilak, David A

2016-12-01

Current treatments for stress-related psychiatric disorders, such as depression and posttraumatic stress disorder (PTSD), are inadequate. Cognitive behavioral psychotherapies, including exposure therapy, are an alternative to pharmacotherapy, but the neurobiological mechanisms are unknown. Preclinical models demonstrating therapeutic effects of behavioral interventions are required to investigate such mechanisms. Exposure therapy bears similarity to extinction learning. Thus, we investigated the therapeutic effects of extinction learning as a behavioral intervention to model exposure therapy in rats, testing its effectiveness in reversing chronic stress-induced deficits in cognitive flexibility and coping behavior that resemble dimensions of depression and PTSD. Rats were fear-conditioned by pairing a tone with footshock, and then exposed to chronic unpredictable stress (CUS) that induces deficits in cognitive set-shifting and active coping behavior. They then received an extinction learning session as a therapeutic intervention by repeated exposure to the tone with no shock. Effects on cognitive flexibility and coping behavior were assessed 24 h later on the attentional set-shifting test or shock-probe defensive burying test, respectively. Extinction reversed the CUS-induced deficits in cognitive flexibility and coping behavior, and increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex (mPFC) of stress-compromised rats, suggesting a role for activity-dependent protein synthesis in the therapeutic effect. Inhibiting protein synthesis by microinjecting anisomycin into mPFC blocked the therapeutic effect of extinction on cognitive flexibility. These results demonstrate the utility of extinction as a model by which to study mechanisms underlying exposure therapy, and suggest these mechanisms involve protein synthesis in the mPFC, the further study of which may identify novel therapeutic targets.

Therapeutic Effects of Extinction Learning as a Model of Exposure Therapy in Rats

PubMed Central

Fucich, Elizabeth A; Paredes, Denisse; Morilak, David A

2016-01-01

Current treatments for stress-related psychiatric disorders, such as depression and posttraumatic stress disorder (PTSD), are inadequate. Cognitive behavioral psychotherapies, including exposure therapy, are an alternative to pharmacotherapy, but the neurobiological mechanisms are unknown. Preclinical models demonstrating therapeutic effects of behavioral interventions are required to investigate such mechanisms. Exposure therapy bears similarity to extinction learning. Thus, we investigated the therapeutic effects of extinction learning as a behavioral intervention to model exposure therapy in rats, testing its effectiveness in reversing chronic stress-induced deficits in cognitive flexibility and coping behavior that resemble dimensions of depression and PTSD. Rats were fear-conditioned by pairing a tone with footshock, and then exposed to chronic unpredictable stress (CUS) that induces deficits in cognitive set-shifting and active coping behavior. They then received an extinction learning session as a therapeutic intervention by repeated exposure to the tone with no shock. Effects on cognitive flexibility and coping behavior were assessed 24 h later on the attentional set-shifting test or shock-probe defensive burying test, respectively. Extinction reversed the CUS-induced deficits in cognitive flexibility and coping behavior, and increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex (mPFC) of stress-compromised rats, suggesting a role for activity-dependent protein synthesis in the therapeutic effect. Inhibiting protein synthesis by microinjecting anisomycin into mPFC blocked the therapeutic effect of extinction on cognitive flexibility. These results demonstrate the utility of extinction as a model by which to study mechanisms underlying exposure therapy, and suggest these mechanisms involve protein synthesis in the mPFC, the further study of which may identify novel therapeutic targets. PMID:27417516

Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Paulin, Laura M.; Diette, Gregory B.; Blanc, Paul D.; Putcha, Nirupama; Eisner, Mark D.; Kanner, Richard E.; Belli, Andrew J.; Christenson, Stephanie; Tashkin, Donald P.; Han, MeiLan; Barr, R. Graham

2015-01-01

Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. Objectives: To determine the impact of occupational exposures on COPD morbidity. Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04–1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (−26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (−3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden. PMID:25562375

Catalog of Wargaming and Military Simulation Models.

DTIC Science & Technology

1982-05-01

ix War Games and Simulations ............................ 1-823 Functional Index ................................ Appendix A Data Collection Sheet...34AGTM (An Air and Ground Theatre Model); User’s Guide and Program Description," Jan 1974 (NU) TIME REQUIREMENTS: Collection of the data base can be...to exposures. Facilities can be provided in any series to collect and output data on any specific subject, appropriate to the level of the game. 97

A Comparison of Three IRT Approaches to Examinee Ability Change Modeling in a Single-Group Anchor Test Design

ERIC Educational Resources Information Center

Paek, Insu; Park, Hyun-Jeong; Cai, Li; Chi, Eunlim

2014-01-01

Typically a longitudinal growth modeling based on item response theory (IRT) requires repeated measures data from a single group with the same test design. If operational or item exposure problems are present, the same test may not be employed to collect data for longitudinal analyses and tests at multiple time points are constructed with unique…

Sequential Exposure of Bortezomib and Vorinostat is Synergistic in Multiple Myeloma Cells

PubMed Central

Nanavati, Charvi; Mager, Donald E.

2018-01-01

Purpose To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. Methods U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures. p21 and cleaved PARP were measured using immunoblotting to assess critical biomarker dynamics. For xenografts, data were extracted from literature and modeled with a PK/PD model with an interaction parameter. Results Estimated model parameters for simultaneous in vitro and xenograft treatments suggested additive drug effects. The sequence of bortezomib preincubation for 24 hours, followed by vorinostat for 24 hours, resulted in an estimated interaction term significantly less than 1, suggesting synergistic effects. p21 and cleaved PARP were also up-regulated the most in this sequence. Conclusions Semi-mechanistic pharmacodynamic modeling suggests synergistic pharmacodynamic interactions for the sequential administration of bortezomib followed by vorinostat. Increased p21 and cleaved PARP expression can potentially explain mechanisms of their enhanced effects, which require further PK/PD systems analysis to suggest an optimal dosing regimen. PMID:28101809

On-line photolithography modeling using spectrophotometry and Prolith/2

NASA Astrophysics Data System (ADS)

Engstrom, Herbert L.; Beacham, Jeanne E.

1994-05-01

Spectrophotometry has been applied to optimizing photolithography processes in semiconductor manufacturing. For many years thin film measurement systems have been used in manufacturing for controlling film deposition processes. The combination of film thickness mapping with photolithography modeling has expanded the applications of this technology. Experimental measurements of dose-to-clear, the minimum light exposure dose required to fully develop a photoresist, are described. It is shown how dose-to-clear and photoresist contrast may be determined rapidly and conveniently from measurements of a dose exposure matrix on a monitor wafer. Such experimental measurements may underestimate the dose-to- clear because of thickness variations of the photoresist and underlying layers on the product wafer. Online modeling of the photolithographic process together with film thickness maps of the entire wafer can overcome this problem. Such modeling also provides maps of dose-to- clear and resist linewidth that can be used to estimate and optimize yield.

Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing

PubMed Central

Wetmore, Barbara A.; Wambaugh, John F.; Allen, Brittany; Ferguson, Stephen S.; Sochaski, Mark A.; Setzer, R. Woodrow; Houck, Keith A.; Strope, Cory L.; Cantwell, Katherine; Judson, Richard S.; LeCluyse, Edward; Clewell, Harvey J.; Thomas, Russell S.; Andersen, Melvin E.

2015-01-01

We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compared against regulatory exposure estimates, providing an activity-to-exposure ratio (AER) useful for a risk-based ranking strategy. As ToxCast efforts expand (ie, Phase II) beyond food-use pesticides toward a wider chemical domain that lacks exposure and toxicity information, prediction tools become increasingly important. In this study, in vitro hepatic clearance and plasma protein binding were measured to estimate OEDs for a subset of Phase II chemicals. OEDs were compared against high-throughput (HT) exposure predictions generated using probabilistic modeling and Bayesian approaches generated by the U.S. Environmental Protection Agency (EPA) ExpoCast program. This approach incorporated chemical-specific use and national production volume data with biomonitoring data to inform the exposure predictions. This HT exposure modeling approach provided predictions for all Phase II chemicals assessed in this study whereas estimates from regulatory sources were available for only 7% of chemicals. Of the 163 chemicals assessed in this study, 3 or 13 chemicals possessed AERs < 1 or < 100, respectively. Diverse bioactivities across a range of assays and concentrations were also noted across the wider chemical space surveyed. The availability of HT exposure estimation and bioactivity screening tools provides an opportunity to incorporate a risk-based strategy for use in testing prioritization. PMID:26251325

40 CFR 158.1000 - Applicator exposure-general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1000 Applicator exposure—general... Occupational Safety and Health Administration (OSHA), provide adequate protection from risk under FIFRA for a particular pesticide use pattern, exposure data may not be required for that use pattern. Applicants should...

40 CFR 158.1000 - Applicator exposure-general requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1000 Applicator exposure—general... Occupational Safety and Health Administration (OSHA), provide adequate protection from risk under FIFRA for a particular pesticide use pattern, exposure data may not be required for that use pattern. Applicants should...

40 CFR 158.1000 - Applicator exposure-general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1000 Applicator exposure—general... Occupational Safety and Health Administration (OSHA), provide adequate protection from risk under FIFRA for a particular pesticide use pattern, exposure data may not be required for that use pattern. Applicants should...

40 CFR 158.1000 - Applicator exposure-general requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1000 Applicator exposure—general... Occupational Safety and Health Administration (OSHA), provide adequate protection from risk under FIFRA for a particular pesticide use pattern, exposure data may not be required for that use pattern. Applicants should...

40 CFR 158.1000 - Applicator exposure-general requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1000 Applicator exposure—general... Occupational Safety and Health Administration (OSHA), provide adequate protection from risk under FIFRA for a particular pesticide use pattern, exposure data may not be required for that use pattern. Applicants should...

Atmospheric constituents and surface-level UVB: Implications for a paleoaltimetry proxy and attempts to reconstruct UV exposure during volcanic episodes

NASA Astrophysics Data System (ADS)

Thomas, Brian C.; Goracke, Byron D.; Dalton, Sean M.

2016-11-01

Chemical and morphological features of spores and pollens have been linked to changes in solar ultraviolet radiation (specifically UVB, 280-315 nm) at Earth's surface. Variation in UVB exposure as inferred from these features has been suggested as a proxy for paleoaltitude; such proxies are important in understanding the uplift history of high altitude plateaus, which in turn is important for testing models of the tectonic processes responsible for such uplift. While UVB irradiance does increase with altitude above sea level, a number of other factors affect the irradiance at any given place and time. In this modeling study we use the TUV atmospheric radiative transfer model to investigate dependence of surface-level UVB irradiance and relative biological impact on a number of constituents in Earth's atmosphere that are variable over long and short time periods. We consider changes in O3 column density, and SO2 and sulfate aerosols due to periods of volcanic activity, including that associated with the formation of the Siberian Traps. We find that UVB irradiance may be highly variable under volcanic conditions and variations in several of these atmospheric constituents can easily mimic or overwhelm changes in UVB irradiance due to changes in altitude. On the other hand, we find that relative change with altitude is not very sensitive to different sets of atmospheric conditions. Any paleoaltitude proxy based on UVB exposure requires confidence that the samples under comparison were located at roughly the same latitude, under very similar O3 and SO2 columns, with similar atmospheric aerosol conditions. In general, accurate estimates of the surface-level UVB exposure at any time and location require detailed radiative transfer modeling taking into account a number of atmospheric factors; this result is important for paleoaltitude proxies as well as attempts to reconstruct the UV environment through geologic time and to tie extinctions, such as the end-Permian mass extinction, to UVB irradiance changes.

Human exposure modeling in a life cycle framework for chemicals and products

EPA Science Inventory

A chemical enters into commerce to serve a specific function in a product or process. This decision triggers both the manufacture of the chemical and its potential release over the life cycle of the product. Efficiently evaluating chemical safety and sustainability requires combi...

ECOSYSTEM SERVICES AND BEYOND: INTEGRATION OF ECOSYSTEM SCIENCE AND MULTIMEDIA EXPOSURE MODELING FOR ENVIRONMENTAL PROTECTION

EPA Science Inventory

Decision-making for ecosystem protection and resource management requires an integrative science and technology applied with a sufficiently comprehensive systems approach. Single media (e.g., air, soil and water) approaches that evaluate aspects of an ecosystem in a stressor-by-...

Benzofuran ketone dosage-dependent rayless goldenrod (Isocoma pluriflora) toxicosis in a caprine model

USDA-ARS?s Scientific Manuscript database

The objectives of this study were to determine the dosage of benzofuran ketone compounds (tremetone, 3-hydroxytremetone, dehydrotremetone, and 3-oxyangeloyltremetone) and the duration of exposure to these compounds required to produce clinical signs and the associated pathological changes of rayles ...

20180318 - Rapid collection of experimental physicochemical property data to inform various models and testing methods (ACS Spring)

EPA Science Inventory

In order to determine the potential toxicological effects, toxicokinetics, and route(s) of exposure for chemicals, their structures and corresponding physicochemical properties are required. With this data, the risk for thousands of environmental chemicals can be prioritized. How...

Using exhaled carbon monoxide and carboxyhemoglobin to evaluate the effectiveness of a chimney stove model in Peru.

PubMed

Eppler, Adam R; Fitzgerald, Christopher; Dorner, Stephen C; Aguilar-Villalobos, Manuel; Rathbun, Stephen L; Adetona, Olorunfemi; Naeher, Luke P

2013-01-01

Measurement of biological indicators of physiological change may be useful in evaluating the effectiveness of stove models, which are intended to reduce indoor smoke exposure and potential health effects. We examined changes in exhaled carbon monoxide (CO), percentage carboxy-hemoglobin, and total hemoglobin in response to the installation of a chimney stove model by the Juntos National Program in Huayatan, Peru in 2008. Biomarkers were measured in a convenience sample comprising 35 women who met requirements for participation, and were measured before and three weeks after installation of a chimney stove. The relationships between exposure to indoor smoke and biomarker measurements were also analyzed using simple linear regression models. Exhaled CO reduced from 6.71 ppm (95% CI 5.84-7.71) to 3.14 ppm (95% CI 2.77-3.66) three weeks after stove installation (P < 0.001) while % COHb reduced from 1.76% (95% CI 1.62-1.91) to 1.18% (95% CI 1.12-1.25; P < 0.001). Changes in exhaled CO and % COHb from pre- to post-chimney stove installation were not correlated with corresponding changes in exposure to CO and PM2.5 even though the exposures also reduced after stove installation. Exhaled CO and % COHb both showed improvement with reduction in concentration after the installation of the chimney cook stoves, indicating a positive physiological response subsequent to the intervention.

THE EPA/ORD/NERL'S HUMAN EXPOSURE MEASUREMENTS PROGRAM - CHILDREN'S FOCUS

EPA Science Inventory

The U.S. EPA's National Exposure Research Laboratory (NERL) conducts research in support of the Food Quality Protection Act (FQPA) of 1996. FQPA requires that children's risks to pesticide exposures be considered during the tolerance-setting process. The Act requires exposure...

75 FR 27239 - Revising the Notification Requirements in the Exposure Determination Provisions of the Hexavalent...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-14

... Exposure Determination Provisions of the Hexavalent Chromium Standards AGENCY: Occupational Safety and... employee notification requirements in the exposure determination provisions of the Hexavalent Chromium (Cr... 1910 Exposure determination, General industry employment, Health, Hexavalent chromium (Cr(VI...

40 CFR 158.1070 - Post-application exposure data requirements table.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Post-application exposure data... (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1070 Post-application... table to determine the post-application data requirements for a particular pesticide product. Notes that...

40 CFR 158.1070 - Post-application exposure data requirements table.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Post-application exposure data... (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1070 Post-application... table to determine the post-application data requirements for a particular pesticide product. Notes that...

40 CFR 158.1070 - Post-application exposure data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Post-application exposure data... (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Human Exposure § 158.1070 Post-application... table to determine the post-application data requirements for a particular pesticide product. Notes that...

Causal mediation analysis for longitudinal data with exogenous exposure.

PubMed

Bind, M-A C; Vanderweele, T J; Coull, B A; Schwartz, J D

2016-01-01

Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM-1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Natural and Induced Environment in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Wilson, John W.; Badavi, Francis F.; Kim, Myung-Hee Y.; Clowdsley, Martha S.; Heinbockel, John H.; Cucinotta, Francis A.; Badhwar, Gautam D.; Atwell, William; Huston, Stuart L.

2002-01-01

The long-term exposure of astronauts on the developing International Space Station (ISS) requires an accurate knowledge of the internal exposure environment for human risk assessment and other onboard processes. The natural environment is moderated by the solar wind which varies over the solar cycle. The neutron environment within the Shuttle in low Earth orbit has two sources. A time dependent model for the ambient environment is used to evaluate the natural and induced environment. The induced neutron environment is evaluated using measurements on STS-31 and STS-36 near the 1990 solar maximum.

Status update: is smoke on your mind? Using social media to assess smoke exposure

NASA Astrophysics Data System (ADS)

Ford, Bonne; Burke, Moira; Lassman, William; Pfister, Gabriele; Pierce, Jeffrey R.

2017-06-01

Exposure to wildland fire smoke is associated with negative effects on human health. However, these effects are poorly quantified. Accurately attributing health endpoints to wildland fire smoke requires determining the locations, concentrations, and durations of smoke events. Most current methods for assessing these smoke events (ground-based measurements, satellite observations, and chemical transport modeling) are limited temporally, spatially, and/or by their level of accuracy. In this work, we explore using daily social media posts from Facebook regarding smoke, haze, and air quality to assess population-level exposure for the summer of 2015 in the western US. We compare this de-identified, aggregated Facebook dataset to several other datasets that are commonly used for estimating exposure, such as satellite observations (MODIS aerosol optical depth and Hazard Mapping System smoke plumes), daily (24 h) average surface particulate matter measurements, and model-simulated (WRF-Chem) surface concentrations. After adding population-weighted spatial smoothing to the Facebook data, this dataset is well correlated (R2 generally above 0.5) with the other methods in smoke-impacted regions. The Facebook dataset is better correlated with surface measurements of PM2. 5 at a majority of monitoring sites (163 of 293 sites) than the satellite observations and our model simulation. We also present an example case for Washington state in 2015, for which we combine this Facebook dataset with MODIS observations and WRF-Chem-simulated PM2. 5 in a regression model. We show that the addition of the Facebook data improves the regression model's ability to predict surface concentrations. This high correlation of the Facebook data with surface monitors and our Washington state example suggests that this social-media-based proxy can be used to estimate smoke exposure in locations without direct ground-based particulate matter measurements.

Pediatric tuberculous meningitis: model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children

PubMed Central

Savic, Radojka M.; Ruslami, Rovina; Hibma, Jennifer E.; Hesseling, Anneke; Ramachandran, Geetha; Ganiem, A. Rizal; Swaminathan, Soumya; McIlleron, Helen; Gupta, Amita; Thakur, Kiran; van Crevel, Reinout; Aarnoutse, Rob; Dooley, Kelly E.

2016-01-01

Pediatric TB meningitis (TBM) is a highly-morbid, oft-fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic and outcomes data from adult TBM trials plus plasma pharmacokinetic data from children. A population pharmacokinetic/pharmacodynamic model using adult data defined rifampin target exposures (plasma AUC0–24=92 mg*h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously. From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19–33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results. PMID:26260983

Ethanol exposure during the early first trimester equivalent impairs reflexive motor activity and heightens fearfulness in an avian model.

PubMed

Smith, Susan M; Flentke, George R; Kragtorp, Katherine A; Tessmer, Laura

2011-02-01

Prenatal alcohol exposure is a leading cause of childhood neurodevelopmental disability. The adverse behavioral effects of alcohol exposure during the second and third trimester are well documented; less clear is whether early first trimester-equivalent exposures also alter behavior. We investigated this question using an established chick model of alcohol exposure. In ovo embryos experienced a single, acute ethanol exposure that spanned gastrulation through neuroectoderm induction and early brain patterning (19-22h incubation). At 7 days posthatch, the chicks were evaluated for reflexive motor function (wingflap extension, righting reflex), fearfulness (tonic immobility [TI]), and fear/social reinstatement (open-field behavior). Chicks exposed to a peak ethanol level of 0.23-0.28% were compared against untreated and saline-treated controls. Birds receiving early ethanol exposure had a normal righting reflex and a significantly reduced wingflap extension in response to a sudden descent. The ethanol-treated chicks also displayed heightened fearfulness, reflected in increased frequency of TI, and they required significantly fewer trials for its induction. In an open-field test, ethanol treatment did not affect latency to move, steps taken, vocalizations, defecations, or escape attempts. The current findings demonstrate that early ethanol exposure can increase fearfulness and impair aspects of motor function. Importantly, the observed dysfunctions resulted from an acute ethanol exposure during the period when the major brain components are induced and patterned. The equivalent period in human development is 3-4 weeks postconception. The current findings emphasize that ethanol exposure during the early first trimester equivalent can produce neurodevelopmental disability in the offspring. Copyright © 2011 Elsevier Inc. All rights reserved.

Predicting indoor pollutant concentrations, and applications to air quality management

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

Lorenzetti, David M.

Because most people spend more than 90% of their time indoors, predicting exposure to airborne pollutants requires models that incorporate the effect of buildings. Buildings affect the exposure of their occupants in a number of ways, both by design (for example, filters in ventilation systems remove particles) and incidentally (for example, sorption on walls can reduce peak concentrations, but prolong exposure to semivolatile organic compounds). Furthermore, building materials and occupant activities can generate pollutants. Indoor air quality depends not only on outdoor air quality, but also on the design, maintenance, and use of the building. For example, ''sick building'' symptomsmore » such as respiratory problems and headaches have been related to the presence of air-conditioning systems, to carpeting, to low ventilation rates, and to high occupant density (1). The physical processes of interest apply even in simple structures such as homes. Indoor air quality models simulate the processes, such as ventilation and filtration, that control pollutant concentrations in a building. Section 2 describes the modeling approach, and the important transport processes in buildings. Because advection usually dominates among the transport processes, Sections 3 and 4 describe methods for predicting airflows. The concluding section summarizes the application of these models.« less

Robust discovery of genetic associations incorporating gene-environment interaction and independence.

PubMed

Tchetgen Tchetgen, Eric

2011-03-01

This article considers the detection and evaluation of genetic effects incorporating gene-environment interaction and independence. Whereas ordinary logistic regression cannot exploit the assumption of gene-environment independence, the proposed approach makes explicit use of the independence assumption to improve estimation efficiency. This method, which uses both cases and controls, fits a constrained retrospective regression in which the genetic variant plays the role of the response variable, and the disease indicator and the environmental exposure are the independent variables. The regression model constrains the association of the environmental exposure with the genetic variant among the controls to be null, thus explicitly encoding the gene-environment independence assumption, which yields substantial gain in accuracy in the evaluation of genetic effects. The proposed retrospective regression approach has several advantages. It is easy to implement with standard software, and it readily accounts for multiple environmental exposures of a polytomous or of a continuous nature, while easily incorporating extraneous covariates. Unlike the profile likelihood approach of Chatterjee and Carroll (Biometrika. 2005;92:399-418), the proposed method does not require a model for the association of a polytomous or continuous exposure with the disease outcome, and, therefore, it is agnostic to the functional form of such a model and completely robust to its possible misspecification.

Toxicity of tributyltin (TBT) to the freshwater planarian Schmidtea mediterranea.

PubMed

Ofoegbu, Pearl U; Simão, Fátima C P; Cruz, Andreia; Mendo, Sónia; Soares, Amadeu M V M; Pestana, João L T

2016-04-01

The freshwater planarian Schmidtea mediterranea, one of the best characterized animal models for regeneration research and developmental biology, is being recognised as a useful species for ecotoxicological studies. Sensitive endpoints related to planarians' behaviour and regeneration can be easily evaluated after exposure to environmental stressors. In this work the sensitivity of S. mediterranea to a gradient of environmentally relevant concentrations of TBT was studied using multiple endpoints like survival, locomotion, head regeneration and DNA damage. In addition, a feeding assay based on planarian's predatory behaviour was performed. Results indicated that TBT is toxic to planarians with LC50's of 1.87 μg L(-1) Sn and 1.31 μg L(-1) Sn at 48 h and 96 h of exposure respectively. Sub-lethal exposures to TBT significantly reduced locomotion and feeding, delayed head regeneration and caused DNA damage in planarians. The behavioural endpoints (feeding and locomotion) and head regeneration were the most sensitive parameters followed by DNA damage. Similar to other aquatic model organisms, S. mediterranea showed high sensitivity towards TBT exposure. Based on our results, and though further research is required concerning their sensitivity to other pollutants, the use of freshwater planarians as a model species in ecotoxicology is discussed. Copyright © 2016. Published by Elsevier Ltd.

THE US EPA'S DERMAL EXPOSURE RESEARCH PROGRAM IN SUPPORT OF THE FOOD QUALITY PROTECTION ACT

EPA Science Inventory

The Food Quality Protection Act of 1996 (FQPA) requires that children's risks to pesticide exposures be considered during the tolerance-setting process. FQPA requires exposure assessments to be conducted for all pesticides sources, not just food sources. It also requires tha...

Model System to Define Pharmacokinetic Requirements for Antimalarial Drug Efficacy

PubMed Central

Bakshi, Rahul P.; Nenortas, Elizabeth; Tripathi, Abhai K.; Sullivan, David J.; Shapiro, Theresa A.

2013-01-01

Malaria presents a tremendous public health burden and new therapies are needed. Massive compound libraries screened against Plasmodium falciparum have yielded thousands of lead compounds, resulting in an acute need for rational criteria to select the best candidates for development. We reasoned that, akin to antibacterials, antimalarials might have an essential pharmacokinetic requirement for efficacy: action governed either by total exposure or peak concentration (AUC/CMAX), or by duration above a defined minimum concentration (Time above Minimum Inhibitory Concentration, TMIC). We devised an in vitro system for P. falciparum, capable of mimicking the dynamic fluctuations of a drug in vivo. Utilizing this apparatus, we find that chloroquine is TMIC-dependent while the efficacy of artemisinin is driven by CMAX. The latter was confirmed in a mouse model of malaria. These characteristics can explain the clinical success of two antimalarial drugs with widely different kinetics in humans. Chloroquine, which persists for weeks, is ideally suited for its TMIC mechanism, whereas great efficacy despite short exposure (t1/2 in blood 3 h or less) is attained by CMAX-driven artemisinins. This validated preclinical model system can be used to select those antimalarial lead compounds whose CMAX or TMIC requirement for efficacy match pharmacokinetics obtained in vivo. The apparatus can also be used to explore the kinetic-dependence of other pharmacodynamic endpoints in parasites. PMID:24089407

Comparative assessment of chlorine, heat, ozone, and UV light for killing Legionella pneumophila within a model plumbing system.

PubMed Central

Muraca, P; Stout, J E; Yu, V L

1987-01-01

Nosocomial Legionnaires disease can be acquired by exposure to the organism from the hospital water distribution system. As a result, many hospitals have instituted eradication procedures, including hypercholorination and thermal eradication. We compared the efficacy of ozonation, UV light, hyperchlorination, and heat eradication using a model plumbing system constructed of copper piping, brass spigots, Plexiglas reservoir, electric hot water tank, and a pump. Legionella pneumophila was added to the system at 10(7) CFU/ml. Each method was tested under three conditions; (i) nonturbid water at 25 degrees C, (ii) turbid water at 25 degrees C, and (iii) nonturbid water at 43 degrees C. UV light and heat killed L. pneumophila most rapidly and required minimal maintenance. Both UV light and heat (60 degrees C) produced a 5 log kill in less than 1 h. In contrast, both chlorine and ozone required 5 h of exposure to produce a 5 log decrease. Neither turbidity nor the higher temperature of 43 degrees C impaired the efficacy of any of the disinfectant methods. Surprisingly, higher temperature enhanced the disinfecting efficacy of chlorine. However, higher temperature accelerated the decomposition of the chlorine residual such that an additional 120% volume of chlorine was required. All four methods proved efficacious in eradicating L. pneumophila from a model plumbing system. Images PMID:3566272

Examining the Contemporaneous, Short-Term, and Long-Term Effects of Secondary Exposure to Violence on Adolescent Substance Use.

