WorldWideScience

Sample records for modeling human exposure

  1. Human Exposure Modeling - Databases to Support Exposure Modeling

    Science.gov (United States)

    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.

  2. Variation in calculated human exposure. Comparison of calculations with seven European human exposure models

    NARCIS (Netherlands)

    Swartjes F; ECO

    2003-01-01

    Twenty scenarios, differing with respect to land use, soil type and contaminant, formed the basis for calculating human exposure from soil contaminants with the use of models contributed by seven European countries (one model per country). Here, the human exposures to children and children

  3. Modelling Human Exposure to Chemicals in Food

    NARCIS (Netherlands)

    Slob W

    1993-01-01

    Exposure to foodborne chemicals is often estimated using the average consumption pattern in the human population. To protect the human population instead of the average individual, however, interindividual variability in consumption behaviour must be taken into account. This report shows how food

  4. MODELING ENERGY EXPENDITURE AND OXYGEN CONSUMPTION IN HUMAN EXPOSURE MODELS: ACCOUNTING FOR FATIGUE AND EPOC

    Science.gov (United States)

    Human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the modeled Individual's physical activity level as described in an activity diary. Activity level is quantified via standardized val...

  5. MODELING ENERGY EXPENDITURE AND OXYGEN CONSUMPTION IN HUMAN EXPOSURE MODELS: ACCOUNTING FOR FATIGUE AND EPOC

    Science.gov (United States)

    Human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the modeled Individual's physical activity level as described in an activity diary. Activity level is quantified via standardized val...

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

    Science.gov (United States)

    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...

  7. Probabilistic estimation of residential air exchange rates for population-based human exposure modeling

    Science.gov (United States)

    Residential air exchange rates (AERs) are a key determinant in the infiltration of ambient air pollution indoors. Population-based human exposure models using probabilistic approaches to estimate personal exposure to air pollutants have relied on input distributions from AER meas...

  8. A Chain Modeling Approach To Estimate the Impact of Soil Cadmium Pollution on Human Dietary Exposure

    NARCIS (Netherlands)

    Franz, E.; Romkens, P.F.A.M.; Raamsdonk, van L.W.D.; Fels-Klerx, van der H.J.

    2008-01-01

    Cadmium in soil poses a risk for human health, due to its accumulation in food and feed crops. The extent of accumulation depends strongly on soil type and the degree of pollution. The objective of the present study was to develop a predictive model to estimate human dietary cadmium exposure from so

  9. Mathematical Models of Human Hematopoiesis Following Acute Radiation Exposure

    Science.gov (United States)

    2014-05-01

    the model predicts. Radiation dose from skin contamination can result in cutaneous injury leading to systemic responses and may im- pact the observed...medical and performance consequences from radiation and combined injuries , thereby enhancing our understanding of the potential impact of a nuclear...subsequently. In addition to the insight gained from combined injury modeling, the models of hematopoiesis and radiation alone provide clini- cally

  10. Mixtures of endocrine disrupting contaminants modelled on human high end exposures

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Kortenkamp, A.; Petersen, Marta Axelstad

    2012-01-01

    in vivo endocrine disrupting effects and information about human exposures was available, including phthalates, pesticides, UV‐filters, bisphenol A, parabens and the drug paracetamol. The mixture ratio was chosen to reflect high end human intakes. To make decisions about the dose levels for studies...... though each individual chemical is present at low, ineffective doses, but the effects of mixtures modelled based on human intakes have not previously been investigated. To address this issue for the first time, we selected 13 chemicals for a developmental mixture toxicity study in rats where data about...... in the rat, we employed the point of departure index (PODI) approach, which sums up ratios between estimated exposure levels and no‐observed‐adverse‐effect‐level (NOAEL) values of individual substances. For high end human exposures to the 13 selected chemicals, we calculated a PODI of 0.016. As only a PODI...

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

    DEFF Research Database (Denmark)

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A

    2015-01-01

    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...

  12. An agent-based model of exposure to human toxocariasis: a multi-country validation.

    Science.gov (United States)

    Kanobana, K; Devleesschauwer, B; Polman, K; Speybroeck, N

    2013-07-01

    Seroprevalence data illustrate that human exposure to Toxocara is frequent. Environmental contamination with Toxocara spp. eggs is assumed to be the best indicator of human exposure, but increased risk of exposure has also been associated with many other factors. Reported associations are inconsistent, however, and there is still ambiguity regarding the factors driving the onset of Toxocara antibody positivity. The objective of this work was to assess the validity of our current conceptual understanding of the key processes driving human exposure to Toxocara. We constructed an agent-based model predicting Toxocara antibody positivity (as a measure of exposure) in children. Exposure was assumed to depend on the joint probability of 3 parameters: (1) environmental contamination with Toxocara spp. eggs, (2) larvation of these eggs and (3) the age-related contact with these eggs. This joint probability was linked to processes of acquired humoral immunity, influencing the rate of antibody seroreversion. The results of the simulation were validated against published data from 5 different geographical settings. Using simple rules and a stochastic approach with parameter estimates derived from the respective contexts, plausible serological patterns emerged from the model in nearly all settings. Our approach leads to novel insights in the transmission dynamics of Toxocara.

  13. Local-Scale Air Quality Modeling in Support of Human Health and Exposure Research (Invited)

    Science.gov (United States)

    Isakov, V.

    2010-12-01

    Spatially- and temporally-sparse information on air quality is a key concern for air-pollution-related environmental health studies. Monitor networks are sparse in both space and time, are costly to maintain, and are often designed purposely to avoid detecting highly localized sources. Recent studies have shown that more narrowly defining the geographic domain of the study populations and improvements in the measured/estimated ambient concentrations can lead to stronger associations between air pollution and hospital admissions and mortality records. Traditionally, ambient air quality measurements have been used as a primary input to support human health and exposure research. However, there is increasing evidence that the current ambient monitoring network is not capturing sharp gradients in exposure due to the presence of high concentration levels near, for example, major roadways. Many air pollutants exhibit large concentration gradients near large emitters such as major roadways, factories, ports, etc. To overcome these limitations, researchers are now beginning to use air quality models to support air pollution exposure and health studies. There are many advantages to using air quality models over traditional approaches based on existing ambient measurements alone. First, models can provide spatially- and temporally-resolved concentrations as direct input to exposure and health studies and thus better defining the concentration levels for the population in the geographic domain. Air quality models have a long history of use in air pollution regulations, and supported by regulatory agencies and a large user community. Also, models can provide bidirectional linkages between sources of emissions and ambient concentrations, thus allowing exploration of various mitigation strategies to reduce risk to exposure. In order to provide best estimates of air concentrations to support human health and exposure studies, model estimates should consider local-scale features

  14. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1995-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  15. A model of human nasal epithelial cells adapted for direct and repeated exposure to airborne pollutants.

    Science.gov (United States)

    Bardet, Gaëlle; Achard, Sophie; Loret, Thomas; Desauziers, Valérie; Momas, Isabelle; Seta, Nathalie

    2014-08-17

    Airway epithelium lining the nasal cavity plays a pivotal role in respiratory tract defense and protection mechanisms. Air pollution induces alterations linked to airway diseases such as asthma. Only very few in vitro studies to date have succeeded in reproducing physiological conditions relevant to cellular type and chronic atmospheric pollution exposure. We therefore, set up an in vitro model of human Airway Epithelial Cells of Nasal origin (hAECN) close to real human cell functionality, specifically adapted to study the biological effects of exposure to indoor gaseous pollution at the environmental level. hAECN were exposed under air-liquid interface, one, two, or three-times at 24 h intervals for 1 h, to air or formaldehyde (200 μg/m(3)), an indoor air gaseous pollutant. All experiments were ended at day 4, when both cellular viability and cytokine production were assessed. Optimal adherence and confluence of cells were obtained 96 h after cell seeding onto collagen IV-precoated insert. Direct and repeated exposure to formaldehyde did not produce any cellular damage or IL-6 production change, although weak lower IL-8 production was observed only after the third exposure. Our model is significantly better than previous ones due to cell type and the repeated exposure protocol.

  16. Modelling of human exposure to air pollution in the urban environment: a GPS-based approach.

    Science.gov (United States)

    Dias, Daniela; Tchepel, Oxana

    2014-03-01

    The main objective of this work was the development of a new modelling tool for quantification of human exposure to traffic-related air pollution within distinct microenvironments by using a novel approach for trajectory analysis of the individuals. For this purpose, mobile phones with Global Positioning System technology have been used to collect daily trajectories of the individuals with higher temporal resolution and a trajectory data mining, and geo-spatial analysis algorithm was developed and implemented within a Geographical Information System to obtain time-activity patterns. These data were combined with air pollutant concentrations estimated for several microenvironments. In addition to outdoor, pollutant concentrations in distinct indoor microenvironments are characterised using a probabilistic approach. An example of the application for PM2.5 is presented and discussed. The results obtained for daily average individual exposure correspond to a mean value of 10.6 and 6.0-16.4 μg m(-3) in terms of 5th-95th percentiles. Analysis of the results shows that the use of point air quality measurements for exposure assessment will not explain the intra- and inter-variability of individuals' exposure levels. The methodology developed and implemented in this work provides time-sequence of the exposure events thus making possible association of the exposure with the individual activities and delivers main statistics on individual's air pollution exposure with high spatio-temporal resolution.

  17. Dose-rate models for human survival after exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T.D.; Morris, M.D.; Young, R.W.

    1986-01-01

    This paper reviews new estimates of the L/sub 50/ in man by Mole and by Rotblat, the biological processes contributing to hematologic death, the collection of animal experiments dealing with hematologic death, and the use of regression analysis to make new estimates of human mortality based on all relevant animal studies. Regression analysis of animal mortality data has shown that mortality is dependent strongly on dose rate, species, body weight, and time interval over which the exposure is delivered. The model has predicted human LD/sub 50/s of 194, 250, 310, and 360 rad to marrow when the exposure time is a minute, an hour, a day, and a week, respectively.

  18. Comparative Benchmark Dose Modeling as a Tool to Make the First Estimate of Safe Human Exposure Levels to Lunar Dust

    Science.gov (United States)

    James, John T.; Lam, Chiu-wing; Scully, Robert R.

    2013-01-01

    Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.

  19. Forecasting human exposure to atmospheric pollutants in Portugal - A modelling approach

    Science.gov (United States)

    Borrego, C.; Sá, E.; Monteiro, A.; Ferreira, J.; Miranda, A. I.

    2009-12-01

    Air pollution has become one main environmental concern because of its known impact on human health. Aiming to inform the population about the air they are breathing, several air quality modelling systems have been developed and tested allowing the assessment and forecast of air pollution ambient levels in many countries. However, every day, an individual is exposed to different concentrations of atmospheric pollutants as he/she moves from and to different outdoor and indoor places (the so-called microenvironments). Therefore, a more efficient way to prevent the population from the health risks caused by air pollution should be based on exposure rather than air concentrations estimations. The objective of the present study is to develop a methodology to forecast the human exposure of the Portuguese population based on the air quality forecasting system available and validated for Portugal since 2005. Besides that, a long-term evaluation of human exposure estimates aims to be obtained using one-year of this forecasting system application. Additionally, a hypothetical 50% emission reduction scenario has been designed and studied as a contribution to study emission reduction strategies impact on human exposure. To estimate the population exposure the forecasting results of the air quality modelling system MM5-CHIMERE have been combined with the population spatial distribution over Portugal and their time-activity patterns, i.e. the fraction of the day time spent in specific indoor and outdoor places. The population characterization concerning age, work, type of occupation and related time spent was obtained from national census and available enquiries performed by the National Institute of Statistics. A daily exposure estimation module has been developed gathering all these data and considering empirical indoor/outdoor relations from literature to calculate the indoor concentrations in each one of the microenvironments considered, namely home, office/school, and other

  20. Dermal absorption and skin damage following hydrofluoric acid exposure in an ex vivo human skin model.

    Science.gov (United States)

    Dennerlein, Kathrin; Kiesewetter, Franklin; Kilo, Sonja; Jäger, Thomas; Göen, Thomas; Korinth, Gintautas; Drexler, Hans

    2016-04-25

    The wide industrial use of hydrofluoric acid (HF) poses a high risk for accidental dermal exposure. Despite local and systemic hazards associated with HF, information on percutaneous penetration and tissue damage is rare. In the present ex vivo study, the dermal absorption of HF (detected in terms of fluoride ions) was quantified and the skin damaging potential as a function of concentration and exposure duration was assessed. Percutaneous penetration of HF (c=5, 30, and 50%) at 3 exposure durations (3, 5, and 10 min) was investigated in a static diffusion cell model using freshly excised human skin. Alterations of skin were histologically evaluated. HF rapidly penetrated through skin under formation of a considerable intradermal reservoir (∼ 13-67% of total absorbed fluoride). Histologically, epidermal alterations were detected already after exposure to 5% HF for 3 min. The degree of skin damage increased with rising concentration and exposure duration leading to coagulation necrosis. For HF concentrations of ≥ 30%, skin damage progressed into deeper skin layers. Topically applied HF concentration was the principal parameter determining HF induced skin effects. The intradermal HF retention capacity associated with progression and prolongation of HF induced skin effects must be considered in the review of skin decontamination procedures.

  1. Developmental exposure to estrogen alters differentiation and epigenetic programming in a human fetal prostate xenograft model.

    Directory of Open Access Journals (Sweden)

    Camelia M Saffarini

    Full Text Available Prostate cancer is the most frequent non-cutaneous malignancy in men. There is strong evidence in rodents that neonatal estrogen exposure plays a role in the development of this disease. However, there is little information regarding the effects of estrogen in human fetal prostate tissue. This study explored early life estrogen exposure, with and without a secondary estrogen and testosterone treatment in a human fetal prostate xenograft model. Histopathological lesions, proliferation, and serum hormone levels were evaluated at 7, 30, 90, and 200-day time-points after xenografting. The expression of 40 key genes involved in prostatic glandular and stromal growth, cell-cycle progression, apoptosis, hormone receptors and tumor suppressors was evaluated using a custom PCR array. Epigenome-wide analysis of DNA methylation was performed on whole tissue, and laser capture-microdissection (LCM isolated epithelial and stromal compartments of 200-day prostate xenografts. Combined initial plus secondary estrogenic exposures had the most severe tissue changes as revealed by the presence of hyperplastic glands at day 200. Gene expression changes corresponded with the cellular events in the KEGG prostate cancer pathway, indicating that initial plus secondary exposure to estrogen altered the PI3K-Akt signaling pathway, ultimately resulting in apoptosis inhibition and an increase in cell cycle progression. DNA methylation revealed that differentially methylated CpG sites significantly predominate in the stromal compartment as a result of estrogen-treatment, thereby providing new targets for future investigation. By using human fetal prostate tissue and eliminating the need for species extrapolation, this study provides novel insights into the gene expression and epigenetic effects related to prostate carcinogenesis following early life estrogen exposure.

  2. Development and Evaluation of a New Air Exchange Rate Algorithm for the Stochastic Human Exposure and Dose Simulation Model

    Science.gov (United States)

    between-home and between-city variability in residential pollutant infiltration. This is likely a result of differences in home ventilation, or air exchange rates (AER). The Stochastic Human Exposure and Dose Simulation (SHEDS) model is a population exposure model that uses a pro...

  3. Evaluation of AirGIS: a GIS-based air pollution and human exposure modelling system

    DEFF Research Database (Denmark)

    Ketzel, Matthias; Berkowicz, Ruwim; Hvidberg, Martin

    2011-01-01

    This study describes in brief the latest extensions of the Danish Geographic Information System (GIS)-based air pollution and human exposure modelling system (AirGIS), which has been developed in Denmark since 2001 and gives results of an evaluation with measured air pollution data. The system...... shows, in general, a good performance for both long-term averages (annual and monthly averages), short-term averages (hourly and daily) as well as when reproducing spatial variation in air pollution concentrations. Some shortcomings and future perspectives of the system are discussed too....