PubMed

Zimmerman, Gregory M; Kushner, Mackenzie

2017-09-01

The relationship between secondary exposure to violence-defined as witnessing violence in the home, community, or school-and adolescent substance use is well-documented. Yet, multi-wave empirical studies examining this relationship are sparse. In addition, studies have only begun to examine whether this relationship varies by the situational components of the violent event. Using data from the Project on Human Development in Chicago Neighborhoods (PHDCN), this study examines the contemporaneous, short-term, and long-term effects of secondary exposure to violence on substance use, and whether witnessing violence in which a weapon is present has a different impact on adolescent substance use than does witnessing violence without a weapon. Hierarchical logistic regression models on a racially and ethnically diverse sample of 1670 youth (51.5% female) residing in 79 neighborhoods indicated that: (1) the effects of secondary exposure to violence on alcohol and marijuana use were enduring, albeit attenuated, over time; (2) the effect of secondary exposure to violence on illicit drug use was suppressed in the short-term but significant in the long-term; (3) witnessing violence without a weapon was salient for alcohol and marijuana use at all time points; and (4) witnessing violence with a weapon impacted illicit drug use in the long-term. The results suggest that addressing the consequences of secondary exposure to violence requires prolonged intervention efforts and that the study of secondary exposure to violence requires a more nuanced approach that accounts for situational aspects of the violent event.

Effect of the shape of the exposure-response function on estimated hospital costs in a study on non-elective pneumonia hospitalizations related to particulate matter.

PubMed

Devos, Stefanie; Cox, Bianca; van Lier, Tom; Nawrot, Tim S; Putman, Koen

2016-09-01

We used log-linear and log-log exposure-response (E-R) functions to model the association between PM2.5 exposure and non-elective hospitalizations for pneumonia, and estimated the attributable hospital costs by using the effect estimates obtained from both functions. We used hospital discharge data on 3519 non-elective pneumonia admissions from UZ Brussels between 2007 and 2012 and we combined a case-crossover design with distributed lag models. The annual averted pneumonia hospitalization costs for a reduction in PM2.5 exposure from the mean (21.4μg/m(3)) to the WHO guideline for annual mean PM2.5 (10μg/m(3)) were estimated and extrapolated for Belgium. Non-elective hospitalizations for pneumonia were significantly associated with PM2.5 exposure in both models. Using a log-linear E-R function, the estimated risk reduction for pneumonia hospitalization associated with a decrease in mean PM2.5 exposure to 10μg/m(3) was 4.9%. The corresponding estimate for the log-log model was 10.7%. These estimates translate to an annual pneumonia hospital cost saving in Belgium of €15.5 million and almost €34 million for the log-linear and log-log E-R function, respectively. Although further research is required to assess the shape of the association between PM2.5 exposure and pneumonia hospitalizations, we demonstrated that estimates for health effects and associated costs heavily depend on the assumed E-R function. These results are important for policy making, as supra-linear E-R associations imply that significant health benefits may still be obtained from additional pollution control measures in areas where PM levels have already been reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

PHYSIOLOGICALLY-BASED PHARMACOKINETICS/PHARMACODYNAMIC MODELING AND CUMULATIVE RISK ASSESSMENT: CASE STUDY FOR THE N-METHYL CARBMATE PESTICIDES

EPA Science Inventory

The Food Quality Protection Act of 1996 [PL 104-170: 110 STAT. 1513] requires EPA to consider potential cumulative human health risks resulting from aggregate exposure to pesticide chemicals acting through a common mechanism of toxicity. This includes all anticipated dietary e...

Evidence-based planning for forest adaptation

Treesearch

Lee Hannah; Thomas E. Lovejoy

2014-01-01

Forest conservation under climate change requires conserving species both in their present ranges and where they may exist in the future as climate changes. Several debates in the literature are pioneering this relatively novel ground. For instance, conservation planning using species distribution models is advocated because it uses information on both exposure to...

TECHNOLOGY REQUIRED FOR ALTERNATIVE ANALYSES FOR A CHANGING ENVIRONMENT (TRACE) IN SUPPORT OF THE CLEAN WATER ACT

EPA Science Inventory

Recent trends in current and evolving environmental regulatory strategies dictate that EPA will have to rely more heavily on predictive modeling technologies in carrying out the increasingly complex array of exposure and risk assessments necessary in developing scientifically def...

Investigating the Impact of Lack of Motorcycle Annual Average Daily Traffic Data in Crash Modeling and the Estimation of Crash Modification Factors

DOT National Transportation Integrated Search

2016-10-01

The development of safety performance functions (SPFs) and crash modification factors (CMFs) requires data on traffic exposure. The analysis of motorcycle crashes can be especially challenging in this regard because few jurisdictions collect motorcyc...

Modeling U-shaped dose-response curves for manganese using categorical regression.

PubMed

Milton, Brittany; Krewski, Daniel; Mattison, Donald R; Karyakina, Nataliya A; Ramoju, Siva; Shilnikova, Natalia; Birkett, Nicholas; Farrell, Patrick J; McGough, Doreen

2017-01-01

Manganese is an essential nutrient which can cause adverse effects if ingested to excess or in insufficient amounts, leading to a U-shaped exposure-response relationship. Methods have recently been developed to describe such relationships by simultaneously modeling the exposure-response curves for excess and deficiency. These methods incorporate information from studies with diverse adverse health outcomes within the same analysis by assigning severity scores to achieve a common response metric for exposure-response modeling. We aimed to provide an estimate of the optimal dietary intake of manganese to balance adverse effects from deficient or excess intake. We undertook a systematic review of the literature from 1930 to 2013 and extracted information on adverse effects from manganese deficiency and excess to create a database on manganese toxicity following oral exposure. Although data were available for seven different species, only the data from rats was sufficiently comprehensive to support analytical modelling. The toxicological outcomes were standardized on an 18-point severity scale, allowing for a common analysis of all available toxicological data. Logistic regression modelling was used to simultaneously estimate the exposure-response profile for dietary deficiency and excess for manganese and generate a U-shaped exposure-response curve for all outcomes. Data were available on the adverse effects of 6113 rats. The nadir of the U-shaped joint response curve occurred at a manganese intake of 2.70mg/kgbw/day with a 95% confidence interval of 2.51-3.02. The extremes of both deficient and excess intake were associated with a 90% probability of some measurable adverse event. The manganese database supports estimation of optimal intake based on combining information on adverse effects from systematic review of published experiments. There is a need for more studies on humans. Translation of our results from rats to humans will require adjustment for interspecies differences in sensitivity to manganese. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™).

PubMed

Wills, John W; Hondow, Nicole; Thomas, Adam D; Chapman, Katherine E; Fish, David; Maffeis, Thierry G; Penny, Mark W; Brown, Richard A; Jenkins, Gareth J S; Brown, Andy P; White, Paul A; Doak, Shareen H

2016-09-09

The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models are required to minimise reliance on animal testing. BASF Levasil® silica nanoparticles (16 and 85 nm) were used to adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials administered topically or into the growth medium. 3D dose-responses were compared to a 2D micronucleus assay using monocultured human B cells (TK6) after standardising dose between 2D / 3D assays by total nanoparticle mass to cell number. Cryogenic vitrification, scanning electron microscopy and dynamic light scattering techniques were applied to characterise in-medium and air-liquid interface exposures. Advanced transmission electron microscopy imaging modes (high angle annular dark field) and X-ray spectrometry were used to define nanoparticle penetration / cellular uptake in the intact 3D models and 2D monocultured cells. For all 2D exposures, significant (p < 0.002) increases in genotoxicity were observed (≥100 μg/mL) alongside cell viability decreases (p < 0.015) at doses ≥200 μg/mL (16 nm-SiO2) and ≥100 μg/mL (85 nm-SiO2). In contrast, 2D-equivalent exposures to the 3D models (≤300 μg/mL) caused no significant DNA damage or impact on cell viability. Further increasing dose to the 3D models led to probable air-liquid interface suffocation. Nanoparticle penetration / cell uptake analysis revealed no exposure to the live cells of the 3D model occurred due to the protective nature of the skin model's 3D cellular microarchitecture (topical exposures) and confounding barrier effects of the collagen cell attachment layer (in-medium exposures). 2D monocultured cells meanwhile showed extensive internalisation of both silica particles causing (geno)toxicity. The results establish the importance of tissue microarchitecture in defining nanomaterial exposure, and suggest 3D in vitro models could play a role in bridging the gap between in vitro and in vivo outcomes in nanotoxicology. Robust exposure characterisation and uptake assessment methods (as demonstrated) are essential to interpret nano(geno)toxicity studies successfully.

Pregnant women models analyzed for RF exposure and temperature increase in 3T RF shimmed birdcages.

PubMed

Murbach, Manuel; Neufeld, Esra; Samaras, Theodoros; Córcoles, Juan; Robb, Fraser J; Kainz, Wolfgang; Kuster, Niels

2017-05-01

MRI is increasingly used to scan pregnant patients. We investigated the effect of 3 Tesla (T) two-port radiofrequency (RF) shimming in anatomical pregnant women models. RF shimming improves B 1 + uniformity, but may at the same time significantly alter the induced current distribution and result in large changes in both the level and location of the absorbed RF energy. In this study, we evaluated the electrothermal exposure of pregnant women in the third, seventh, and ninth month of gestation at various imaging landmarks in RF body coils, including modes with RF shimming. Although RF shimmed configurations may lower the local RF exposure for the mother, they can increase the thermal load on the fetus. In worst-case configurations, whole-body exposure and local peak temperatures-up to 40.8°C-are equal in fetus and mother. Two-port RF shimming can significantly increase the fetal exposure in pregnant women, requiring further research to derive a very robust safety management. For the time being, restriction to the CP mode, which reduces fetal SAR exposure compared with linear-horizontal polarization modes, may be advisable. Results from this study do not support scanning pregnant patients above the normal operating mode. Magn Reson Med 77:2048-2056, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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

Associations between Australian clinical medical practitioner exposure to workplace aggression and workforce participation intentions.

PubMed

Hills, Danny J

2016-02-01

The aim of the present study was to determine the association between clinician exposure to workplace aggression from any source in the previous 12 months and workforce participation intentions. A cross-sectional survey, in the third wave of the Medicine in Australia: Balancing Employment and Life (MABEL) study, was conducted between March 2010 and June 2011. Respondents were a representative sample of 9449 Australian general practitioners (GPs) and GP registrars (n = 3515), specialists (n = 3875), hospital non-specialists (n = 1171) and specialists in training (n = 888). Associations between aggression exposure and workforce participation intentions were determined using logistic regression modelling. In adjusted models, aggression exposure was positively associated with a greater likelihood of intending to reduce clinical workload in the next 5 years (odds ratio (OR) = 1.15, 95% confidence interval (CI) 1.02-1.29) and intending to leave patient care within 5 years (OR = 1.20, 95% CI 1.07-1.35). When also accounting for well being factors, aggression exposure remained positively associated with intending to leave patient care within 5 years (OR = 1.13, 95% CI 1.00-1.27). Exposure to workplace aggression presents a risk to the retention of medical practitioners in clinical practice and a potential risk to community access to quality medical care. More concerted efforts in preventing and minimising workplace aggression in clinical medical practice are required.

Exposure to Carbon Ions Triggers Proinflammatory Signals and Changes in Homeostasis and Epidermal Tissue Organization to a Similar Extent as Photons

PubMed Central

Simoniello, Palma; Wiedemann, Julia; Zink, Joana; Thoennes, Eva; Stange, Maike; Layer, Paul G.; Kovacs, Maximilian; Podda, Maurizio; Durante, Marco; Fournier, Claudia

2016-01-01

The increasing application of charged particles in radiotherapy requires a deeper understanding of early and late side effects occurring in skin, which is exposed in all radiation treatments. We measured cellular and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure. Model systems for human skin from healthy donors of different complexity, i.e., keratinocytes, coculture of skin cells, 3D skin equivalents, and skin explants, were used to investigate the alterations induced by carbon ions (spread-out Bragg peak, dose-averaged LET 100 keV/μm) in comparison to X-ray and UV-B exposure. After exposure to ionizing radiation, in none of the model systems, apoptosis/necrosis was observed. Carbon ions triggered inflammatory signaling and accelerated differentiation of keratinocytes to a similar extent as X-rays at the same doses. High doses of carbon ions were more effective than X-rays in reducing proliferation and inducing abnormal differentiation. In contrast, changes identified following low-dose exposure (≤0.5 Gy) were induced more effectively after X-ray exposure, i.e., enhanced proliferation and change in the polarity of basal cells. PMID:26779439

Lead remediation and changes in human lead exposure: some physiological and biokinetic dimensions.

PubMed

Mushak, Paul

2003-02-15

This paper presents a qualitative and quantitative analysis of the various aspects of lead remediation effectiveness with particular reference to human health risk assessment. One of the key elements of lead remediation efforts at such sites as those under the Superfund program deals with populations at elevated exposure and toxicity risk in the proximity of, or at, the site of remediation, especially remediation workers, workers at other tasks on sites that were remediated down to some action level of lead concentration in soils, and groups at risk in nearby communities. A second element has to do with how one measures or models lead exposure changes with special reference to baseline and post-remediation conditions. Various biomarkers of lead exposure can be employed, but their use requires detailed knowledge of what results using each means. The most commonly used approach is measurement of blood lead (Pb-B). Recognized limitations in the use of Pb-B has led to the use of predictive Pb exposure models, which are less vulnerable to the many behavioral, physiological, and environmental parameters that can distort isolated or 'single shot' Pb-B testings. A third aspect covered in this paper presents various physiological factors that affect the methods by which one evaluates Pb remediation effectiveness. Finally, this article offers an integrated look at how lead remediation actions directed at one lead source or pathway affect the total lead exposure picture for human populations at elevated lead exposure and toxicity risk.

New High Throughput Methods to Estimate Chemical ...

EPA Pesticide Factsheets

EPA has made many recent advances in high throughput bioactivity testing. However, concurrent advances in rapid, quantitative prediction of human and ecological exposures have been lacking, despite the clear importance of both measures for a risk-based approach to prioritizing and screening chemicals. A recent report by the National Research Council of the National Academies, Exposure Science in the 21st Century: A Vision and a Strategy (NRC 2012) laid out a number of applications in chemical evaluation of both toxicity and risk in critical need of quantitative exposure predictions, including screening and prioritization of chemicals for targeted toxicity testing, focused exposure assessments or monitoring studies, and quantification of population vulnerability. Despite these significant needs, for the majority of chemicals (e.g. non-pesticide environmental compounds) there are no or limited estimates of exposure. For example, exposure estimates exist for only 7% of the ToxCast Phase II chemical list. In addition, the data required for generating exposure estimates for large numbers of chemicals is severely lacking (Egeghy et al. 2012). This SAP reviewed the use of EPA's ExpoCast model to rapidly estimate potential chemical exposures for prioritization and screening purposes. The focus was on bounded chemical exposure values for people and the environment for the Endocrine Disruptor Screening Program (EDSP) Universe of Chemicals. In addition to exposure, the SAP

Modeling Joint Exposures and Health Outcomes for Cumulative Risk Assessment: The Case of Radon and Smoking

PubMed Central

Chahine, Teresa; Schultz, Bradley D.; Zartarian, Valerie G.; Xue, Jianping; Subramanian, SV; Levy, Jonathan I.

2011-01-01

Community-based cumulative risk assessment requires characterization of exposures to multiple chemical and non-chemical stressors, with consideration of how the non-chemical stressors may influence risks from chemical stressors. Residential radon provides an interesting case example, given its large attributable risk, effect modification due to smoking, and significant variability in radon concentrations and smoking patterns. In spite of this fact, no study to date has estimated geographic and sociodemographic patterns of both radon and smoking in a manner that would allow for inclusion of radon in community-based cumulative risk assessment. In this study, we apply multi-level regression models to explain variability in radon based on housing characteristics and geological variables, and construct a regression model predicting housing characteristics using U.S. Census data. Multi-level regression models of smoking based on predictors common to the housing model allow us to link the exposures. We estimate county-average lifetime lung cancer risks from radon ranging from 0.15 to 1.8 in 100, with high-risk clusters in areas and for subpopulations with high predicted radon and smoking rates. Our findings demonstrate the viability of screening-level assessment to characterize patterns of lung cancer risk from radon, with an approach that can be generalized to multiple chemical and non-chemical stressors. PMID:22016710

Assessing exposure to transformation products of soil-applied organic contaminants in surface water: comparison of model predictions and field data.

PubMed

Kern, Susanne; Singer, Heinz; Hollender, Juliane; Schwarzenbach, René P; Fenner, Kathrin

2011-04-01

Transformation products (TPs) of chemicals released to soil, for example, pesticides, are regularly detected in surface and groundwater with some TPs even dominating observed pesticide levels. Given the large number of TPs potentially formed in the environment, straightforward prioritization methods based on available data and simple, evaluative models are required to identify TPs with a high aquatic exposure potential. While different such methods exist, none of them has so far been systematically evaluated against field data. Using a dynamic multimedia, multispecies model for TP prioritization, we compared the predicted relative surface water exposure potential of pesticides and their TPs with experimental data for 16 pesticides and 46 TPs measured in a small river draining a Swiss agricultural catchment. Twenty TPs were determined quantitatively using solid-phase extraction liquid chromatography mass spectrometry (SPE-LC-MS/MS), whereas the remaining 26 TPs could only be detected qualitatively because of the lack of analytical reference standards. Accordingly, the two sets of TPs were used for quantitative and qualitative model evaluation, respectively. Quantitative comparison of predicted with measured surface water exposure ratios for 20 pairs of TPs and parent pesticides indicated agreement within a factor of 10, except for chloridazon-desphenyl and chloridazon-methyl-desphenyl. The latter two TPs were found to be present in elevated concentrations during baseflow conditions and in groundwater samples across Switzerland, pointing toward high concentrations in exfiltrating groundwater. A simple leaching relationship was shown to qualitatively agree with the observed baseflow concentrations and to thus be useful in identifying TPs for which the simple prioritization model might underestimate actual surface water concentrations. Application of the model to the 26 qualitatively analyzed TPs showed that most of those TPs categorized as exhibiting a high aquatic exposure potential could be confirmed to be present in the majority of water samples investigated. On the basis of these results, we propose a generally applicable, model-based approach to identify those TPs of soil-applied organic contaminants that exhibit a high aquatic exposure potential to prioritize them for higher-tier, experimental investigations.

Equivalent magnetic vector potential model for low-frequency magnetic exposure assessment

NASA Astrophysics Data System (ADS)

Diao, Y. L.; Sun, W. N.; He, Y. Q.; Leung, S. W.; Siu, Y. M.

2017-10-01

In this paper, a novel source model based on a magnetic vector potential for the assessment of induced electric field strength in a human body exposed to the low-frequency (LF) magnetic field of an electrical appliance is presented. The construction of the vector potential model requires only a single-component magnetic field to be measured close to the appliance under test, hence relieving considerable practical measurement effort—the radial basis functions (RBFs) are adopted for the interpolation of discrete measurements; the magnetic vector potential model can then be directly constructed by summing a set of simple algebraic functions of RBF parameters. The vector potentials are then incorporated into numerical calculations as the equivalent source for evaluations of the induced electric field in the human body model. The accuracy and effectiveness of the proposed model are demonstrated by comparing the induced electric field in a human model to that of the full-wave simulation. This study presents a simple and effective approach for modelling the LF magnetic source. The result of this study could simplify the compliance test procedure for assessing an electrical appliance regarding LF magnetic exposure.

Equivalent magnetic vector potential model for low-frequency magnetic exposure assessment.

PubMed

Diao, Y L; Sun, W N; He, Y Q; Leung, S W; Siu, Y M

2017-09-21

In this paper, a novel source model based on a magnetic vector potential for the assessment of induced electric field strength in a human body exposed to the low-frequency (LF) magnetic field of an electrical appliance is presented. The construction of the vector potential model requires only a single-component magnetic field to be measured close to the appliance under test, hence relieving considerable practical measurement effort-the radial basis functions (RBFs) are adopted for the interpolation of discrete measurements; the magnetic vector potential model can then be directly constructed by summing a set of simple algebraic functions of RBF parameters. The vector potentials are then incorporated into numerical calculations as the equivalent source for evaluations of the induced electric field in the human body model. The accuracy and effectiveness of the proposed model are demonstrated by comparing the induced electric field in a human model to that of the full-wave simulation. This study presents a simple and effective approach for modelling the LF magnetic source. The result of this study could simplify the compliance test procedure for assessing an electrical appliance regarding LF magnetic exposure.

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

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

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

1995-12-31

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

How much, how long, what, and where: air pollution exposure assessment for epidemiologic studies of respiratory disease.

PubMed

Brauer, Michael

2010-05-01

Epidemiology has played an important role in the understanding of air pollution as a risk factor for respiratory disease and in the evidence base for air quality standards. With the widespread availability of genetic information and increasingly sophisticated measurements of molecular markers of adverse effects, there is a need for more specific and precise assessment of exposure to maximize the potential information to be derived from epidemiologic studies. Here advances in air pollution exposure assessment and their applications to studies of respiratory disease are reviewed, with a focus on recent studies of traffic-related air pollution and asthma. Although continuous measurements of personal exposures for all study subjects for a complete study period might be considered the desired "gold standard" for exposure, this is rarely, if ever, achieved due to feasibility constraints. Given this, exposure is typically estimated using models. Recent applications of geospatial (e.g., land use regression) models to studies of respiratory disease have made possible new study designs focused on spatial variability in exposure within urban areas and have provided new insights into the potential role of traffic-related air pollution (TRAP) as a risk factor for the development of childhood asthma. Substantial uncertainty remains, however, regarding what agent(s) within TRAP might be responsible for the observed associations. Future research will require increasing the specificity of exposure assessment to identify the potential roles of individual air pollution components, to elucidate potential mechanisms, and to facilitate studies of mixtures and gene-air pollution interactions.

Burning daylight: balancing vitamin D requirements with sensible sun exposure.

PubMed

Stalgis-Bilinski, Kellie L; Boyages, John; Salisbury, Elizabeth L; Dunstan, Colin R; Henderson, Stuart I; Talbot, Peter L

2011-04-04

To examine the feasibility of balancing sunlight exposure to meet vitamin D requirements with sun protection guidelines. We used standard erythemal dose and Ultraviolet Index (UVI) data for 1 June 1996 to 30 December 2005 for seven Australian cities to estimate duration of sun exposure required for fair-skinned individuals to synthesise 1000 IU (25 µg) of vitamin D, with 11% and 17% body exposure, for each season and hour of the day. Periods were classified according to whether the UVI was < 3 or ≥ 3 (when sun protection measures are recommended), and whether required duration of exposure was ≤ 30 min, 31-60 min, or > 60 min. Duration of sunlight exposure required to achieve 1000 IU of vitamin D synthesis. Duration of sunlight exposure required to synthesise 1000 IU of vitamin D varied by time of day, season and city. Although peak UVI periods are typically promoted as between 10 am and 3 pm, UVI was often ≥ 3 before 10 am or after 3 pm. When the UVI was < 3, there were few opportunities to synthesise 1000 IU of vitamin D within 30 min, with either 11% or 17% body exposure. There is a delicate line between balancing the beneficial effects of sunlight exposure while avoiding its damaging effects. Physiological and geographical factors may reduce vitamin D synthesis, and supplementation may be necessary to achieve adequate vitamin D status for individuals at risk of deficiency. ©The Medical Journal of Australia 2011

Underwater noise modelling for environmental impact assessment

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

Farcas, Adrian; Thompson, Paul M.; Merchant, Nathan D., E-mail: nathan.merchant@cefas.co.uk

Assessment of underwater noise is increasingly required by regulators of development projects in marine and freshwater habitats, and noise pollution can be a constraining factor in the consenting process. Noise levels arising from the proposed activity are modelled and the potential impact on species of interest within the affected area is then evaluated. Although there is considerable uncertainty in the relationship between noise levels and impacts on aquatic species, the science underlying noise modelling is well understood. Nevertheless, many environmental impact assessments (EIAs) do not reflect best practice, and stakeholders and decision makers in the EIA process are often unfamiliarmore » with the concepts and terminology that are integral to interpreting noise exposure predictions. In this paper, we review the process of underwater noise modelling and explore the factors affecting predictions of noise exposure. Finally, we illustrate the consequences of errors and uncertainties in noise modelling, and discuss future research needs to reduce uncertainty in noise assessments.« less

Demonstration of a modelling-based multi-criteria decision analysis procedure for prioritisation of occupational risks from manufactured nanomaterials.

PubMed

Hristozov, Danail; Zabeo, Alex; Alstrup Jensen, Keld; Gottardo, Stefania; Isigonis, Panagiotis; Maccalman, Laura; Critto, Andrea; Marcomini, Antonio

2016-11-01

Several tools to facilitate the risk assessment and management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a multi-criteria decision analysis algorithm, which combines advanced exposure and dose-response modelling to calculate margins of exposure (MoE) for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios (ES) involving the production and handling of nanoscale titanium dioxide, zinc oxide (ZnO), silver and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these ES. The ZnO MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritisation results. In order to study how variations in the input data affect our results, we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables.

Blood manganese as an exposure biomarker: State of the evidence

PubMed Central

Baker, Marissa G.; Simpson, Christopher D.; Stover, Bert; Sheppard, Lianne; Checkoway, Harvey; Racette, Brad A.; Seixas, Noah S.

2014-01-01

Despite evidence of adverse health effects resulting from exposure to manganese (Mn), biomarkers of exposure are poorly understood. To enhance understanding, mean blood Mn (MnB) and mean air Mn (MnA) were extracted from 63 exposure groups in 24 published papers, and the relationship was modeled using segmented regression. On a log/log scale, a positive association between MnA and MnB was observed among studies reporting MnA concentrations above about 10 μg/m3, although interpretation is limited by largely cross-sectional data, study design variability, and differences in exposure monitoring methods. Based on the results of the segmented regression, we hypothesize that below the concentration of about 10 μg/m3, Mn in the body is dominated by dietary Mn, and additional inhaled Mn only causes negligible changes in Mn levels unless the inhaled amount is substantial. However, stronger study designs are required to account for temporal characteristics of the MnA to MnB relationships which reflect the underlying physiology and toxicokinetics of Mn uptake and distribution. Thus, we present an inception cohort study design we have conducted among apprentice welders, and the analytical strengths this study design offers. To determine if blood could be a useful biomarker for Mn to be utilized by industrial hygienists in general industry requires additional time-specific analyses, which our inception cohort study design will allow. PMID:24579750

Assessment and Requirements of Nuclear Reaction Databases for GCR Transport in the Atmosphere and Structures

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Shinn, J. L.; Tripathi, R. K.

1998-01-01

The transport properties of galactic cosmic rays (GCR) in the atmosphere, material structures, and human body (self-shielding) am of interest in risk assessment for supersonic and subsonic aircraft and for space travel in low-Earth orbit and on interplanetary missions. Nuclear reactions, such as knockout and fragmentation, present large modifications of particle type and energies of the galactic cosmic rays in penetrating materials. We make an assessment of the current nuclear reaction models and improvements in these model for developing required transport code data bases. A new fragmentation data base (QMSFRG) based on microscopic models is compared to the NUCFRG2 model and implications for shield assessment made using the HZETRN radiation transport code. For deep penetration problems, the build-up of light particles, such as nucleons, light clusters and mesons from nuclear reactions in conjunction with the absorption of the heavy ions, leads to the dominance of the charge Z = 0, 1, and 2 hadrons in the exposures at large penetration depths. Light particles are produced through nuclear or cluster knockout and in evaporation events with characteristically distinct spectra which play unique roles in the build-up of secondary radiation's in shielding. We describe models of light particle production in nucleon and heavy ion induced reactions and make an assessment of the importance of light particle multiplicity and spectral parameters in these exposures.

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.

Childhood thyroid radioiodine exposure and subsequent infertility in the intermountain fallout cohort.

PubMed

Stone, Mary Bishop; Stanford, Joseph B; Lyon, Joseph L; VanDerslice, James A; Alder, Stephen C

2013-01-01

Above-ground and underground nuclear weapon detonation at the Nevada Test Site (1951-1992) has resulted in radioiodine exposure for nearby populations. Although the long-term effect of environmental radioiodine exposure on thyroid disease has been well studied, little is known regarding the effect of childhood radioiodine exposure on subsequent fertility. We investigated early childhood thyroid radiation exposure from nuclear testing fallout (supplied predominantly by radioactive isotopes of iodine) and self-reported lifetime incidence of male or female infertility or sterility. Participants were members of the 1965 Intermountain Fallout Cohort, schoolchildren at the time of exposure who were reexamined during two subsequent study phases to collect dietary and reproductive histories. Thyroid radiation exposure was calculated via an updated dosimetry model. We used multivariable logistic regression with robust sandwich estimators to estimate odds ratios for infertility, adjusted for potential confounders and (in separate models) for a medically confirmed history of thyroid disease. Of 1,389 participants with dosimetry and known fertility history, 274 were classified as infertile, including 30 classified as sterile. Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI: 0.82, 1.67 and AOR = 1.35; 95% CI: 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively]. The odds ratios were attenuated (AOR = 1.08; 95% CI: 0.75, 1.55 and AOR = 1.29; 95% CI: 0.91, 1.83 for the middle and upper tertiles, respectively) after adjusting for thyroid disease. There was no association of childhood radiation dose and sterility. Our findings suggest that childhood radioiodine exposure from nuclear testing may be related to subsequent adult infertility. Further research is required to confirm this.

Bioavailability and bioaccumulation of metal-based engineered nanomaterials in aquatic environments: concepts and processes: chapter 5

USGS Publications Warehouse

Luoma, Samuel N.; Khan, Farhan R.; Croteau, Marie-Noële

2014-01-01

Bioavailability of Me-ENMs to aquatic organisms links their release into the environment to ecological implications. Close examination shows some important differences in the conceptual models that define bioavailability for metals and Me-ENMs. Metals are delivered to aquatic animals from Me-ENMs via water, ingestion, and incidental surface exposure. Both metal released from the Me-ENM and uptake of the nanoparticle itself contribute to bioaccumulation. Some mechanisms of toxicity and some of the metrics describing exposure may differ from metals alone. Bioavailability is driven by complex interaction of particle attributes, environmental transformations, and biological traits. Characterization of Me-ENMs is an essential part of understanding bioavailability and requires novel methodologies. The relative importance of the array of processes that could affect Me-ENM bioavailability remains poorly known, but new approaches and models are developing rapidly. Enough is known, however, to conclude that traditional approaches to exposure assessment for metals would not be adequate to assess risks from Me-ENMs.

Quantitative microbial risk assessment model for Legionnaires' disease: assessment of human exposures for selected spa outbreaks.

PubMed

Armstrong, Thomas W; Haas, Charles N

2007-08-01

Evaluation of a quantitative microbial risk assessment (QMRA) model for Legionnaires' disease (LD) required Legionella exposure estimates for several well-documented LD outbreaks. Reports for a whirlpool spa and two natural spring spa outbreaks provided data for the exposure assessment, as well as rates of infection and mortality. Exposure estimates for the whirlpool spa outbreak employed aerosol generation, water composition, exposure duration data, and building ventilation parameters with a two-zone model. Estimates for the natural hot springs outbreaks used bacterial water to air partitioning coefficients and exposure duration information. The air concentration and dose calculations used input parameter distributions with Monte Carlo simulations to estimate exposures as probability distributions. The assessment considered two sets of assumptions about the transfer of Legionella from the water phase to the aerosol emitted from the whirlpool spa. The estimated air concentration near the whirlpool spa was 5 to 18 colony forming units per cubic meter (CFU/m(3)) and 50 to 180 CFU/m(3) for each of the alternate assumptions. The estimated 95th percentile ranges of Legionella dose for workers within 15 m of the whirlpool spa were 0.13-3.4 CFU and 1.3-34.5 CFU, respectively. The modeling for hot springs Spas 1 and 2 resulted in estimated arithmetic mean air concentrations of 360 and 17 CFU/m(3), respectively, and 95 percentile ranges for Legionella dose of 28 to 67 CFU and 1.1 to 3.7 CFU, respectively. The Legionella air concentration estimates fall in the range of limited reports on air concentrations of Legionella (0.33 to 190 CFU/m(3)) near showers, aerated faucets, and baths during filling with Legionella-contaminated water. These measurements may provide some indication that the estimates are of a reasonable magnitude, but they do not clarify the exposure estimates accuracy, since they were not obtained during LD outbreaks. Further research to improve the data used for the Legionella exposure assessment would strengthen the results. Several of the primary additional data needs include improved data for bacterial water to air partitioning coefficients, better accounting of time-activity-distance patterns and exposure potential in outbreak reports, and data for Legionella-containing aerosol viability decay instead of loss of capability for growth in culture.

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

PubMed

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

2017-03-16

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

Pathogen Treatment Guidance and Monitoring Approaches fro ...

EPA Pesticide Factsheets

On-site non-potable water reuse is increasingly used to augment water supplies, but traditional fecal indicator approaches for defining and monitoring exposure risks are limited when applied to these decentralized options. This session emphasizes risk-based modeling to define pathogen log-reduction requirements coupled with alternative targets for monitoring enabled by genomic sequencing (i.e., the microbiome of reuse systems). 1. Discuss risk-based modeling to define pathogen log-reduction requirements 2. Review alternative targets for monitoring 3. Gain an understanding of how new tools can help improve successful development of sustainable on-site non-potable water reuse Presented at the Water Wastewater Equipment Treatment & Transport Show.

Elimination of water pathogens with solar radiation using an automated sequential batch CPC reactor.

PubMed

Polo-López, M I; Fernández-Ibáñez, P; Ubomba-Jaswa, E; Navntoft, C; García-Fernández, I; Dunlop, P S M; Schmid, M; Byrne, J A; McGuigan, K G

2011-11-30

Solar disinfection (SODIS) of water is a well-known, effective treatment process which is practiced at household level in many developing countries. However, this process is limited by the small volume treated and there is no indication of treatment efficacy for the user. Low cost glass tube reactors, together with compound parabolic collector (CPC) technology, have been shown to significantly increase the efficiency of solar disinfection. However, these reactors still require user input to control each batch SODIS process and there is no feedback that the process is complete. Automatic operation of the batch SODIS process, controlled by UVA-radiation sensors, can provide information on the status of the process, can ensure the required UVA dose to achieve complete disinfection is received and reduces user work-load through automatic sequential batch processing. In this work, an enhanced CPC photo-reactor with a concentration factor of 1.89 was developed. The apparatus was automated to achieve exposure to a pre-determined UVA dose. Treated water was automatically dispensed into a reservoir tank. The reactor was tested using Escherichia coli as a model pathogen in natural well water. A 6-log inactivation of E. coli was achieved following exposure to the minimum uninterrupted lethal UVA dose. The enhanced reactor decreased the exposure time required to achieve the lethal UVA dose, in comparison to a CPC system with a concentration factor of 1.0. Doubling the lethal UVA dose prevented the need for a period of post-exposure dark inactivation and reduced the overall treatment time. Using this reactor, SODIS can be automatically carried out at an affordable cost, with reduced exposure time and minimal user input. Copyright © 2011 Elsevier B.V. All rights reserved.

10 CFR 35.70 - Surveys of ambient radiation exposure rate.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the surveys required by paragraph (a) of this section in an area(s) where patients or human research... 10 Energy 1 2013-01-01 2013-01-01 false Surveys of ambient radiation exposure rate. 35.70 Section... Requirements § 35.70 Surveys of ambient radiation exposure rate. (a) In addition to the surveys required by...

10 CFR 35.70 - Surveys of ambient radiation exposure rate.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the surveys required by paragraph (a) of this section in an area(s) where patients or human research... 10 Energy 1 2014-01-01 2014-01-01 false Surveys of ambient radiation exposure rate. 35.70 Section... Requirements § 35.70 Surveys of ambient radiation exposure rate. (a) In addition to the surveys required by...

10 CFR 35.70 - Surveys of ambient radiation exposure rate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the surveys required by paragraph (a) of this section in an area(s) where patients or human research... 10 Energy 1 2010-01-01 2010-01-01 false Surveys of ambient radiation exposure rate. 35.70 Section... Requirements § 35.70 Surveys of ambient radiation exposure rate. (a) In addition to the surveys required by...

10 CFR 35.70 - Surveys of ambient radiation exposure rate.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the surveys required by paragraph (a) of this section in an area(s) where patients or human research... 10 Energy 1 2012-01-01 2012-01-01 false Surveys of ambient radiation exposure rate. 35.70 Section... Requirements § 35.70 Surveys of ambient radiation exposure rate. (a) In addition to the surveys required by...

10 CFR 35.70 - Surveys of ambient radiation exposure rate.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the surveys required by paragraph (a) of this section in an area(s) where patients or human research... 10 Energy 1 2011-01-01 2011-01-01 false Surveys of ambient radiation exposure rate. 35.70 Section... Requirements § 35.70 Surveys of ambient radiation exposure rate. (a) In addition to the surveys required by...

Global Dynamic Exposure and the OpenBuildingMap

NASA Astrophysics Data System (ADS)

Schorlemmer, D.; Beutin, T.; Hirata, N.; Hao, K. X.; Wyss, M.; Cotton, F.; Prehn, K.

2015-12-01

Detailed understanding of local risk factors regarding natural catastrophes requires in-depth characterization of the local exposure. Current exposure capture techniques have to find the balance between resolution and coverage. We aim at bridging this gap by employing a crowd-sourced approach to exposure capturing focusing on risk related to earthquake hazard. OpenStreetMap (OSM), the rich and constantly growing geographical database, is an ideal foundation for us. More than 2.5 billion geographical nodes, more than 150 million building footprints (growing by ~100'000 per day), and a plethora of information about school, hospital, and other critical facility locations allow us to exploit this dataset for risk-related computations. We will harvest this dataset by collecting exposure and vulnerability indicators from explicitly provided data (e.g. hospital locations), implicitly provided data (e.g. building shapes and positions), and semantically derived data, i.e. interpretation applying expert knowledge. With this approach, we can increase the resolution of existing exposure models from fragility classes distribution via block-by-block specifications to building-by-building vulnerability. To increase coverage, we will provide a framework for collecting building data by any person or community. We will implement a double crowd-sourced approach to bring together the interest and enthusiasm of communities with the knowledge of earthquake and engineering experts. The first crowd-sourced approach aims at collecting building properties in a community by local people and activists. This will be supported by tailored building capture tools for mobile devices for simple and fast building property capturing. The second crowd-sourced approach involves local experts in estimating building vulnerability that will provide building classification rules that translate building properties into vulnerability and exposure indicators as defined in the Building Taxonomy 2.0 developed by the Global Earthquake Model (GEM). These indicators will then be combined with a hazard model using the GEM OpenQuake engine to compute a risk model. The free/open framework we will provide can be used on commodity hardware for local to regional exposure capturing and for communities to understand their earthquake risk.

Case Study: Organotypic human in vitro models of embryonic ...

EPA Pesticide Factsheets

Morphogenetic fusion of tissues is a common event in embryonic development and disruption of fusion is associated with birth defects of the eye, heart, neural tube, phallus, palate, and other organ systems. Embryonic tissue fusion requires precise regulation of cell-cell and cell-matrix interactions that drive proliferation, differentiation, and morphogenesis. Chemical low-dose exposures can disrupt morphogenesis across space and time by interfering with key embryonic fusion events. The Morphogenetic Fusion Task uses computer and in vitro models to elucidate consequences of developmental exposures. The Morphogenetic Fusion Task integrates multiple approaches to model responses to chemicals that leaad to birth defects, including integrative mining on ToxCast DB, ToxRefDB, and chemical structures, advanced computer agent-based models, and human cell-based cultures that model disruption of cellular and molecular behaviors including mechanisms predicted from integrative data mining and agent-based models. The purpose of the poster is to indicate progress on the CSS 17.02 Virtual Tissue Models Morphogenesis Task 1 products for the Board of Scientific Counselors meeting on Nov 16-17.

Satellite constraints on surface concentrations of particulate matter

NASA Astrophysics Data System (ADS)

Ford Hotmann, Bonne

Because of the increasing evidence of the widespread adverse effects on human health from exposure to poor air quality and the recommendations of the World Health Organization to significantly reduce PM2.5 in order to reduce these risks, better estimates of surface air quality globally are required. However, surface measurements useful for monitoring particulate exposure are scarce, especially in developing countries which often experience the worst air pollution. Therefore, other methods are necessary to augment estimates in regions with limited surface observations. The prospect of using satellite observations to infer surface air quality is attractive; however, it requires knowledge of the complicated relationship between satellite-observed aerosol optical depth (AOD) and surface concentrations. This dissertation explores how satellite observations can be used in conjunction with a chemical transport model (GEOS-Chem) to better understand this relationship. First, we investigate the seasonality in aerosols over the Southeastern United States using observations from several satellite instruments (MODIS, MISR, CALIOP) and surface network sites (IMPROVE, SEARCH, AERONET). We find that the strong summertime enhancement in satellite-observed aerosol optical depth (factor 2-3 enhancement over wintertime AOD) is not present in surface mass concentrations (25-55% summertime enhancement). Goldstein et al. [2009] previously attributed this seasonality in AOD to biogenic organic aerosol; however, surface observations show that organic aerosol only accounts for ~35% of PM2.5 mass and exhibits similar seasonality to total surface PM2.5. The GEOS-Chem model generally reproduces these surface aerosol measurements, but under represents the AOD seasonality observed by satellites. We show that seasonal differences in water uptake cannot sufficiently explain the magnitude of AOD increase. As CALIOP profiles indicate the presence of additional aerosol in the lower troposphere (below 700 hPa), which cannot be explained by vertical mixing; we conclude that the discrepancy is due to a missing source of aerosols above the surface layer in summer. Next, we examine the usefulness of deriving premature mortality estimates from "satellite-based" PM2.5 concentrations. In particular, we examine how uncertainties in the model AOD-to-surface-PM2.5 relationship, satellite retrieved AOD, and particulars of the concentration-response function can impact these mortality estimates. We find that the satellite-based estimates suggest premature mortality due to chronic PM2.5 exposure is 2-16% higher in the U.S. and 4-13% lower in China compared to model-based estimates. However, this difference is overshadowed by the uncertainty in the methodology, which we quantify to be on order of 20% for the model-to- surface-PM2.5 relationship, 10% for the satellite AOD and 30-60% or greater with regards to the application of concentration response functions. Because there is a desire for acute exposure estimates, especially with regards to extreme events, we also examine how premature mortality due to acute exposure can be estimated from global models and satellite-observations. We find similar differences between model and satellite-based mortality estimates as with chronic exposure. However the range of uncertainty is much larger on these shorter timescales. This work suggests that although satellites can be useful for constraining model estimates of PM2.5, national mortality estimates from the two methods are not significantly different. In order to improve the efficacy of satellite-based PM2.5 mortality estimates, future work will need to focus on improving the model representation of the regional AOD-to-surface-PM2.5 relationship, reducing biases in satellite-retrieved AOD and advancing our understanding of personal and population-level responses to PM2.5 exposure.

Documentation of the Ecological Risk Assessment Computer Model ECORSK.5

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

Anthony F. Gallegos; Gilbert J. Gonzales

1999-06-01

The FORTRAN77 ecological risk computer model--ECORSK.5--has been used to estimate the potential toxicity of surficial deposits of radioactive and non-radioactive contaminants to several threatened and endangered (T and E) species at the Los Alamos National Laboratory (LANL). These analyses to date include preliminary toxicity estimates for the Mexican spotted owl, the American peregrine falcon, the bald eagle, and the southwestern willow flycatcher. This work has been performed as required for the Record of Decision for the construction of the Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility at LANL as part of the Environmental Impact Statement. The model is dependent onmore » the use of the geographic information system and associated software--ARC/INFO--and has been used in conjunction with LANL's Facility for Information Management and Display (FIMAD) contaminant database. The integration of FIMAD data and ARC/INFO using ECORSK.5 allows the generation of spatial information from a gridded area of potential exposure called an Ecological Exposure Unit. ECORSK.5 was used to simulate exposures using a modified Environmental Protection Agency Quotient Method. The model can handle a large number of contaminants within the home range of T and E species. This integration results in the production of hazard indices which, when compared to risk evaluation criteria, estimate the potential for impact from consumption of contaminants in food and ingestion of soil. The assessment is considered a Tier-2 type of analysis. This report summarizes and documents the ECORSK.5 code, the mathematical models used in the development of ECORSK.5, and the input and other requirements for its operation. Other auxiliary FORTRAN 77 codes used for processing and graphing output from ECORSK.5 are also discussed. The reader may refer to reports cited in the introduction to obtain greater detail on past applications of ECORSK.5 and assumptions used in deriving model parameters.« less

Respiratory Health - Exposure Measurements and Modeling in the Fragrance and Flavour Industry.

PubMed

Angelini, Eric; Camerini, Gerard; Diop, Malick; Roche, Patrice; Rodi, Thomas; Schippa, Christine; Thomas, Thierry

2016-01-01

Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH) identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring), 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to various exposure scenarios, with the experimental values measured under real conditions. After examination of the predicted results, 98% of the values obtained with the proposed new model were above the experimental values measured in real conditions. This must be compared with the results of the classical ECETOC-TRA system, which generates only 37% of overestimated values. As the values generated by the new model intended to help decision-makers of the industry to implement adapted protective action and information, and considering the high variability of the working environments, it was of the utmost importance to us not to underestimate the exposure level. The proposed correction factors have been designed to achieve this goal. We wish to propose the present method as an improved monitoring tool to improve respiratory health and safety in the flavor and fragrance manufacturing facilities.

Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel

PubMed Central

Pietrofesa, Ralph A.; Velalopoulou, Anastasia; Lehman, Stacey L.; Arguiri, Evguenia; Solomides, Pantelis; Koch, Cameron J.; Mishra, Om P.; Koumenis, Constantinos; Goodwin, Thomas J.; Christofidou-Solomidou, Melpo

2016-01-01

Spaceflight occasionally requires multiple extravehicular activities (EVA) that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10) were exposed to >95% O2 for 8 h only (O2), 0.25 Gy ionizing γ-radiation (IR) only, or a double-hit combination of both challenges (O2 + IR) followed by 16 h of normoxia (ambient air containing 21% O2 and 5% CO2) (1 cycle = 24 h, 2 cycles = 48 h). Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05) decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP), apoptotic (cleaved caspase-3 and BAX), and antioxidant (HO-1 and Nqo1) proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O2 + IR exacerbated cell death and DNA damage compared to individual exposures O2 or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia exposure that leads to oxidative lung cell injury, DNA damage, apoptosis, and cell cycle arrest. PMID:27322243

Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel.

PubMed

Pietrofesa, Ralph A; Velalopoulou, Anastasia; Lehman, Stacey L; Arguiri, Evguenia; Solomides, Pantelis; Koch, Cameron J; Mishra, Om P; Koumenis, Constantinos; Goodwin, Thomas J; Christofidou-Solomidou, Melpo

2016-06-16

Spaceflight occasionally requires multiple extravehicular activities (EVA) that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10) were exposed to >95% O₂ for 8 h only (O₂), 0.25 Gy ionizing γ-radiation (IR) only, or a double-hit combination of both challenges (O₂ + IR) followed by 16 h of normoxia (ambient air containing 21% O₂ and 5% CO₂) (1 cycle = 24 h, 2 cycles = 48 h). Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05) decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP), apoptotic (cleaved caspase-3 and BAX), and antioxidant (HO-1 and Nqo1) proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O₂ + IR exacerbated cell death and DNA damage compared to individual exposures O₂ or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia exposure that leads to oxidative lung cell injury, DNA damage, apoptosis, and cell cycle arrest.

The Low Earth Orbit validation of a dynamic and anisotropic trapped radiation model through ISS measurements

NASA Astrophysics Data System (ADS)

Badavi, Francis F.; Nealy, John E.; Wilson, John W.

2011-10-01

The International Space Station (ISS) provides the proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the experimental validation of radiation environmental models, nuclear transport code algorithms and nuclear reaction cross sections. Indeed, prior measurements on the Space Transportation System (STS; Shuttle) have provided vital information impacting both the environmental models and the nuclear transport code development by requiring dynamic models of the Low Earth Orbit (LEO) environment. Previous studies using Computer Aided Design (CAD) models of the evolving ISS configurations with Thermo-Luminescent Detector (TLD) area monitors, demonstrated that computational dosimetry requires environmental models with accurate non-isotropic as well as dynamic behavior, detailed information on rack loading, and an accurate six degree of freedom (DOF) description of ISS trajectory and orientation. It is imperative that we understand ISS exposures dynamically for crew career planning, and insure that the regulatory requirements of keeping exposure as low as reasonably achievable (ALARA) are adequately implemented. This is especially true as ISS nears some form of completion with increasing complexity, resulting in a larger drag coefficient, and requiring operation at higher altitudes with increased exposure rates. In this paper ISS environmental model is configured for 11A (circa mid 2005), and uses non-isotropic and dynamic geomagnetic transmission and trapped proton models. ISS 11A and LEO model validations are important steps in preparation for the design and validation for the next generation manned vehicles. While the described cutoff rigidity, trapped proton and electron formalisms as coded in a package named GEORAD (GEOmagnetic RADiation) and a web interface named OLTARIS (On-line Tool for the Assessment of Radiation in Space) are applicable to the LEO, Medium Earth Orbit (MEO) and Geosynchronous Earth Orbit (GEO) at quiet solar periods, in this report, the validation of the models using available measurements are limited to STS and ISS nominal operational altitudes (300-400 km) range at LEO where the dominant fields within the vehicle are the trapped proton and attenuated Galactic Cosmic Ray (GCR) ions. The described formalism applies to trapped electron at LEO, MEO and GEO as well. Due to the scarcity of available electron measurements, the trapped electron capabilities of the GEORAD are not discussed in this report, but are accessible through OLTARIS web interface. GEORAD and OLTARIS interests are in the study of long term effects (i.e. a meaningful portion of solar cycle). Therefore, GEORAD does not incorporate any short term external field contribution due to solar activity. Finally, we apply these environmental models to selected target points within ISS 6A (circa early 2001), 7A (circa late 2001), and 11A during its passage through the South Atlantic Anomaly (SAA) to assess the validity of the environmental models at ISS altitudes.

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

PubMed

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

1996-12-01

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

Estimates of galactic cosmic ray shielding requirements during solar minimum

NASA Technical Reports Server (NTRS)

Townsend, Lawrence W.; Nealy, John E.; Wilson, John W.; Simonsen, Lisa C.

1990-01-01

Estimates of radiation risk from galactic cosmic rays are presented for manned interplanetary missions. The calculations use the Naval Research Laboratory cosmic ray spectrum model as input into the Langley Research Center galactic cosmic ray transport code. This transport code, which transports both heavy ions and nucleons, can be used with any number of layers of target material, consisting of up to five different arbitrary constituents per layer. Calculated galactic cosmic ray fluxes, dose and dose equivalents behind various thicknesses of aluminum, water and liquid hydrogen shielding are presented for the solar minimum period. Estimates of risk to the skin and the blood-forming organs (BFO) are made using 0-cm and 5-cm depth dose/dose equivalent values, respectively, for water. These results indicate that at least 3.5 g/sq cm (3.5 cm) of water, or 6.5 g/sq cm (2.4 cm) of aluminum, or 1.0 g/sq cm (14 cm) of liquid hydrogen shielding is required to reduce the annual exposure below the currently recommended BFO limit of 0.5 Sv. Because of large uncertainties in fragmentation parameters and the input cosmic ray spectrum, these exposure estimates may be uncertain by as much as a factor of 2 or more. The effects of these potential exposure uncertainties or shield thickness requirements are analyzed.

Automated Simultaneous Assembly of Multistage Testlets for a High-Stakes Licensing Examination

ERIC Educational Resources Information Center

Breithaupt, Krista; Hare, Donovan R.

2007-01-01

Many challenges exist for high-stakes testing programs offering continuous computerized administration. The automated assembly of test questions to exactly meet content and other requirements, provide uniformity, and control item exposure can be modeled and solved by mixed-integer programming (MIP) methods. A case study of the computerized…

Unpacking Neighborhood Influences on Education Outcomes: Setting the Stage for Future Research. NBER Working Paper No. 16055

ERIC Educational Resources Information Center

Harding, David J.; Gennetian, Lisa; Winship, Christopher; Sanbonmatsu, Lisa; Kling, Jeffrey R.

2010-01-01

We motivate future neighborhood research through a simple model that considers youth educational outcomes as a function of neighborhood context, neighborhood exposure, individual vulnerability to neighborhood effects, and non-neighborhood educational inputs--with a focus on effect heterogeneity. Research using this approach would require three…

GAS-PHASE MASS TRANSFER MODEL FOR PREDICTING VOLATILE ORGANIC COMPOUND (VOC) EMISSION RATES FROM INDOOR POLLUTANT SOURCES

EPA Science Inventory

Analysis of the impact of sources on indoor pollutant concentrations and occupant exposure to indoor pollutants requires knowledge of the emission rates from the sources. Emission rates are often determined by chamber testing and the data from the chamber test are fitted to an em...

MODEL EVALUATION SCIENCE TO MEET TODAY'S QUALITY ASSURANCE REQUIREMENTS FOR REGULATORY USE: ADDRESSING UNCERTAINTY, SENSITIVITY, AND PARAMETERIZATION

EPA Science Inventory

The EPA/ORD National Exposure Research Lab's (NERL) UA/SA/PE research program addresses both tactical and strategic needs in direct support of ORD's client base. The design represents an integrated approach in achieving the highest levels of quality assurance in environmental de...

MEETING IN TUCSON: MODEL EVALUATION SCIENCE TO MEET TODAY'S QUALITY ASSURANCE REQUIREMENTS FOR REGULATORY USE: ADDRESSING UNCERTAINTY, SENSITIVITY, AND PARAMETERIZATION

EPA Science Inventory

The EPA/ORD National Exposure Research Lab's (NERL) UA/SA/PE research program addresses both tactical and strategic needs in direct support of ORD's client base. The design represents an integrated approach in achieving the highest levels of quality assurance in environmental dec...

Chronic PTSD Treated with Metacognitive Therapy: An Open Trial

ERIC Educational Resources Information Center

Wells, Adrian; Welford, Mary; Fraser, Janelle; King, Paul; Mendel, Elizabeth; Wisely, Julie; Knight, Alice; Rees, David

2008-01-01

This paper reports on an open trial of metacognitive therapy (MCT) for chronic PTSD. MCT does not require imaginal reliving, prolonged exposure, or challenging of thoughts about trauma. It is based on an information-processing model of factors that impede normal and in-built recovery processes. It is targeted at modifying maladaptive styles of…

Survey mirrors and lenses and their required surface accuracy. Volume 1. Technical report. Final report for September 15, 1978-December 1, 1979

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

Beesing, M. E.; Buchholz, R. L.; Evans, R. A.

1980-01-01

An investigation of the optical performance of a variety of concentrating solar collectors is reported. The study addresses two important issues: the accuracy of reflective or refractive surfaces required to achieve specified performance goals, and the effect of environmental exposure on the performance concentrators. To assess the importance of surface accuracy on optical performance, 11 tracking and nontracking concentrator designs were selected for detailed evaluation. Mathematical models were developed for each design and incorporated into a Monte Carlo ray trace computer program to carry out detailed calculations. Results for the 11 concentrators are presented in graphic form. The models andmore » computer program are provided along with a user's manual. A survey data base was established on the effect of environmental exposure on the optical degradation of mirrors and lenses. Information on environmental and maintenance effects was found to be insufficient to permit specific recommendations for operating and maintenance procedures, but the available information is compiled and reported and does contain procedures that other workers have found useful.« less

Increase of Long-chain Branching by Thermo-oxidative Treatment of LDPE

NASA Astrophysics Data System (ADS)

Rolón-Garrido, Víctor H.; Luo, Jinji; Wagner, Manfred H.

2011-07-01

Low-density polyethylene (LDPE) was exposed to thermal and thermo-oxidative treatment at 170 °C, and subsequently characterized by linear-viscoelastic measurements and in uniaxial extension. The Molecular Stress Function (MSF) model was used to quantify the elongational viscosities measured. For the thermally treated samples, exposure times between 2 and 6 hours were applied. Formation of long-chain branching (LCB) was found to occur only during the first two hours of thermal treatment. At longer exposure times, no difference in the level of strain hardening was observed. This was quantified by use of the MSF model: the nonlinear parameter fmax2 increased from fmax2 = 14 for the virgin sample to fmax2 = 22 for the samples thermally treated between 2 and 6 hours. For the thermo-oxidatively treated samples, which were exposed to air during thermal treatment between 30 and 90 minutes, the level of strain hardening increases drastically up to fmax2 = 55 with increasing exposure times from 30 up to 75 min due to LCB formation, and then decreases for an exposure time of 90 minutes due to chain scission dominating LCB formation. The nonlinear parameter β of the MSF model was found to be β = 2 for all samples, indicating that the general type of the random branching structure remains the same under all thermal conditions. Consequently only the parameter fmax2 of the MSF model and the linear-viscoelastic spectra were required to describe quantitatively the experimental observations. The strain hardening index, which is sometimes used to quantify strain hardening, follows accurately the trend of the MSF model parameter fmax2.

The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence.