  4. Modeling of road traffic noise and estimated human exposure in Fulton County, Georgia, USA.

    Science.gov (United States)

    Seong, Jeong C; Park, Tae H; Ko, Joon H; Chang, Seo I; Kim, Minho; Holt, James B; Mehdi, Mohammed R

    2011-11-01

    Environmental noise is a major source of public complaints. Noise in the community causes physical and socio-economic effects and has been shown to be related to adverse health impacts. Noise, however, has not been actively researched in the United States compared with the European Union countries in recent years. In this research, we aimed at modeling road traffic noise and analyzing human exposure in Fulton County, Georgia, United States. We modeled road traffic noise levels using the United States Department of Transportation Federal Highway Administration Traffic Noise Model implemented in SoundPLAN®. After analyzing noise levels with raster, vector and façade maps, we estimated human exposure to high noise levels. Accurate digital elevation models and building heights were derived from Light Detection And Ranging survey datasets and building footprint boundaries. Traffic datasets were collected from the Georgia Department of Transportation and the Atlanta Regional Commission. Noise level simulation was performed with 62 computers in a distributed computing environment. Finally, the noise-exposed population was calculated using geographic information system techniques. Results show that 48% of the total county population [N=870,166 residents] is potentially exposed to 55 dB(A) or higher noise levels during daytime. About 9% of the population is potentially exposed to 67 dB(A) or higher noises. At nighttime, 32% of the population is expected to be exposed to noise levels higher than 50 dB(A). This research shows that large-scale traffic noise estimation is possible with the help of various organizations. We believe that this research is a significant stepping stone for analyzing community health associated with noise exposures in the United States.

  5. The High-Throughput Stochastic Human Exposure and Dose Simulation Model (SHEDS-HT) & The Chemical and Products Database (CPDat)

    Science.gov (United States)

    The Stochastic Human Exposure and Dose Simulation Model – High-Throughput (SHEDS-HT) is a U.S. Environmental Protection Agency research tool for predicting screening-level (low-tier) exposures to chemicals in consumer products. This course will present an overview of this m...

  6. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  7. A geographic approach to modelling human exposure to traffic air pollution using GIS

    Energy Technology Data Exchange (ETDEWEB)

    Solvang Jensen, S.

    1998-10-01

    A new exposure model has been developed that is based on a physical, single media (air) and single source (traffic) micro environmental approach that estimates traffic related exposures geographically with the postal address as exposure indicator. The micro environments: residence, workplace and street (road user exposure) may be considered. The model estimates outdoor levels for selected ambient air pollutants (benzene, CO, NO{sub 2} and O{sub 3}). The influence of outdoor air pollution on indoor levels can be estimated using average (I/O-ratios. The model has a very high spatial resolution (the address), a high temporal resolution (one hour) and may be used to predict past, present and future exposures. The model may be used for impact assessment of control measures provided that the changes to the model inputs are obtained. The exposure model takes advantage of a standard Geographic Information System (GIS) (ArcView and Avenue) for generation of inputs, for visualisation of input and output, and uses available digital maps, national administrative registers and a local traffic database, and the Danish Operational Street Pollution Model (OSPM). The exposure model presents a new approach to exposure determination by integration of digital maps, administrative registers, a street pollution model and GIS. New methods have been developed to generate the required input parameters for the OSPM model: to geocode buildings using cadastral maps and address points, to automatically generate street configuration data based on digital maps, the BBR and GIS; to predict the temporal variation in traffic and related parameters; and to provide hourly background levels for the OSPM model. (EG) 109 refs.

  8. A geographic approach to modelling human exposure to traffic air pollution using GIS. Separate appendix report

    Energy Technology Data Exchange (ETDEWEB)

    Solvang Jensen, S.

    1998-10-01

    A new exposure model has been developed that is based on a physical, single media (air) and single source (traffic) micro environmental approach that estimates traffic related exposures geographically with the postal address as exposure indicator. The micro environments: residence, workplace and street (road user exposure) may be considered. The model estimates outdoor levels for selected ambient air pollutants (benzene, CO, NO{sub 2} and O{sub 3}). The influence of outdoor air pollution on indoor levels can be estimated using average (I/O-ratios. The model has a very high spatial resolution (the address), a high temporal resolution (one hour) and may be used to predict past, present and future exposures. The model may be used for impact assessment of control measures provided that the changes to the model inputs are obtained. The exposure model takes advantage of a standard Geographic Information System (GIS) (ArcView and Avenue) for generation of inputs, for visualisation of input and output, and uses available digital maps, national administrative registers and a local traffic database, and the Danish Operational Street Pollution Model (OSPM). The exposure model presents a new approach to exposure determination by integration of digital maps, administrative registers, a street pollution model and GIS. New methods have been developed to generate the required input parameters for the OSPM model: to geocode buildings using cadastral maps and address points, to automatically generate street configuration data based on digital maps, the BBR and GIS; to predict the temporal variation in traffic and related parameters; and to provide hourly background levels for the OSPM model. (EG)

  9. Human Exposure Database System (HEDS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Human Exposure Database System (HEDS) provides public access to data sets, documents, and metadata from EPA on human exposure. It is primarily intended for...

  10. Mechanistic modeling of the interrelationships between indoor/outdoor air quality and human exposure in a GIS framework

    Energy Technology Data Exchange (ETDEWEB)

    Isukapalli, S.S.; Purushothaman, V.; Georgopoulos, P.G.

    1999-07-01

    Evaluation of human exposure to atmospheric contaminants such as ozone and particulate matter (PM) is often based on measured data from fixed ambient (outdoors) Air Monitoring Stations. This results in an artificial characterization of indoor exposures, as concentrations and physicochemical attributes of indoor pollutants vary significantly and are different from corresponding outdoor values. A mechanistically-based modeling approach is presented here that aims to improve estimates for the outdoor/indoor relationships of photochemical pollutants and of associated fine particles and, subsequently, of human exposure assessments. New approaches for refining the spatial, temporal, and indoor/outdoor patterns of gas phase photochemical contaminants and PM are currently being developed and tested. These approaches are combined with information from either ambient monitoring networks or from ambient air quality models that consider aerosol physics and chemistry coupled with gas phase photochemistry (e.g. UAM-AERO). This process utilizes Geographic Information Systems (GIS) and Relational Database (RD) methods, to facilitate detailed exposure scenario construction (involving e.g. the geographic location of an individual considered in time) and to aid in the estimation of population exposure over selected geographic areas. The combination of monitor data or air quality modeling with microenvironmental modeling in a GIS framework can potentially provide a useful platform for more accurate assessments of human exposure to co-occurring gas and particulate phase air pollutants.

  11. Toxicokinetic modeling of captan fungicide and its tetrahydrophthalimide biomarker of exposure in humans.

    Science.gov (United States)

    Heredia-Ortiz, Roberto; Bouchard, Michèle

    2012-08-13

    Measurement of tetrahydrophthalimide (THPI) in urine has been used for the biomonitoring of exposure to the widely used captan fungicide in workers. To allow a better understanding of the toxicokinetics of captan and its key biomarker of exposure, a human multi-compartment model was built to simulate the transformation of captan into THPI and its subsequent excretion while accounting for other non-monitored metabolites. The mathematical parameters of the model were determined from best-fits to the time courses of THPI in blood and urine of five volunteers administered orally 1mg/kg and dermally 10mg/kg of captan. In the case of oral administration, the mean elimination half-life of THPI from the body (either through faeces, urine or metabolism) was found to be 13.43 h. In the case of dermal application, mean THPI elimination half-life was estimated to be 21.27 h and was governed by the dermal absorption rate. The average final fractions of administered dose recovered in urine as THPI were 3.6% and 0.02%, for oral and dermal administration, respectively. Furthermore, according to the model, after oral exposure, only 8.6% of the THPI formed in the GI reaches the bloodstream. As for the dermal absorption fraction of captan, it was estimated to be 0.09%. Finally, the average blood clearance rate of THPI calculated from the oral and dermal data was 0.18 ± 0.03 ml/h and 0.24 ± 0.6 ml/h while the predicted volume of distribution was 3.5 ± 0.6l and 7.5 ± 1.9l, respectively. Our mathematical model is in complete accordance with both independent measurements of THPI levels in blood (R(2)=0.996 for oral and R(2)=0.908 for dermal) and urine (R(2)=0.979 for oral and R(2)=0.982 for dermal) as well as previous experimental data published in the literature.

  12. Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling.

    Science.gov (United States)

    Zhang, Jin; Heimbach, Tycho; Scheer, Nico; Barve, Avantika; Li, Wenkui; Lin, Wen; He, Handan

    2016-04-01

    NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (fmCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate fmCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human fmCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.

  13. A Geographic Approach to Modelling Human Exposure to Traffic Air Pollution using GIS

    DEFF Research Database (Denmark)

    Jensen, S. S.

    at the address all the time, and an exposure estimate is also defined that takes into account the time the person spends at the address assuming standardised time-profiles depending on age groups. The exposure model takes advantage of a standard Geographic Information System (GIS) (ArcView and Avenue...... the exposure model. Input requirements are: digital maps including buildings, geocoded addresses, geocoded roads, geocoded cadastres; data from the Building and Dwelling Register (BBR); traffic data (ADT of passenger cars, van, lorries and busses) for linking to a segmented road network; population data...

  14. Modeling Human Exposure to Phthalate Esters: A Comparison of Indirect and Biomonitoring Estimation Methods

    Science.gov (United States)

    Clark, Kathryn E.; David, Raymond M.; Guinn, Richard; Kramarz, Kurt W.; Lampi, Mark A.; Staples, Charles A.

    2011-01-01

    Humans are potentially exposed to phthalate esters (PEs) through ingestion, inhalation, and dermal contact. Studies quantifying exposure to PEs include “biomarker studies” and “indirect studies.” Biomarker studies use measurements of PE metabolites in urine to back-calculate exposure to the parent diester, while indirect studies use the concentration of the PE in each medium of exposure and the rate of intake of that medium to quantify intake of the PE. In this review, exposure estimates from biomarker and indirect studies are compiled and compared for seven PEs to determine if there are regional differences and if there is a preferred approach. The indirect and biomarker methods generally agree with each other within an order of magnitude and discrepancies are explained by difficulties in accounting for use of consumer products, uncertainty concerning absorption, regional differences, and temporal changes. No single method is preferred for estimating intake of all PEs; it is suggested that biomarker estimates be used for low molecular weight PEs for which it is difficult to quantify all sources of exposure and either indirect or biomarker methods be used for higher molecular weight PEs. The indirect methods are useful in identifying sources of exposure while the biomarker methods quantify exposure. PMID:23087593

  15. Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi-route exposure.

    Science.gov (United States)

    Kenyon, Elaina M; Eklund, Christopher; Leavens, Teresa; Pegram, Rex A

    2016-09-01

    As a result of its presence in water as a volatile disinfection byproduct, bromodichloromethane (BDCM), which is mutagenic, poses a potential health risk from exposure via oral, dermal and inhalation routes. We developed a refined human physiologically based pharmacokinetic (PBPK) model for BDCM (including new chemical-specific human parameters) to evaluate the impact of BDCM exposure during showering and bathing on important measures of internal dose compared with oral exposure. The refined model adequately predicted data from the published literature for oral, dermal and bathing/showering exposures. A liter equivalency approach (L-eq) was used to estimate BDCM concentration in a liter of water consumed by the oral route that would be required to produce the same internal dose of BDCM resulting from a 20-min bath or a 10-min shower in water containing 10 µg l(-1) BDCM. The oral liter equivalent concentrations for the bathing scenario were 605, 803 and 5 µg l(-1) BDCM for maximum venous blood concentration (Cmax), the area under the curve (AUCv) and the amount metabolized in the liver per hour (MBDCM), respectively. For a 10-min showering exposure, the oral L-eq concentrations were 282, 312 and 2.1 µg l(-1) for Cmax, AUC and MBDCM, respectively. These results demonstrate large contributions of dermal and inhalation exposure routes to the internal dose of parent chemical reaching the systemic circulation, which could be transformed to mutagenic metabolites in extrahepatic target tissues. Thus, consideration of the contribution of multiple routes of exposure when evaluating risks from water-borne BDCM is needed, and this refined human model will facilitate improved assessment of internal doses from real-world exposures. Published 2015. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  16. Modelling risk of tick exposure in southern Scandinavia using machine learning techniques, satellite imagery, and human population density maps

    DEFF Research Database (Denmark)

    Kjær, Lene Jung; Korslund, L.; Kjelland, V.

    Vector-borne diseases such as Lyme disease and tick-borne encephalitis have become more common in recent decades and present a real health problem in many parts of Europe. Risk assessment, control, and prevention of these diseases require a better understanding of vector abundance as well as risk...... factors determining human exposure to ticks. There is a great need for analyses and models that can predict how vectors and their associated diseases are distributed and how this relates to high risk areas for human exposure.As a part of the ScandTick Innovation project, we surveyed ticks at approximately...... distribution (probability of presence) in southern Scandinavia. Together with the predicted distribution maps, we used human density maps to determine areas with high risk of exposure to ticks. For nymphs, the predicted distribution found corresponded well with known distributions of ticks in Scandinavia...

  17. A quantitative exposure model simulating human norovirus transmission during preparation of deli sandwiches.

    Science.gov (United States)

    Stals, Ambroos; Jacxsens, Liesbeth; Baert, Leen; Van Coillie, Els; Uyttendaele, Mieke

    2015-03-02

    Human noroviruses (HuNoVs) are a major cause of food borne gastroenteritis worldwide. They are often transmitted via infected and shedding food handlers manipulating foods such as deli sandwiches. The presented study aimed to simulate HuNoV transmission during the preparation of deli sandwiches in a sandwich bar. A quantitative exposure model was developed by combining the GoldSim® and @Risk® software packages. Input data were collected from scientific literature and from a two week observational study performed at two sandwich bars. The model included three food handlers working during a three hour shift on a shared working surface where deli sandwiches are prepared. The model consisted of three components. The first component simulated the preparation of the deli sandwiches and contained the HuNoV reservoirs, locations within the model allowing the accumulation of NoV and the working of intervention measures. The second component covered the contamination sources being (1) the initial HuNoV contaminated lettuce used on the sandwiches and (2) HuNoV originating from a shedding food handler. The third component included four possible intervention measures to reduce HuNoV transmission: hand and surface disinfection during preparation of the sandwiches, hand gloving and hand washing after a restroom visit. A single HuNoV shedding food handler could cause mean levels of 43±18, 81±37 and 18±7 HuNoV particles present on the deli sandwiches, hands and working surfaces, respectively. Introduction of contaminated lettuce as the only source of HuNoV resulted in the presence of 6.4±0.8 and 4.3±0.4 HuNoV on the food and hand reservoirs. The inclusion of hand and surface disinfection and hand gloving as a single intervention measure was not effective in the model as only marginal reductions of HuNoV levels were noticeable in the different reservoirs. High compliance of hand washing after a restroom visit did reduce HuNoV presence substantially on all reservoirs. The

  18. A probabilistic modeling approach to assess human inhalation exposure risks to airborne aflatoxin B 1 (AFB 1)

    Science.gov (United States)

    Liao, Chung-Min; Chen, Szu-Chieh

    To assess how the human lung exposure to airborne aflatoxin B 1 (AFB 1) during on-farm activities including swine feeding, storage bin cleaning, corn harvest, and grain elevator loading/unloading, we present a probabilistic risk model, appraised with empirical data. The model integrates probabilistic exposure profiles from a compartmental lung model with the reconstructed dose-response relationships based on an empirical three-parameter Hill equation model, describing AFB 1 cytotoxicity for inhibition response in human bronchial epithelial cells, to quantitatively estimate the inhalation exposure risks. The risk assessment results implicate that exposure to airborne AFB 1 may pose no significance to corn harvest and grain elevator loading/unloading activities, yet a relatively high risk for swine feeding and storage bin cleaning. Applying a joint probability function method based on exceedence profiles, we estimate that a potential high risk for the bronchial region (inhibition=56.69% with 95% confidence interval (CI): 35.05-72.87%) and bronchiolar region (inhibition=44.93% with 95% CI: 21.61 - 66.78%) is alarming during swine feeding activity. We parameterized the proposed predictive model that should encourage a risk-management framework for discussion of carcinogenic risk in occupational settings where inhalation of AFB 1-contaminated dust occurs.