PubMed

Tsai, Song-Yen; Chou, Hung-Yi; The, Hee-Wen; Chen, Chao-Meei; Chen, Chien-Jen

2003-08-01

This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0+/-605824.2 and 13782.2+/-12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.

40 CFR 158.2260 - Applicator exposure.

Code of Federal Regulations, 2014 CFR

2014-07-01

... exposure data, provided the human pharmacokinetics of the pesticide or metabolite/analog compounds (i.e... 158.2260 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2260 Applicator exposure. (a...

40 CFR 158.2260 - Applicator exposure.

Code of Federal Regulations, 2013 CFR

2013-07-01

... exposure data, provided the human pharmacokinetics of the pesticide or metabolite/analog compounds (i.e... 158.2260 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2260 Applicator exposure. (a...

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

PubMed

Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Calculating excess lifetime risk in relative risk models.

PubMed Central

Vaeth, M; Pierce, D A

1990-01-01

When assessing the impact of radiation exposure it is common practice to present the final conclusions in terms of excess lifetime cancer risk in a population exposed to a given dose. The present investigation is mainly a methodological study focusing on some of the major issues and uncertainties involved in calculating such excess lifetime risks and related risk projection methods. The age-constant relative risk model used in the recent analyses of the cancer mortality that was observed in the follow-up of the cohort of A-bomb survivors in Hiroshima and Nagasaki is used to describe the effect of the exposure on the cancer mortality. In this type of model the excess relative risk is constant in age-at-risk, but depends on the age-at-exposure. Calculation of excess lifetime risks usually requires rather complicated life-table computations. In this paper we propose a simple approximation to the excess lifetime risk; the validity of the approximation for low levels of exposure is justified empirically as well as theoretically. This approximation provides important guidance in understanding the influence of the various factors involved in risk projections. Among the further topics considered are the influence of a latent period, the additional problems involved in calculations of site-specific excess lifetime cancer risks, the consequences of a leveling off or a plateau in the excess relative risk, and the uncertainties involved in transferring results from one population to another. The main part of this study relates to the situation with a single, instantaneous exposure, but a brief discussion is also given of the problem with a continuous exposure at a low-dose rate. PMID:2269245

Calculating excess lifetime risk in relative risk models.

PubMed

Vaeth, M; Pierce, D A

1990-07-01

When assessing the impact of radiation exposure it is common practice to present the final conclusions in terms of excess lifetime cancer risk in a population exposed to a given dose. The present investigation is mainly a methodological study focusing on some of the major issues and uncertainties involved in calculating such excess lifetime risks and related risk projection methods. The age-constant relative risk model used in the recent analyses of the cancer mortality that was observed in the follow-up of the cohort of A-bomb survivors in Hiroshima and Nagasaki is used to describe the effect of the exposure on the cancer mortality. In this type of model the excess relative risk is constant in age-at-risk, but depends on the age-at-exposure. Calculation of excess lifetime risks usually requires rather complicated life-table computations. In this paper we propose a simple approximation to the excess lifetime risk; the validity of the approximation for low levels of exposure is justified empirically as well as theoretically. This approximation provides important guidance in understanding the influence of the various factors involved in risk projections. Among the further topics considered are the influence of a latent period, the additional problems involved in calculations of site-specific excess lifetime cancer risks, the consequences of a leveling off or a plateau in the excess relative risk, and the uncertainties involved in transferring results from one population to another. The main part of this study relates to the situation with a single, instantaneous exposure, but a brief discussion is also given of the problem with a continuous exposure at a low-dose rate.

Injury risk and noise exposure in firefighter training operations

PubMed Central

Neitzel, Richard L.; Long, Rachel; Sun, Kan; Sayler, Stephanie; von Thaden, Terry L.

2016-01-01

Introduction Firefighters have high rate of injuries and illnesses, as well as exposures to high levels of noise. This study explored the relationship between noise exposure and injury among firefighters. Methods We recruited firefighters undergoing vehicle extrication and structural collapse emergency response training at a highly realistic training facility. Demographics, health status, body mass index, and history of serious injuries (i.e., injuries requiring first aid treatment, treatment in a medical clinic or office, or treatment at a hospital) were assessed at baseline, and daily activities, injury events, and near-misses were assessed daily using surveys. Participants' noise exposures were monitored for one 24-hour period using noise dosimeters. We used a mixed-effects logistic regression model to estimate the odds of injury events and near-misses associated with noise exposure as an independent variable. Results Of 56 subjects, twenty (36%) reported that they had ever suffered a serious injury during firefighting activities, and nine (16%) reported a serious injury within the past year. We estimated rates of 6.6 lifetime serious injuries per 100 FTE 16.1 serious injuries per 100 FTE within the past year. Our models indicated a significant increase in injury events and near misses among those with higher BMI, and as well as a dose-response relationship between near-misses/injuries and increasing noise levels. Noise levels >90 dBA in the 30 min prior to time of injury or near-miss were associated with substantially increased odds ratios for injury or near-miss. Our models further indicated that perceived job demands were significantly associated with increased risk of injury or near-miss. Conclusion Our results suggest that noise exposures may need to be incorporated into injury prevention programs for firefighters to reduce injuries among this high-risk occupational group. PMID:26712895

An Algorithm for the Transport of Anisotropic Neutrons

NASA Technical Reports Server (NTRS)

Tweed, J.

2005-01-01

One major obstacle to human space exploration is the possible limitations imposed by the adverse effect of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar particle events (SPE) were of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated GCR exposures can be high. Because cancer induction rates increase behind low to rather large thicknesses of aluminum shielding, according to available biological data on mammalian exposures to GCR like ions, the shield requirements for a Mars mission are prohibitively expensive in terms of mission launch costs. Therefore, a critical issue in the Human Exploration and Development of Space enterprise is cost effective mitigation of risk associated with ionizing radiation exposure. In order to estimate astronaut risk to GCR exposure and associated cancer risks and health hazards, it is necessary to do shield material studies. To determine an optimum radiation shield material it is necessary to understand nuclear interaction processes such as fragmentation and secondary particle production which is a function of energy dependent cross sections. This requires knowledge of material transmission characteristics either through laboratory testing or improved theoretical modeling. Here ion beam transport theory is of importance in that testing of materials in the laboratory environment generated by particle accelerators is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are a major emphasis of the present work.

HIF-1 and SKN-1 coordinate the transcriptional response to hydrogen sulfide in Caenorhabditis elegans.

PubMed

Miller, Dana L; Budde, Mark W; Roth, Mark B

2011-01-01

Hydrogen sulfide (H₂S) has dramatic physiological effects on animals that are associated with improved survival. C. elegans grown in H₂S are long-lived and thermotolerant. To identify mechanisms by which adaptation to H₂S effects physiological functions, we have measured transcriptional responses to H₂S exposure. Using microarray analysis we observe rapid changes in the abundance of specific mRNAs. The number and magnitude of transcriptional changes increased with the duration of H₂S exposure. Functional annotation suggests that genes associated with protein homeostasis are upregulated upon prolonged exposure to H₂S. Previous work has shown that the hypoxia-inducible transcription factor, HIF-1, is required for survival in H₂S. In fact, we show that hif-1 is required for most, if not all, early transcriptional changes in H₂S. Moreover, our data demonstrate that SKN-1, the C. elegans homologue of NRF2, also contributes to H₂S-dependent changes in transcription. We show that these results are functionally important, as skn-1 is essential to survive exposure to H₂S. Our results suggest a model in which HIF-1 and SKN-1 coordinate a broad transcriptional response to H₂S that culminates in a global reorganization of protein homeostasis networks.

Tardigrades as a Potential Model Organism in Space Research

NASA Astrophysics Data System (ADS)

Jönsson, K. Ingemar

2007-10-01

Exposure of living organisms to open space requires a high level of tolerance to desiccation, cold, and radiation. Among animals, only anhydrobiotic species can fulfill these requirements. The invertebrate phylum Tardigrada includes many anhydrobiotic species, which are adapted to survive in very dry or cold environmental conditions. As a likely by-product of the adaptations for desiccation and freezing, tardigrades also show a very high tolerance to a number of other, unnatural conditions, including exposure to ionizing radiation. This makes tardigrades an interesting candidate for experimental exposure to open space. This paper reviews the tolerances that make tardigrades suitable for astrobiological studies and the reported radiation tolerance in other anhydrobiotic animals. Several studies have shown that tardigrades can survive γ-irradiation well above 1 kilogray, and desiccated and hydrated (active) tardigrades respond similarly to irradiation. Thus, tolerance is not restricted to the dry anhydrobiotic state, and I discuss the possible involvement of an efficient, but yet undocumented, mechanism for DNA repair. Other anhydrobiotic animals (Artemia, Polypedium), when dessicated, show a higher tolerance to γ-irradiation than hydrated animals, possibly due to the presence of high levels of the protective disaccharide trehalose in the dry state. Tardigrades and other anhydrobiotic animals provide a unique opportunity to study the effects of space exposure on metabolically inactive but vital metazoans.

Tardigrades as a potential model organism in space research.

PubMed

Jönsson, K Ingemar

2007-10-01

Exposure of living organisms to open space requires a high level of tolerance to desiccation, cold, and radiation. Among animals, only anhydrobiotic species can fulfill these requirements. The invertebrate phylum Tardigrada includes many anhydrobiotic species, which are adapted to survive in very dry or cold environmental conditions. As a likely by-product of the adaptations for desiccation and freezing, tardigrades also show a very high tolerance to a number of other, unnatural conditions, including exposure to ionizing radiation. This makes tardigrades an interesting candidate for experimental exposure to open space. This paper reviews the tolerances that make tardigrades suitable for astrobiological studies and the reported radiation tolerance in other anhydrobiotic animals. Several studies have shown that tardigrades can survive gamma-irradiation well above 1 kilogray, and desiccated and hydrated (active) tardigrades respond similarly to irradiation. Thus, tolerance is not restricted to the dry anhydrobiotic state, and I discuss the possible involvement of an efficient, but yet undocumented, mechanism for DNA repair. Other anhydrobiotic animals (Artemia, Polypedium), when dessicated, show a higher tolerance to gamma-irradiation than hydrated animals, possibly due to the presence of high levels of the protective disaccharide trehalose in the dry state. Tardigrades and other anhydrobiotic animals provide a unique opportunity to study the effects of space exposure on metabolically inactive but vital metazoans.

Validation of 2D flood models with insurance claims

NASA Astrophysics Data System (ADS)

Zischg, Andreas Paul; Mosimann, Markus; Bernet, Daniel Benjamin; Röthlisberger, Veronika

2018-02-01

Flood impact modelling requires reliable models for the simulation of flood processes. In recent years, flood inundation models have been remarkably improved and widely used for flood hazard simulation, flood exposure and loss analyses. In this study, we validate a 2D inundation model for the purpose of flood exposure analysis at the river reach scale. We validate the BASEMENT simulation model with insurance claims using conventional validation metrics. The flood model is established on the basis of available topographic data in a high spatial resolution for four test cases. The validation metrics were calculated with two different datasets; a dataset of event documentations reporting flooded areas and a dataset of insurance claims. The model fit relating to insurance claims is in three out of four test cases slightly lower than the model fit computed on the basis of the observed inundation areas. This comparison between two independent validation data sets suggests that validation metrics using insurance claims can be compared to conventional validation data, such as the flooded area. However, a validation on the basis of insurance claims might be more conservative in cases where model errors are more pronounced in areas with a high density of values at risk.

Exposure assessment of process-related contaminants in food by biomarker monitoring

DOE PAGES

Rietjens, Ivonne M. C. M.; Dussort, P.; Gunther, Helmut; ...

2018-01-04

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state ofmore » the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. Here, in spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.« less

Exposure assessment of process-related contaminants in food by biomarker monitoring

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

Rietjens, Ivonne M. C. M.; Dussort, P.; Gunther, Helmut

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state ofmore » the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. Here, in spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.« less

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists.

PubMed

Miller, Steven L; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Prager, Eric M; Almeida-Suhett, Camila P; Apland, James P; Braga, Maria F M

2015-04-15

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD50 of 62μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2mg/kg, administered 20 min after soman exposure (1.2×LD50), terminated seizures. ATS at 0.5mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1h post-exposure, prevents brain pathology and behavioral deficits. Published by Elsevier Inc.

Consumer exposure scenarios: development, challenges and possible solutions.

PubMed

Van Engelen, J G M; Heinemeyer, G; Rodriguez, C

2007-12-01

Exposure scenarios (ES) under REACH (Registration, Evaluation, and Authorisation of Chemicals; new EU legislation) aim to describe safe conditions of product and substance use. Both operational conditions and risk management measures (RMMs) are part of the ES. For consumer use of chemicals, one of the challenges will be to identify all of the consumer uses of a given chemical and then quantify the exposure derived from each of them. Product use categories can be established to identify in a systematic fashion how products are used. These product categories comprise products that are used similarly (e.g. paints, adhesives). They deliver information about product use characteristics, and provide an easy-to-handle tool for exchanging standardised information. For practical reasons, broad ES will have to be developed, which cover a wide range of products and use. The challenge will be to define them broadly, but not in a way that they provide such an overestimation of exposure that a next iteration or a more complex model is always needed. Tiered and targeted approaches for estimation of exposure at the right level of detail may offer the best solution. RMMs relevant for consumers include those inherent to product design (controllable) and those that are communicated to consumers as directions for use (non-controllable). Quantification of the effect of non-controllable RMMs on consumer exposure can prove to be difficult. REACH requires aggregation of exposure from all relevant identified sources. Development of appropriate methodology for realistic aggregation of exposure will be no small challenge and will likely require probabilistic approaches and comprehensive databases on populations' habits, practices and behaviours. REACH regulation aims at controlling the use of chemicals so that exposure to every chemical can be demonstrated to be safe for consumers, workers, and the environment when considered separately, but also when considered in an integrated way. This integration will be another substantial challenge for the future.

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

Frank, Evan A.; Birch, M. Eileen; Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu

Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wallmore » CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector function of AMs. • MyD88 may be a potential target for intervention in CNT lung exposures.« less

Neutron Environment Calculations for Low Earth Orbit

NASA Technical Reports Server (NTRS)

Clowdsley, M. S.; Wilson, J. W.; Shinn, J. L.; Badavi, F. F.; Heinbockel, J. H.; Atwell, W.

2001-01-01

The long term exposure of astronauts on the developing International Space Station (ISS) requires an accurate knowledge of the internal exposure environment for human risk assessment and other onboard processes. The natural environment is moderated by the solar wind, which varies over the solar cycle. The HZETRN high charge and energy transport code developed at NASA Langley Research Center can be used to evaluate the neutron environment on ISS. A time dependent model for the ambient environment in low earth orbit is used. This model includes GCR radiation moderated by the Earth's magnetic field, trapped protons, and a recently completed model of the albedo neutron environment formed through the interaction of galactic cosmic rays with the Earth's atmosphere. Using this code, the neutron environments for space shuttle missions were calculated and comparisons were made to measurements by the Johnson Space Center with onboard detectors. The models discussed herein are being developed to evaluate the natural and induced environment data for the Intelligence Synthesis Environment Project and eventual use in spacecraft optimization.

Toxicokinetic Model Development for the Insensitive Munitions Component 2,4-Dinitroanisole.

PubMed

Sweeney, Lisa M; Goodwin, Michelle R; Hulgan, Angela D; Gut, Chester P; Bannon, Desmond I

2015-01-01

The Armed Forces are developing new explosives that are less susceptible to unintentional detonation (insensitive munitions [IMX]). 2,4-Dinitroanisole (DNAN) is a component of IMX. Toxicokinetic data for DNAN are required to support interpretation of toxicology studies and refinement of dose estimates for human risk assessment. Male Sprague-Dawley rats were dosed by gavage (5, 20, or 80 mg DNAN/kg), and blood and tissue samples were analyzed to determine the levels of DNAN and its metabolite 2,4-dinitrophenol (DNP). These data and data from the literature were used to develop preliminary physiologically based pharmacokinetic (PBPK) models. The model simulations indicated saturable metabolism of DNAN in rats at higher tested doses. The PBPK model was extrapolated to estimate the toxicokinetics of DNAN and DNP in humans, allowing the estimation of human-equivalent no-effect levels of DNAN exposure from no-observed adverse effect levels determined in laboratory animals, which may guide the selection of exposure limits for DNAN. © The Author(s) 2015.

Health risk assessment of exposure to TriCresyl Phosphates (TCPs) in aircraft: a commentary.

PubMed

de Ree, Hans; van den Berg, Martin; Brand, Teus; Mulder, Gerard J; Simons, Ries; Veldhuijzen van Zanten, Brinio; Westerink, Remco H S

2014-12-01

Possible exposure to TriCresyl Phosphates (TCPs) has led to concerns among airline crew members. One isomer, Tri-ortho-Cresyl Phosphate (ToCP) is known to be neurotoxic and exposure to ToCP via contaminated cabin air has been suggested to be associated with the alleged Aerotoxic syndrome. The symptoms associated with Aerotoxic syndrome are diverse, including headaches, loss of balance, numbness and neurobehavioral abnormalities such as emotional instability, depression and cognitive dysfunction. Other ortho-isomers are toxic as well, but the non-ortho isomers are regarded as less toxic. In a collaborative effort to increase insight into the possible association between exposure to TCPs via contaminated cabin air and Aerotoxic syndrome, we performed an exposure- and toxicological risk assessment. Measurements in KLM 737 aircraft have demonstrated the presence of non-ortho isomers in low concentrations, though ToCP and other ortho-isomers could not be detected. Based on this exposure assessment, we established a toxicological risk model that also takes into account human differences in bioactivation and detoxification to derive a hazard quotient. From this model it appears unlikely that the health effects and alleged Aerotoxic syndrome are due to exposure to ToCP. Alternative explanations for the reported symptoms are discussed, but evaluation of the current findings in light of the criteria for occupational disease leads to the conclusion that the Aerotoxic Syndrome cannot be regarded as such. Additional research is thus required to unravel the underlying causes for the reported health complaints. Copyright © 2014 Elsevier Inc. All rights reserved.

Emissions from residential energy use dominate exposure to ambient fine particulate matter in India

NASA Astrophysics Data System (ADS)

Conibear, L.; Butt, E. W.; Knote, C. J.; Arnold, S.; Spracklen, D. V.

2017-12-01

Exposure to ambient particulate matter of less than 2.5 µm in diameter (PM2.5) is a leading cause of disease burden in India. Information on the source contributions to the burden of disease attributable to ambient PM2.5 exposure is critical to support the national and sub-national control of air pollution. Previous studies analysing the contributions of different emission sectors to disease burden in India have been limited by coarse model resolutions and a lack of extensive PM2.5 observations before 2016. We use a regional numerical weather prediction model online-coupled with chemistry, evaluated against extensive surface observations, to make the first high resolution study of the contributions of seven emission sectors to the disease burden associated with ambient PM2.5 exposure in India. We find that residential energy use is the dominant contributing emission sector. Removing air pollution emissions from residential energy use would reduce population-weighted annual mean ambient PM2.5 concentrations by 52%, reducing the number of premature mortalities caused by exposure to ambient PM2.5 by 26%, equivalent to 268,000 (95% uncertainty interval (95UI): 167,000-360,000) lives every year. The smaller fractional reduction in mortality burden is due to the non-linear exposure-response relationship at the high PM2.5 concentrations observed across India and consequently large reductions in emissions are required to reduce the health burden from ambient PM2.5 exposure in India. Keywords: ambient air quality, India, residential energy use, health impact, particulate matter, WRF-Chem

Spatial-temporal modeling of the association between air pollution exposure and preterm birth: identifying critical windows of exposure.

PubMed

Warren, Joshua; Fuentes, Montserrat; Herring, Amy; Langlois, Peter

2012-12-01

Exposure to high levels of air pollution during the pregnancy is associated with increased probability of preterm birth (PTB), a major cause of infant morbidity and mortality. New statistical methodology is required to specifically determine when a particular pollutant impacts the PTB outcome, to determine the role of different pollutants, and to characterize the spatial variability in these results. We develop a new Bayesian spatial model for PTB which identifies susceptible windows throughout the pregnancy jointly for multiple pollutants (PM(2.5) , ozone) while allowing these windows to vary continuously across space and time. We geo-code vital record birth data from Texas (2002-2004) and link them with standard pollution monitoring data and a newly introduced EPA product of calibrated air pollution model output. We apply the fully spatial model to a region of 13 counties in eastern Texas consisting of highly urban as well as rural areas. Our results indicate significant signal in the first two trimesters of pregnancy with different pollutants leading to different critical windows. Introducing the spatial aspect uncovers critical windows previously unidentified when space is ignored. A proper inference procedure is introduced to correctly analyze these windows. © 2012, The International Biometric Society.

Marginal Structural Cox Models for Estimating the Association Between β-Interferon Exposure and Disease Progression in a Multiple Sclerosis Cohort

PubMed Central

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Zhao, Yinshan; Shirani, Afsaneh; Kingwell, Elaine; Evans, Charity; van der Kop, Mia; Oger, Joel; Tremlett, Helen

2014-01-01

Longitudinal observational data are required to assess the association between exposure to β-interferon medications and disease progression among relapsing-remitting multiple sclerosis (MS) patients in the “real-world” clinical practice setting. Marginal structural Cox models (MSCMs) can provide distinct advantages over traditional approaches by allowing adjustment for time-varying confounders such as MS relapses, as well as baseline characteristics, through the use of inverse probability weighting. We assessed the suitability of MSCMs to analyze data from a large cohort of 1,697 relapsing-remitting MS patients in British Columbia, Canada (1995–2008). In the context of this observational study, which spanned more than a decade and involved patients with a chronic yet fluctuating disease, the recently proposed “normalized stabilized” weights were found to be the most appropriate choice of weights. Using this model, no association between β-interferon exposure and the hazard of disability progression was found (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity analyses, truncated normalized unstabilized weights were used in additional MSCMs and to construct inverse probability weight-adjusted survival curves; the findings did not change. Additionally, qualitatively similar conclusions from approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence in the findings. PMID:24939980

[Rational estimation of drug dosage through pharmacometric modeling: The case of a long-acting depot antipsychotic].

PubMed

Simon, N; Azorin, J-M

2015-04-01

Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named "population approach") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic polymorphism of the P450 2D6 cytochrome) and showed that with an injectable sustained release form, a monthly dose of 400mg would allow 90% of patients to gain exposure in the therapeutic range. In case of a drug inhibition and/or of a slow metabolizing profile, dosage adjustment is necessary. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Full-chain health impact assessment of traffic-related air pollution and childhood asthma.

PubMed

Khreis, Haneen; de Hoogh, Kees; Nieuwenhuijsen, Mark J

2018-05-01

Asthma is the most common chronic disease in children. Traffic-related air pollution (TRAP) may be an important exposure contributing to its development. In the UK, Bradford is a deprived city suffering from childhood asthma rates higher than national and regional averages and TRAP is of particular concern to the local communities. We estimated the burden of childhood asthma attributable to air pollution and specifically TRAP in Bradford. Air pollution exposures were estimated using a newly developed full-chain exposure assessment model and an existing land-use regression model (LUR). We estimated childhood population exposure to NO x and, by conversion, NO 2 at the smallest census area level using a newly developed full-chain model knitting together distinct traffic (SATURN), vehicle emission (COPERT) and atmospheric dispersion (ADMS-Urban) models. We compared these estimates with measurements and estimates from ESCAPE's LUR model. Using the UK incidence rate for childhood asthma, meta-analytical exposure-response functions, and estimates from the two exposure models, we estimated annual number of asthma cases attributable to NO 2 and NO x in Bradford, and annual number of asthma cases specifically attributable to traffic. The annual average census tract levels of NO 2 and NO x estimated using the full-chain model were 15.41 and 25.68 μg/m 3 , respectively. On average, 2.75 μg/m 3 NO 2 and 4.59 μg/m 3 NO x were specifically contributed by traffic, without minor roads and cold starts. The annual average census tract levels of NO 2 and NO x estimated using the LUR model were 21.93 and 35.60 μg/m 3 , respectively. The results indicated that up to 687 (or 38% of all) annual childhood asthma cases in Bradford may be attributable to air pollution. Up to 109 cases (6%) and 219 cases (12%) may be specifically attributable to TRAP, with and without minor roads and cold starts, respectively. This is the first study undertaking full-chain health impact assessment of TRAP and childhood asthma in a disadvantaged population with public concern about TRAP. It further adds to scarce literature exploring the impact of different exposure assessments. In conservative estimates, air pollution and TRAP are estimated to cause a large, but largely preventable, childhood asthma burden. Future progress with childhood asthma requires a move beyond the prevalent disease control-based approach toward asthma prevention. Copyright © 2018 Elsevier Ltd. 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.

Effects of low-level prenatal lead exposure on child IQ at 4 and 8 years in a UK birth cohort study.

PubMed

Taylor, Caroline M; Kordas, Katarzyna; Golding, Jean; Emond, Alan M

2017-09-01

The association between childhood exposure to lead (Pb) and deficits in cognitive function is well established. The association with prenatal exposure, however, is not well understood, even though the potential adverse effects are equally important. To evaluate the association between low prenatal exposure to lead and IQ in children, to determine whether there were sex differences in the associations, and to evaluate the moderation effect of prenatal Pb exposure on child IQ. Whole blood samples from pregnant women enrolled in ALSPAC (n=4285) and from offspring at age 30 months (n=235) were analysed for Pb. Associations between prenatal blood lead concentrations (B-Pb) and child IQ at age 4 and 8 years (WPPSI and WISC-III, respectively) were examined in adjusted regression models. There was no association of prenatal lead exposure with child IQ at 4 or 8 years old in adjusted regression models, and no moderation of the association between child B-Pb and IQ. However, there was a positive association for IQ at age 8 years in girls with a predicted increase in IQ (points) per 1μg/dl of: verbal 0.71, performance 0.57, total 0.73. In boys, the coefficients tended to be negative (-0.15, -0.42 and -0.29 points, respectively). Prenatal lead exposure was not associated with adverse effects on child IQ at age 4 or 8 years in this study. There was, however, some evidence to suggest that boys are more susceptible than girls to prenatal exposure to lead. Further investigation in other cohorts is required. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Pediatric tuberculous meningitis: Model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children.

PubMed

Savic, R M; Ruslami, R; Hibma, J E; Hesseling, A; Ramachandran, G; Ganiem, A R; Swaminathan, S; McIlleron, H; Gupta, A; Thakur, K; van Crevel, R; Aarnoutse, R; Dooley, K E

2015-12-01

Pediatric tuberculous meningitis (TBM) is a highly morbid, often fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic (PK) and outcomes data from adult TBM trials plus plasma PK data from children. A population PK/pharmacodynamic (PD) model using adult data defined rifampin target exposures (plasma area under the curve (AUC)0-24 = 92 mg*h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously (i.v.). From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19-33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results. © 2015 American Society for Clinical Pharmacology and Therapeutics.

DEVELOPMENT OF CHEMICAL METHODS TO CHARACTERIZE EXPOSURE TO EDCS IN THE NEUSE RIVER BASIN

EPA Science Inventory

To develop a quantitative health and environmental risk assessment of endocrine disrupting compounds (EDCs), information on exposures is essential. A full exposure assessment has complex requirements that require preliminary information to direct further research in this area....

Radiation combined injury models to study the effects of interventions and wound biomechanics.

PubMed

Zawaski, Janice A; Yates, Charles R; Miller, Duane D; Kaffes, Caterina C; Sabek, Omaima M; Afshar, Solmaz F; Young, Daniel A; Yang, Yunzhi; Gaber, M Waleed

2014-12-01

In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and burn and/or wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize wound closure. The first was an open wound model in mice to study the effect of wound size in combination with whole-body 6 Gy irradiation on the rate of wound closure, animal weight and survival (morbidity). In this model the addition of interventions, wound closure, subcutaneous vehicle injection, topical antiseptic and topical antibiotics were studied to measure their effect on healing and survival. The second was a rat closed wound model to study the biomechanical properties of a healed wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and wound pathology by staining with hematoxylin and eosin, trichrome, CD68 and Ki67. In the mouse open wound model, we found that wound size and morbidity were positively correlated, while wound size and survival were negatively correlated. Regardless of the wound size, the addition of radiation exposure delayed the healing of the wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ∼9 days. In the rat closed wound model we found that radiation exposure significantly decreased all wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of collagen/epithelial hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing wound size in combination with radiation exposure. We also demonstrated that the most effective interventions mitigated insensible fluid loss, which could help to define the most appropriate requirements of a successful countermeasure.