  19. CSOIL 2000 an exposure model for human risk assessment of soil contamination. A model description

    NARCIS (Netherlands)

    Brand E; Otte PF; Lijzen JPA; LER

    2007-01-01

    This RIVM description of the CSOIL 2000 model deals, for the first time, with all aspects of the model. CSOIL 2000 can be used to derive intervention values. Intervention values are calculated for contaminated soil and represent a measure for determining when contaminated soil needs to be

  20. CSOIL 2000 an exposure model for human risk assessment of soil contamination. A model description

    NARCIS (Netherlands)

    Brand E; Otte PF; Lijzen JPA; LER

    2007-01-01

    This RIVM description of the CSOIL 2000 model deals, for the first time, with all aspects of the model. CSOIL 2000 can be used to derive intervention values. Intervention values are calculated for contaminated soil and represent a measure for determining when contaminated soil needs to be remediated

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

    Science.gov (United States)

    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.

  2. Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations.

    Science.gov (United States)

    Worley, Rachel Rogers; Yang, Xiaoxia; Fisher, Jeffrey

    2017-09-01

    Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures. Published by Elsevier Inc.

  3. Using probabilistic modeling to evaluate human exposure to organotin in drinking water transported by polyvinyl chloride pipe.

    Science.gov (United States)

    Fristachi, Anthony; Xu, Ying; Rice, Glenn; Impellitteri, Christopher A; Carlson-Lynch, Heather; Little, John C

    2009-11-01

    The leaching of organotin (OT) heat stabilizers from polyvinyl chloride (PVC) pipes used in residential drinking water systems may affect the quality of drinking water. These OTs, principally mono- and di-substituted species of butyltins and methyltins, are a potential health concern because they belong to a broad class of compounds that may be immune, nervous, and reproductive system toxicants. In this article, we develop probability distributions of U.S. population exposures to mixtures of OTs encountered in drinking water transported by PVC pipes. We employed a family of mathematical models to estimate OT leaching rates from PVC pipe as a function of both surface area and time. We then integrated the distribution of estimated leaching rates into an exposure model that estimated the probability distribution of OT concentrations in tap waters and the resulting potential human OT exposures via tap water consumption. Our study results suggest that human OT exposures through tap water consumption are likely to be considerably lower than the World Health Organization (WHO) "safe" long-term concentration in drinking water (150 microg/L) for dibutyltin (DBT)--the most toxic of the OT considered in this article. The 90th percentile average daily dose (ADD) estimate of 0.034 +/- 2.92 x 10(-4)microg/kg day is approximately 120 times lower than the WHO-based ADD for DBT (4.2 microg/kg day).

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

    Directory of Open Access Journals (Sweden)

    Kevin McNally

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  6. Indoor-to-outdoor particle concentration ratio model for human exposure analysis

    Science.gov (United States)

    Lee, Jae Young; Ryu, Sung Hee; Lee, Gwangjae; Bae, Gwi-Nam

    2016-02-01

    This study presents an indoor-to-outdoor particle concentration ratio (IOR) model for improved estimates of indoor exposure levels. This model is useful in epidemiological studies with large population, because sampling indoor pollutants in all participants' house is often necessary but impractical. As a part of a study examining the association between air pollutants and atopic dermatitis in children, 16 parents agreed to measure the indoor and outdoor PM10 and PM2.5 concentrations at their homes for 48 h. Correlation analysis and multi-step multivariate linear regression analysis was performed to develop the IOR model. Temperature and floor level were found to be powerful predictors of the IOR. Despite the simplicity of the model, it demonstrated high accuracy in terms of the root mean square error (RMSE). Especially for long-term IOR estimations, the RMSE was as low as 0.064 and 0.063 for PM10 and PM2.5, respectively. When using a prediction model in an epidemiological study, understanding the consequence of the modeling error and justifying the use of the model is very important. In the last section, this paper discussed the impact of the modeling error and developed a novel methodology to justify the use of the model.

  7. Ultraviolet Radiation: Human Exposure and Health Risks.

    Science.gov (United States)

    Tenkate, Thomas D.

    1998-01-01

    Provides an overview of human exposure to ultraviolet radiation and associated health effects as well as risk estimates for acute and chronic conditions resulting from such exposure. Demonstrates substantial reductions in health risk that can be achieved through preventive actions. Also includes a risk assessment model for skin cancer. Contains 36…

  8. The application of equilibrium models to incidence situations using the example of the exposure pathway human milk

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, Martin; Karcher, Klaus; Nosske, Dietmar [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany)

    2012-06-15

    The radiation exposure after a short-term release of radioactive substances is often calculated assuming equilibrium conditions. An example is that of the German Incident Calculation Bases for nuclear power plants with pressurized water reactors. Here, the contamination of human milk is calculated using transfer factors. Applying this equilibrium model to incident situations raises the question whether baby's radiation exposure is adequately assessed. This contribution shows that compliance with the relevant dose limits of paragraph 49 of the German Radiation Protection Ordinance is ensured for design basis accidents on the assumption that the hypothetical breastfeeding period starts at the beginning of the activity release. Comparative analyses were performed against the biokinetic models applied by ICRP for radiation protection purposes, taking the reference nuclides {sup 137}Cs, {sup 90}Sr, {sup 131}I, {sup 241}Am and long-lived plutonium isotopes as examples. (orig.)

  9. Realistic numerical modelling of human head tissue exposure to electromagnetic waves from cellular phones

    Science.gov (United States)

    Scarella, Gilles; Clatz, Olivier; Lanteri, Stéphane; Beaume, Grégory; Oudot, Steve; Pons, Jean-Philippe; Piperno, Sergo; Joly, Patrick; Wiart, Joe

    2006-06-01

    The ever-rising diffusion of cellular phones has brought about an increased concern for the possible consequences of electromagnetic radiation on human health. Possible thermal effects have been investigated, via experimentation or simulation, by several research projects in the last decade. Concerning numerical modeling, the power absorption in a user's head is generally computed using discretized models built from clinical MRI data. The vast majority of such numerical studies have been conducted using Finite Differences Time Domain methods, although strong limitations of their accuracy are due to heterogeneity, poor definition of the detailed structures of head tissues (staircasing effects), etc. In order to propose numerical modeling using Finite Element or Discontinuous Galerkin Time Domain methods, reliable automated tools for the unstructured discretization of human heads are also needed. Results presented in this article aim at filling the gap between human head MRI images and the accurate numerical modeling of wave propagation in biological tissues and its thermal effects. To cite this article: G. Scarella et al., C. R. Physique 7 (2006).

  10. HAMLET -Human Model MATROSHKA for Radiation Exposure Determination of Astronauts -Current status and results

    Science.gov (United States)

    Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Burmeister, Soenke; Labrenz, Johannes; Hager, Luke; Palfalvi, Jozsef K.; Hajek, Michael; Puchalska, Monika; Sihver, Lembit

    The exploration of space as seen in specific projects from the European Space Agency (ESA) acts as groundwork for human long duration space missions. One of the main constraints for long duration human missions is radiation. The radiation load on astronauts and cosmonauts in space (as for the ISS) is a factor of 100 higher than the natural radiation on Earth and will further increase should humans travel to Mars. In preparation for long duration space missions it is important to evaluate the impact of space radiation in order to secure the safety of the astronauts and minimize their radiation risks. To determine the radiation risk on humans one has to measure the radiation doses to radiosensitive organs within the human body. One way to approach this is the ESA facility MATROSHKA (MTR), under the scientific and project lead of DLR. It is dedicated to determining the radiation load on astronauts within and outside the International Space Station (ISS), and was launched in January 2004. MTR is currently preparing for its fourth experimental phase inside the Japanese Experimental Module (JEM) in summer 2010. MTR, which mimics a human head and torso, is an anthropomorphic phantom containing over 6000 radiation detectors to determine the depth dose and organ dose distribution in the body. It is the largest international research initiative ever performed in the field of space dosimetry and combines the expertise of leading research institutions around the world, thereby generating a huge pool of data of potentially immense value for research. Aiming at optimal scientific exploitation, the FP7 project HAMLET aims to process and compile the data acquired individually by the participating laboratories of the MATROSHKA experiment. Based on experimental input from the MATROSHKA experiment phases as well as on radiation transport calculations, a three-dimensional model for the distribution of radiation dose in an astronaut's body will be built up. The scientific achievements

  11. Refined biokinetic model for humans exposed to cobalt dietary supplements and other sources of systemic cobalt exposure.

    Science.gov (United States)

    Unice, Kenneth M; Kerger, Brent D; Paustenbach, Dennis J; Finley, Brent L; Tvermoes, Brooke E

    2014-06-05

    An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1 mg Co/day of a Co supplement for 3 months. Three key experimental observations from the human dosing studies were incorporated into the model: (1) an increase in the measured fraction of large molecular serum protein bound Co from 95% during dosing to 99% after dosing; (2) a linear decrease in Co red blood cell concentration after dosing; and (3) Co renal clearance consistent with estimated glomerular filtration rates and free Co²⁺ concentration. The model was refined by adding compartments accounting for (1) albumin bound Co in intravascular fluid (serum); (2) albumin bound Co in extravascular fluid with physiologic exchange rates of albumin bound Co between extravascular and intravascular fluid; and (3) a novel sequential cascade of compartments representing red blood cell ages between 1 and 120 days. Reasonable agreement between the modeled and measured urine, serum, and whole blood concentrations were observed (r>0.84, slope=0.79-1.0) with gastrointestinal absorption rates between 9% and 66%. In addition, model predictions agreed well with data from several external studies representing healthy human volunteers, dialysis patients, anephric patients, a Co-poisoning incident and whole body retention studies. Our revised model considerably improves the state of knowledge on human Co kinetics, and should be helpful for evaluating elevated blood Co concentrations in currently exposed populations, such as metal-on-metal (MoM) hip implant patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Evaluation of an oral subchronic exposure of deoxynivalenol on the composition of human gut microbiota in a model of human microbiota-associated rats.

    Directory of Open Access Journals (Sweden)

    Manuel J Saint-Cyr

    Full Text Available BACKGROUND: Deoxynivalenol (DON, a mycotoxin produced by Fusarium species, is one of the most prevalent mycotoxins present in cereal crops worldwide. Due to its toxic properties, high stability and prevalence, the presence of DON in the food chain represents a health risk for both humans and animals. The gastrointestinal microbiota represents potentially the first target for these food contaminants. Thus, the effects of mycotoxins on the human gut microbiota is clearly an issue that needs to be addressed in further detail. Using a human microbiota-associated rat model, the aim of the present study was to evaluate the impact of a chronic exposure of DON on the composition of human gut microbiota. METHODOLOGY/PRINCIPAL FINDINGS: Four groups of 5 germ free male rats each, housed in 4 sterile isolators, were inoculated with a different fresh human fecal flora. Rats were then fed daily by gavage with a solution of DON at 100 µg/kg bw for 4 weeks. Fecal samples were collected at day 0 before the beginning of the treatment; days 7, 16, 21, and 27 during the treatment; and 10 days after the end of the treatment at day 37. DON effect was assessed by real-time PCR quantification of dominant and subdominant bacterial groups in feces. Despite a different intestinal microbiota in each isolator, similar trends were generally observed. During oral DON exposure, a significant increase of 0.5 log10 was observed for the Bacteroides/Prevotella group during the first 3 weeks of administration. Concentration levels for Escherichia coli decreased at day 27. This significant decrease (0.9 log10 CFU/g remained stable until the end of the experiment. CONCLUSIONS/SIGNIFICANCE: We have demonstrated an impact of oral DON exposure on the human gut microbiota composition. These findings can serve as a template for risk assessment studies of food contaminants on the human gut microbiota.

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

    Science.gov (United States)

    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.

  14. Atmospheric Ionizing Radiation and Human Exposure

    Science.gov (United States)

    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.

  15. Association between chemical pattern in breast milk and congenital cryptorchidism: modelling of complex human exposures

    DEFF Research Database (Denmark)

    Krysiak-Baltyn, Konrad; Toppari, J.; Skakkebaek, N. E.;

    2012-01-01

    in 130 breast milk samples from Danish and Finnish mothers. Half the newborns were healthy controls, whereas the other half was boys with congenital cryptorchidism. The measured chemicals included polychlorinated biphenyls (PCBs), polybrominated diphenyl‐ethers, dioxins (OCDD/PCDFs), phthalates...... for multiple testing, exposure to nine chemicals was significantly different between the cases and controls in the Danish cohort, but not in the Finnish cohort. The multivariate analysis indicated that Danish samples exhibited a stronger correlation between chemical exposure patterns in breast milk...... and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute...

  16. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    Act of 1979, as amended, Title 50, U.S.C., App. 2401 et seq. Violations of these export laws are subject to severe criminal penalties ...DTRA-TR-16-059 DISTRIBUTION A. Approved for public release: distribution is unlimited. Exposure to burn and radiation elicit epithelial cell death in...villus cells, promoting early cell death before migration is complete (Carter et al., 2014, Wolf et al., 1999). This response is fast and strong but

  17. Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Løhr, Mille; Roursgaard, Martin

    2014-01-01

    microtissue model to investigate the toxicological effects associated with a single or multiple exposure of a panel of engineered NMs (Ag, ZnO, MWCNT and a positively charged TiO2).ResultsHere we demonstrate that the repeated exposure of the NMs is more damaging to the liver tissue as in comparison...... with accumulative production of nanomaterials, there is an urgent need to consider the possibility of detrimental health consequences of engineered NM exposure. It has been shown that exposure via inhalation, intratracheal instillation or ingestion can result in NM translocation to the liver. Traditional in vitro......BackgroundThe liver has a crucial role in metabolic homeostasis as well as being the principal detoxification centre of the body, removing xenobiotics and waste products which could potentially include some nanomaterials (NM). With the ever increasing public and occupational exposure associated...

  18. Ascorbate prevents cell death from prolonged exposure to glutamate in an in vitro model of human dopaminergic neurons.

    Science.gov (United States)

    Ballaz, Santiago; Morales, Ingrid; Rodríguez, Manuel; Obeso, José A

    2013-12-01

    Ascorbate (vitamin C) is a nonenzymatic antioxidant highly concentrated in the brain. In addition to mediating redox balance, ascorbate is linked to glutamate neurotransmission in the striatum, where it renders neuroprotection against excessive glutamate stimulation. Oxidative stress and glutamatergic overactivity are key biochemical features accompanying the loss of dopaminergic neurons in the substantia nigra that characterizes Parkinson's disease (PD). At present, it is not clear whether antiglutamate agents and ascorbate might be neuroprotective agents for PD. Thus, we tested whether ascorbate can prevent cell death from prolonged exposure to glutamate using dopaminergic neurons of human origin. To this purpose, dopamine-like neurons were obtained by differentiation of SH-SY5Y cells and then cultured for 4 days without antioxidant (antiaging) protection to evaluate glutamate toxicity and ascorbate protection as a model system of potential factors contributing to dopaminergic neuron death in PD. Glutamate dose dependently induced toxicity in dopaminergic cells largely by the stimulation of AMPA and metabotropic receptors and to a lesser extent by N-methyl-D-aspartate and kainate receptors. At relatively physiological levels of extracellular concentration, ascorbate protected cells against glutamate excitotoxicity. This neuroprotection apparently relies on the inhibition of oxidative stress, because ascorbate prevented the pro-oxidant action of the scavenging molecule quercetin, which occurred over the course of prolonged exposure, as is also seen with glutamate. Our findings show the relevance of ascorbate as a neuroprotective agent and emphasize an often underappreciated role of oxidative stress in glutamate excitotoxicity. Occurrence of a glutamate-ascorbate link in dopaminergic neurons may explain previous contradictions regarding their putative role in PD.

  19. Human inhalation exposures to toluene, ethylbenzene, and m-xylene and physiologically based pharmacokinetic modeling of exposure biomarkers in exhaled air, blood, and urine.

    Science.gov (United States)

    Marchand, Axelle; Aranda-Rodriguez, Rocio; Tardif, Robert; Nong, Andy; Haddad, Sami

    2015-04-01

    Urinary biomarkers of exposure are used widely in biomonitoring studies. The commonly used urinary biomarkers for the aromatic solvents toluene (T), ethylbenzene (E), and m-xylene (X) are o-cresol, mandelic acid, and m-methylhippuric acid. The toxicokinetics of these biomarkers following inhalation exposure have yet to be described by physiologically based pharmacokinetic (PBPK) modeling. Five male volunteers were exposed for 6 h in an inhalation chamber to 1/8 or 1/4 of the time-weighted average exposure value (TWAEV) for each solvent: toluene, ethylbenzene, and m-xylene were quantified in blood and exhaled air and their corresponding urine biomarkers were measured in urine. Published PBPK model for parent compounds was used and simulations were compared with experimental blood and exhaled air concentration data. If discrepancies existed, Vmax and Km were optimized. Urinary excretion was modeled using parameters found in literature assuming simply stoichiometric yields from parent compound metabolism and first-order urinary excretion rate. Alternative models were also tested for (1) the possibility that CYP1A2 is the only enzyme implicated in o-cresol and (2) a 2-step model for describing serial metabolic steps for mandelic acid. Models adapted in this study for urinary excretion will be further used to interpret urinary biomarker kinetic data from mixed exposures of these solvents. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Ethanol consumption modifies the body turnover of cadmium: a study in a rat model of human exposure.

    Science.gov (United States)

    Brzóska, Malgorzata M; Galażyn-Sidorczuk, Malgorzata; Dzwilewska, Ilona

    2013-08-01

    Ethanol (Et) abusers may also be exposed to excessive amounts of cadmium (Cd). Thus, the study was aimed at estimating the influence of Et on the body turnover of Cd in a rat model reflecting excessive alcohol consumption in humans chronically exposed to moderate and relatively high levels of this metal. For this purpose, Cd apparent absorption, retention in the body and concentration in the blood, stomach, duodenum, liver, kidney, spleen, brain, heart, testis and femur as well as its fecal and urinary excretion in the rats exposed to 5 and 50mg Cd l(-1) (in drinking water; for 16 weeks from the fifth week of the animal's life) and/or Et (5 g kg(-1) b.w. per 24 h, by oral gavage; for 12 weeks from the ninth week of life) were estimated. Moreover, the duodenal, liver and kidney pool of the nonmetallothionein (Mt)-bound Cd was evaluated. The administration of Et during the exposure to 5 or 50mg Cd l(-1) increased Cd accumulation in the gastrointestinal tract and its urinary excretion, and decreased Cd concentration in the blood, femur and numerous soft tissues (including liver and kidney) as well as the total pool of this metal in internal organs. Et modified or not the pool of the non-Mt-bound Cd, depending on the level of treatment with this metal. The results show that excessive Et consumption during Cd exposure may decrease the body burden of this metal, at least partly, by its lower absorption and increased urinary excretion. Based on this study, it can be concluded that Cd concentration in the blood and tissues of alcohol abusers chronically exposed to moderate and relatively high levels of this metal may be lower, whereas its urinary excretion is higher than in their nondrinking counterparts. However, since Et is toxic itself, the decreased body burden of Cd owing to alcohol consumption does not allow for the conclusion that the risk of health damage may be lower at co-exposure to these xenobiotics. In a further study, it will be investigated how the Et

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

    Science.gov (United States)

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

    2017-06-01

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

  2. Space Radiation and Human Exposures, A Primer.

    Science.gov (United States)

    Nelson, Gregory A

    2016-04-01

    The space radiation environment is a complex field comprised primarily of charged particles spanning energies over many orders of magnitude. The principal sources of these particles are galactic cosmic rays, the Sun and the trapped radiation belts around the earth. Superimposed on a steady influx of cosmic rays and a steady outward flux of low-energy solar wind are short-term ejections of higher energy particles from the Sun and an 11-year variation of solar luminosity that modulates cosmic ray intensity. Human health risks are estimated from models of the radiation environment for various mission scenarios, the shielding of associated vehicles and the human body itself. Transport models are used to propagate the ambient radiation fields through realistic shielding levels and materials to yield radiation field models inside spacecraft. Then, informed by radiobiological experiments and epidemiology studies, estimates are made for various outcome measures associated with impairments of biological processes, losses of function or mortality. Cancer-associated risks have been formulated in a probabilistic model while management of non-cancer risks are based on permissible exposure limits. This article focuses on the various components of the space radiation environment and the human exposures that it creates.

  3. Assessing the Cytotoxicity of Black Carbon As A Model for Ultrafine Anthropogenic Aerosol Across Human and Murine Cells: A Chronic Exposure Model of Nanosized Particulate Matter

    Science.gov (United States)

    Salinas, E.

    2015-12-01

    Combustion-derived nanomaterials or ultrafine (Juarez, Chihuahua, Mexico, comprising the Paso del Norte air basin. A study conducted by scientists from the Research Triangle Park in North Carolina, analyzed sites adjacent to heavy-traffic highways in El Paso and elucidated higher UFP concentrations in comparison to previously published work exploring pollution and adverse health effects in the basin. UFPs can penetrate deep into the alveolar sacs of the lung, reaching distant alveolar sacs and inducing a series of immune responses that are detrimental to the body: evidence suggests that UFPs can also cross the alveolar-blood barrier and potentially endanger the body's immune response. The physical properties of UFPs and the dynamics of local atmospheric and topographical conditions indicate that emissions of nanosized carbonaceous aerosols could pose significant threats to biological tissues upon inhalation by local residents of the Paso del Norte. This study utilizes Black Carbon (BC) as a model for environmental UFPs and its effects on the immunological response. An in vitro approach is used to measure the ability of BC to promote cell death upon long-term exposure. Human epithelial lung cells (A549), human peripheral-blood monocytes (THP-1), murine macrophages (RAW264.7), and murine epithelial lung cells (LA-4) were treated with BC and assessed for metabolic activity after chronic exposure utilizing three distinct and independent cell viability assays. The cell viability experiments included a chronic study at 7, 10, and 14 days of UFP exposure at six different concentrations of BC: 100μM, 300μM, 600μM, 1,250μM, 2,500μM, and 5,000μM conducting the Trypan Blue (TB) Exclusion Assay, Calcein-AM Viability Assay, and CellTiter-Glo Viability Assay.

  4. Simulating Human and Environmental Exposure from Hand-Held Knapsack Pesticide Application: Be-WetSpa-Pest, an Integrative, Spatially Explicit Modeling Approach.

    Science.gov (United States)

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

    2016-05-25

    This paper 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 easily to other regions in developing countries with similar conditions.

  5. Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

    Science.gov (United States)

    Denkins, P.; Badhwar, G.; Obot, V.; Wilson, B.; Jejelewo, O.

    2001-01-01

    NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, 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 solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation

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

    Science.gov (United States)

    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

  7. Modelling exposure opportunities

    DEFF Research Database (Denmark)

    Sabel, Clive E.; Gatrell, Anthony C.; Löytönen, Markku;

    2000-01-01

    emergence of the disease, with specific reference to the rare neurological condition, motor neurone disease (MND), using a dataset obtained from the Finnish Death Certificate registry, for MND deaths between the period 1985-1995. A space-time approach is adopted, whereby patterns in both time and space......This paper addresses the issues surrounding an individual's exposure to potential environmental risk factors, which can be implicated in the aetiology of a disease. We hope to further elucidate the 'lag' or latency period between the initial exposure to potential pathogens and the physical...

  8. A PROBABILISTIC MODELING FRAMEWORK FOR PREDICTING POPULATION EXPOSURES TO BENZENE

    Science.gov (United States)

    The US Environmental Protection Agency (EPA) is modifying their probabilistic Stochastic Human Exposure Dose Simulation (SHEDS) model to assess aggregate exposures to air toxics. Air toxics include urban Hazardous Air Pollutants (HAPS) such as benzene from mobile sources, part...

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

    Science.gov (United States)

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

  10. Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study

    OpenAIRE

    Virginia Rivulgo; Mónica Sparo; Mónica Ceci; Elida Fumuso; Alejandra Confalonieri; Gastón Delpech; Sánchez Bruni, Sergio F.

    2013-01-01

    Azithromycin(AZM)therapeutic failure and relapses of patients treated with generic -35 formulations have been observed in clinical practice.The main goal of this research was 36 to compare in a pre-clinical study the serum exposure and lung tissue concentrationof 37 two commercial formulations AZM-based in murine model. The current study involved 38 264 healthy Balb-C.Mice were divided in two groups (n=44): Animals of Group A 39 (Reference Formulation ?R-) were orally treated with AZM suspens...

  11. Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study

    OpenAIRE

    Virginia Rivulgo; Mónica Sparo; Mónica Ceci; Elida Fumuso; Alejandra Confalonieri; Gastón Delpech; Sánchez Bruni, Sergio F.

    2016-01-01

    Azithromycin(AZM)therapeutic failure and relapses of patients treated with generic -35 formulations have been observed in clinical practice.The main goal of this research was 36 to compare in a pre-clinical study the serum exposure and lung tissue concentrationof 37 two commercial formulations AZM-based in murine model. The current study involved 38 264 healthy Balb-C.Mice were divided in two groups (n=44): Animals of Group A 39 (Reference Formulation ?R-) were orally treated with AZM suspens...

  12. Merging Models and Biomonitoring Data to Characterize Sources andPathways of Human Exposure to Organophosphorous Pesticides in the SalinasValley of California

    Energy Technology Data Exchange (ETDEWEB)

    McKone, Thomas E.; Castorina, Rosemary; Kuwabara, Yu; Harnly,Martha E.; Eskenazi, Brenda; Bradman, Asa

    2006-06-01

    By drawing on human biomonitoring data and limited environmental samples together with outputs from the CalTOX multimedia, multipathway source-to-dose model, we characterize cumulative intake of organophosphorous (OP) pesticides in an agricultural region of California. We assemble regional OP pesticide use, environmental sampling, and biological tissue monitoring data for a large and geographically dispersed population cohort of 592 pregnant Latina women in California (the CHAMACOS cohort). We then use CalTOX with regional pesticide usage data to estimate the magnitude and uncertainty of exposure and intake from local sources. We combine model estimates of intake from local sources with food intake based on national residue data to estimate for the CHAMACOS cohort cumulative median OP intake, which corresponds to expected levels of urinary dialkylphosphate (DAP) metabolite excretion for this cohort. From these results we develop premises about relative contributions from different sources and pathways of exposure. We evaluate these premises by comparing the magnitude and variation of DAPs in the CHAMACOS cohort with the whole U.S. population using data from the National Health and Nutrition Evaluation Survey (NHANES). This comparison supports the premise that in both populations diet is the common and dominant exposure pathway. Both the model results and biomarker comparison supports the observation that the CHAMACOS population has a statistically significant higher intake of OP pesticides that appears as an almost constant additional dose among all participants. We attribute the magnitude and small variance of this intake to non-dietary exposure in residences from local sources.

  13. Modeled population exposures to ozone

    Data.gov (United States)

    U.S. Environmental Protection Agency — Population exposures to ozone from APEX modeling for combinations of potential future air quality and demographic change scenarios. This dataset is not publicly...

  14. Polycyclic aromatic hydrocarbons in edible grain: a pilot study of agricultural crops as a human exposure pathway for environmental contaminants using wheat as a model crop.

    Science.gov (United States)

    Kobayashi, Reiko; Okamoto, Robert A; Maddalena, Randy L; Kado, Norman Y

    2008-06-01

    The concentrations of polycyclic aromatic hydrocarbons (PAHs) were investigated in a pilot study of field wheat grain as a model indicator for environmental contamination. The edible grain would serve as a portal for human exposure. Wheat grain was initially studied since it is one of the major food crops consumed internationally by many including infants and children. Wheat grain samples from five different geographical growing locations in California that span approximately 450 km were collected during the same growing season. The same variety of grain was harvested and analyzed for PAHs that ranged from 2- to 6-rings. PAHs were detected in all grain samples and were mainly 2- to 4-ring PAHs with naphthalene the most abundant among them. There were geographical differences in the levels of PAHs in the grain. The sources of the PAHs were not known in this pilot study, but the principal component analysis indicates that the major source is similar in all locations except for naphthalene. Grain naphthalene concentrations may reflect local naphthalene emissions. Diesel-fueled harvesting operations did not appear to contribute to the observed PAH concentrations in the grain. An estimate of naphthalene intake from eating grain compared to inhalation intake demonstrated the potential importance of field contamination of grain as a possible portal of human exposure. The relationship between PAH concentrations in grain and air should be quantitatively investigated to better quantitate exposure and to identify effective measures to lower the risk from PAH exposure through eating grain.

  15. Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Freiin von Neubeck, Claere H.; Shankaran, Harish; Karin, Norman J.; Kauer, Paula M.; Chrisler, William B.; Wang, Xihai; Robinson, Robert J.; Waters, Katrina M.; Tilton, Susan C.; Sowa, Marianne B.

    2012-04-17

    The concern over possible health risks from exposures to low doses of ionizing radiation has been driven largely by the increase in medical exposures, the routine implementation of X-ray backscatter devices for airport security screening, and, most recently, the nuclear incident in Japan. Due to a paucity of direct epidemiological data at very low doses, cancer risk must be estimated from high dose exposure scenarios. However, there is increasing evidence that low and high dose exposures result in different signaling events and may have different mechanisms of cancer induction. We have examined the radiation induced temporal response of an in vitro three dimensional (3D) human skin tissue model using microarray-based transcriptional profiling. Our data shows that exposure to 100 mGy of X-rays is sufficient to affect gene transcription. Cell type specific analysis showed significant changes in gene expression with the levels of > 1400 genes altered in the dermis and > 400 genes regulated in the epidermis. The two cell types rarely exhibited overlapping responses at the mRNA level. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measurements validated the microarray data in both regulation direction and value. Key pathways identified relate to cell cycle regulation, immune responses, hypoxia, reactive oxygen signaling, and DNA damage repair. We discuss in particular the role of proliferation and emphasizing how the disregulation of cellular signaling in normal tissue may impact progression towards radiation induced secondary diseases.

  16. AirPEx: Air Pollution Exposure Model

    OpenAIRE

    Freijer JI; Bloemen HJTh; de Loos S; Marra M; Rombout PJA; Steentjes GM; Veen MP van; LBO

    1997-01-01

    Analysis of inhalatory exposure to air pollution is an important area of investigation when assessing the risks of air pollution for human health. Inhalatory exposure research focuses on the exposure of humans to air pollutants and the entry of these pollutants into the human respiratory tract. The principal grounds for studying the inhalatory exposure of humans to air pollutants are formed by the need for realistic exposure/dose estimates to evaluate the health effects of these pollutants. T...