Modeling human risk: Cell & molecular biology in context

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

NONE

It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small butmore » highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.« less

Estimation of respirable dust exposure among coal miners in South Africa.

PubMed

Naidoo, Rajen; Seixas, Noah; Robins, Thomas

2006-06-01

The use of retrospective occupational hygiene data for epidemiologic studies is useful in determining exposure-outcome relationships, but the potential for exposure misclassification is high. Although dust sampling in the South African coal industry has been a legal requirement for several decades, these historical data are not readily adequate for estimating past exposures. This study describes the respirable coal mine dust levels in three South African coal mines over time. Each of the participating mining operations had well-documented dust sampling information that was used to describe historical trends in dust exposure. Investigator-collected personal dust samples were taken using standardized techniques from the face, backbye (underground jobs not at the coal face), and surface from 50 miners at each mine, repeated over three sampling cycles. Job histories and exposure information was obtained from a sample of 684 current miners and 188 ex-miners. Linear models were developed to estimate the exposure levels associated with work in each mine, exposure zone, and over time using a combination of operator-collected historical data and investigator-collected samples. The estimated levels were then combined with work history information to calculate cumulative exposure metrics for the miner cohort. The mean historical and investigator-collected respirable dust levels were within international norms and South African standards. Silica content of the dust samples was also below the 5% regulatory action level. Mean respirable dust concentrations at the face, based on investigator-collected samples, were 0.9 mg/m(3), 1.3 mg/m(3), and 1.9 mg/m(3) at Mines 1, 2, and 3, respectively. The operator-collected samples showed considerable variability across exposure zones, mines, and time, with the annual means at the face ranging from 0.4 mg/m(3) to 2.9 mg/m(3). Statistically significant findings were found between operator- and investigator-collected dust samples. Model-based arithmetic mean dust estimates at the face were 1.2 mg/m(3), 2.0 mg/m(3), and 0.9 mg/m(3) for Mines 1, 2, and 3, respectively. Using these levels, the mean cumulative exposure for the cohort was 56.8 mg-years/m(3). Current miners had a mean cumulative exposure of 66.5 mg-years/m(3), compared with ex-miners of 26.8 mg-years/m(3). Improvements in dust management or the use of different sampling equipment could account for the significant differences seen between operator- and investigator-collected data. Regression modeling for estimating mean dust levels over time using combined historical and investigator-collected data seems a reasonable method and useful in constructing models to describe cumulative exposures in a cohort of current and ex-miners.

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

Sisniega, A.; Vaquero, J. J., E-mail: juanjose.vaquero@uc3m.es; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid ES28007

Purpose: The availability of accurate and simple models for the estimation of x-ray spectra is of great importance for system simulation, optimization, or inclusion of photon energy information into data processing. There is a variety of publicly available tools for estimation of x-ray spectra in radiology and mammography. However, most of these models cannot be used directly for modeling microfocus x-ray sources due to differences in inherent filtration, energy range and/or anode material. For this reason the authors propose in this work a new model for the simulation of microfocus spectra based on existing models for mammography and radiology, modifiedmore » to compensate for the effects of inherent filtration and energy range. Methods: The authors used the radiology and mammography versions of an existing empirical model [tungsten anode spectral model interpolating polynomials (TASMIP)] as the basis of the microfocus model. First, the authors estimated the inherent filtration included in the radiology model by comparing the shape of the spectra with spectra from the mammography model. Afterwards, the authors built a unified spectra dataset by combining both models and, finally, they estimated the parameters of the new version of TASMIP for microfocus sources by calibrating against experimental exposure data from a microfocus x-ray source. The model was validated by comparing estimated and experimental exposure and attenuation data for different attenuating materials and x-ray beam peak energy values, using two different x-ray tubes. Results: Inherent filtration for the radiology spectra from TASMIP was found to be equivalent to 1.68 mm Al, as compared to spectra obtained from the mammography model. To match the experimentally measured exposure data the combined dataset required to apply a negative filtration of about 0.21 mm Al and an anode roughness of 0.003 mm W. The validation of the model against real acquired data showed errors in exposure and attenuation in line with those reported for other models for radiology or mammography. Conclusions: A new version of the TASMIP model for the estimation of x-ray spectra in microfocus x-ray sources has been developed and validated experimentally. Similarly to other versions of TASMIP, the estimation of spectra is very simple, involving only the evaluation of polynomial expressions.« less

Models to study gravitational biology of Mammalian reproduction

NASA Technical Reports Server (NTRS)

Tou, Janet; Ronca, April; Grindeland, Richard; Wade, Charles

2002-01-01

Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.

Space Radiation Analysis for the Mark III Spacesuit

NASA Technical Reports Server (NTRS)

Atwell, Bill; Boeder, Paul; Ross, Amy

2013-01-01

NASA has continued the development of space systems by applying and integrating improved technologies that include safety issues, lightweight materials, and electronics. One such area is extravehicular (EVA) spacesuit development with the most recent Mark III spacesuit. In this paper the Mark III spacesuit is discussed in detail that includes the various components that comprise the spacesuit, materials and their chemical composition that make up the spacesuit, and a discussion of the 3-D CAD model of the Mark III spacesuit. In addition, the male (CAM) and female (CAF) computerized anatomical models are also discussed in detail. We combined the spacesuit and the human models, that is, we developed a method of incorporating the human models in the Mark III spacesuit and performed a ray-tracing technique to determine the space radiation shielding distributions for all of the critical body organs. These body organ shielding distributions include the BFO (Blood-Forming Organs), skin, eye, lungs, stomach, and colon, to name a few, for both the male and female. Using models of the trapped (Van Allen) proton and electron environments, radiation exposures were computed for a typical low earth orbit (LEO) EVA mission scenario including the geostationary (GEO) high electron environment. A radiation exposure assessment of these mission scenarios is made to determine whether or not the crew radiation exposure limits are satisfied, and if not, the additional shielding material that would be required to satisfy the crew limits.

Parametric Modeling for Fluid Systems

NASA Technical Reports Server (NTRS)

Pizarro, Yaritzmar Rosario; Martinez, Jonathan

2013-01-01

Fluid Systems involves different projects that require parametric modeling, which is a model that maintains consistent relationships between elements as is manipulated. One of these projects is the Neo Liquid Propellant Testbed, which is part of Rocket U. As part of Rocket U (Rocket University), engineers at NASA's Kennedy Space Center in Florida have the opportunity to develop critical flight skills as they design, build and launch high-powered rockets. To build the Neo testbed; hardware from the Space Shuttle Program was repurposed. Modeling for Neo, included: fittings, valves, frames and tubing, between others. These models help in the review process, to make sure regulations are being followed. Another fluid systems project that required modeling is Plant Habitat's TCUI test project. Plant Habitat is a plan to develop a large growth chamber to learn the effects of long-duration microgravity exposure to plants in space. Work for this project included the design and modeling of a duct vent for flow test. Parametric Modeling for these projects was done using Creo Parametric 2.0.

TSK 6498 - DEVELOPMENT OF MOLECULAR INDICATORS OF EXPOSURE TO ENDOCRINE DISRUPTING COMPOUNDS, PESTICIDES & OTHER XENOBIOTIC AGENTS.

EPA Science Inventory

Accurate and precise characterization of exposure of aquatic ecological resources to chemical stressors is required for ecological risk assessment. Within this assessment, the study of the vulnerability of these resources requires comparative exposure assessments across watershe...

Activity measurement and effective dose modelling of natural radionuclides in building material.

PubMed

Maringer, F J; Baumgartner, A; Rechberger, F; Seidel, C; Stietka, M

2013-11-01

In this paper the assessment of natural radionuclides' activity concentration in building materials, calibration requirements and related indoor exposure dose models is presented. Particular attention is turned to specific improvements in low-level gamma-ray spectrometry to determine the activity concentration of necessary natural radionuclides in building materials with adequate measurement uncertainties. Different approaches for the modelling of the effective dose indoor due to external radiation resulted from natural radionuclides in building material and results of actual building material assessments are shown. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Inorganic Arsenic, Methylated Arsenicals, and Arsenobetaine on Atherosclerosis in the apoE−/− Mouse Model and the Role of As3mt-Mediated Methylation

PubMed Central

Negro Silva, Luis Fernando; Lemaire, Maryse; Lemarié, Catherine A.; Plourde, Dany; Bolt, Alicia M.; Chiavatti, Christopher; Bohle, D. Scott; Slavkovich, Vesna; Graziano, Joseph H.; Lehoux, Stéphanie

2017-01-01

Background: Arsenic is metabolized through a series of oxidative methylation reactions by arsenic (3) methyltransferase (As3MT) to yield methylated intermediates. Although arsenic exposure is known to increase the risk of atherosclerosis, the contribution of arsenic methylation and As3MT remains undefined. Objectives: Our objective was to define whether methylated arsenic intermediates were proatherogenic and whether arsenic biotransformation by As3MT was required for arsenic-enhanced atherosclerosis. Methods: We utilized the apoE−/− mouse model to compare atherosclerotic plaque size and composition after inorganic arsenic, methylated arsenical, or arsenobetaine exposure in drinking water. We also generated apoE−/−/As3mt−/− double knockout mice to test whether As3MT-mediated biotransformation was required for the proatherogenic effects of inorganic arsenite. Furthermore, As3MT expression and function were assessed in in vitro cultures of plaque-resident cells. Finally, bone marrow transplantation studies were performed to define the contribution of As3MT-mediated methylation in different cell types to the development of atherosclerosis after inorganic arsenic exposure. Results: We found that methylated arsenicals, but not arsenobetaine, are proatherogenic and that As3MT is required for arsenic to induce reactive oxygen species and promote atherosclerosis. Importantly, As3MT was expressed and functional in multiple plaque-resident cell types, and transplant studies indicated that As3MT is required in extrahepatic tissues to promote atherosclerosis. Conclusion: Taken together, our findings indicate that As3MT acts to promote cardiovascular toxicity of arsenic and suggest that human AS3MT SNPs that correlate with enzyme function could predict those most at risk to develop atherosclerosis among the millions that are exposed to arsenic. https://doi.org/10.1289/EHP806 PMID:28728140

A hybrid solution using computational prediction and measured data to accurately determine process corrections with reduced overlay sampling

NASA Astrophysics Data System (ADS)

Noyes, Ben F.; Mokaberi, Babak; Mandoy, Ram; Pate, Alex; Huijgen, Ralph; McBurney, Mike; Chen, Owen

2017-03-01

Reducing overlay error via an accurate APC feedback system is one of the main challenges in high volume production of the current and future nodes in the semiconductor industry. The overlay feedback system directly affects the number of dies meeting overlay specification and the number of layers requiring dedicated exposure tools through the fabrication flow. Increasing the former number and reducing the latter number is beneficial for the overall efficiency and yield of the fabrication process. An overlay feedback system requires accurate determination of the overlay error, or fingerprint, on exposed wafers in order to determine corrections to be automatically and dynamically applied to the exposure of future wafers. Since current and future nodes require correction per exposure (CPE), the resolution of the overlay fingerprint must be high enough to accommodate CPE in the overlay feedback system, or overlay control module (OCM). Determining a high resolution fingerprint from measured data requires extremely dense overlay sampling that takes a significant amount of measurement time. For static corrections this is acceptable, but in an automated dynamic correction system this method creates extreme bottlenecks for the throughput of said system as new lots have to wait until the previous lot is measured. One solution is using a less dense overlay sampling scheme and employing computationally up-sampled data to a dense fingerprint. That method uses a global fingerprint model over the entire wafer; measured localized overlay errors are therefore not always represented in its up-sampled output. This paper will discuss a hybrid system shown in Fig. 1 that combines a computationally up-sampled fingerprint with the measured data to more accurately capture the actual fingerprint, including local overlay errors. Such a hybrid system is shown to result in reduced modelled residuals while determining the fingerprint, and better on-product overlay performance.

Judging The Efficacy of Anthrax Fumigations

DTIC Science & Technology

2003-11-20

FUMIGATIONS IN RESPONSE TO 2001 ANTHRAX ATTACKS Most fumigations modeled after biomedical sterilization processes, with established ranges for process...exposure to VHP All BIs recovered aseptically negative for growth of B. stearothermophilus Positive control BIs (5% of BIs) demonstrate growth Negative...of 10 zones was re-fumigated; second fumigation met all requirements HISTORICAL CRITERIA FOR SUCCESSFUL TREATMENT Biomedical sterilizations – FDA

STATUS OF SEMI-CONTINUOUS MONITORING INSTRUMENTATION FOR GAS AND WATER SOLUBLE PARTICLE COMPONENTS NEEDED FOR DIAGNOSTIC TESTING OF AMBIENT AIR QUALITY SIMULATION MODELS

EPA Science Inventory

This status report documents the effort by the National Exposure Research Laboratory (NERL), Office of Research and Development (ORD) of the U.S. Environmental Protection Agency (U.S. EPA) to provide methods of measurement, including calibration procedures, that meet the requir...

OVERVIEW OF SESSION GOALS WITH EXAMPLES OF THE EVOLUTION OF MULTI-MEDIA MODELING FOR INFORMING REGULATORY DECISIONS AT THE U.S. ENVIRONMENTAL PROTECTION AGENCY

EPA Science Inventory

The presence of high concentrations of mercury in fish tissue worldwide has resulted in increased concern of the exposure risks of fish-eating populations. To develop effective regulations and management practices requires a solid quantitative assessment of the entire mercury ex...

Impact of a Teacher-as-Coach Model: Improving Paraprofessionals Fidelity of Implementation of Discrete Trial Training for Students with Moderate-to-Severe Developmental Disabilities

ERIC Educational Resources Information Center

Mason, Rose A.; Schnitz, Alana G.; Wills, Howard P.; Rosenbloom, Raia; Kamps, Debra M.; Bast, Darcey

2017-01-01

Ensuring educational progress for students with moderate-to-severe developmental disabilities requires exposure to well executed evidence-based practices. This necessitates that the special education workforce, including paraprofessionals, be well-trained. Yet evidence regarding effective training mechanisms for paraprofessionals is limited. A…

Advances in EPA’s Rapid Exposure and Dosimetry Project (Interagency Alternatives Assessment Webinar)

EPA Science Inventory

Estimates of human and ecological exposures are required as critical input to risk-based prioritization and screening of chemicals. The CSS Rapid Exposure and Dosimetry project seeks to develop the data, tools, and evaluation approaches required to generate rapid and scientifical...

The solar UV exposure time required for vitamin D3 synthesis in the human body estimated by numerical simulation and observation in Japan

NASA Astrophysics Data System (ADS)

Nakajima, Hideaki; Miyauchi, Masaatsu; Hirai, Chizuko

2013-04-01

After the discovery of Antarctic ozone hole, the negative effect of exposure of human body to harmful solar ultraviolet (UV) radiation is widely known. However, there is positive effect of exposure to UV radiation, i.e., vitamin D synthesis. Although the importance of solar UV radiation for vitamin D3 synthesis in the human body is well known, the solar exposure time required to prevent vitamin D deficiency has not been well determined. This study attempted to identify the time of solar exposure required for vitamin D3 synthesis in the body by season, time of day, and geographic location (Sapporo, Tsukuba, and Naha, in Japan) using both numerical simulations and observations. According to the numerical simulation for Tsukuba at noon in July under a cloudless sky, 2.3 min of solar exposure are required to produce 5.5 μg vitamin D3 per 600 cm2 skin. This quantity of vitamin D represents the recommended intake for an adult by the Ministry of Health, Labour and Welfare, and the 2010 Japanese Dietary Reference Intakes (DRIs). In contrast, it took 49.5 min to produce the same amount of vitamin D3 at Sapporo in the northern part of Japan in December, at noon under a cloudless sky. The necessary exposure time varied considerably with the time of the day. For Tsukuba at noon in December, 14.5 min were required, but at 09:00 68.7 min were required and at 15:00 175.8 min were required for the same meteorological conditions. Naha receives high levels of UV radiation allowing vitamin D3 synthesis almost throughout the year. According to our results, we are further developing an index to quantify the necessary time of UV radiation exposure to produce required amount of vitamin D3 from a UV radiation data.

Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models

NASA Astrophysics Data System (ADS)

Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

2015-04-01

The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow pitch angle (PA) and east-west (EW) effects. Within SAA, the EW anisotropy results in different level of exposure to each side of the ISS Zvezda SM, allowing angular evaluation of the anisotropic proton spectrum. While the combined magnitude of PA and EW effects at LEO depends on a multitude of factors such as trapped proton energy, orientation and altitude of the spacecraft along the velocity vector, this paper draws quantitative conclusions on the combined anisotropic magnitude differences within ISS SM target point between AP8 and AP9 models.

Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models.

PubMed

Badavi, Francis F; Walker, Steven A; Santos Koos, Lindsey M

2015-04-01

The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow pitch angle (PA) and east-west (EW) effects. Within SAA, the EW anisotropy results in different level of exposure to each side of the ISS Zvezda SM, allowing angular evaluation of the anisotropic proton spectrum. While the combined magnitude of PA and EW effects at LEO depends on a multitude of factors such as trapped proton energy, orientation and altitude of the spacecraft along the velocity vector, this paper draws quantitative conclusions on the combined anisotropic magnitude differences within ISS SM target point between AP8 and AP9 models. Copyright © 2015 The Committee on Space Research (COSPAR). All rights reserved.

40 CFR 158.1070 - Post-application exposure data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... applicable residue dissipation data to dermal exposure data is required. 3. Turf grass transferable residue dissipation data are required when pesticides are applied to turf grass. Dislodgeable foliar residue dissipation data are required when pesticides are applied to the foliage of plants other than turf grass. 4...

40 CFR 158.1070 - Post-application exposure data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... applicable residue dissipation data to dermal exposure data is required. 3. Turf grass transferable residue dissipation data are required when pesticides are applied to turf grass. Dislodgeable foliar residue dissipation data are required when pesticides are applied to the foliage of plants other than turf grass. 4...

Revealing the underlying drivers of disaster risk: a global analysis

NASA Astrophysics Data System (ADS)

Peduzzi, Pascal

2017-04-01

Disasters events are perfect examples of compound events. Disaster risk lies at the intersection of several independent components such as hazard, exposure and vulnerability. Understanding the weight of each component requires extensive standardisation. Here, I show how footprints of past disastrous events were generated using GIS modelling techniques and used for extracting population and economic exposures based on distribution models. Using past event losses, it was possible to identify and quantify a wide range of socio-politico-economic drivers associated with human vulnerability. The analysis was applied to about nine thousand individual past disastrous events covering earthquakes, floods and tropical cyclones. Using a multiple regression analysis on these individual events it was possible to quantify each risk component and assess how vulnerability is influenced by various hazard intensities. The results show that hazard intensity, exposure, poverty, governance as well as other underlying factors (e.g. remoteness) can explain the magnitude of past disasters. Analysis was also performed to highlight the role of future trends in population and climate change and how this may impacts exposure to tropical cyclones in the future. GIS models combined with statistical multiple regression analysis provided a powerful methodology to identify, quantify and model disaster risk taking into account its various components. The same methodology can be applied to various types of risk at local to global scale. This method was applied and developed for the Global Risk Analysis of the Global Assessment Report on Disaster Risk Reduction (GAR). It was first applied on mortality risk in GAR 2009 and GAR 2011. New models ranging from global assets exposure and global flood hazard models were also recently developed to improve the resolution of the risk analysis and applied through CAPRA software to provide probabilistic economic risk assessments such as Average Annual Losses (AAL) and Probable Maximum Losses (PML) in GAR 2013 and GAR 2015. In parallel similar methodologies were developed to highlitght the role of ecosystems for Climate Change Adaptation (CCA) and Disaster Risk Reduction (DRR). New developments may include slow hazards (such as e.g. soil degradation and droughts), natech hazards (by intersecting with georeferenced critical infrastructures) The various global hazard, exposure and risk models can be visualized and download through the PREVIEW Global Risk Data Platform.

Soil and Water Assessment Tool model predictions of annual maximum pesticide concentrations in high vulnerability watersheds.

PubMed

Winchell, Michael F; Peranginangin, Natalia; Srinivasan, Raghavan; Chen, Wenlin

2018-05-01

Recent national regulatory assessments of potential pesticide exposure of threatened and endangered species in aquatic habitats have led to increased need for watershed-scale predictions of pesticide concentrations in flowing water bodies. This study was conducted to assess the ability of the uncalibrated Soil and Water Assessment Tool (SWAT) to predict annual maximum pesticide concentrations in the flowing water bodies of highly vulnerable small- to medium-sized watersheds. The SWAT was applied to 27 watersheds, largely within the midwest corn belt of the United States, ranging from 20 to 386 km 2 , and evaluated using consistent input data sets and an uncalibrated parameterization approach. The watersheds were selected from the Atrazine Ecological Exposure Monitoring Program and the Heidelberg Tributary Loading Program, both of which contain high temporal resolution atrazine sampling data from watersheds with exceptionally high vulnerability to atrazine exposure. The model performance was assessed based upon predictions of annual maximum atrazine concentrations in 1-d and 60-d durations, predictions critical in pesticide-threatened and endangered species risk assessments when evaluating potential acute and chronic exposure to aquatic organisms. The simulation results showed that for nearly half of the watersheds simulated, the uncalibrated SWAT model was able to predict annual maximum pesticide concentrations within a narrow range of uncertainty resulting from atrazine application timing patterns. An uncalibrated model's predictive performance is essential for the assessment of pesticide exposure in flowing water bodies, the majority of which have insufficient monitoring data for direct calibration, even in data-rich countries. In situations in which SWAT over- or underpredicted the annual maximum concentrations, the magnitude of the over- or underprediction was commonly less than a factor of 2, indicating that the model and uncalibrated parameterization approach provide a capable method for predicting the aquatic exposure required to support pesticide regulatory decision making. Integr Environ Assess Manag 2018;14:358-368. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

FDTD calculations of SAR for child voxel models in different postures between 10 MHz and 3 GHz.

PubMed

Findlay, R P; Lee, A-K; Dimbylow, P J

2009-08-01

Calculations of specific energy absorption rate (SAR) have been performed on the rescaled NORMAN 7-y-old voxel model and the Electronics and Telecommunications Research Institute (ETRI) child 7-y-old voxel model in the standing arms down, arms up and sitting postures. These calculations were for plane-wave exposure under isolated and grounded conditions between 10 MHz and 3 GHz. It was found that there was little difference at each resonant frequency between the whole-body averaged SAR values calculated for the NORMAN and ETRI 7-y-old models for each of the postures studied. However, when compared with the arms down posture, raising the arms increased the SAR by up to 25%. Electric field values required to produce the International Commission on Non-Ionizing Radiation Protection and Institute of Electrical and Electronic Engineers public basic restriction were calculated, and compared with reference levels for the different child models and postures. These showed that, under certain worst-case exposure conditions, the reference levels may not be conservative.

Secondhand smoke avoidance by preteens living with smokers: To leave or stay?

PubMed Central

Ding, Ding; Wahlgren, Dennis R.; Liles, Sandy; Jones, Jennifer A.; Hughes, Suzanne C.; Hovell, Melbourne F.

2010-01-01

Introduction Secondhand smoke (SHS) is hazardous to children’s health. Designing interventions to reduce exposure requires understanding children’s behavior in the presence of smokers, yet little is known about this behavior. Purpose To determine whether children’s avoidance of SHS is associated with lower exposure and to explore predictors of avoidance based on a behavioral ecological model. Method Preteens aged 8–13 (N=358) living with a smoker identified their primary source of SHS exposure, and reported whether they left (avoided exposure) or stayed the last time they were exposed to that person’s smoke. The SHS avoidance measure was validated by examining associations with SHS exposure. Multivariable Logistic Regression was used to determine predictors of SHS avoidance. Results Based on urine cotinine and reported exposure, preteens who left the presence of SHS had lower exposure than those who stayed. Preteens were more likely to leave SHS if they were less physically mature, had not tried smoking, had a firm commitment not to smoke, did not assist family smoking, had family/friends who discouraged breathing SHS, or had friends who disliked smoking. Discussion Most SHS exposure reduction interventions have targeted changes in smokers’ behavior. Reductions can also be achieved by changing exposed nonsmokers’ behavior, such as avoiding the exposure. Future studies should measure young people’s SHS avoidance and test interventions to increase their avoidance practices. PMID:20634003

Image information content and patient exposure.

PubMed

Motz, J W; Danos, M

1978-01-01

Presently, patient exposure and x-ray tube kilovoltage are determined by image visibility requirements on x-ray film. With the employment of image-processing techniques, image visibility may be manipulated and the exposure may be determined only by the desired information content, i.e., by the required degree of tissue-density descrimination and spatial resolution. This work gives quantitative relationships between the image information content and the patient exposure, give estimates of the minimum exposures required for the detection of image signals associated with particular radiological exams. Also, for subject thickness larger than approximately 5 cm, the results show that the maximum information content may be obtained at a single kilovoltage and filtration with the simultaneous employment of image-enhancement and antiscatter techniques. This optimization may be used either to reduce the patient exposure or to increase the retrieved information.

Calculated values of atomic oxygen fluences and solar exposure on selected surfaces of LDEF

NASA Technical Reports Server (NTRS)

Gillis, J. R.; Pippin, H. G.; Bourassa, R. J.; Gruenbaum, P. E.

1995-01-01

Atomic oxygen (AO) fluences and solar exposure have been modeled for selected hardware from the Long Duration Exposure Facility (LDEF). The atomic oxygen exposure was modeled using the microenvironment modeling code SHADOWV2. The solar exposure was modeled using the microenvironment modeling code SOLSHAD version 1.0.

A dynamic Monte Carlo model for predicting radiant exposure distribution in dental composites: model development and verifications

NASA Astrophysics Data System (ADS)

Chen, Yin-Chu; Ferracane, Jack L.; Prahl, Scott A.

2005-03-01

Photo-cured dental composites are widely used in dental practices to restore teeth due to the esthetic appearance of the composites and the ability to cure in situ. However, their complex optical characteristics make it difficult to understand the light transport within the composites and to predict the depth of cure. Our previous work showed that the absorption and scattering coefficients of the composite changed after the composite was cured. The static Monte Carlo simulation showed that the penetration of radiant exposures differed significantly for cured and uncured optical properties. This means that a dynamic model is required for accurate prediction of radiant exposure in the composites. The purpose of this study was to develop and verify a dynamic Monte Carlo (DMC) model simulating light propagation in dental composites that have dynamic optical properties while photons are absorbed. The composite was divided into many small cubes, each of which had its own scattering and absorption coefficients. As light passed through the composite, the light was scattered and absorbed. The amount of light absorbed in each cube was calculated using Beer's Law and was used to determine the next optical properties in that cube. Finally, the predicted total reflectance and transmittance as well as the optical property during curing were verified numerically and experimentally. Our results showed that the model predicted values agreed with the theoretical values within 1% difference. The DMC model results are comparable with experimental results within 5% differences.

20171003 - Exposure Research in EPA’s Chemical Safety for Sustainability Research Program (ACC LRI SST Science Discussion)

EPA Science Inventory

Estimates of human and ecological exposures are required as critical input to risk-based prioritization and screening of chemicals. This project seeks to develop the data, tools, and evaluation approaches required to generate rapid and scientifically-defensible exposure predictio...

Reliability of Current Biokinetic and Dosimetric Models for Radionuclides: A Pilot Study

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

Leggett, Richard Wayne; Eckerman, Keith F; Meck, Robert A.

2008-10-01

This report describes the results of a pilot study of the reliability of the biokinetic and dosimetric models currently used by the U.S. Nuclear Regulatory Commission (NRC) as predictors of dose per unit internal or external exposure to radionuclides. The study examines the feasibility of critically evaluating the accuracy of these models for a comprehensive set of radionuclides of concern to the NRC. Each critical evaluation would include: identification of discrepancies between the models and current databases; characterization of uncertainties in model predictions of dose per unit intake or unit external exposure; characterization of variability in dose per unit intakemore » or unit external exposure; and evaluation of prospects for development of more accurate models. Uncertainty refers here to the level of knowledge of a central value for a population, and variability refers to quantitative differences between different members of a population. This pilot study provides a critical assessment of models for selected radionuclides representing different levels of knowledge of dose per unit exposure. The main conclusions of this study are as follows: (1) To optimize the use of available NRC resources, the full study should focus on radionuclides most frequently encountered in the workplace or environment. A list of 50 radionuclides is proposed. (2) The reliability of a dose coefficient for inhalation or ingestion of a radionuclide (i.e., an estimate of dose per unit intake) may depend strongly on the specific application. Multiple characterizations of the uncertainty in a dose coefficient for inhalation or ingestion of a radionuclide may be needed for different forms of the radionuclide and different levels of information of that form available to the dose analyst. (3) A meaningful characterization of variability in dose per unit intake of a radionuclide requires detailed information on the biokinetics of the radionuclide and hence is not feasible for many infrequently studied radionuclides. (4) The biokinetics of a radionuclide in the human body typically represents the greatest source of uncertainty or variability in dose per unit intake. (5) Characterization of uncertainty in dose per unit exposure is generally a more straightforward problem for external exposure than for intake of a radionuclide. (6) For many radionuclides the most important outcome of a large-scale critical evaluation of databases and biokinetic models for radionuclides is expected to be the improvement of current models. Many of the current models do not fully or accurately reflect available radiobiological or physiological information, either because the models are outdated or because they were based on selective or uncritical use of data or inadequate model structures. In such cases the models should be replaced with physiologically realistic models that incorporate a wider spectrum of information.« less

Fractional poisson--a simple dose-response model for human norovirus.