  17. Tracking the pathways of human exposure to perfluorocarboxylates.

    Science.gov (United States)

    Vestergren, Robin; Cousins, Ian T

    2009-08-01

    Recent analyses of perfluorooctanoate (PFOA) in human blood sera show that the background-exposed population in industrialized countries worldwide exhibits a narrow concentration range; arithmetic means of published studies range between 2 and 8 microg/L PFOA, with the exception of a few outlier studies. The globally comparable human serum concentrations of PFOA and characteristic dominance of PFOA with respect to other perfluorocarboxylate (PFCA) homologues indicate that exposure pathways of humans differ from those of wildlife, where perfluorononanoate (PFNA) is often the dominant homologue. The observed correlations between perfluorooctane sulfonate (PFOS) and PFOA in human serum together with a simultaneous downward time trend of these compounds in human blood sera and blood spots from the year 2000 onward indicate a connection between historical perfluorooctanesulfonyl (POSF) production (phased out by the major manufacturer in 2000-2002) and exposure to both PFOS and PFOA. A comparison of estimated daily intakes to humans based on samples from exposure media (collected post 2000) indicates that food intake is the major contemporary exposure pathway for the background population, whereas drinking water exposure is dominant for populations near sources of contaminated drinking water. A one-compartment pharmacokinetic model used to back-calculate daily intakes from serum levels is shown to provide agreement within a factor of 1.5-5.5 of the daily intakes derived from exposure media, which provides further supporting evidence that dietary exposure is a major ongoing exposure pathway of PFOA to the background population.

  18. Community Engagement in Observational Human Exposure Studies

    Science.gov (United States)

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

  19. PARTNERING TO IMPROVE HUMAN EXPOSURE METHODS

    Science.gov (United States)

    Methods development research is an application-driven scientific area that addresses programmatic needs. The goals are to reduce measurement uncertainties, address data gaps, and improve existing analytical procedures for estimating human exposures. Partnerships have been develop...

  20. Mathematical equations and system identification models for a portable pneumatic bladder system designed to reduce human exposure to whole body shock and vibration

    Science.gov (United States)

    Aziz Ayyad, Ezzat

    A mathematical representation is sought to model the behavior of a portable pneumatic foam bladder designed to mitigate the effects of human exposure to shock and whole body random vibration. Fluid Dynamics principles are used to derive the analytic differential equations used for the physical equations Model. Additionally, combination of Wiener and Hammerstein block oriented representation techniques have been selected to create system identification (SID) block oriented models. A number of algorithms have been iterated to obtain numerical solutions for the system of equations which was found to be coupled and non-linear, with no analytic closed form solution. The purpose is to be able to predict the response of such system due to random vibrations and shock within reasonable margin of error. The constructed models were found to be accurate within accepted confidence level. Beside the analytic set of physical equations model representation, a linear SID model was selected to take advantage of the available vast amount of mathematical tools available to further analyze and redesign the bladder as a dynamic system. Measured field-test and lab test data have been collected from several helicopter and land terrain vehicle experiments. Numerous excitation and response acceleration measurement records were collected and used to prove the agreement with predictions. The estimation of two selected models were later applied to standard metrics in the frequency domain realization and compared with measurement responses. The collected test records are obtained from measured data at the US Army fields and facilities and at UNLV-CMEST environmental lab. The emerged models have been validated for conformity with actual accelerometer measurement responses and found within accepted error tolerance that is in both time and frequency domains. Further, standard metrics have been used to further confirm the confidence in the validation results. When comparing model prediction with

  1. Cancer risk assessment of human exposure to polycyclic aromatic hydrocarbons (PAHs) via indoor and outdoor dust based on probit model.

    Science.gov (United States)

    Kang, Yuan; Shao, Dingding; Li, Ning; Yang, Gelin; Zhang, Qiuyun; Zeng, Lixuan; Luo, Jiwen; Zhong, Wenfeng

    2015-03-01

    In the present study, the polycyclic aromatic hydrocarbons (PAHs) in indoor dust and outdoor dust including road and window dust around the traffic road in Hunan Province, China, were sampled and detected. The ∑PAHs in indoor dust ranged from 5007-24,236 ng g(-1), with a median of 14,049 ng g(-1). The ∑PAHs in road dust ranged from 3644-12,875 ng g(-1), with a median of 10,559 ng g(-1). The ∑PAHs in window dust ranged from 803-12,590 ng g(-1), with a median of 5459 ng g(-1). Similar pattern of PAHs was observed in road and window dust except in H3W and H4W samples, which was dominated by naphthalene (Nap), benzo(b+k)fluoranthene (B(b+k)F), phenanthrene (Phe), and fluorine (Fle). Indoor dust showed slightly different PAHs profiles, which was dominated by Nap, fluoranthene (Fla) and Phe. Risk assessment indicated that dermal contact and dust ingestion exposure pathways were more important than the inhalation pathway. Cancer risk of PAHs via dust varied from 2.73 × 10(-8)-8.04 × 10(-6), with a median of 2.06 × 10(-6) for children, and from 2 × 10(-8)-5.89 × 10(-6), with a median of 1.52 × 10(-6) for adult. Probit model showed that 76 and 71 % of samples in the sampling area would result in the risk of children and adult exposure to PAHs via dust higher than the acceptable level (1 × 10(-6)), respectively.

  2. 76 FR 365 - Exposure Modeling Public Meeting

    Science.gov (United States)

    2011-01-04

    ... meeting will include presentations related to the spatial context of terrestrial exposure modeling... degradation rates. Developments in terrestrial exposure modeling. Determining the fate and transport of... photography and GIS data. Dermal contact, movement, and amphibian pesticide exposure. List of...

  3. AirPEx: Air Pollution Exposure Model

    NARCIS (Netherlands)

    Freijer JI; Bloemen HJTh; Loos S de; Marra M; Rombout PJA; Steentjes GM; Veen MP van; LBO

    1997-01-01

    Analysis of inhalatory exposure to air pollution is an important area of investigation when assessing the risks of air pollution for human health. Inhalatory exposure research focuses on the exposure of humans to air pollutants and the entry of these pollutants into the human respiratory tract. The

  4. Susceptibility of human populations to environmental exposure to organic contaminants.

    Science.gov (United States)

    Undeman, Emma; Brown, Trevor N; Wania, Frank; McLachlan, Michael S

    2010-08-15

    Environmental exposure to organic contaminants is a complex function of environmental conditions, food chain characteristics, and chemical properties. In this study the susceptibility of various human populations to environmental exposure to neutral organic contaminants was compared. An environmental fate model and a linked bioaccumulation model were parametrized to describe ecosystems in different climatic regions (temperate, arctic, tropical, and steppe). The human body burden resulting from constant emissions of hypothetical chemicals was estimated for each region. An exposure susceptibility index was defined as the body burden in the region of interest normalized to the burden of the same chemical in a reference human from the temperate region eating an average diet. For most persistent chemicals emitted to air, the Arctic had the highest susceptibility index (max 520). Susceptibility to exposure was largely determined by the food web properties. The properties of the physical environment only had a marked effect when air or water, not food, was the dominant source of human exposure. Shifting the mode of emission markedly changed the relative susceptibility of the ecosystems in some cases. The exposure arising from chemical use clearly varies between ecosystems, which makes an understanding of ecosystem susceptibility to exposure important for chemicals management.

  5. Probabilistic modelling of human exposure to intense sweeteners in Italian teenagers: validation and sensitivity analysis of a probabilistic model including indicators of market share and brand loyalty.

    Science.gov (United States)

    Arcella, D; Soggiu, M E; Leclercq, C

    2003-10-01

    For the assessment of exposure to food-borne chemicals, the most commonly used methods in the European Union follow a deterministic approach based on conservative assumptions. Over the past few years, to get a more realistic view of exposure to food chemicals, risk managers are getting more interested in the probabilistic approach. Within the EU-funded 'Monte Carlo' project, a stochastic model of exposure to chemical substances from the diet and a computer software program were developed. The aim of this paper was to validate the model with respect to the intake of saccharin from table-top sweeteners and cyclamate from soft drinks by Italian teenagers with the use of the software and to evaluate the impact of the inclusion/exclusion of indicators on market share and brand loyalty through a sensitivity analysis. Data on food consumption and the concentration of sweeteners were collected. A food frequency questionnaire aimed at identifying females who were high consumers of sugar-free soft drinks and/or of table top sweeteners was filled in by 3982 teenagers living in the District of Rome. Moreover, 362 subjects participated in a detailed food survey by recording, at brand level, all foods and beverages ingested over 12 days. Producers were asked to provide the intense sweeteners' concentration of sugar-free products. Results showed that consumer behaviour with respect to brands has an impact on exposure assessments. Only probabilistic models that took into account indicators of market share and brand loyalty met the validation criteria.

  6. Assessment of Human Exposure to ENMs.

    Science.gov (United States)

    Jiménez, Araceli Sánchez; van Tongeren, Martie

    2017-01-01

    Human exposure assessment of engineered nanomaterials (ENMs) is hampered, among other factors, by the difficulty to differentiate ENM from other nanomaterials (incidental to processes or naturally occurring) and the lack of a single metric that can be used for health risk assessment. It is important that the exposure assessment is carried out throughout the entire life-cycle as releases can occur at the different stages of the product life-cycle, from the synthesis, manufacture of the nano-enable product (occupational exposure) to the professional and consumer use of nano-enabled product (consumer exposure) and at the end of life.Occupational exposure surveys should follow a tiered approach, increasing in complexity in terms of instruments used and sampling strategy applied with higher tiers in order tailor the exposure assessment to the specific materials used and workplace exposure scenarios and to reduce uncertainty in assessment of exposure. Assessment of consumer exposure and of releases from end-of-life processes currently relies on release testing of nano-enabled products in laboratory settings.

  7. Protective effect of Aronia melanocarpa polyphenols against cadmium-induced disorders in bone metabolism: a study in a rat model of lifetime human exposure to this heavy metal.

    Science.gov (United States)

    Brzóska, Malgorzata M; Rogalska, Joanna; Galazyn-Sidorczuk, Malgorzata; Jurczuk, Maria; Roszczenko, Alicja; Tomczyk, Michal

    2015-03-05

    It was investigated, in a female rat model of low and moderate lifetime human exposure to cadmium (Cd), whether polyphenols from Aronia melanocarpa berries (chokeberry; AMP) may offer protection from this heavy metal-induced disorders in bone metabolism. For this purpose, numerous indices of bone formation (osteocalcin, alkaline phosphatase, osteoprotegerin) and resorption (carboxy-terminal cross-linking telopeptides of type I collagen, soluble receptor activator of nuclear factor-κB ligand) in the serum and/or distal femur epiphysis (trabecular bone region), as well as bone mineral status (volumetric bone mineral density of the femur and content of mineral components, including calcium, in the bone tissue at the distal femur epiphysis) were evaluated in female Wistar rats that received a 0.1% aqueous extract of AMP, as the only drinking fluid (prepared from lyophilized extract by Adamed Consumer Healthcare), and/or Cd in diet (1 and 5mg/kg) for 3, 10, 17, and 24 months. Examination of the phytochemical profile of the aronia extract revealed high content of polyphenols (612.40 ± 3.33 mg/g), including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids. Among detected compounds anthocyanins were identified as dominating. The exposure to Cd, dose- and duration-dependently, enhanced resorption and inhibited formation of the bone tissue resulting in its decreased mineralization. The administration of AMP under the exposure to 1 and 5 mgCd/kg diet provided important protection from this heavy metal-induced disturbances in the bone turnover and changes in the bone mineral status, and the beneficial impact of polyphenols resulted from their independent action and interaction with Cd. These findings suggest that consumption of Aronia melanocarpa polyphenols may play a role in prevention against female skeleton damage due to chronic exposure to Cd and that chokeberry represents the good natural plant candidate for further investigations of its prophylactic use

  8. The use of discriminant analysis for evaluation of early-response multiple biomarkers of radiation exposure using non-human primate 6-Gy whole-body radiation model

    Energy Technology Data Exchange (ETDEWEB)

    Ossetrova, N.I. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: ossetrova@afrri.usuhs.mil; Farese, A.M.; MacVittie, T.J. [Marlene and Stewart Greenebaum Cancer Center, Bressler Research Building, Room 7-039, University of Maryland-Baltimore, 655 West Baltimore Street, Baltimore, MD 21201 (United States); Manglapus, G.L.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    The present need to rapidly identify severely irradiated individuals in mass-casualty and population-monitoring scenarios prompted an evaluation of potential protein biomarkers to provide early diagnostic information after exposure. The level of specific proteins measured using immunodiagnostic technologies may be useful as protein biomarkers to provide early diagnostic information for acute radiation exposures. Herein we present results from on-going studies using a non-human primate (NHP) 6-Gy X-rays ( 0.13Gymin{sup -1}) whole-body radiation model. Protein targets were measured by enzyme-linked immunosorbent assay (ELISA) in blood plasma before, 1, and 2 days after exposure. Exposure of 10 NHPs to 6 Gy resulted in the up-regulation of plasma levels of (a) p21 WAF1/CIP1, (b) interleukin 6 (IL-6), (c) tissue enzyme salivary {alpha}-amylase, and (d) C-reactive protein. Data presented show the potential utility of protein biomarkers selected from distinctly different pathways to detect radiation exposure. A correlation analysis demonstrated strong correlations among different combinations of four candidate radiation-responsive blood protein biomarkers. Data analyzed with use of multivariate discriminant analysis established very successful separation of NHP groups: 100% discrimination power for animals with correct classification for separation between groups before and 1 day after irradiation, and 95% discrimination power for separation between groups before and 2 days after irradiation. These results also demonstrate proof-in-concept that multiple protein biomarkers provide early diagnostic information to the medical community, along with classical biodosimetric methodologies, to effectively manage radiation casualty incidents.

  9. Modeling deterministic effects in hematopoietic system caused by chronic exposure to ionizing radiation in large human cohorts.

    Science.gov (United States)

    Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akleyev, Alexander V; Yashin, Anatoly I

    2010-09-01

    A new model of the hematopoietic system for humans chronically exposed to ionizing radiation allows for quantitative description of the initial hematopoiesis inhibition and subsequent increase in the risks of late stochastic effects such as leukemia. This model describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the three blood cell types (leukocytes, erythrocytes, and platelets). The model parameters are estimated from the results of other experiments. They include the steady-state numbers of hematopoietic stem cells and peripheral blood cell lines for an unexposed organism, amplification parameters for each blood cell line, parameters describing the proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity in respect to cell death and non-lethal cell damages. The dynamic model of hematopoiesis is applied to the data on a subcohort of the Techa River residents with hematological measurements (e.g., blood counts) performed in 1950-1956 (which totals to about 3,500 exposed individuals). Among well-described effects observed in these data are the slope values of the dose-effect curves describing the hematopoietic inhibition and the dose rate patterns of the fractions of cytopenic states (e.g., leukopenia, thrombocytopenia). The model has been further generalized by inclusion of the component describing the risk of late stochastic effects. The risks of the development of late effects (such as leukemia) in population groups with specific patterns of early reactions in hematopoiesis (such as leukopenia induced by ionizing radiation) are investigated using simulation studies and compared to data.

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

    Science.gov (United States)

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

    2010-12-01

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

  11. Effects of tissue conductivity and electrode area on internal electric fields in a numerical human model for ELF contact current exposures

    Science.gov (United States)

    Tarao, H.; Kuisti, H.; Korpinen, L.; Hayashi, N.; Isaka, K.

    2012-05-01

    Contact currents flow through the human body when a conducting object with different potential is touched. There are limited reports on numerical dosimetry for contact current exposure compared with electromagnetic field exposures. In this study, using an anatomical human adult male model, we performed numerical calculation of internal electric fields resulting from 60 Hz contact current flowing from the left hand to the left foot as a basis case. Next, we performed a variety of similar calculations with varying tissue conductivity and contact area, and compared the results with the basis case. We found that very low conductivity of skin and a small electrode size enhanced the internal fields in the muscle, subcutaneous fat and skin close to the contact region. The 99th percentile value of the fields in a particular tissue type did not reliably account for these fields near the electrode. In the arm and leg, the internal fields for the muscle anisotropy were identical to those in the isotropy case using a conductivity value longitudinal to the muscle fibre. Furthermore, the internal fields in the tissues abreast of the joints such as the wrist and the elbow, including low conductivity tissues, as well as the electrode contact region, exceeded the ICNIRP basic restriction for the general public with contact current as the reference level value.

  12. Parameter variation effects on temperature elevation in a steady-state, one-dimensional thermal model for millimeter wave exposure of one- and three-layer human tissue

    Energy Technology Data Exchange (ETDEWEB)

    Kanezaki, Akio; Shirai, Hiroshi [Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551 (Japan); Hirata, Akimasa; Watanabe, Soichi, E-mail: ahirata@nitech.ac.j [National Institute of Information and Communications Technology, 4-2-1 Nukuikitamachi, Koganei-shi, Tokyo 184-8795 (Japan)

    2010-08-21

    The present study describes theoretical parametric analysis of the steady-state temperature elevation in one-dimensional three-layer (skin, fat and muscle) and one-layer (skin only) models due to millimeter-wave exposure. The motivation of this fundamental investigation is that some variability of warmth sensation in the human skin has been reported. An analytical solution for a bioheat equation was derived by using the Laplace transform for the one-dimensional human models. Approximate expressions were obtained to investigate the dependence of temperature elevation on different thermal and tissue thickness parameters. It was shown that the temperature elevation on the body surface decreases monotonically with the blood perfusion rate, heat conductivity and heat transfer from the body to air. Also revealed were the conditions where maximum and minimum surface temperature elevations were observed for different thermal and tissue thickness parameters. The surface temperature elevation in the three-layer model is 1.3-2.8 times greater than that in the one-layer model. The main reason for this difference is attributed to the adiabatic nature of the fat layer. By considering the variation range of thermal and tissue thickness parameters which causes the maximum and minimum temperature elevations, the dominant parameter influencing the surface temperature elevation was found to be the heat transfer coefficient between the body surface and air.

  13. UVB exposure of a humanized skin model reveals unexpected dynamic of keratinocyte proliferation and Wnt inhibitor balancing.

    Science.gov (United States)

    Michalczyk, Teresa; Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Klar, Agnes S; Meuli, Martin; Reichmann, Ernst

    2017-07-17

    We developed human dermo-epidermal skin substitutes which are presently applied in phase I and II clinical trials. Here we used these very same skin equivalents containing melanocytes, named MelSkin, as an experimental skin model. We investigated the effects of UVB irradiation on the skin grafts transplanted on immune-compromised rats. The irradiation induces a strong wound healing response going along with massive proliferation of basal keratinocytes, basically quiescent under non-irradiated, homeostatic conditions. As a consequence of UVB irradiation, the initially clearly defined basal keratinocyte (mono)layer expands into about three layers of keratinocytes, all of which still express the basal keratinocyte marker Keratin15. In contrast, epidermal melanocytes remain quiescent under these circumstances. Moreover, the Wnt inhibitors Dickkopf 3 and Wif1 are downregulated upon UVB irradiation in basal keratinocytes, whereas melanocytes continue to express Wnt inhibitors. These findings suggest that there is 1) a suprabasal population, proliferating in the homeostatic state, hence maintaining the integrity of the epidermis, and 2) a basal, usually quiescent keratinocyte population that is induced to massively proliferate upon irradiation. Importantly, the finding that MelSkin responds in a physiological fashion to UVB is of paramount importance in light of the planned clinical application. This article is protected by copyright. All rights reserved.

  14. Human biological monitoring of occupational genotoxic exposures

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Sorsa, M

    1993-01-01

    ) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors......Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e...... for and the biomonitoring results should preferentially be linked with accurate ambient air monitoring. In persons occupationally exposed to styrene the endpoints of DNA-damage and DNA-repair in genetic monitoring are methods of choice in exposure situations above the current Danish (25 ppm) or Finnish (20 ppm...

  15. Linking Meteorology, Air Quality Models and Observations to Characterize Human Exposures in Support of the Environmental Health Studies

    Science.gov (United States)

    Epidemiologic studies are critical in establishing the association between exposure to air pollutants and adverse health effects. Results of epidemiologic studies are used by U.S. EPA in developing air quality standards to protect the public from the health effects of air polluta...

  16. A translatable predictor of human radiation exposure.

    Directory of Open Access Journals (Sweden)

    Joseph Lucas

    Full Text Available Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB and humans treated with total body irradiation (TBI. Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

  17. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model.

    Directory of Open Access Journals (Sweden)

    C Preston Neff

    Full Text Available Sexual HIV-1 transmission by vaginal route is the most predominant mode of viral transmission, resulting in millions of new infections every year. In the absence of an effective vaccine, there is an urgent need to develop other alternative methods of pre-exposure prophylaxis (PrEP. Many novel drugs that are currently approved for clinical use also show great potential to prevent viral sexual transmission when administered systemically. A small animal model that permits rapid preclinical evaluation of potential candidates for their systemic PrEP efficacy will greatly enhance progress in this area of investigation. We have previously shown that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and displays CD4 T cell loss typical to that seen in the human. Thus far systemic PrEP studies have been primarily limited to RT inhibitors exemplified by tenofovir and emtricitabine. In these proof-of-concept studies we evaluated two new classes of clinically approved drugs with different modes of action namely, an integrase inhibitor raltegravir and a CCR5 inhibitor maraviroc as potential systemically administered chemo-prophylactics. Our results showed that oral administration of either of these drugs fully protects against vaginal HIV-1 challenge in the RAG-hu mouse model. Based on these results both these drugs show great promise for further development as orally administered PrEPs.

  18. USEPA SHEDS MODEL: METHODOLOGY FOR EXPOSURE ASSESSMENT FOR WOOD PRESERVATIVES

    Science.gov (United States)

    A physically-based, Monte Carlo probabilistic model (SHEDS-Wood: Stochastic Human Exposure and Dose Simulation model for wood preservatives) has been applied to assess the exposure and dose of children to arsenic (As) and chromium (Cr) from contact with chromated copper arsenat...

  19. ASSESSMENT OF HUMAN EXPOSURE TO TOLUENE DIISOCYANATE

    Directory of Open Access Journals (Sweden)

    OLIVIA ANCA RUSU

    2011-03-01

    Full Text Available Assessment of human exposure to toluene diisocyanate. Toluene diisocyanate (TDI, an aromatic compound, may be dangerous for human health. Diisocyanates have wide industrial use in the fabrication of flexible and rigid foams, fibers, elastomers, and coatings such as paints and varnishes. Isocyanates are known skin and respiratory sensitizers, and proper engineering controls should be in place to prevent exposure to isocyanate liquid and vapor; exposure to TDI vapors is well documented to increase asthma risk. The study focused on the exposure of workers and nearby populations to toluene diisocyanate in a Polyurethane Foam Factory located in Baia Mare, Romania. Workplace air measurements were performed in different departments of the plant, after sampling either in fixed points or as personal monitoring. Sampling in four different locations of Baia Mare town was carried out, - during and after the foaming process. TDI sampling was performed on silica cartridge followed by GC-MS analysis. TDI concentration at workplace was lower than 0,035 mg/m³, which represents the permissible exposure limit, while in the city the TDI concentration had shown values below 0,20 μg/m³. Health assessment of a group of 49 workers was based on questionnaire interview, determination of TDI antibodies and lung function tests. Data collected until this stage do not show any negative effects of TDI on the employees health. Since this plant had only recently begun operating, continuous workplace and ambient air TDI monitoring, along with workers health surveillance, is deemed necessary.

  20. Perspectives for integrating human and environmental exposure assessments.

    Science.gov (United States)

    Ciffroy, P; Péry, A R R; Roth, N

    2016-10-15

    Integrated Risk Assessment (IRA) has been defined by the EU FP7 HEROIC Coordination action as "the mutual exploitation of Environmental Risk Assessment for Human Health Risk Assessment and vice versa in order to coherently and more efficiently characterize an overall risk to humans and the environment for better informing the risk analysis process" (Wilks et al., 2015). Since exposure assessment and hazard characterization are the pillars of risk assessment, integrating Environmental Exposure assessment (EEA) and Human Exposure assessment (HEA) is a major component of an IRA framework. EEA and HEA typically pursue different targets, protection goals and timeframe. However, human and wildlife species also share the same environment and they similarly inhale air and ingest water and food through often similar overlapping pathways of exposure. Fate models used in EEA and HEA to predict the chemicals distribution among physical and biological media are essentially based on common properties of chemicals, and internal concentration estimations are largely based on inter-species (i.e. biota-to-human) extrapolations. Also, both EEA and HEA are challenged by increasing scientific complexity and resources constraints. Altogether, these points create the need for a better exploitation of all currently existing data, experimental approaches and modeling tools and it is assumed that a more integrated approach of both EEA and HEA may be part of the solution. Based on the outcome of an Expert Workshop on Extrapolations in Integrated Exposure Assessment organized by the HEROIC project in January 2014, this paper identifies perspectives and recommendations to better harmonize and extrapolate exposure assessment data, models and methods between Human Health and Environmental Risk Assessments to support the further development and promotion of the concept of IRA. Ultimately, these recommendations may feed into guidance showing when and how to apply IRA in the regulatory decision

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

    Science.gov (United States)

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

  2. The Application of Global Sensitivity Analysis in the Development of a Physiologically Based Pharmacokinetic Model for m-Xylene and Ethanol Co-Exposure in Humans

    Directory of Open Access Journals (Sweden)

    George D Loizou

    2015-06-01

    Full Text Available Global sensitivity analysis (SA was used during the development phase of a binary chemical physiologically based pharmacokinetic (PBPK model used for the analysis of m-xylene and ethanol co-exposure in humans. SA was used to identify those parameters which had the most significant impact on variability of venous blood and exhaled m-xylene and urinary excretion of the major metabolite of m-xylene metabolism, 3-methyl hippuric acid. This information informed the selection of parameters for estimation/calibration by fitting to measured biological monitoring (BM data in a Bayesian framework using Markov chain Monte Carlo (MCMC simulation. Data generated in controlled human studies were shown to be useful for investigating the structure and quantitative outputs of PBPK models as well as the biological plausibility and variability of parameters for which measured values were not available. This approach ensured that a priori knowledge in the form of prior distributions was ascribed only to those parameters that were identified as having the greatest impact on variability. This is an efficient approach which helps reduce computational cost.

  3. Pharmacokinetic Modeling and Monte Carlo Simulation to Predict Interindividual Variability in Human Exposure to Oseltamivir and Its Active Metabolite, Ro 64-0802.

    Science.gov (United States)

    Ito, Mototsugu; Kusuhara, Hiroyuki; Ose, Atsushi; Kondo, Tsunenori; Tanabe, Kazunari; Nakayama, Hideki; Horita, Shigeru; Fujita, Takuya; Sugiyama, Yuichi

    2017-01-01

    Oseltamivir (Tamiflu®) is a prodrug of Ro 64-0802, a selective inhibitor of influenza virus neuraminidase. There is a possible relationship between oseltamivir treatment and neuropsychiatric adverse events; although this has not been established, close monitoring is recommended on the prescription label. The objective of this study was to predict interindividual variability of human exposure to oseltamivir and its active metabolite Ro 64-0802. By leveraging mathematical models and computations, physiological parameters in virtual subjects were generated with population means and coefficient of variations collected from the literature or produced experimentally. Postulated functional changes caused by genetic mutations in four key molecules, carboxylesterase 1A1, P-glycoprotein, organic anion transporter 3, and multidrug resistance-associated protein 4, were also taken into account. One hundred thousand virtual subjects were generated per simulation, which was iterated 20 times with different random number generator seeds. Even in the most exaggerated case, the systemic areas under the concentration-time curve (AUCs) of oseltamivir and Ro 64-0802 were increased by at most threefold compared with the population mean. By contrast, the brain AUCs of oseltamivir and Ro 64-0802 were increased up to about sevenfold and 40-fold, respectively, compared with the population means. This unexpectedly high exposure to oseltamivir or Ro 64-0802, which occurs extremely rarely, might trigger adverse central nervous system effects in the clinical setting.

  4. Human exposure to soil contamination: a qualitative and quantitative analysis towards proposals for human toxicological intervention values (partly revised edition)

    NARCIS (Netherlands)

    Berg R van den; LBG

    1994-01-01

    In view of a revision of the Dutch Soil Protection act, proposals are presented in this report for human toxicologically based intervention values for soil and groundwater, calculated from human toxicological guideline values and human exposure. To this purpose the exposure model CSOIL is presented

  5. CAirTOX: A compartment model for assessing the fate of and human exposure to toxic-chemical emissions to air

    Energy Technology Data Exchange (ETDEWEB)

    McKone, T.E.

    1993-10-01

    CAirTOX has been developed as a spreadsheet model to assist in making a risk assessment of toxic air emissions. With CAirTOX, one can address how contaminants released to an air basin can lead to contamination of soil, food, surface water, and sediments. The modeling effort includes a multimedia transport and transformation model, exposure scenario models, and efforts to quantify uncertainty in multimedia, multiple-pathway exposure assessments. The multimedia transport and transformation model is a steady-state, but non-equilibrium model that can be used to assess concentrations of contaminants released continuously to air. In Part 1, the authors describe the multimedia transport and transformation model used to determine the fate of air emissions. In Part 2, they describe inputs and data needs for CAirTOX and the development of a set of landscape factors, which can be used to represent regional air basin/water-shed systems in California. In Part 3, they describe the multiple-pathway exposure scenarios and exposure algorithms. In Part 4, they compare the HRA approach and results and the CAirTOX exposure equations. In Part 5, they consider model sensitivity and uncertainty to determine how variability and uncertainty in model inputs affects the precision, accuracy, and credibility of the model output.

  6. A Modeling Investigation of Human Exposure to Select Traffic-Related Air Pollutants in the Tampa Area: Spatiotemporal Distributions of Concentrations, Social Distributions of Exposures, and Impacts of Urban Design on Both

    Science.gov (United States)

    Yu, Haofei

    Increasing vehicle dependence in the United States has resulted in substantial emissions of traffic-related air pollutants that contribute to the deterioration of urban air quality. Exposure to urban air pollutants trigger a number of public health concerns, including the potential of inequality of exposures and health effects among population subgroups. To better understand the impact of traffic-related pollutants on air quality, exposure, and exposure inequality, modeling methods that can appropriately characterize the spatiotemporally resolved concentration distributions of traffic-related pollutants need to be improved. These modeling methods can then be used to investigate the impacts of urban design and transportation management choices on air quality, pollution exposures, and related inequality. This work will address these needs with three objectives: 1) to improve modeling methods for investigating interactions between city and transportation design choices and air pollution exposures, 2) to characterize current exposures and the social distribution of exposures to traffic-related air pollutants for the case study area of Hillsborough County, Florida, and 3) to determine expected impacts of urban design and transportation management choices on air quality, air pollution exposures, and exposure inequality. To achieve these objectives, the impacts of a small-scale transportation management project, specifically the '95 Express' high occupancy toll lane project, on pollutant emissions and nearby air quality was investigated. Next, a modeling method capable of characterizing spatiotemporally resolved pollutant emissions, concentrations, and exposures was developed and applied to estimate the impact of traffic-related pollutants on exposure and exposure inequalities among several population subgroups in Hillsborough County, Florida. Finally, using these results as baseline, the impacts of sprawl and compact urban forms, as well as vehicle fleet electrification

  7. Modeling of noise pollution and estimated human exposure around İstanbul Atatürk Airport in Turkey.

    Science.gov (United States)

    Ozkurt, Nesimi; Sari, Deniz; Akdag, Ali; Kutukoglu, Murat; Gurarslan, Aliye

    2014-06-01

    The level of aircraft noise exposure around İstanbul Atatürk Airport was calculated according to the European Noise Directive. These calculations were based on the actual flight data for each flight in the year 2011. The study area was selected to cover of 25km radius centered on the Aerodrome Reference Point of the airport. The geographical data around İstanbul Atatürk Airport was used to prepare elevation, residential building, auxiliary building, hospital and school layers in SoundPlan software. It was found that 1.2% of the land area of İstanbul City exceeds the threshold of 55dB(A) during daytime. However, when the exceedance of threshold of 65dB(A)is investigated, the affected area is found quite small (0.2% of land area of city). About 0.3% of the land area of İstanbul City has noise levels exceeding 55dB(A) during night-time. Our results show that about 4% of the resident population was exposed to 55dB(A) or higher noises during daytime in İstanbul. When applying the second threshhold criteria, nearly 1% of the population is exposed to noise levels greater than 65dB(A). At night-time, 1.3% of the population is exposed to 55dB(A) or higher noise levels.