PubMed

Messner, Michael J; Berger, Philip; Nappier, Sharon P

2014-10-01

This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (<100), estimation error is small for the fractional Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.

The influence of role models in undergraduate nurse education.

PubMed

Jack, Kirsten; Hamshire, Claire; Chambers, Alison

2017-12-01

To explore the concept of role modelling in undergraduate nurse education and its effect on the personal and professional development of student nurses. Effective educative strategies are important for student nurses, who have to cope with learning in both clinical and university settings. Given the contemporary issues facing nurse education and practice in the United Kingdom (UK), it is timely and important to undertake pedagogical research into the concept of role modelling as an effective educative method. A descriptive narrative approach. Unstructured interviews were conducted with 14 current/recently discontinued students from Adult and Mental Health branches of nursing degree programmes in the north-west region of England, United Kingdom (UK). Data were thematically analysed. Students valued exposure to positive role models in clinical and university settings and viewed them as beneficial to their learning. Exposure to negative role models occurred, and this provided students with opportunities to consider the type of nurse they aspired to become. In some cases, students' exposure to perceived poor practice had an adverse effect on their learning and led to negative feelings about nursing work. Clinical staff might be perceived as more relevant role models than those in the university setting although there were still opportunities for academic staff to model professional behaviours. The study found that role modelling is an effective way to support learning and led to student satisfaction across both clinical and university settings. The findings support the use of role models in nurse education, and further research about conscious positive modelling of practice is required. Exploring the use of role models is important when examining ways in which the quality of nurse education might be developed. © 2017 John Wiley & Sons Ltd.

Integration of multiple theories for the simulation of laser interference lithography processes

NASA Astrophysics Data System (ADS)

Lin, Te-Hsun; Yang, Yin-Kuang; Fu, Chien-Chung

2017-11-01

The periodic structure of laser interference lithography (LIL) fabrication is superior to other lithography technologies. In contrast to traditional lithography, LIL has the advantages of being a simple optical system with no mask requirements, low cost, high depth of focus, and large patterning area in a single exposure. Generally, a simulation pattern for the periodic structure is obtained through optical interference prior to its fabrication through LIL. However, the LIL process is complex and combines the fields of optical and polymer materials; thus, a single simulation theory cannot reflect the real situation. Therefore, this research integrates multiple theories, including those of optical interference, standing waves, and photoresist characteristics, to create a mathematical model for the LIL process. The mathematical model can accurately estimate the exposure time and reduce the LIL process duration through trial and error.

Integration of multiple theories for the simulation of laser interference lithography processes.

PubMed

Lin, Te-Hsun; Yang, Yin-Kuang; Fu, Chien-Chung

2017-11-24

The periodic structure of laser interference lithography (LIL) fabrication is superior to other lithography technologies. In contrast to traditional lithography, LIL has the advantages of being a simple optical system with no mask requirements, low cost, high depth of focus, and large patterning area in a single exposure. Generally, a simulation pattern for the periodic structure is obtained through optical interference prior to its fabrication through LIL. However, the LIL process is complex and combines the fields of optical and polymer materials; thus, a single simulation theory cannot reflect the real situation. Therefore, this research integrates multiple theories, including those of optical interference, standing waves, and photoresist characteristics, to create a mathematical model for the LIL process. The mathematical model can accurately estimate the exposure time and reduce the LIL process duration through trial and error.

Constitutive Modeling and Testing of Polymer Matrix Composites Incorporating Physical Aging at Elevated Temperatures

NASA Technical Reports Server (NTRS)

Veazie, David R.

1998-01-01

Advanced polymer matrix composites (PMC's) are desirable for structural materials in diverse applications such as aircraft, civil infrastructure and biomedical implants because of their improved strength-to-weight and stiffness-to-weight ratios. For example, the next generation military and commercial aircraft requires applications for high strength, low weight structural components subjected to elevated temperatures. A possible disadvantage of polymer-based composites is that the physical and mechanical properties of the matrix often change significantly over time due to the exposure of elevated temperatures and environmental factors. For design, long term exposure (i.e. aging) of PMC's must be accounted for through constitutive models in order to accurately assess the effects of aging on performance, crack initiation and remaining life. One particular aspect of this aging process, physical aging, is considered in this research.

Study on the association between residential exposure to N, N-dimethylformamide and hospitalization for respiratory disease

NASA Astrophysics Data System (ADS)

Wang, Cui; Tian, WeiLi; Wei, YuMei; Li, XiaoXiao; Zhang, QingYu; Huang, ChanKe

2013-10-01

Some studies have confirmed the adverse effects of N, N-dimethylformamide (DMF) on the different organs in occupational exposure workers. However, to the best of our knowledge, risk assessment in the general population has not been available. In this study, a time series analysis of the relationship between DMF exposure and respiratory hospitalization was performed in Longwan district of China in 2008. Generalized additive model (GAMs) reflected that a 101.0 μg m-3 (inter-quartile range) increase in the 1-day lag concentration of DMF resulted in a 1.17 (95% CI: 1.09-1.25) increased relative risk of hospitalization for respiratory problems. The dose-response curve representing the relationship between DMF and the logarithm of the number of hospitalization was adequately linear at 4-200 μg m-3. We proposed a risk on respiratory disease in non-occupational DMF exposure. More information is required to verify this observation and the other endpoints to general population should be investigated during long-term DMF exposure.

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.

Radiation exposure levels within timber industries in Calabar, Nigeria

PubMed Central

Inyang, S. O.; Inyang, I. S.; Egbe, N. O.

2009-01-01

The UNSCEAR (2000) observed that there could be some exposure at work which would require regulatory control but is not really considered. This study was, therefore, set up to evaluate the effective dose in timber industries in Calabar, Nigeria to determine if the evaluated dose levels could lead to any radiological health effect in the workers, and also determine if the industries require regulatory control. The gamma ray exposure at four timber industries measured using an exposure meter were converted to effective dose and compared with the public and occupational values. The evaluated effective dose values in the timber industries were below public and occupational exposure limits and may not necessarily result in any radiological health hazard. Therefore, they may not require regulatory control. PMID:20098544

Respiratory Health – Exposure Measurements and Modeling in the Fragrance and Flavour Industry

PubMed Central

Angelini, Eric; Camerini, Gerard; Diop, Malick; Roche, Patrice; Rodi, Thomas; Schippa, Christine; Thomas, Thierry

2016-01-01

Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH) identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring), 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to various exposure scenarios, with the experimental values measured under real conditions. After examination of the predicted results, 98% of the values obtained with the proposed new model were above the experimental values measured in real conditions. This must be compared with the results of the classical ECETOC-TRA system, which generates only 37% of overestimated values. As the values generated by the new model intended to help decision-makers of the industry to implement adapted protective action and information, and considering the high variability of the working environments, it was of the utmost importance to us not to underestimate the exposure level. The proposed correction factors have been designed to achieve this goal. We wish to propose the present method as an improved monitoring tool to improve respiratory health and safety in the flavor and fragrance manufacturing facilities. PMID:26863607

[Evaluation of dental X-ray apparatus in terms of patient exposure to ionizing radiation].

PubMed

Olszewski, Jerzy; Wrzesień, Małgorzata

2017-06-27

The use of X-ray in dental procedures causes exposure of the patient to ionizing radiation. This exposure depends primarily on the parameters used in tooth examination. The aim of the study was to determine the patients exposure and to assess the technical condition of X-ray tubes. Seventeen hundred dental offices were covered by the questionnaire survey and 740 questionnaires were sent back. Direct measurements were performed in 100 units by using the thermoluminescent detectors and X-ray films. The results showed that the most commonly used exposure time is 0.22±0.16 s. The average entrance dose for the parameters used most commonly by dentists is 1.7±1.4 mGy. The average efficiency of X-ray tube estimated on the basis of exposures is 46.5±23.7 μGy/mAs. The study results indicate that the vast majority of X-ray tubes meet the requirements specified in the binding regulations. Med Pr 2017;67(4):491-496. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Copper-Based Aquatic Algaecide Adsorption and Accumulation Kinetics: Influence of Exposure Concentration and Duration for Controlling the Cyanobacterium Lyngbya wollei.

PubMed

Bishop, West M; Lynch, Clayton L; Willis, Ben E; Cope, W Gregory

2017-09-01

Filamentous mat-forming cyanobacteria are increasingly impairing uses of freshwater resources. To effectively manage, a better understanding of control measures is needed. Copper (Cu)-based algaecide formulations are often applied to reactively control nuisance cyanobacterial blooms. This laboratory research assessed typical field exposure scenarios for the ability of Cu to partition to, and accumulate in Lyngbya wollei. Exposure factors (Cu concentration × duration) of 4, 8, 16, 24, 32 h were tested across three aqueous Cu concentrations (1, 2, 4 ppm). Results indicated that internally accumulated copper correlated with control of L. wollei, independent of adsorbed copper. L. wollei control was determined by filament viability and chlorophyll a concentrations. Similar exposure factors elicited similar internalized copper levels and consequent responses of L. wollei. Ultimately, a "concentration-exposure-time" (CET) model was created to assist water resource managers in selecting an appropriate treatment regime for a specific in-water infestation. By assessing the exposure concentration and duration required to achieve the internal threshold of copper (i.e., critical burden) that elicits control, water management objectives can be achieved while simultaneously decreasing the environmental loading of copper and potential for non-target species risks.

Development of a multi-exposure speckle imaging for mice brain imaging

NASA Astrophysics Data System (ADS)

Soleimanzad, Haleh; Gurden, Hirac; Pain, Frédéric

2017-02-01

In the last decade, Laser Speckle Contrast Imaging (LSCI) has been proposed and validated for imaging cerebral blood flow at the rodent brain surface in vivo. The technique relies on the calculation of the spatial speckle contrast, which is related to the velocity of scatterers (red blood cells). The implementation of the technique requires a partial craniotomy so that the brain tissues of interest can be illuminated with a laser diode. However, the studies of changes in the microcirculation during disease progression or treatment require longitudinal studies (i.e. imaging is done repeatedly over weeks or even months). Practically, the less invasive way to obtain such data is to image through the thinned skull without a craniotomy. However the presence of static scatterers (skull) will affect the speckle calculation and produce a bias in the estimation of the microcirculation changes. An extension to LSCI, termed Multi-Exposure Speckle Imaging (MESI) was proposed and validated a few years ago that address these limitations. It relies on a model of the speckle contrast as a function of the exposure time and the proportion of static scatterers. Here, we used MESI with the aim of repeatedly imaging the olfactory bulb of mice models of obesity. First, we have developed a MESI set up which was characterized on microfluidic flow phantoms with different flow-rates and channel diameters to simulate blood flow in animal model characteristics. Second, we show that MESI can discriminate flows in the presence of static scatterers and it can measure flow changes consistently. Finally we provide an in vivo validation of the technique in mice with and without a craniotomy.

Estimating human-equivalent no observed adverse-effect levels for VOCs (volatile organic compounds) based on minimal knowledge of physiological parameters. Technical paper

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

Overton, J.H.; Jarabek, A.M.

1989-01-01

The U.S. EPA advocates the assessment of health-effects data and calculation of inhaled reference doses as benchmark values for gauging systemic toxicity to inhaled gases. The assessment often requires an inter- or intra-species dose extrapolation from no observed adverse effect level (NOAEL) exposure concentrations in animals to human equivalent NOAEL exposure concentrations. To achieve this, a dosimetric extrapolation procedure was developed based on the form or type of equations that describe the uptake and disposition of inhaled volatile organic compounds (VOCs) in physiologically-based pharmacokinetic (PB-PK) models. The procedure assumes allometric scaling of most physiological parameters and that the value ofmore » the time-integrated human arterial-blood concentration must be limited to no more than to that of experimental animals. The scaling assumption replaces the need for most parameter values and allows the derivation of a simple formula for dose extrapolation of VOCs that gives equivalent or more-conservative exposure concentrations values than those that would be obtained using a PB-PK model in which scaling was assumed.« less

Comparison of the near field/far field model and the advanced reach tool (ART) model V1.5: exposure estimates to benzene during parts washing with mineral spirits.

PubMed

LeBlanc, Mallory; Allen, Joseph G; Herrick, Robert F; Stewart, James H

2018-03-01

The Advanced Reach Tool V1.5 (ART) is a mathematical model for occupational exposures conceptually based on, but implemented differently than, the "classic" Near Field/Far Field (NF/FF) exposure model. The NF/FF model conceptualizes two distinct exposure "zones"; the near field, within approximately 1m of the breathing zone, and the far field, consisting of the rest of the room in which the exposure occurs. ART has been reported to provide "realistic and reasonable worst case" estimates of the exposure distribution. In this study, benzene exposure during the use of a metal parts washer was modeled using ART V1.5, and compared to actual measured workers samples and to NF/FF model results from three previous studies. Next, the exposure concentrations expected to be exceeded 25%, 10% and 5% of the time for the exposure scenario were calculated using ART. Lastly, ART exposure estimates were compared with and without Bayesian adjustment. The modeled parts washing benzene exposure scenario included distinct tasks, e.g. spraying, brushing, rinsing and soaking/drying. Because ART can directly incorporate specific types of tasks that are part of the exposure scenario, the present analysis identified each task's determinants of exposure and performance time, thus extending the work of the previous three studies where the process of parts washing was modeled as one event. The ART 50th percentile exposure estimate for benzene (0.425ppm) more closely approximated the reported measured mean value of 0.50ppm than the NF/FF model estimates of 0.33ppm, 0.070ppm or 0.2ppm obtained from other modeling studies of this exposure scenario. The ART model with the Bayesian analysis provided the closest estimate to the measured value (0.50ppm). ART (with Bayesian adjustment) was then used to assess the 75th, the 90th and 95th percentile exposures, predicting that on randomly selected days during this parts washing exposure scenario, 25% of the benzene exposures would be above 0.70ppm; 10% above 0.95ppm; and 5% above 1.15ppm. These exposure estimates at the three different percentiles of the ART exposure distribution refer to the modeled exposure scenario not a specific workplace or worker. This study provides a detailed comparison of modeling tools currently available to occupational hygienists and other exposure assessors. Possible applications are considered. Copyright © 2017 Elsevier GmbH. All rights reserved.

A Guide to Making Stochastic and Single Point Predictions using the Cold Exposure Survival Model (CESM)

DTIC Science & Technology

2008-01-01

required soldiers to traverse knee to neck deep 14°C water. Recently, the proliferation of wilderness activities such as mountain climbing, backcountry...Red Cross Cold Water Survival Curves (Figure 2). While useful as a “ rule of thumb” estimate of hypothermia survival, models such as Molnar’s [8] are...low body fat (e.g. body builders) are an exception to this rule . The advantage of having a little more mass can be demonstrated by CESM by

Post-Stress Combined Administration of Beta-Receptor and Glucocorticoid Antagonists as a Novel Preventive Treatment in an Animal Model of PTSD

DTIC Science & Technology

2010-05-01

prenatal stress as a factor in vulnerability to develop PTSD upon adult exposure to traumatic stress. Thus, although the duration of this Concept...including fear conditioning and extinction; and 3) test the combined drug treatment using the established model. Although we developed a reliable test...our lab, but had to be modified and adjusted to suit the time frame required by the design of these experiments. Others we had to develop , set up

POPULATION EXPOSURES TO PARTICULATE MATTER: A COMPARISON OF EXPOSURE MODEL PREDICTIONS AND MEASUREMENT DATA

EPA Science Inventory

The US EPA National Exposure Research Laboratory (NERL) is currently developing an integrated human exposure source-to-dose modeling system (HES2D). This modeling system will incorporate models that use a probabilistic approach to predict population exposures to environmental ...

Investigation of Hydrogen Sulfide Exposure and Lung Function, Asthma and Chronic Obstructive Pulmonary Disease in a Geothermal Area of New Zealand

PubMed Central

Bates, Michael N.; Crane, Julian; Balmes, John R.; Garrett, Nick

2015-01-01

Background Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world’s largest population exposed to ambient H2S—from geothermal sources. Objectives We investigated associations of H2S with lung function, COPD and asthma in this population. Methods 1,204 of 1,639 study participants, aged 18–65 years during 2008–2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. Results None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. Conclusions The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H2S exposures require confirmation in other studies. PMID:25822819

Investigation of hydrogen sulfide exposure and lung function, asthma and chronic obstructive pulmonary disease in a geothermal area of New Zealand.

PubMed

Bates, Michael N; Crane, Julian; Balmes, John R; Garrett, Nick

2015-01-01

Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world's largest population exposed to ambient H2S-from geothermal sources. We investigated associations of H2S with lung function, COPD and asthma in this population. 1,204 of 1,639 study participants, aged 18-65 years during 2008-2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H2S exposures require confirmation in other studies.

INEEL AIR MODELING PROTOCOL ext

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

C. S. Staley; M. L. Abbott; P. D. Ritter

2004-12-01

Various laws stemming from the Clean Air Act of 1970 and the Clean Air Act amendments of 1990 require air emissions modeling. Modeling is used to ensure that air emissions from new projects and from modifications to existing facilities do not exceed certain standards. For radionuclides, any new airborne release must be modeled to show that downwind receptors do not receive exposures exceeding the dose limits and to determine the requirements for emissions monitoring. For criteria and toxic pollutants, emissions usually must first exceed threshold values before modeling of downwind concentrations is required. This document was prepared to provide guidancemore » for performing environmental compliance-driven air modeling of emissions from Idaho National Engineering and Environmental Laboratory facilities. This document assumes that the user has experience in air modeling and dose and risk assessment. It is not intended to be a "cookbook," nor should all recommendations herein be construed as requirements. However, there are certain procedures that are required by law, and these are pointed out. It is also important to understand that air emissions modeling is a constantly evolving process. This document should, therefore, be reviewed periodically and revised as needed. The document is divided into two parts. Part A is the protocol for radiological assessments, and Part B is for nonradiological assessments. This document is an update of and supersedes document INEEL/INT-98-00236, Rev. 0, INEEL Air Modeling Protocol. This updated document incorporates changes in some of the rules, procedures, and air modeling codes that have occurred since the protocol was first published in 1998.« less

Testing nanomaterial toxicity in unicellular eukaryotic algae and fish cell lines.

PubMed

Kroll, Alexandra; Kühnel, Dana; Schirmer, Kristin

2013-01-01

Nanoecotoxicology as a sub-discipline of ecotoxicology aims to identify and predict effects elicited on ecosystems by nano-sized materials (NM). Two key groups of model organisms in this context are algae and fish. In this chapter, we present considerations for testing NM with respect to their impact on unicellular algae and cell lines derived from various organs of fish.Based on currently available literature on NM effects in unicellular algae and fish cell lines, and our own experience, we provide guidance on test design, including principle test considerations, materials, NM presentation to cells, exposure, bioavailability, and effect assessment. Assessment needs to be based on a meaningful choice of exposure scenario(s) related to the research question. As a first step, one needs to address whether effects of NMs are to be investigated under environmentally relevant or probable conditions, which may include processes such as agglomeration, or whether NM effects from mono-dispersed particles are of interest, which may require special steps to ensure stable NM suspension. Moreover, whether effects on cells are to be studied in the short- or long-term is important with regard to experimental design. Preparation of NM suspensions, which can be done in aqueous media different from the exposure medium, is addressed with regard to energy input, sterility (as required for algae and fish cell exposure) and particle purity.Specified for the two model systems, algae and fish cell lines, availability and choice of culture media are presented and discussed with regard to impact on NM behavior. Light, temperature, and agitation, which are variables during exposure, are discussed. We further provide guidance on the characterization of the NM in the chosen aqueous exposure media regarding size, zeta potential and electrophoretic mobility. The state of NM in exposure media is decisive for their bioavailability and therefore for potential particle effects. Therefore, we present ways of deriving a mass balance and quantitative/qualitative information on the uptake and distribution of NM in cells.As NM have a high surface-to-volume ratio and possess specific physical-chemical properties, which make them prone to interfere with various compounds and certain types of toxicity tests, potential interferences and appropriate controls are introduced. Furthermore, different types of dose metrics, which is still a strongly debated issue in nanotoxicology, are highlighted. We also consider laboratory safety regarding NM handling and disposal.

Ares I Scale Model Acoustic Tests Instrumentation for Acoustic and Pressure Measurements

NASA Technical Reports Server (NTRS)

Vargas, Magda B.; Counter, Douglas D.

2011-01-01

The Ares I Scale Model Acoustic Test (ASMAT) was a development test performed at the Marshall Space Flight Center (MSFC) East Test Area (ETA) Test Stand 116. The test article included a 5% scale Ares I vehicle model and tower mounted on the Mobile Launcher. Acoustic and pressure data were measured by approximately 200 instruments located throughout the test article. There were four primary ASMAT instrument suites: ignition overpressure (IOP), lift-off acoustics (LOA), ground acoustics (GA), and spatial correlation (SC). Each instrumentation suite incorporated different sensor models which were selected based upon measurement requirements. These requirements included the type of measurement, exposure to the environment, instrumentation check-outs and data acquisition. The sensors were attached to the test article using different mounts and brackets dependent upon the location of the sensor. This presentation addresses the observed effect of the sensors and mounts on the acoustic and pressure measurements.

Long-term exposure to microwave radiation provokes cancer growth: evidences from radars and mobile communication systems.

PubMed

Yakymenko, I; Sidorik, E; Kyrylenko, S; Chekhun, V

2011-06-01

In this review we discuss alarming epidemiological and experimental data on possible carcinogenic effects of long term exposure to low intensity microwave (MW) radiation. Recently, a number of reports revealed that under certain conditions the irradiation by low intensity MW can substantially induce cancer progression in humans and in animal models. The carcinogenic effect of MW irradiation is typically manifested after long term (up to 10 years and more) exposure. Nevertheless, even a year of operation of a powerful base transmitting station for mobile communication reportedly resulted in a dramatic increase of cancer incidence among population living nearby. In addition, model studies in rodents unveiled a significant increase in carcinogenesis after 17-24 months of MW exposure both in tumor-prone and intact animals. To that, such metabolic changes, as overproduction of reactive oxygen species, 8-hydroxi-2-deoxyguanosine formation, or ornithine decarboxylase activation under exposure to low intensity MW confirm a stress impact of this factor on living cells. We also address the issue of standards for assessment of biological effects of irradiation. It is now becoming increasingly evident that assessment of biological effects of non-ionizing radiation based on physical (thermal) approach used in recommendations of current regulatory bodies, including the International Commission on Non-Ionizing Radiation Protection (ICNIRP) Guidelines, requires urgent reevaluation. We conclude that recent data strongly point to the need for re-elaboration of the current safety limits for non-ionizing radiation using recently obtained knowledge. We also emphasize that the everyday exposure of both occupational and general public to MW radiation should be regulated based on a precautionary principles which imply maximum restriction of excessive exposure.

Characterization and prediction of chemical functions and weight fractions in consumer products.

PubMed

Isaacs, Kristin K; Goldsmith, Michael-Rock; Egeghy, Peter; Phillips, Katherine; Brooks, Raina; Hong, Tao; Wambaugh, John F

2016-01-01

Assessing exposures from the thousands of chemicals in commerce requires quantitative information on the chemical constituents of consumer products. Unfortunately, gaps in available composition data prevent assessment of exposure to chemicals in many products. Here we propose filling these gaps via consideration of chemical functional role. We obtained function information for thousands of chemicals from public sources and used a clustering algorithm to assign chemicals into 35 harmonized function categories (e.g., plasticizers, antimicrobials, solvents). We combined these functions with weight fraction data for 4115 personal care products (PCPs) to characterize the composition of 66 different product categories (e.g., shampoos). We analyzed the combined weight fraction/function dataset using machine learning techniques to develop quantitative structure property relationship (QSPR) classifier models for 22 functions and for weight fraction, based on chemical-specific descriptors (including chemical properties). We applied these classifier models to a library of 10196 data-poor chemicals. Our predictions of chemical function and composition will inform exposure-based screening of chemicals in PCPs for combination with hazard data in risk-based evaluation frameworks. As new information becomes available, this approach can be applied to other classes of products and the chemicals they contain in order to provide essential consumer product data for use in exposure-based chemical prioritization.

Potential for adult-based epidemiological studies to characterize overall cancer risks associated with a lifetime of CT scans.

PubMed

Shuryak, Igor; Lubin, Jay H; Brenner, David J

2014-06-01

Recent epidemiological studies have suggested that radiation exposure from pediatric CT scanning is associated with small excess cancer risks. However, the majority of CT scans are performed on adults, and most radiation-induced cancers appear during middle or old age, in the same age range as background cancers. Consequently, a logical next step is to investigate the effects of CT scanning in adulthood on lifetime cancer risks by conducting adult-based, appropriately designed epidemiological studies. Here we estimate the sample size required for such studies to detect CT-associated risks. This was achieved by incorporating different age-, sex-, time- and cancer type-dependent models of radiation carcinogenesis into an in silico simulation of a population-based cohort study. This approach simulated individual histories of chest and abdominal CT exposures, deaths and cancer diagnoses. The resultant sample sizes suggest that epidemiological studies of realistically sized cohorts can detect excess lifetime cancer risks from adult CT exposures. For example, retrospective analysis of CT exposure and cancer incidence data from a population-based cohort of 0.4 to 1.3 million (depending on the carcinogenic model) CT-exposed UK adults, aged 25-65 in 1980 and followed until 2015, provides 80% power for detecting cancer risks from chest and abdominal CT scans.

Systems Toxicology: From Basic Research to Risk Assessment

PubMed Central

2014-01-01

Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment. PMID:24446777

Systems toxicology: from basic research to risk assessment.

PubMed

Sturla, Shana J; Boobis, Alan R; FitzGerald, Rex E; Hoeng, Julia; Kavlock, Robert J; Schirmer, Kristin; Whelan, Maurice; Wilks, Martin F; Peitsch, Manuel C

2014-03-17

Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment.

A Decision Support Framework for Evaluation of Engineered ...

EPA Pesticide Factsheets

Engineered nanomaterials (ENM) are currently being developed and applied at rates that far exceed our ability to evaluate their potential for environmental or human health risks. The gap between material development and capacity for assessment grows wider every day. Transformative approaches are required that enhance our ability to forecast potential exposure and adverse health risks based on limited information such as the physical and chemical parameters of ENM, their proposed uses, and functional assays reflective of key ENM - environmental interactions. We are developing a framework that encompasses the potential for release of nanomaterials across a product life cycle, environmental transport, transformations and fate, exposure to sensitive species, including humans, and the potential for causing adverse effects. Each component of the framework is conceive of as a sequential segmented model depicting the movement, transformations and actions of ENM through environmental or biological compartments, and along which targeted functional assays can be developed that are indicative of projected rates of ENM movement or action. The eventual goal is to allow simple predictive models to be built that incorporate the data from key functional assays and thereby allow rapid screening of the projected margin of exposure for proposed applications of ENM enabled products. In this way, cases where a substantially safe margin of exposure is forecast can be reduced in

Characterization and Prediction of Chemical Functions and ...

EPA Pesticide Factsheets

Assessing exposures from the thousands of chemicals in commerce requires quantitative information on the chemical constituents of consumer products. Unfortunately, gaps in available composition data prevent assessment of exposure to chemicals in many products. Here we propose filling these gaps via consideration of chemical functional role. We obtained function information for thousands of chemicals from public sources and used a clustering algorithm to assign chemicals into 35 harmonized function categories (e.g., plasticizers, antimicrobials, solvents). We combined these functions with weight fraction data for 4115 personal care products (PCPs) to characterize the composition of 66 different product categories (e.g., shampoos). We analyzed the combined weight fraction/function dataset using machine learning techniques to develop quantitative structure property relationship (QSPR) classifier models for 22 functions and for weight fraction, based on chemical-specific descriptors (including chemical properties). We applied these classifier models to a library of 10196 data-poor chemicals. Our predictions of chemical function and composition will inform exposure-based screening of chemicals in PCPs for combination with hazard data in risk-based evaluation frameworks. As new information becomes available, this approach can be applied to other classes of products and the chemicals they contain in order to provide essential consumer product data for use in exposure-b

Applying Aggregate Exposure Pathway and Adverse Outcome ...