  8. Assessing Sources of Human Methylmercury Exposure Using Stable Mercury Isotopes

    DEFF Research Database (Denmark)

    Li, Miling; Sherman, Laura S; Blum, Joel D

    2014-01-01

    Seafood consumption is the primary route of methylmercury (MeHg) exposure for most populations. Inherent uncertainties in dietary survey data point to the need for an empirical tool to confirm exposure sources. We therefore explore the utility of Hg stable isotope ratios in human hair as a new...... method for discerning MeHg exposure sources. We characterized Hg isotope fractionation between humans and their diets using hair samples from Faroese whalers exposed to MeHg predominantly from pilot whales. We observed an increase of 1.75‰ in δ(202)Hg values between pilot whale muscle tissue and Faroese...... whalers' hair but no mass-independent fractionation. We found a similar offset in δ(202)Hg between consumed seafood and hair samples from Gulf of Mexico recreational anglers who are exposed to lower levels of MeHg from a variety of seafood sources. An isotope mixing model was used to estimate individual...

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

    Science.gov (United States)

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

  10. Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: Evidence from a novel translational in vitro model**

    Science.gov (United States)

    The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

  11. Modelling of long-term behaviour of caesium and strontium radionuclides in the Arctic environment and human exposure

    Energy Technology Data Exchange (ETDEWEB)

    Golikov, Vladislav E-mail: bazil@sg5816.spb.edu; Logacheva, Irina; Bruk, Gennadi; Shutov, Vladimir; Balonov, Mikhail; Strand, Per; Borghuis, Sander; Howard, Brenda; Wright, Simon

    2004-07-01

    In this paper a compartment model of the highly vulnerable Arctic terrestrial food chain 'lichen-reindeer-man' is outlined. Based upon an analysis of measured {sup 137}Cs and {sup 90}Sr contents in lichen and reindeer meat from 1961 up to 2001, site specific model parameters for two regions in north-western Arctic Russia and for Kautokeino municipality in Arctic Norway have been determined. The dynamics of radionuclide activity concentrations in the 'lichen-reindeer-man' food chain for all areas was satisfactorily described by a double exponential function with short-term and long-term effective ecological half-lives between 1-2 and 10-12 years, respectively, for both {sup 137}Cs and {sup 90}Sr. Using parameter values derived from the model, life-time internal effective doses due to consumption of reindeer meat by reindeer-breeders after an assumed single pulse deposit of 1 kBq m{sup -2} of {sup 137}Cs were estimated to be 11.4 mSv (Kola Peninsula), 5 mSv (Nenets Autonomous Area), and 2 mSv (Kautokeino, Norway). Differences in vulnerability to radiocaesium deposition were due to differences in transfer between lichen and reindeer and in diet between the three regions.

  12. Modelling of long-term behaviour of caesium and strontium radionuclides in the Arctic environment and human exposure.

    Science.gov (United States)

    Golikov, Vladislav; Logacheva, Irina; Bruk, Gennadi; Shutov, Vladimir; Balonov, Mikhail; Strand, Per; Borghuis, Sander; Howard, Brenda; Wright, Simon

    2004-01-01

    In this paper a compartment model of the highly vulnerable Arctic terrestrial food chain "lichen-reindeer-man" is outlined. Based upon an analysis of measured (137)Cs and (90)Sr contents in lichen and reindeer meat from 1961 up to 2001, site specific model parameters for two regions in north-western Arctic Russia and for Kautokeino municipality in Arctic Norway have been determined. The dynamics of radionuclide activity concentrations in the "lichen-reindeer-man" food chain for all areas was satisfactorily described by a double exponential function with short-term and long-term effective ecological half-lives between 1-2 and 10-12 years, respectively, for both (137)Cs and (90)Sr. Using parameter values derived from the model, life-time internal effective doses due to consumption of reindeer meat by reindeer-breeders after an assumed single pulse deposit of 1 kBq m(-2) of (137)Cs were estimated to be 11.4 mSv (Kola Peninsula), 5 mSv (Nenets Autonomous Area), and 2 mSv (Kautokeino, Norway). Differences in vulnerability to radiocaesium deposition were due to differences in transfer between lichen and reindeer and in diet between the three regions.

  13. Integrating population dynamics into mapping human exposure to seismic hazard

    Directory of Open Access Journals (Sweden)

    S. Freire

    2012-11-01

    Full Text Available Disaster risk is not fully characterized without taking into account vulnerability and population exposure. Assessment of earthquake risk in urban areas would benefit from considering the variation of population distribution at more detailed spatial and temporal scales, and from a more explicit integration of this improved demographic data with existing seismic hazard maps. In the present work, "intelligent" dasymetric mapping is used to model population dynamics at high spatial resolution in order to benefit the analysis of spatio-temporal exposure to earthquake hazard in a metropolitan area. These night- and daytime-specific population densities are then classified and combined with seismic intensity levels to derive new spatially-explicit four-class-composite maps of human exposure. The presented approach enables a more thorough assessment of population exposure to earthquake hazard. Results show that there are significantly more people potentially at risk in the daytime period, demonstrating the shifting nature of population exposure in the daily cycle and the need to move beyond conventional residence-based demographic data sources to improve risk analyses. The proposed fine-scale maps of human exposure to seismic intensity are mainly aimed at benefiting visualization and communication of earthquake risk, but can be valuable in all phases of the disaster management process where knowledge of population densities is relevant for decision-making.

  14. A flexible matrix-based human exposure assessment framework suitable for LCA and CAA

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Ernstoff, Alexi; Huang, Lei

    2016-01-01

    of near-and far-field pathways and helps to understand the contribution of individual pathways to overall human exposure in various product application contexts. When combined with toxicity information this approach is a resourceful way to inform LCA and CAA and minimize human exposure to toxic chemicals......Humans can be exposed to chemicals via near-field exposure pathways (e.g. through consumer product use) and far-field exposure pathways (e.g. through environmental emissions along product life cycles). Pathways are often complex where chemicals can transfer directly from products to humans during...... use or exchange between near-and far-field compartments until sub -fractions reach humans via inhalation, ingestion or dermal uptake. Currently, however, multimedia exposure models mainly focus on far-field exposure pathways. Metrics and modeling approaches used in far-field, emission-based models...

  15. [Human exposure to trihalomethanes in drinking water].

    Science.gov (United States)

    Tominaga, M Y; Midio, A F

    1999-08-01

    Halogenated hydrocarbon compounds, some of them recognized as carcinogenic to different animal species can be found in drinking water. Chloroform, bromodichloromethane, dibromochloromethane and bromoform are the most important trihalomethanes found in potable water. They are produced in natural waters during chlorinated desinfection by the halogenation of precursors, specially humic and fulvic compounds. The review, in the MEDLINE covers the period from 1974 to 1998, presents the general aspects of the formation of trihalomethanes, sources of human exposure and their toxicological meaning for exposed organisms: toxicokinetic disposition and spectrum of toxic effects (carcinogenic, mutagenic and teratogenic).

  16. Three dimensional visualisation of human facial exposure to solar ultraviolet.

    Science.gov (United States)

    Downs, Nathan; Parisi, Alfio

    2007-01-01

    A three dimensional computer model of the human face has been developed to represent solar ultraviolet exposures recorded by dosimeter measurements on a manikin headform under low cloud conditions and various solar zenith angles. Additionally, polysulfone dosimeters have been successfully miniaturised to provide the detailed measurements required across the face. The headform used in this research was scanned at 709 individual locations to make a wireframe mesh consisting of 18 vertical contours and 49 horizontal contours covering half the manikin's frontal facial topography. Additionally, the back of the headform and neck have also been scanned at 576 locations. Each scanned location has been used as a viable dosimeter position on the headform and represents a grid intersection point on the developed computer wireframe. A series of exposures recorded by dosimeters have been translated into three dimensional exposure ratio maps, representing ambient solar ultraviolet exposure. High dosimeter density has allowed for the development of individual topographic contour models which take into account complex variation in the face and improve upon previously employed techniques which utilise fewer dosimeters to interpolate exposure across facial contours. Exposure ratios for solar zenith angle ranges of 0 degrees -30 degrees, 30 degrees -50 degrees, and 50 degrees -80 degrees have been developed.

  17. Human performance analysis of industrial radiography radiation exposure events

    Energy Technology Data Exchange (ETDEWEB)

    Reece, W.J.; Hill, S.G.

    1995-12-01

    A set of radiation overexposure event reports were reviewed as part of a program to examine human performance in industrial radiography for the US Nuclear Regulatory Commission. Incident records for a seven year period were retrieved from an event database. Ninety-five exposure events were initially categorized and sorted for further analysis. Descriptive models were applied to a subset of severe overexposure events. Modeling included: (1) operational sequence tables to outline the key human actions and interactions with equipment, (2) human reliability event trees, (3) an application of an information processing failures model, and (4) an extrapolated use of the error influences and effects diagram. Results of the modeling analyses provided insights into the industrial radiography task and suggested areas for further action and study to decrease overexposures.

  18. Repeated whole cigarette smoke exposure alters cell differentiation and augments secretion of inflammatory mediators in air-liquid interface three-dimensional co-culture model of human bronchial tissue.

    Science.gov (United States)

    Ishikawa, Shinkichi; Ito, Shigeaki

    2017-02-01

    In vitro models of human bronchial epithelium are useful for toxicological testing because of their resemblance to in vivo tissue. We constructed a model of human bronchial tissue which has a fibroblast layer embedded in a collagen matrix directly below a fully-differentiated epithelial cell layer. The model was applied to whole cigarette smoke (CS) exposure repeatedly from an air-liquid interface culture while bronchial epithelial cells were differentiating. The effects of CS exposure on differentiation were determined by histological and gene expression analyses on culture day 21. We found a decrease in ciliated cells and perturbation of goblet cell differentiation. We also analyzed the effects of CS exposure on the inflammatory response, and observed a significant increase in secretion of IL-8, GRO-α, IL-1β, and GM-CSF. Interestingly, secretion of these mediators was augmented with repetition of whole CS exposure. Our data demonstrate the usefulness of our bronchial tissue model for in vitro testing and the importance of exposure repetition in perturbing the differentiation and inflammation processes.

  19. Modeling Exposure of Mammalian Predatorsto Anticoagulant Rodenticides

    DEFF Research Database (Denmark)

    Topping, Christopher John; Elmeros, Morten

    2016-01-01

    high. We postulate that this is caused by widespread exposure due to widespread use of AR in Denmark in and around buildings. To investigate this theory a spatio-temporal model of AR use and mammalian predator distribution was created. This model was supported by data from an experimental study of mice...... and creates an exposure map based on spatio-temporal modelling of movement of mice-vectored AR (based on Apodemus flavicollis). Simulated predator territories are super-imposed over this exposure map to create an exposure index. Predictions from the model concur with field studies of AR prevalence both before...... and after the change in AR use. In most cases incidence of exposure to AR is predicted to be greater than 90%, although cessation of use in woodlots and Christmas tree plantations should reduce mean exposure concentrations. Model results suggest that the driver of high AR incidence in non-target small...

  20. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  1. EFFECTS OF ARSENIC EXPOSURE IN HUMAN HEALTH

    Directory of Open Access Journals (Sweden)

    Aline Sueli de Lima Rodrigues

    2008-10-01

    Full Text Available In recent years, ingestion of inorganic arsenic from drinking water has emerged as an important public health concern. It enters drinking water supplies from natural deposits in the earth or from agricultural and industrial practices, mainly the mining. The health consequences of chronic arsenic exposure include increased risk for various forms of cancer and numerous pathologic effects, such as cutaneous effects (hyperpigmentation and hyperkeratoses, gastrointestinal effects, vascular effects, diabetes mellitus, and peripheral neuropathy. This way, this study presents through a critical revision of the literature, the more relevant current aspects on the immunological consequences, carcinogenic and resulting genetics of the human intoxication for arsenic. They were identified and analyzed 50 works published on the subject among the years of 1979 and 2008, being used as main sources LILACS-BIREME MEDLINE/Index Medicus, SciELO and PubMed. The specific Arsênio e saúde humana effects of the intoxication for arsenic about the human health are not still completely elucidated. Thus, is possible that this element affects functions still unknown, becoming important the scientificexploration on the subject.

  2. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  3. A statistical framework for the validation of a population exposure model based on personal exposure data

    Science.gov (United States)

    Rodriguez, Delphy; Valari, Myrto; Markakis, Konstantinos; Payan, Sébastien

    2016-04-01

    Currently, ambient pollutant concentrations at monitoring sites are routinely measured by local networks, such as AIRPARIF in Paris, France. Pollutant concentration fields are also simulated with regional-scale chemistry transport models such as CHIMERE (http://www.lmd.polytechnique.fr/chimere) under air-quality forecasting platforms (e.g. Prev'Air http://www.prevair.org) or research projects. These data may be combined with more or less sophisticated techniques to provide a fairly good representation of pollutant concentration spatial gradients over urban areas. Here we focus on human exposure to atmospheric contaminants. Based on census data on population dynamics and demographics, modeled outdoor concentrations and infiltration of outdoor air-pollution indoors we have developed a population exposure model for ozone and PM2.5. A critical challenge in the field of population exposure modeling is model validation since personal exposure data are expensive and therefore, rare. However, recent research has made low cost mobile sensors fairly common and therefore personal exposure data should become more and more accessible. In view of planned cohort field-campaigns where such data will be available over the Paris region, we propose in the present study a statistical framework that makes the comparison between modeled and measured exposures meaningful. Our ultimate goal is to evaluate the exposure model by comparing modeled exposures to monitor data. The scientific question we address here is how to downscale modeled data that are estimated on the county population scale at the individual scale which is appropriate to the available measurements. To assess this question we developed a Bayesian hierarchical framework that assimilates actual individual data into population statistics and updates the probability estimate.

  4. Evaluation of ozone exposure indices in exposure-response modeling.

    Science.gov (United States)

    Lee, E H; Tingey, D T; Hogsett, W E

    1988-01-01

    In exposure-response modeling, a major concern is the numerical definition of exposure in relating crop loss to O3, yet few indices have been considered. This paper addresses research in which plant growth was regressed for soybean, wheat, cotton, corn, and sorghum against 613 numerical exposure indices using the Box-Tidwell model. When the minimum sum of squared errors criterion was used, optimum performance was not attained for any single index; however, near optimum performances were achieved by two censored cumulative indices and from a class of indices called the generalized, phenologically weighted, cumulative impact indices (GPWCIs). The top-performing GPWCIs accumulated concentrations, used sigmoid weighting schemes emphasizing O3 concentrations of 0.06 ppm (118 microg m(-3)) or higher, and had phenological weighting schemes with greatest weight occurring 20 to 40 days prior to crop maturity. These findings indicate that (1) peak concentrations are important, but lower concentrations should be included in the calculations, (2) increased plant sensitivity occurs between flowering and maturity, and (3) plants respond to cumulative exposure impact.

  5. Assessing human variability in kinetics for exposures to multiple environmental chemicals: a physiologically based pharmacokinetic modeling case study with dichloromethane, benzene, toluene, ethylbenzene, and m-xylene.