EPA Pesticide Factsheets

Hazard assessment for nanomaterials often involves applying in vitro dose-response data to estimate potential health risks that arise from exposure to products that contain nanomaterials. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biological mechanisms that lead to apical adverse health outcomes in living organisms. The Adverse Outcome Pathway (AOP) framework addresses this uncertainty by acting as a scaffold onto which in vitro toxicity testing and other data can be arranged to aid in the interpretation of these results in terms of biologically-relevant responses, as an AOP connects an upstream molecular initiating event (MIE) to a downstream adverse outcome. In addition to hazard assessment, risk estimation also requires reconciling in vitro concentrations sufficient to produce bioactivity with in vivo concentrations that can trigger a MIE at the relevant biological target. Such target site exposures (TSEs) can be estimated by integrating pharmacokinetic considerations with environmental and exposure factors. Environmental and exposure data have been historically scattered in various resources, such as monitoring data for air pollutants or exposure models for specific chemicals. The Aggregate Exposure Pathway (AEP) framework is introduced to organize existing knowledge concerning biologically, chemically, and physically plausible, as well as empirically supported, links between the i

Low Pathogenic Avian Influenza Exposure Risk Assessment in Australian Commercial Chicken Farms.

PubMed

Scott, Angela Bullanday; Toribio, Jenny-Ann; Singh, Mini; Groves, Peter; Barnes, Belinda; Glass, Kathryn; Moloney, Barbara; Black, Amanda; Hernandez-Jover, Marta

2018-01-01

This study investigated the pathways of exposure to low pathogenic avian influenza (LPAI) virus among Australian commercial chicken farms and estimated the likelihood of this exposure occurring using scenario trees and a stochastic modeling approach following the World Organization for Animal Health methodology for risk assessment. Input values for the models were sourced from scientific literature and an on-farm survey conducted during 2015 and 2016 among Australian commercial chicken farms located in New South Wales and Queensland. Outputs from the models revealed that the probability of a first LPAI virus exposure to a chicken in an Australian commercial chicken farms from one wild bird at any point in time is extremely low. A comparative assessment revealed that across the five farm types (non-free-range meat chicken, free-range meat chicken, cage layer, barn layer, and free range layer farms), free-range layer farms had the highest probability of exposure (7.5 × 10 -4 ; 5% and 95%, 5.7 × 10 -4 -0.001). The results indicate that the presence of a large number of wild birds on farm is required for exposure to occur across all farm types. The median probability of direct exposure was highest in free-range farm types (5.6 × 10 -4 and 1.6 × 10 -4 for free-range layer and free-range meat chicken farms, respectively) and indirect exposure was highest in non-free-range farm types (2.7 × 10 -4 , 2.0 × 10 -4 , and 1.9 × 10 -4 for non-free-range meat chicken, cage layer, and barn layer farms, respectively). The probability of exposure was found to be lowest in summer for all farm types. Sensitivity analysis revealed that the proportion of waterfowl among wild birds on the farm, the presence of waterfowl in the range and feed storage areas, and the prevalence of LPAI in wild birds are the most influential parameters for the probability of Australian commercial chicken farms being exposed to avian influenza (AI) virus. These results highlight the importance of ensuring good biosecurity on farms to minimize the risk of exposure to AI virus and the importance of continuous surveillance of LPAI prevalence including subtypes in wild bird populations.

Low Pathogenic Avian Influenza Exposure Risk Assessment in Australian Commercial Chicken Farms

PubMed Central

Scott, Angela Bullanday; Toribio, Jenny-Ann; Singh, Mini; Groves, Peter; Barnes, Belinda; Glass, Kathryn; Moloney, Barbara; Black, Amanda; Hernandez-Jover, Marta

2018-01-01

This study investigated the pathways of exposure to low pathogenic avian influenza (LPAI) virus among Australian commercial chicken farms and estimated the likelihood of this exposure occurring using scenario trees and a stochastic modeling approach following the World Organization for Animal Health methodology for risk assessment. Input values for the models were sourced from scientific literature and an on-farm survey conducted during 2015 and 2016 among Australian commercial chicken farms located in New South Wales and Queensland. Outputs from the models revealed that the probability of a first LPAI virus exposure to a chicken in an Australian commercial chicken farms from one wild bird at any point in time is extremely low. A comparative assessment revealed that across the five farm types (non-free-range meat chicken, free-range meat chicken, cage layer, barn layer, and free range layer farms), free-range layer farms had the highest probability of exposure (7.5 × 10−4; 5% and 95%, 5.7 × 10−4—0.001). The results indicate that the presence of a large number of wild birds on farm is required for exposure to occur across all farm types. The median probability of direct exposure was highest in free-range farm types (5.6 × 10−4 and 1.6 × 10−4 for free-range layer and free-range meat chicken farms, respectively) and indirect exposure was highest in non-free-range farm types (2.7 × 10−4, 2.0 × 10−4, and 1.9 × 10−4 for non-free-range meat chicken, cage layer, and barn layer farms, respectively). The probability of exposure was found to be lowest in summer for all farm types. Sensitivity analysis revealed that the proportion of waterfowl among wild birds on the farm, the presence of waterfowl in the range and feed storage areas, and the prevalence of LPAI in wild birds are the most influential parameters for the probability of Australian commercial chicken farms being exposed to avian influenza (AI) virus. These results highlight the importance of ensuring good biosecurity on farms to minimize the risk of exposure to AI virus and the importance of continuous surveillance of LPAI prevalence including subtypes in wild bird populations. PMID:29755987

PMO Delivery System Using Bubble Liposomes and Ultrasound Exposure for Duchenne Muscular Dystrophy Treatment.

PubMed

Negishi, Yoichi; Ishii, Yuko; Nirasawa, Kei; Sasaki, Eri; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo

2018-01-01

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients. We previously developed polyethylene glycol (PEG)-modified liposomes containing ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe an efficient PMO delivery strategy using the combination of BLs and ultrasound exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL technique can increase the PMO-mediated exon-skipping efficiency, leading to significantly increased dystrophin expression. Thus, the combination of BLs and ultrasound exposure may be a feasible PMO delivery method to improve therapeutic efficacy and reduce the PMO dosage for DMD treatment.

Ice Elevation Changes in the Ellsworth Mountains, Antarctica Using Multiple Cosmogenic Nuclides

NASA Astrophysics Data System (ADS)

Marrero, S.; Hein, A.; Sugden, D.; Woodward, J.; Dunning, S.; Reid, K.

2014-12-01

Well-dated geologic data points provide important indicators that can be used for the reconstruction of ice sheet dynamics and as constraints in ice sheet models predicting future change. Cosmogenic nuclides, which accumulate in rocks exposed at the earth's surface, can be used to directly date the exposure age of the rock surfaces that have been created through glacial erosion or deposition. The technique requires a detailed understanding of the local geomorphology as well as awareness of the post-depositional processes that may affect the interpretation of exposure ages. Initial surface exposure ages (10Be, 26Al, 21Ne, and 36Cl ) from local limestone bedrock and other glacially deposited exotic lithologies provide a history spanning from 0 to 1.1 Ma in the Patriot, Independence, and Marble Hills in the southern Ellsworth Mountains, Antarctica. Using the new surface exposure ages combined with geomorphological mapping, we will discuss the implications for the glacial history of the southern Ellsworth Mountains.

Using Multiple Cosmogenic Nuclides to Investigate Ice Elevation Changes in the Ellsworth Mountains, Antarctica

NASA Astrophysics Data System (ADS)

Marrero, Shasta; Hein, Andy; Sugden, David; Woodward, John; Dunning, Stuart; Freeman, Stewart; Shanks, Richard

2015-04-01

Well-dated geologic data points provide important indicators that can be used for the reconstruction of ice sheet dynamics and as constraints in ice sheet models predicting future change. Cosmogenic nuclides, which accumulate in rocks exposed at the earth's surface, can be used to directly date the exposure age of the rock surfaces that have been created through glacial erosion or deposition. The technique requires a detailed understanding of the local geomorphology as well as awareness of the post-depositional processes that may affect the interpretation of exposure ages. Surface exposure ages (10Be, 26Al, 21Ne, and 36Cl) from local limestone bedrock and other glacially deposited exotic lithologies provide a history spanning from 0 to more than 1 million years in the Patriot, Independence, and Marble Hills in the southern Ellsworth Mountains, Antarctica. Using the new surface exposure ages combined with geomorphological mapping, we will discuss the implications for the glacial history of the southern Ellsworth Mountains.

Predictive validity of behavioural animal models for chronic pain

PubMed Central

Berge, Odd-Geir

2011-01-01

Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there are also examples of successful modelling. Significant differences in how methods are implemented and results are reported means that a literature-based comparison between preclinical data and clinical trials will not reveal whether a particular model is generally predictive. Limited reports on negative outcomes prevents reliable estimate of specificity of any model. Animal models tend to be validated with standard analgesics and may be biased towards tractable pain mechanisms. But preclinical publications rarely contain drug exposure data, and drugs are usually given in high doses and as a single administration, which may lead to drug distribution and exposure deviating significantly from clinical conditions. The greatest challenge for predictive modelling is, however, the heterogeneity of the target patient populations, in terms of both symptoms and pharmacology, probably reflecting differences in pathophysiology. In well-controlled clinical trials, a majority of patients shows less than 50% reduction in pain. A model that responds well to current analgesics should therefore predict efficacy only in a subset of patients within a diagnostic group. It follows that successful translation requires several models for each indication, reflecting critical pathophysiological processes, combined with data linking exposure levels with effect on target. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21371010

Foam cell formation by particulate matter (PM) exposure: a review.

PubMed

Cao, Yi; Long, Jimin; Ji, Yuejia; Chen, Gui; Shen, Yuexin; Gong, Yu; Li, Juan

2016-11-01

Increasing evidence suggests that exposure of particulate matter (PM) from traffic vehicles, e.g., diesel exhaust particles (DEP), was associated with adverse vascular effects, e.g., acceleration of atherosclerotic plaque progression. By analogy, engineered nanoparticles (NPs) could also induce similar effects. The formation of lipid laden foam cells, derived predominately from macrophages and vascular smooth muscle cells (VSMC), is closely associated with the development of atherosclerosis and adverse vascular effects. We reviewed current studies about particle exposure-induced lipid laden foam cell formation. In vivo studies using animal models have shown that exposure of air pollution by PM promoted lipid accumulation in alveolar macrophages or foam cells in plaques, which was likely associated with pulmonary inflammation or systemic oxidative stress, but not blood lipid profile. In support of these findings, in vitro studies showed that direct exposure of cultured macrophages to DEP or NP exposure, with or without further exposure to external lipids, promoted intracellular lipid accumulation. The mechanisms remained unknown. Although a number studies found increased reactive oxygen species (ROS) or an adaptive response to oxidative stress, the exact role of oxidative stress in mediating particle-induced foam cell formation requires future research. There is currently lack of reports concerning VSMC as a source for foam cells induced by particle exposure. In the future, it is necessary to explore the role of foam cell formation in particle exposure-induced atherosclerosis development. In addition, the formation of VSMC derived foam cells by particle exposure may also need extensive studies.

Air pollution-induced placental epigenetic alterations in early life: a candidate miRNA approach

PubMed Central

Tsamou, Maria; Vrijens, Karen; Madhloum, Narjes; Lefebvre, Wouter; Vanpoucke, Charlotte; Nawrot, Tim S

2018-01-01

ABSTRACT Particulate matter (PM) exposure during in utero life may entail adverse health outcomes in later-life. Air pollution's adverse effects are known to alter gene expression profiles, which can be regulated by microRNAs (miRNAs). We investigate the potential influence of air pollution exposure in prenatal life on placental miRNA expression. Within the framework of the ENVIRONAGE birth cohort, we measured the expression of six candidate miRNAs in placental tissue from 210 mother-newborn pairs by qRT-PCR. Trimester-specific PM2.5 exposure levels were estimated for each mother's home address using a spatiotemporal model. Multiple regression models were used to study miRNA expression and in utero exposure to PM2.5 over various time windows during pregnancy. The placental expression of miR-21 (−33.7%, 95% CI: −53.2 to −6.2, P = 0.022), miR-146a (−30.9%, 95% CI: −48.0 to −8.1, P = 0.012) and miR-222 (−25.4%, 95% CI: −43.0 to −2.4, P = 0.034) was inversely associated with PM2.5 exposure during the 2nd trimester of pregnancy, while placental expression of miR-20a and miR-21 was positively associated with 1st trimester exposure. Tumor suppressor phosphatase and tensin homolog (PTEN) was identified as a common target of the miRNAs significantly associated with PM exposure. Placental PTEN expression was strongly and positively associated (+59.6% per 5 µg/m³ increment, 95% CI: 26.9 to 100.7, P < 0.0001) with 3rd trimester PM2.5 exposure. Further research is required to establish the role these early miRNA and mRNA expression changes might play in PM-induced health effects. We provide molecular evidence showing that in utero PM2.5 exposure affects miRNAs expression as well as its downstream target PTEN. PMID:27104955

Dose-rate effects of ethylene oxide exposure on developmental toxicity.

PubMed

Weller, E; Long, N; Smith, A; Williams, P; Ravi, S; Gill, J; Henessey, R; Skornik, W; Brain, J; Kimmel, C; Kimmel, G; Holmes, L; Ryan, L

1999-08-01

In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

Dose — response relationship between noise exposure and the risk of occupational injury

PubMed Central

Yoon, Jin-Ha; Hong, Jeong-Suk; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

2015-01-01

Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers’ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively). Workplace dust exposure was classified as <1 or ≥1 mg/m3, and noise exposure as <80, 80-89, or >90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and 3.42 (2.26-5.17) at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury. PMID:25599757

Estimating the time and temperature relationship for causation of deep-partial thickness skin burns.

PubMed

Abraham, John P; Plourde, Brian; Vallez, Lauren; Stark, John; Diller, Kenneth R

2015-12-01

The objective of this study is to develop and present a simple procedure for evaluating the temperature and exposure-time conditions that lead to causation of a deep-partial thickness burn and the effect that the immediate post-burn thermal environment can have on the process. A computational model has been designed and applied to predict the time required for skin burns to reach a deep-partial thickness level of injury. The model includes multiple tissue layers including the epidermis, dermis, hypodermis, and subcutaneous tissue. Simulated exposure temperatures ranged from 62.8 to 87.8°C (145-190°F). Two scenarios were investigated. The first and worst case scenario was a direct exposure to water (characterized by a large convection coefficient) with the clothing left on the skin following the exposure. A second case consisted of a scald insult followed immediately by the skin being washed with cool water (20°C). For both cases, an Arrhenius injury model was applied whereby the extent and depth of injury were calculated and compared for the different post-burn treatments. In addition, injury values were compared with experiment data from the literature to assess verification of the numerical methodology. It was found that the clinical observations of injury extent agreed with the calculated values. Furthermore, inundation with cool water decreased skin temperatures more quickly than the clothing insulating case and led to a modest decrease in the burn extent. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Development of a single-meal fish consumption advisory for methyl mercury

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

Ginsberg, G.L.; Toal, B.F.

2000-02-01

Methyl mercury (meHg) contamination of fish is the leading cause of fish consumption advisories in the US. These advisories have focused upon repeated or chronic exposure, whereas risks during pregnancy may also exist from a single-meal exposure if the fish tissue concentration is high enough. In this study, acute exposure to meHg from a single fish meal was analyzed by using the one-compartment meHg biokinetic model to predict maternal hair concentrations. These concentrations were evaluated against the mercury hair concentration corresponding to the US Environmental Protection Agency's reference dose (RfD), which is intended to protect against neurodevelopmental effects. The one-compartmentmore » model was validated against blood concentrations from three datasets in which human subjects ingested meHg in fish, either as a single meal or multiple meals. Model simulations of the single-meal scenario at different fish meHg concentrations found that concentrations of 2.0 ppm or higher can be associated with maternal hair concentrations elevated above the RfD level for days to weeks during gestation. A single-meal fish concentration cutoff of {ge} 2.0 ppm is an important consideration, especially because this single high exposure event might be in addition to a baseline meHg body burden from other types of fish consumption. This type of single-meal advisory requires that fish sampling programs provide data for individual rather than composited fish, and take into account seasonal differences that may exist in fish concentrations.« less

Perceived Barriers to Hearing Protection Use by Employees in Amplified Music Venues, a Focus Group Study

ERIC Educational Resources Information Center

Kelly, Aoife C.; Boyd, Sara M.; Henehan, Gary T. M.

2015-01-01

Objective: It is a legal requirement for employees in noisy workplaces such as nightclubs to be provided with suitable information regarding their noise exposure risks, used a focus group approach to examine employees' attitudes to workplace noise and to hearing protection use. The subsequent analysis was based on an adapted Health Belief Model.…

Hanford internal dosimetry program manual

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

Carbaugh, E.H.; Sula, M.J.; Bihl, D.E.

1989-10-01

This document describes the Hanford Internal Dosimetry program. Program Services include administrating the bioassay monitoring program, evaluating and documenting assessments of internal exposure and dose, ensuring that analytical laboratories conform to requirements, selecting and applying appropriate models and procedures for evaluating internal radionuclide deposition and the resulting dose, and technically guiding and supporting Hanford contractors in matters regarding internal dosimetry. 13 refs., 16 figs., 42 tabs.

TIME-INTEGRATED EXPOSURE MEASURES TO IMPROVE THE PREDICTIVE POWER OF EXPOSURE CLASSIFICATION FOR EPIDEMIOLOGIC STUDIES

EPA Science Inventory

Accurate exposure classification tools are required to link exposure with health effects in epidemiological studies. Although long-term integrated exposure measurements are a critical component of exposure assessment, the ability to include these measurements into epidemiologic...

A compartmental model of uranium in human hair for protracted ingestion of natural uranium in drinking water.

PubMed

Li, W B; Karpas, Z; Salonen, L; Kurttio, P; Muikku, M; Wahl, W; Höllriegl, V; Hoeschen, C; Oeh, U

2009-06-01

To predict uranium in human hair due to chronic exposure through drinking water, a compartment representing human hair was added into the uranium biokinetic model developed by the International Commission on Radiological Protection (ICRP). The hair compartmental model was used to predict uranium excretion in human hair as a bioassay indicator due to elevated uranium intakes. Two excretion pathways, one starting from the compartment of plasma and the other from the compartment of intermediate turnover soft tissue, are assumed to transfer uranium to the compartment of hair. The transfer rate was determined from reported uranium contents in urine and in hair, taking into account the hair growth rate of 0.1 g d(-1). The fractional absorption in the gastrointestinal tract of 0.6% was found to fit best to describe the measured uranium levels among the users of drilled wells in Finland. The ingestion dose coefficient for (238)U, which includes its progeny of (234)Th, (234m)Pa, and (234)Pa, was calculated equal to 1.3 x 10(-8) Sv Bq(-1) according to the hair compartmental model. This estimate is smaller than the value of 4.5 x 10(-8) Sv Bq(-1) published by ICRP for the members of the public. In this new model, excretion of uranium through urine is better represented when excretion to the hair compartment is accounted for and hair analysis can provide a means for assessing the internal body burden of uranium. The model is applicable for chronic exposure as well as for an acute exposure incident. In the latter case, the hair sample can be collected and analyzed even several days after the incident, whereas urinalysis requires sample collection shortly after the exposure. The model developed in this study applies to ingestion intakes of uranium.

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...

Exposure Cessation During Adulthood Did Not Prevent Immunotoxicity Caused by Developmental Exposure to Low-Level Trichloroethylene in Drinking Water.

PubMed

Gilbert, Kathleen M; Bai, Shasha; Barnette, Dustyn; Blossom, Sarah J

2017-06-01

Exposure to the water pollutant trichloroethylene (TCE) can promote autoimmunity in both humans and rodents. Using a mouse model we have shown that chronic adult exposure to TCE at 500 μg/ml in drinking water generates autoimmune hepatitis in female MRL+/+ mice. There is increasing evidence that developmental exposure to certain chemicals can be more toxic than adult exposure. This study was designed to test whether exposure to a much lower level of TCE (0.05 μg/ml) during gestation, lactation, and early life generated autoimmunity similar to that found following adult exposure to higher concentrations of TCE. When female MRL+/+ mice were examined at postnatal day (PND) 259 we found that developmental/early life exposure [gestational day 0 to PND 154] to TCE at a concentration 10 000 fold lower than that shown to be effective for adult exposure triggered autoimmune hepatitis. This effect was observed despite exposure cessation at PND 154. In concordance with the liver pathology, female MRL+/+ exposed during development and early life to TCE (0.05 or 500 μg/ml) generated a range of antiliver antibodies detected by Western blotting. Expression of proinflammatory cytokines by CD4+ T cells was also similarly observed at PND 259 in the TCE-exposed mice regardless of concentration. Thus, exposure to TCE at approximately environmental levels from gestational day 0 to PND 154 generated tissue pathology and CD4+ T cell alterations that required higher concentrations if exposure was limited to adulthood. TCE exposure cessation at PND 154 did not prevent the immunotoxicity. © 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.

RECENT ENHANCEMENTS TO THE DIETARY EXPOSURE POTENTIAL MODEL

EPA Science Inventory

Presentation describes recent enhancements & new applications of the Dietary Exposure Potential Model (DEPM), a model developed to assist in design & interpretation of dietary exposure measurements. Model is an interactive system that provides dietary exposure estimates using dat...

Cocaine Self-Administration in Male and Female Rats Perinatally Exposed to PCBs: Evaluating Drug Use in an Animal Model of Environmental Contaminant Exposure

PubMed Central

Miller, Mellessa M.; Meyer, Abby E.; Sprowles, Jenna L. N.; Sable, Helen J. K.

2017-01-01

Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants known to adversely impact human health. Ortho-substituted PCBs affect the nervous system, including the brain dopaminergic system. The reinforcing effects of psychostimulants are typically modulated via the dopaminergic system, so this study used a preclinical (i.e., rodent) model to evaluate whether developmental contaminant exposure altered intravenous self-administration (i.v. SA) for the psychostimulant cocaine. Long Evans rats were perinatally exposed to 6 or 3 mg/kg/day of PCBs throughout gestation and lactation and compared to non-exposed controls. Rats were trained to lever press for a food reinforcer in an operant chamber under a fixed-ratio 5 (FR5) schedule and later underwent jugular catheterization. Food reinforcers were switched for infusions of 250 μg of cocaine, but the response requirement to earn the reinforcer remained. Active lever presses and infusions were higher in males during response acquisition and maintenance. The same sex effect was observed during later sessions which evaluated responding for cocaine doses ranging from 31.25 – 500 μg. PCB-exposed males (not females) exhibited an increase in cocaine infusions (with a similar trend in active lever presses) during acquisition, but no PCB-related differences were observed during maintenance, examination of the cocaine dose-response relationship, or progressive ratio sessions. Overall, these results indicated perinatal PCB exposure enhanced early cocaine drug-seeking in this preclinical model of developmental contaminant exposure (particularly the males), but no differences were seen during later cocaine SA sessions. As such, additional questions regarding substance abuse proclivity may be warranted in epidemiological studies evaluating environmental contaminant exposures. PMID:28287790

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

Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov; Gilbert, Ethel; Curtis, Rochelle

Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studiesmore » of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.« less

Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

NASA Astrophysics Data System (ADS)

Dixon, C. Edward

2011-06-01

Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

On the extinction probability in models of within-host infection: the role of latency and immunity.

PubMed

Yan, Ada W C; Cao, Pengxing; McCaw, James M

2016-10-01

Not every exposure to virus establishes infection in the host; instead, the small amount of initial virus could become extinct due to stochastic events. Different diseases and routes of transmission have a different average number of exposures required to establish an infection. Furthermore, the host immune response and antiviral treatment affect not only the time course of the viral load provided infection occurs, but can prevent infection altogether by increasing the extinction probability. We show that the extinction probability when there is a time-dependent immune response depends on the chosen form of the model-specifically, on the presence or absence of a delay between infection of a cell and production of virus, and the distribution of latent and infectious periods of an infected cell. We hypothesise that experimentally measuring the extinction probability when the virus is introduced at different stages of the immune response, alongside the viral load which is usually measured, will improve parameter estimates and determine the most suitable mathematical form of the model.

Air Pollution Exposure Modeling for Health Studies | Science ...

EPA Pesticide Factsheets

Dr. Michael Breen is leading the development of air pollution exposure models, integrated with novel personal sensor technologies, to improve exposure and risk assessments for individuals in health studies. He is co-investigator for multiple health studies assessing the exposure and effects of air pollutants. These health studies include participants with asthma, diabetes, and coronary artery disease living in various U.S. cities. He has developed, evaluated, and applied novel exposure modeling and time-activity tools, which includes the Exposure Model for Individuals (EMI), GPS-based Microenvironment Tracker (MicroTrac) and Exposure Tracker models. At this seminar, Dr. Breen will present the development and application of these models to predict individual-level personal exposures to particulate matter (PM) for two health studies in central North Carolina. These health studies examine the association between PM and adverse health outcomes for susceptible individuals. During Dr. Breen’s visit, he will also have the opportunity to establish additional collaborations with researchers at Harvard University that may benefit from the use of exposure models for cohort health studies. These research projects that link air pollution exposure with adverse health outcomes benefit EPA by developing model-predicted exposure-dose metrics for individuals in health studies to improve the understanding of exposure-response behavior of air pollutants, and to reduce participant

FEM Modeling of a Magnetoelectric Transducer for Autonomous Micro Sensors in Medical Application

NASA Astrophysics Data System (ADS)

Yang, Gang; Talleb, Hakeim; Gensbittel, Aurélie; Ren, Zhuoxiang

2015-11-01

In the context of wireless and autonomous sensors, this paper presents the multiphysics modeling of an energy transducer based on magnetoelectric (ME) composite for biomedical applications. The study considers the power requirement of an implanted sensor, the communication distance, the size limit of the device for minimal invasive insertion as well as the electromagnetic exposure restriction of the human body. To minimize the electromagnetic absorption by the human body, the energy source is provided by an external reader emitting low frequency magnetic field. The modeling is carried out with the finite element method by solving simultaneously the multiple physics problems including the electric load of the conditioning circuit. The simulation results show that with the T-L mode of a trilayer laminated ME composite, the transducer can deliver the required energy in respecting different constraints.

A new surrogate modeling technique combining Kriging and polynomial chaos expansions – Application to uncertainty analysis in computational dosimetry

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

Kersaudy, Pierric, E-mail: pierric.kersaudy@orange.com; Whist Lab, 38 avenue du Général Leclerc, 92130 Issy-les-Moulineaux; ESYCOM, Université Paris-Est Marne-la-Vallée, 5 boulevard Descartes, 77700 Marne-la-Vallée

2015-04-01

In numerical dosimetry, the recent advances in high performance computing led to a strong reduction of the required computational time to assess the specific absorption rate (SAR) characterizing the human exposure to electromagnetic waves. However, this procedure remains time-consuming and a single simulation can request several hours. As a consequence, the influence of uncertain input parameters on the SAR cannot be analyzed using crude Monte Carlo simulation. The solution presented here to perform such an analysis is surrogate modeling. This paper proposes a novel approach to build such a surrogate model from a design of experiments. Considering a sparse representationmore » of the polynomial chaos expansions using least-angle regression as a selection algorithm to retain the most influential polynomials, this paper proposes to use the selected polynomials as regression functions for the universal Kriging model. The leave-one-out cross validation is used to select the optimal number of polynomials in the deterministic part of the Kriging model. The proposed approach, called LARS-Kriging-PC modeling, is applied to three benchmark examples and then to a full-scale metamodeling problem involving the exposure of a numerical fetus model to a femtocell device. The performances of the LARS-Kriging-PC are compared to an ordinary Kriging model and to a classical sparse polynomial chaos expansion. The LARS-Kriging-PC appears to have better performances than the two other approaches. A significant accuracy improvement is observed compared to the ordinary Kriging or to the sparse polynomial chaos depending on the studied case. This approach seems to be an optimal solution between the two other classical approaches. A global sensitivity analysis is finally performed on the LARS-Kriging-PC model of the fetus exposure problem.« less

Population pharmacokinetic analysis of clopidogrel in healthy Jordanian subjects with emphasis optimal sampling strategy.

PubMed

Yousef, A M; Melhem, M; Xue, B; Arafat, T; Reynolds, D K; Van Wart, S A

2013-05-01

Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel-IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM(®) to describe the time course of clopidogrel-IM in plasma and to design a sparse-sampling strategy to predict clopidogrel-IM exposures for use in characterizing anti-platelet activity. Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel-IM using reverse phase high performance liquid chromatography. A two-compartment (2-CMT) PK model with first-order absorption and elimination plus an absorption lag-time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3-12 post-dose samples. A two-compartment model with EHC provided the best fit and reduced bias in C(max) (median prediction error (PE%) of 9.58% versus 12.2%) relative to the basic two-compartment model, AUC(0-24) was similar for both models (median PE% = 1.39%). The OSS for fitting the two-compartment model with EHC required the collection of seven samples (0.25, 1, 2, 4, 5, 6 and 12 h). Reasonably unbiased and precise exposures were obtained when re-fitting this model to a reduced dataset considering only these sampling times. A two-compartment model considering EHC best characterized the time course of clopidogrel-IM in plasma. Use of the suggested OSS will allow for the collection of fewer PK samples when assessing clopidogrel-IM exposures. Copyright © 2013 John Wiley & Sons, Ltd.

Comparisons of discrete and integrative sampling accuracy in estimating pulsed aquatic exposures.

PubMed

Morrison, Shane A; Luttbeg, Barney; Belden, Jason B

2016-11-01

Most current-use pesticides have short half-lives in the water column and thus the most relevant exposure scenarios for many aquatic organisms are pulsed exposures. Quantifying exposure using discrete water samples may not be accurate as few studies are able to sample frequently enough to accurately determine time-weighted average (TWA) concentrations of short aquatic exposures. Integrative sampling methods that continuously sample freely dissolved contaminants over time intervals (such as integrative passive samplers) have been demonstrated to be a promising measurement technique. We conducted several modeling scenarios to test the assumption that integrative methods may require many less samples for accurate estimation of peak 96-h TWA concentrations. We compared the accuracies of discrete point samples and integrative samples while varying sampling frequencies and a range of contaminant water half-lives (t 50  = 0.5, 2, and 8 d). Differences the predictive accuracy of discrete point samples and integrative samples were greatest at low sampling frequencies. For example, when the half-life was 0.5 d, discrete point samples required 7 sampling events to ensure median values > 50% and no sampling events reporting highly inaccurate results (defined as < 10% of the true 96-h TWA). Across all water half-lives investigated, integrative sampling only required two samples to prevent highly inaccurate results and measurements resulting in median values > 50% of the true concentration. Regardless, the need for integrative sampling diminished as water half-life increased. For an 8-d water half-life, two discrete samples produced accurate estimates and median values greater than those obtained for two integrative samples. Overall, integrative methods are the more accurate method for monitoring contaminants with short water half-lives due to reduced frequency of extreme values, especially with uncertainties around the timing of pulsed events. However, the acceptability of discrete sampling methods for providing accurate concentration measurements increases with increasing aquatic half-lives. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of perturbations in serum thyroid hormones during human pregnancy due to dietary iodide and perchlorate exposure using a biologically based dose-response model.

PubMed

Lumen, Annie; Mattie, David R; Fisher, Jeffrey W

2013-06-01

A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake. The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide. Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake. Model simulations suggested that a maternal iodide intake of 75 to 250 µg/day and an environmentally relevant exposure of perchlorate (~0.1 µg/kg/day) did not result in hypothyroxinemia or hypothyroidism. For a daily iodide-sufficient intake of 200 µg/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32.2 µg/kg/day. As iodide intake was lowered to 75 µg/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold. Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54.8 to 21.5 µg/kg/day for daily iodide intake of 250-75 µg/day. This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.

Comparison of modeled estimates of inhalation exposure to aerosols during use of consumer spray products.

PubMed

Park, Jihoon; Yoon, Chungsik; Lee, Kiyoung

2018-05-30

In the field of exposure science, various exposure assessment models have been developed to complement experimental measurements; however, few studies have been published on their validity. This study compares the estimated inhaled aerosol doses of several inhalation exposure models to experimental measurements of aerosols released from consumer spray products, and then compares deposited doses within different parts of the human respiratory tract according to deposition models. Exposure models, including the European Center for Ecotoxicology of Chemicals Targeted Risk Assessment (ECETOC TRA), the Consumer Exposure Model (CEM), SprayExpo, ConsExpo Web and ConsExpo Nano, were used to estimate the inhaled dose under various exposure scenarios, and modeled and experimental estimates were compared. The deposited dose in different respiratory regions was estimated using the International Commission on Radiological Protection model and multiple-path particle dosimetry models under the assumption of polydispersed particles. The modeled estimates of the inhaled doses were accurate in the short term, i.e., within 10 min of the initial spraying, with a differences from experimental estimates ranging from 0 to 73% among the models. However, the estimates for long-term exposure, i.e., exposure times of several hours, deviated significantly from the experimental estimates in the absence of ventilation. The differences between the experimental and modeled estimates of particle number and surface area were constant over time under ventilated conditions. ConsExpo Nano, as a nano-scale model, showed stable estimates of short-term exposure, with a difference from the experimental estimates of less than 60% for all metrics. The deposited particle estimates were similar among the deposition models, particularly in the nanoparticle range for the head airway and alveolar regions. In conclusion, the results showed that the inhalation exposure models tested in this study are suitable for estimating short-term aerosol exposure (within half an hour), but not for estimating long-term exposure. Copyright © 2018 Elsevier GmbH. All rights reserved.

Potential Sources of Bisphenol A in the Neonatal Intensive Care Unit

PubMed Central

Mendonca, Kaitlin; Hauser, Russ; Calafat, Antonia M.; Ye, Xiaoyun; Meeker, John D.; Ackerman, Robin; Cullinane, Judi; Faller, Josephine; Ringer, Steven

2013-01-01

OBJECTIVES: To determine whether nutritional intake and medical devices are bisphenol A (BPA) exposure sources among premature infants in the NICU. METHODS: Mothers and their premature infants cared for in the NICU for the past 3 days were recruited for this exposure assessment study. Forty-three mothers contributed 1 nutrition sample (breast milk or formula) to characterize the infant’s intake. Two urine samples (before and after feeding) were collected from each of 55 infants. Medical device use was categorized as “low” or “high” based on the number and invasiveness of devices used. BPA urinary concentrations used as a biomarker to estimate BPA exposure were measured by online solid-phase extraction, high performance liquid chromatography, isotope dilution, tandem mass spectrometry. Nonparametric equivalence tests, intraclass correlations, and hierarchical linear mixed-effects models were conducted. RESULTS: Breast milk and formula samples did not differ in total BPA concentration nor did infants’ median urinary concentration of total BPA before or after feedings. However, the median urinary total BPA concentration among infants who required the use of 4 or more medical devices in the past 3 days was significantly higher (36.6 µg/L) than among infants who required the use of 0 to 3 devices (13.9 µg/L). The calculated BPA exposures are lower than the US Environmental Protection Agency reference dose, but considerably higher (16- to 32-fold) than among infants or children from the general population. CONCLUSIONS: The number of medical devices used in the past 3 days, but not nutritional intake, was positively associated with exposure to BPA. PMID:23420909

Neuron specific metabolic adaptations following multi-day exposures to oxygen glucose deprivation.

PubMed

Zeiger, Stephanie L H; McKenzie, Jennifer R; Stankowski, Jeannette N; Martin, Jacob A; Cliffel, David E; McLaughlin, BethAnn

2010-11-01

Prior exposure to sub toxic insults can induce a powerful endogenous neuroprotective program known as ischemic preconditioning. Current models typically rely on a single stress episode to induce neuroprotection whereas the clinical reality is that patients may experience multiple transient ischemic attacks (TIAs) prior to suffering a stroke. We sought to develop a neuron-enriched preconditioning model using multiple oxygen glucose deprivation (OGD) episodes to assess the endogenous protective mechanisms neurons implement at the metabolic and cellular level. We found that neurons exposed to a five minute period of glucose deprivation recovered oxygen utilization and lactate production using novel microphysiometry techniques. Using the non-toxic and energetically favorable five minute exposure, we developed a preconditioning paradigm where neurons are exposed to this brief OGD for three consecutive days. These cells experienced a 45% greater survival following an otherwise lethal event and exhibited a longer lasting window of protection in comparison to our previous in vitro preconditioning model using a single stress. As in other models, preconditioned cells exhibited mild caspase activation, an increase in oxidized proteins and a requirement for reactive oxygen species for neuroprotection. Heat shock protein 70 was upregulated during preconditioning, yet the majority of this protein was released extracellularly. We believe coupling this neuron-enriched multi-day model with microphysiometry will allow us to assess neuronal specific real-time metabolic adaptations necessary for preconditioning. Copyright © 2010 Elsevier B.V. All rights reserved.

CURRENT USE AND FUTURE NEEDS OF BIODOSIMETRY IN STUDIES OF LONG-TERM HEALTH RISK FOLLOWING RADIATION EXPOSURE

PubMed Central

Simon, Steven L.; Bouville, André; Kleinerman, Ruth

2009-01-01

Biodosimetry measurements can potentially be an important and integral part of the dosimetric methods used in long-term studies of health risk following radiation exposure. Such studies rely on accurate estimation of doses to the whole body or to specific organs of individuals in order to derive reliable estimates of cancer risk. However, dose estimates based on analytical dose reconstruction (i.e., models) or personnel monitoring measurements, e.g., film-badges, can have substantial uncertainty. Biodosimetry can potentially reduce uncertainty in health risk studies by corroboration of model-based dose estimates or by using them to assess bias in dose models. While biodosimetry has begun to play a more significant role in long-term health risk studies, its use is still generally limited in that context due to one or more factors including, inadequate limits of detection, large inter-individual variability of the signal measured, high per-sample cost, and invasiveness. Presently, the most suitable biodosimetry methods for epidemiologic studies are chromosome aberration frequencies from fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes and electron paramagnetic resonance (EPR) measurements made on tooth enamel. Both types of measurements, however, are usually invasive and require difficult to obtain biological samples. Moreover, doses derived from these methods are not always directly relevant to the tissues of interest. To increase the value of biodosimetry to epidemiologic studies, a number of issues need to be considered including limits of detection, effects of inhomogenous exposure of the body, how to extrapolate from the tissue sampled to the tissues of interest, and how to adjust dosimetry models applied to large populations based on sparse biodosimetry measurements. The requirements of health risk studies suggest a set of characteristics that, if satisfied by new biodosimetry methods, would increase the overall usefulness of biodosimetry to determining radiation health risks. PMID:20065672

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...

Summary of ionizing radiation analysis on the Long Duration Exposure Facility

NASA Technical Reports Server (NTRS)

Parnell, T. A.

1992-01-01

The ionizing radiation measurements flown on the Long Duration Exposure Facility (LDEF) were contained in 15 experiments which utilized passive detectors to pursue objectives in astrophysics and to measure the radiation environment and dosimetric quantities. The spacecraft structure became sufficiently radioactive to permit additional important studies. The induced activity allows extensive radiation mapping in the structure, and independent comparison with experiment dosimetric techniques, and significant studies of secondary effects. The long exposure time, attitude stability, and number and types of measurements produced a unique and critical set of data for low Earth orbit that will not be duplicated for more than a decade. The data allow an unprecedented test, and improvement if required, of models of the radiation environment and the radiation transport methods that are used to calculate the internal radiation and its effects in spacecraft. Results of measurements in the experiments, as well as from radioactivity in the structure, have clearly shown effects from the directional properties of the radiation environment, and progress was made in the dosimetric mapping of LDEF. These measurements have already influenced some Space Station Freedom design requirements. Preliminary results from experiments, reported at this symposium and in earlier papers, show that the 5.8 years exposure considerably enhanced the scientific return of the radiation measurements. The early results give confidence that the experiments will make significant advances in the knowledge of ultra heavy cosmic rays, anomalous cosmic rays, and heavy ions trapped in the radiation belts. Unexpected phenomena were observed, which require explanation. These include stopping iron group ions between the energy ranges anticipated for anomalous and galactic cosmic rays in the LDEF orbit. A surprising concentration of the Be-7 nuclide was discovered on the 'front' surface of LDEF, apparently transported up from the stratosphere with exceptional efficiency.

Estimators for longitudinal latent exposure models: examining measurement model assumptions.

PubMed

Sánchez, Brisa N; Kim, Sehee; Sammel, Mary D

2017-06-15

Latent variable (LV) models are increasingly being used in environmental epidemiology as a way to summarize multiple environmental exposures and thus minimize statistical concerns that arise in multiple regression. LV models may be especially useful when multivariate exposures are collected repeatedly over time. LV models can accommodate a variety of assumptions but, at the same time, present the user with many choices for model specification particularly in the case of exposure data collected repeatedly over time. For instance, the user could assume conditional independence of observed exposure biomarkers given the latent exposure and, in the case of longitudinal latent exposure variables, time invariance of the measurement model. Choosing which assumptions to relax is not always straightforward. We were motivated by a study of prenatal lead exposure and mental development, where assumptions of the measurement model for the time-changing longitudinal exposure have appreciable impact on (maximum-likelihood) inferences about the health effects of lead exposure. Although we were not particularly interested in characterizing the change of the LV itself, imposing a longitudinal LV structure on the repeated multivariate exposure measures could result in high efficiency gains for the exposure-disease association. We examine the biases of maximum likelihood estimators when assumptions about the measurement model for the longitudinal latent exposure variable are violated. We adapt existing instrumental variable estimators to the case of longitudinal exposures and propose them as an alternative to estimate the health effects of a time-changing latent predictor. We show that instrumental variable estimators remain unbiased for a wide range of data generating models and have advantages in terms of mean squared error. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Operation of the computer model for microenvironment atomic oxygen exposure

NASA Technical Reports Server (NTRS)

Bourassa, R. J.; Gillis, J. R.; Gruenbaum, P. E.

1995-01-01

A computer model for microenvironment atomic oxygen exposure has been developed to extend atomic oxygen modeling capability to include shadowing and reflections. The model uses average exposure conditions established by the direct exposure model and extends the application of these conditions to treat surfaces of arbitrary shape and orientation.

Modeling adverse environmental impacts on the reproductive system.

PubMed

Sussman, N B; Mazumdar, S; Mattison, D R

1999-03-01

When priority topics are being established for the study of women's health, it is generally agreed that one important area on which to focus research is reproduction. For example, increasing attention has been directed to environmental exposures that disrupt the endocrine system and alter reproduction. These concerns also suggest the need to give greater attention to the use of animal toxicologic testing to draw inferences about human reproductive risks. Successful reproduction requires multiple simultaneous and sequential processes in both the male and female, and the effect of toxicity on reproduction-related processes is time dependent. Currently, however, the risk assessment approach does not allow for the use of multiple processes or for considering the reproductive process response as a function of time. We discuss several issues in modeling exposure effects on reproductive function for risk assessment and present an overview of approaches for reproductive risk assessment. Recommendations are provided for an effective animal study design for determining reproductive risk that addresses optimization of the duration of dosing, observation of the effects of exposure on validated biomarkers, analysis of several biomarkers for complete characterization of the exposure on the underlying biologic processes, the need for longitudinally observed exposure effects, and a procedure for estimating human reproductive risk from the animal findings. An approach to characterizing reproductive toxicity to estimate the increased fertility risks in a dibromochloropropane (DBCP)-exposed human population is illustrated, using several reproductive biomarkers simultaneously from a longitudinal rabbit inhalation study of DBCP and an interspecies extrapolation method.

Consumer product chemical weight fractions from ingredient lists.

PubMed

Isaacs, Kristin K; Phillips, Katherine A; Biryol, Derya; Dionisio, Kathie L; Price, Paul S

2018-05-01

Assessing human exposures to chemicals in consumer products requires composition information. However, comprehensive composition data for products in commerce are not generally available. Many consumer products have reported ingredient lists that are constructed using specific guidelines. A probabilistic model was developed to estimate quantitative weight fraction (WF) values that are consistent with the rank of an ingredient in the list, the number of reported ingredients, and labeling rules. The model provides the mean, median, and 95% upper and lower confidence limit WFs for ingredients of any rank in lists of any length. WFs predicted by the model compared favorably with those reported on Material Safety Data Sheets. Predictions for chemicals known to provide specific functions in products were also found to reasonably agree with reported WFs. The model was applied to a selection of publicly available ingredient lists, thereby estimating WFs for 1293 unique ingredients in 1123 products in 81 product categories. Predicted WFs, although less precise than reported values, can be estimated for large numbers of product-chemical combinations and thus provide a useful source of data for high-throughput or screening-level exposure assessments.

LONGITUDINAL COHORT METHODS STUDIES

EPA Science Inventory

Accurate exposure classification tools are required to link exposure with health effects in epidemiological studies. Exposure classification for occupational studies is relatively easy compared to predicting residential childhood exposures. Recent NHEXAS (Maryland) study articl...

EXPOSURE RELATED DOSE ESTIMATING MODEL ( ERDEM ) A PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC ( PBPK/PD ) MODEL FOR ASSESSING HUMAN EXPOSURE AND RISK

EPA Science Inventory

The Exposure Related Dose Estimating Model (ERDEM) is a PBPK/PD modeling system that was developed by EPA's National Exposure Research Laboratory (NERL). The ERDEM framework provides the flexibility either to use existing models and to build new PBPK and PBPK/PD models to address...

Modeling Of In-Vehicle Human Exposure to Ambient Fine Particulate Matter

PubMed Central

Liu, Xiaozhen; Frey, H. Christopher

2012-01-01

A method for estimating in-vehicle PM2.5 exposure as part of a scenario-based population simulation model is developed and assessed. In existing models, such as the Stochastic Exposure and Dose Simulation model for Particulate Matter (SHEDS-PM), in-vehicle exposure is estimated using linear regression based on area-wide ambient PM2.5 concentration. An alternative modeling approach is explored based on estimation of near-road PM2.5 concentration and an in-vehicle mass balance. Near-road PM2.5 concentration is estimated using a dispersion model and fixed site monitor (FSM) data. In-vehicle concentration is estimated based on air exchange rate and filter efficiency. In-vehicle concentration varies with road type, traffic flow, windspeed, stability class, and ventilation. Average in-vehicle exposure is estimated to contribute 10 to 20 percent of average daily exposure. The contribution of in-vehicle exposure to total daily exposure can be higher for some individuals. Recommendations are made for updating exposure models and implementation of the alternative approach. PMID:23101000

Modification of the TASMIP x-ray spectral model for the simulation of microfocus x-ray sources

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

Sisniega, A.; Vaquero, J. J., E-mail: juanjose.vaquero@uc3m.es; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid ES28007

2014-01-15

Purpose: The availability of accurate and simple models for the estimation of x-ray spectra is of great importance for system simulation, optimization, or inclusion of photon energy information into data processing. There is a variety of publicly available tools for estimation of x-ray spectra in radiology and mammography. However, most of these models cannot be used directly for modeling microfocus x-ray sources due to differences in inherent filtration, energy range and/or anode material. For this reason the authors propose in this work a new model for the simulation of microfocus spectra based on existing models for mammography and radiology, modifiedmore » to compensate for the effects of inherent filtration and energy range. Methods: The authors used the radiology and mammography versions of an existing empirical model [tungsten anode spectral model interpolating polynomials (TASMIP)] as the basis of the microfocus model. First, the authors estimated the inherent filtration included in the radiology model by comparing the shape of the spectra with spectra from the mammography model. Afterwards, the authors built a unified spectra dataset by combining both models and, finally, they estimated the parameters of the new version of TASMIP for microfocus sources by calibrating against experimental exposure data from a microfocus x-ray source. The model was validated by comparing estimated and experimental exposure and attenuation data for different attenuating materials and x-ray beam peak energy values, using two different x-ray tubes. Results: Inherent filtration for the radiology spectra from TASMIP was found to be equivalent to 1.68 mm Al, as compared to spectra obtained from the mammography model. To match the experimentally measured exposure data the combined dataset required to apply a negative filtration of about 0.21 mm Al and an anode roughness of 0.003 mm W. The validation of the model against real acquired data showed errors in exposure and attenuation in line with those reported for other models for radiology or mammography. Conclusions: A new version of the TASMIP model for the estimation of x-ray spectra in microfocus x-ray sources has been developed and validated experimentally. Similarly to other versions of TASMIP, the estimation of spectra is very simple, involving only the evaluation of polynomial expressions.« less

40 CFR 270.10 - General application requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... associated with transportation to or from the unit; (ii) The potential pathways of human exposure to... resulting from both direct and indirect exposure pathways. The Director may also require a permittee or...

Assessment of outdoor radiofrequency electromagnetic field exposure through hotspot localization using kriging-based sequential sampling.

PubMed

Aerts, Sam; Deschrijver, Dirk; Verloock, Leen; Dhaene, Tom; Martens, Luc; Joseph, Wout

2013-10-01

In this study, a novel methodology is proposed to create heat maps that accurately pinpoint the outdoor locations with elevated exposure to radiofrequency electromagnetic fields (RF-EMF) in an extensive urban region (or, hotspots), and that would allow local authorities and epidemiologists to efficiently assess the locations and spectral composition of these hotspots, while at the same time developing a global picture of the exposure in the area. Moreover, no prior knowledge about the presence of radiofrequency radiation sources (e.g., base station parameters) is required. After building a surrogate model from the available data using kriging, the proposed method makes use of an iterative sampling strategy that selects new measurement locations at spots which are deemed to contain the most valuable information-inside hotspots or in search of them-based on the prediction uncertainty of the model. The method was tested and validated in an urban subarea of Ghent, Belgium with a size of approximately 1 km2. In total, 600 input and 50 validation measurements were performed using a broadband probe. Five hotspots were discovered and assessed, with maximum total electric-field strengths ranging from 1.3 to 3.1 V/m, satisfying the reference levels issued by the International Commission on Non-Ionizing Radiation Protection for exposure of the general public to RF-EMF. Spectrum analyzer measurements in these hotspots revealed five radiofrequency signals with a relevant contribution to the exposure. The radiofrequency radiation emitted by 900 MHz Global System for Mobile Communications (GSM) base stations was always dominant, with contributions ranging from 45% to 100%. Finally, validation of the subsequent surrogate models shows high prediction accuracy, with the final model featuring an average relative error of less than 2dB (factor 1.26 in electric-field strength), a correlation coefficient of 0.7, and a specificity of 0.96. Copyright © 2013 Elsevier Inc. All rights reserved.

Injury Risk and Noise Exposure in Firefighter Training Operations.

PubMed

Neitzel, Richard L; Long, Rachel N; Sun, Kan; Sayler, Stephanie; von Thaden, Terry L

2016-05-01

Firefighters have high rate of injuries and illnesses, as well as exposures to high levels of noise. This study explored the relationship between noise exposure and injury among firefighters. We recruited firefighters undergoing vehicle extrication and structural collapse emergency response training at a highly realistic training facility. Demographics, health status, body mass index (BMI), and history of serious injuries (i.e. injuries requiring first aid treatment, treatment in a medical clinic or office, or treatment at a hospital) were assessed at baseline, and daily activities, injury events, and near misses were assessed daily via surveys. Participants' noise exposures were monitored for one 24-h period using noise dosimeters. We used a mixed-effects logistic regression model to estimate the odds of injury events and near misses associated with noise exposure as an independent variable. Of 56 subjects, 20 (36%) reported that they had ever suffered a serious injury during firefighting activities, and 9 (16%) reported a serious injury within the past year. We estimated rates of 6.6 lifetime serious injuries per 100 FTE 16.1 serious injuries per 100 FTE within the past year. Our models indicated a significant increase in injury events and near misses among those with higher BMI, and as well as a dose-response relationship between near misses/injuries and increasing noise levels. Noise levels >90 dBA in the 30 min prior to time of injury or near miss were associated with substantially increased odds ratios for injury or near miss. Our models further indicated that perceived job demands were significantly associated with increased risk of injury or near miss. Our results suggest that noise exposures may need to be incorporated into injury prevention programs for firefighters to reduce injuries among this high-risk occupational group. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Reducing attenuation in exposure-response relationships by exposure modeling and grouping: the relationship between wood dust exposure and lung function.

PubMed

Teschke, Kay; Spierings, Judith; Marion, Stephen A; Demers, Paul A; Davies, Hugh W; Kennedy, Susan M

2004-12-01

In a study of wood dust exposure and lung function, we tested the effect on the exposure-response relationship of six different exposure metrics using the mean measured exposure of each subject versus the mean exposure based on various methods of grouping subjects, including job-based groups and groups based on an empirical model of the determinants of exposure. Multiple linear regression was used to examine the association between wood dust concentration and forced expiratory volume in 1s (FEV(1)), adjusting for age, sex, height, race, pediatric asthma, and smoking. Stronger point estimates of the exposure-response relationships were observed when exposures were based on increasing levels of aggregation, allowing the relationships to be found statistically significant in four of the six metrics. The strongest point estimates were found when exposures were based on the determinants of exposure model. Determinants of exposure modeling offers the potential for improvement in risk estimation equivalent to or beyond that from job-based exposure grouping.

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. ...

Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment

PubMed Central

Germolec, Dori R.; Luebke, Robert W.; Johnson, Victor J.

2016-01-01

This overview is an update of the unit originally published in 2004. While the basic tenants of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. PMID:26828330

Estimation of body surface area in the musk shrew ( Suncus murinus): a small animal for testing chemotherapy-induced emesis.

PubMed

Eiseman, Julie L; Sciullo, Michael; Wang, Hong; Beumer, Jan H; Horn, Charles C

2017-10-01

Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K m ) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.

Parental decisions, child health and valuation of avoiding arsenic in drinking water in rural Bangladesh.

PubMed

Aziz, Sonia N; Boyle, Kevin J; Crocker, Tom

2015-03-01

Arsenic contamination of groundwater in Bangladesh is a widespread public health hazard. Water sources without high arsenic levels are scarce, affecting people's availability for work and other activities when they have to seek safe water to drink. While children are particularly susceptible to chronic arsenic exposure, limited information and heavy constraints on resources may preclude people in developing countries from taking protective actions. Since parents are primary decision-makers for children, a model of stochastic decision-making analytically linking parent health and child health is used to frame the valuation of avoiding arsenic exposure using an averting behavior model. The results show that safe drinking water programs do work and that people do take protective actions. The results can help guide public health mitigation policies, and examine whether factors such as child health and time required for remediation have an effect on mitigation measures.

Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment.

PubMed

DeWitt, Jamie C; Germolec, Dori R; Luebke, Robert W; Johnson, Victor J

2016-02-01

This overview is an update of the unit originally published in 2004. While the basic tenets of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available, and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. Copyright © 2016 John Wiley & Sons, Inc.

Influence of Exposure and Toxicokinetics on Measures of Aquatic Toxicity for Organic Contaminants: A Case Study Review

PubMed Central

Landrum, Peter F; Chapman, Peter M; Neff, Jerry; Page, David S

2013-01-01

This theoretical and case study review of dynamic exposures of aquatic organisms to organic contaminants examines variables important for interpreting exposure and therefore toxicity. The timing and magnitude of the absorbed dose change when the dynamics of exposure change. Thus, the dose metric for interpreting toxic responses observed during such exposure conditions is generally limited to the specific experiment and cannot be extrapolated to either other experiments with different exposure dynamics or to field exposures where exposure dynamics usually are different. This is particularly true for mixture exposures, for which the concentration and composition and, therefore, the timing and magnitude of exposure to individual components of different potency and potentially different mechanisms of action can vary. Aquatic toxicology needs studies that develop temporal thresholds for absorbed toxicant doses to allow for better extrapolation between conditions of dynamic exposure. Improved experimental designs are required that include high-quality temporal measures of both the exposure and the absorbed dose to allow better interpretation of data. For the short term, initial water concentration can be considered a conservative measure of exposure, although the extent to which this is true cannot be estimated specifically unless the dynamics of exposure as well as the toxicokinetics of the chemicals in the exposure scenario for the organism of interest are known. A better, but still limited, metric for interpreting the exposure and, therefore, toxicity is the peak absorbed dose, although this neglects toxicodynamics, requires appropriate temporal measures of accumulated dose to determine the peak concentration, and requires temporal thresholds for critical body residue for each component of the mixture. Integr Environ Assess Manag 2013; 9: 196–210. © 2012 SETAC PMID:23229376

Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance

USGS Publications Warehouse

Gutreuter, S.; Boogaard, M.A.

2007-01-01

Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2???,5???-dichloro-4???- nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4- nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software. ?? 2007 SETAC.