    Science.gov (United States)

    Valcke, Mathieu; Haddad, Sami

    2015-01-01

    The objective of this study was to compare the magnitude of interindividual variability in internal dose for inhalation exposure to single versus multiple chemicals. Physiologically based pharmacokinetic models for adults (AD), neonates (NEO), toddlers (TODD), and pregnant women (PW) were used to simulate inhalation exposure to "low" (RfC-like) or "high" (AEGL-like) air concentrations of benzene (Bz) or dichloromethane (DCM), along with various levels of toluene alone or toluene with ethylbenzene and xylene. Monte Carlo simulations were performed and distributions of relevant internal dose metrics of either Bz or DCM were computed. Area under the blood concentration of parent compound versus time curve (AUC)-based variability in AD, TODD, and PW rose for Bz when concomitant "low" exposure to mixtures of increasing complexities occurred (coefficient of variation (CV) = 16-24%, vs. 12-15% for Bz alone), but remained unchanged considering DCM. Conversely, AUC-based CV in NEO fell (15 to 5% for Bz; 12 to 6% for DCM). Comparable trends were observed considering production of metabolites (AMET), except for NEO's CYP2E1-mediated metabolites of Bz, where an increased CV was observed (20 to 71%). For "high" exposure scenarios, Cmax-based variability of Bz and DCM remained unchanged in AD and PW, but decreased in NEO (CV= 11-16% to 2-6%) and TODD (CV= 12-13% to 7-9%). Conversely, AMET-based variability for both substrates rose in every subpopulation. This study analyzed for the first time the impact of multiple exposures on interindividual variability in toxicokinetics. Evidence indicates that this impact depends upon chemical concentrations and biochemical properties, as well as the subpopulation and internal dose metrics considered.

  6. Integrating Human Indoor Air Pollutant Exposure within Life Cycle Impact Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Hellweg, Stefanie; Demou, Evangelia; Bruzzi, Raffaella; Meijer, Arjen; Rosenbaum, Ralph K.; Huijbregts, Mark A.J.; McKone, Thomas E.

    2008-12-21

    Neglecting health effects from indoor pollutant emissions and exposure, as currently done in Life Cycle Assessment (LCA), may result in product or process optimizations at the expense of workers? or consumers? health. To close this gap, methods for considering indoor exposure to chemicals are needed to complement the methods for outdoor human exposure assessment already in use. This paper summarizes the work of an international expert group on the integration of human indoor and outdoor exposure in LCA, within the UNEP/SETAC Life Cycle Initiative. A new methodological framework is proposed for a general procedure to include human-health effects from indoor exposure in LCA. Exposure models from occupational hygiene and household indoor air quality studies and practices are critically reviewed and recommendations are provided on the appropriateness of various model alternatives in the context of LCA. A single-compartment box model is recommended for use as a default in LCA, enabling one to screen occupational and household exposures consistent with the existing models to assess outdoor emission in a multimedia environment. An initial set of model parameter values was collected. The comparison between indoor and outdoor human exposure per unit of emission shows that for many pollutants, intake per unit of indoor emission may be several orders of magnitude higher than for outdoor emissions. It is concluded that indoor exposure should be routinely addressed within LCA.

  7. Human exposure to bovine polyomavirus: a zoonosis

    Energy Technology Data Exchange (ETDEWEB)

    Parry, J.V.; Gardner, S.D.

    1986-01-01

    A competitive-type solid phase radioimmunoassay (RIA) was developed for the detection of antibody to bovine polyomavirus. Comparison of RIA and counter-immunoelectrophoresis (CIE) results on 273 cattle sera indicated that both techniques were detecting antibody of like specificity. Human sera from 256 blood donors, 219 people recently vaccinated against polio, rubella or rabies, 50 immunosuppressed patients and 472 people with various occupational exposure to cattle were tested for antibody to bovine polyomavirus, the foetal rhesus monkey kidney strain, (anti-FRKV) by RIA. Apart from one blood donor and one of 108 rabies vaccinees only those in close contact with cattle possessed anti-FRKV. Compared with 62 per cent seropositive in the natural hosts, cattle, 71 per cent of veterinary surgeons, 50 per cent of cattle farmers, 40 per cent of abattoir workers, 16 per cent of veterinary institute technical staff and 10 per cent of veterinary students were anti-FRKV positive. Our findings indicate that the theoretical hazard of FRKV infection from undetected contamination of current tissue culture derived vaccines may, in practice, be remote. Proposed wider use of primate kidney cells as substrates for new vaccines may increase this risk.

  8. Progress in human exposure assessment for biocidal products

    NARCIS (Netherlands)

    Hemmen, J.J. van

    2004-01-01

    An important shortcoming in our present knowledge required for risk assessment of biocidal products is the assessment of human exposure. This knowledge gap has been filled in a preliminary fashion with the TNsG on human exposure to biocidal products (available from the ECB website). Explicit User gu

  9. Human exposure assessment: Approaches for chemicals (REACH) and biocides (BPD)

    NARCIS (Netherlands)

    Hemmen, J.J. van; Gerritsen-Ebben, R.

    2008-01-01

    The approaches that are indicated in the various guidance documents for the assessment of human exposure for chemicals and biocides are summarised. This reflects the TNsG (Technical notes for Guidance) version 2: human exposure assessment for biocidal products (1) under the BPD (Biocidal Products Di

  10. Population-based nutrikinetic modeling of polyphenol exposure

    NARCIS (Netherlands)

    van Velzen, E.J.J.; Westerhuis, J.A.; Grün, C.H.; Jacobs, D.M.; Eilers, P.H.C.; Mulder, Th.P.; Foltz, M.; Garczarek, U.; Kemperman, R.; Vaughan, E. E.; van Duynhoven, J.P.M.; Smilde, A.K.

    2014-01-01

    The beneficial health effects of fruits and vegetables have been attributed to their polyphenol content. These compounds undergo many bioconversions in the body. Modeling polyphenol exposure of humans upon intake is a prerequisite for understanding the modulating effect of the food matrix and the co

  11. Population-based nutrikinetic modelling of phytochemical exposure

    NARCIS (Netherlands)

    Velzen, van E.J.J.; Westerhuis, J.A.; Grün, C.H.; Duynhoven, van J.P.M.; Jacobs, D.M.; Eilers, P.H.C.; Mulder, T.P.; Foltz, M.; Garczarek, U.; Kemperman, R.; Vaughan, E.E.; Smilde, A.K.

    2014-01-01

    The beneficial health effects of fruits and vegetables have been attributed to their polyphenol content. These compounds undergo many bioconversions in the body. Modeling polyphenol exposure of humans upon intake is a prerequisite for understanding the modulating effect of the food matrix and the co

  12. [Advances on research of human exposure to triclosan].

    Science.gov (United States)

    Jin, Chenye; Chen, Yiming; Zhang, Peiqi; Xiong, Zhezhen; Wang, Caifeng; Tian, Ying

    2016-03-01

    Triclosan, a broad-spectrum antimicrobial agent, was reported to have been widely detected in various human biological samples such as urine, blood and human milk among foreign populations. In China, limited reports have been found on human exposure to triclosan, and the reported urinary triclosan concentrations were significantly lower than that of American populations. Besides, the potential influencing factors still remain unclear regarding human exposure to triclosan, but evidences suggest that those in middle age and with higher household income and higher social class tend to have higher urinary triclosan concentrations. Furthermore, triclosan exposure tend to differ by sex, geography, heredity, metabolism and life style.

  13. CONSEXPO 3.0, consumer exposure and uptake models

    NARCIS (Netherlands)

    Veen MP van; LBM

    2001-01-01

    The report provides a modelling approach to consumer exposure to chemicals, based on mathematical contact, exposure and uptake models. For each route of exposure, a number of exposure and uptake models are included. A general framework joins the exposure and uptake models selected by the user. By c

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

    Science.gov (United States)

    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

  15. Assessing exposure to phthalates - the human biomonitoring approach.

    Science.gov (United States)

    Wittassek, Matthias; Koch, Holger Martin; Angerer, Jürgen; Brüning, Thomas

    2011-01-01

    Some phthalates are developmental and reproductive toxicants in animals. Exposure to phthalates is considered to be potentially harmful to human health as well. Based on a comprehensive literature research, we present an overview of the sources of human phthalate exposure and results of exposure assessments with special focus on human biomonitoring data. Among the general population, there is widespread exposure to a number of phthalates. Foodstuff is the major source of phthalate exposure, particularly for the long-chain phthalates such as di(2-ethylhexyl) phthalate. For short-chain phthalates such as di-n-butyl-phthalate, additional pathways are of relevance. In general, children are exposed to higher phthalate doses than adults. Especially, high exposures can occur through some medications or medical devices. By comparing exposure data with existing limit values, one can also assess the risks associated with exposure to phthalates. Within the general population, some individuals exceed tolerable daily intake values for one or more phthalates. In high exposure groups, (intensive medical care, medications) tolerable daily intake transgressions can be substantial. Recent findings from animal studies suggest that a cumulative risk assessment for phthalates is warranted, and a cumulative exposure assessment to phthalates via human biomonitoring is a major step into this direction.

  16. Human exposures to parabens in cosmetics - a literature study

    OpenAIRE

    Aarflot, Ragnhild Lønseth

    2013-01-01

    A literature study was performed in order to assess and compare evidence of human exposure to parabens in cosmetics. The focus of the thesis is on human concentrations, the rate of dermal absorption, metabolism and excretion; in order to increase our understanding of human exposures to endocrine disrupting chemicals in cosmetics. High detection rates of native and total parabens in blood and urine were identified. GMs of native parabens were lower than total paraben levels in urine as expecte...

  17. Modelling survival: exposure pattern, species sensitivity and uncertainty.

    Science.gov (United States)

    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.

  18. Modelling survival: exposure pattern, species sensitivity and uncertainty

    Science.gov (United States)

    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.

  19. Wood smoke in a controlled exposure experiment with human volunteers.

    Science.gov (United States)

    Riddervold, I S; Bønløkke, J H; Mølhave, L; Massling, A; Jensen, B; Grønborg, T K; Bossi, R; Forchhammer, L; Kjærgaard, S K; Sigsgaard, T

    2011-04-01

    Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung function and normal bronchial reactivity were randomly exposed for 3 h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m³ (low) and 400 µg/m³ (high) under controlled environmental conditions. The range for PM₂.₅ load observed for single experiments was 165-303 µg/m³ for the low exposure and 205-662 µg/m³ for the high exposure, whereas particle loads during clean air exposure most often were below the detection limit (humans. The knowledge gained in this study on subjective-rated symptoms may be important for understanding human response to wood-smoke exposure.

  20. Modeling Exposure to Persistent Chemicals in Hazard and Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cowan-Ellsberry, Christina E.; McLachlan, Michael S.; Arnot, Jon A.; MacLeod, Matthew; McKone, Thomas E.; Wania, Frank

    2008-11-01

    Fate and exposure modeling has not thus far been explicitly used in the risk profile documents prepared to evaluate significant adverse effect of candidate chemicals for either the Stockholm Convention or the Convention on Long-Range Transboundary Air Pollution. However, we believe models have considerable potential to improve the risk profiles. Fate and exposure models are already used routinely in other similar regulatory applications to inform decisions, and they have been instrumental in building our current understanding of the fate of POP and PBT chemicals in the environment. The goal of this paper is to motivate the use of fate and exposure models in preparing risk profiles in the POP assessment procedure by providing strategies for incorporating and using models. The ways that fate and exposure models can be used to improve and inform the development of risk profiles include: (1) Benchmarking the ratio of exposure and emissions of candidate chemicals to the same ratio for known POPs, thereby opening the possibility of combining this ratio with the relative emissions and relative toxicity to arrive at a measure of relative risk. (2) Directly estimating the exposure of the environment, biota and humans to provide information to complement measurements, or where measurements are not available or are limited. (3) To identify the key processes and chemical and/or environmental parameters that determine the exposure; thereby allowing the effective prioritization of research or measurements to improve the risk profile. (4) Predicting future time trends including how quickly exposure levels in remote areas would respond to reductions in emissions. Currently there is no standardized consensus model for use in the risk profile context. Therefore, to choose the appropriate model the risk profile developer must evaluate how appropriate an existing model is for a specific setting and whether the assumptions and input data are relevant in the context of the application

  1. Pesticide Flow Analysis to Assess Human Exposure in Greenhouse Flower Production in Colombia

    Directory of Open Access Journals (Sweden)

    Claudia R. Binder

    2013-03-01

    Full Text Available Human exposure assessment tools represent a means for understanding human exposure to pesticides in agricultural activities and managing possible health risks. This paper presents a pesticide flow analysis modeling approach developed to assess human exposure to pesticide use in greenhouse flower crops in Colombia, focusing on dermal and inhalation exposure. This approach is based on the material flow analysis methodology. The transfer coefficients were obtained using the whole body dosimetry method for dermal exposure and the button personal inhalable aerosol sampler for inhalation exposure, using the tracer uranine as a pesticide surrogate. The case study was a greenhouse rose farm in the Bogota Plateau in Colombia. The approach was applied to estimate the exposure to pesticides such as mancozeb, carbendazim, propamocarb hydrochloride, fosetyl, carboxin, thiram, dimethomorph and mandipropamide. We found dermal absorption estimations close to the AOEL reference values for the pesticides carbendazim, mancozeb, thiram and mandipropamide during the study period. In addition, high values of dermal exposure were found on the forearms, hands, chest and legs of study participants, indicating weaknesses in the overlapping areas of the personal protective equipment parts. These results show how the material flow analysis methodology can be applied in the field of human exposure for early recognition of the dispersion of pesticides and support the development of measures to improve operational safety during pesticide management. Furthermore, the model makes it possible to identify the status quo of the health risk faced by workers in the study area.

  2. Human exposure to pulsed fields in the frequency range from 6 to 100 GHz

    Science.gov (United States)

    Laakso, Ilkka; Morimoto, Ryota; Heinonen, Juhani; Jokela, Kari; Hirata, Akimasa

    2017-09-01

    Restrictions on human exposure to electromagnetic waves at frequencies higher than 3-10 GHz are defined in terms of the incident power density to prevent excessive temperature rise in superficial tissue. However, international standards and guidelines differ in their definitions of how the power density is interpreted for brief exposures. This study investigated how the temperature rise was affected by exposure duration at frequencies higher than 6 GHz. Far-field exposure of the human face to pulses shorter than 10 s at frequencies from 6 to 100 GHz was modelled using the finite-difference time-domain method. The bioheat transfer equation was used for thermal modelling. We investigated the effects of frequency, polarization, exposure duration, and depth below the skin surface on the temperature rise. The results indicated limitations in the current human exposure guidelines and showed that radiant exposure, i.e. energy absorption per unit area, can be used to limit temperature rise for pulsed exposure. The data are useful for the development of human exposure guidelines at frequencies higher than 6 GHz.

  3. Pesticide flow analysis to assess human exposure in greenhouse flower production in Colombia.

    Science.gov (United States)

    Lesmes-Fabian, Camilo; Binder, Claudia R

    2013-03-25

    Human exposure assessment tools represent a means for understanding human exposure to pesticides in agricultural activities and managing possible health risks. This paper presents a pesticide flow analysis modeling approach developed to assess human exposure to pesticide use in greenhouse flower crops in Colombia, focusing on dermal and inhalation exposure. This approach is based on the material flow analysis methodology. The transfer coefficients were obtained using the whole body dosimetry method for dermal exposure and the button personal inhalable aerosol sampler for inhalation exposure, using the tracer uranine as a pesticide surrogate. The case study was a greenhouse rose farm in the Bogota Plateau in Colombia. The approach was applied to estimate the exposure to pesticides such as mancozeb, carbendazim, propamocarb hydrochloride, fosetyl, carboxin, thiram, dimethomorph and mandipropamide. We found dermal absorption estimations close to the AOEL reference values for the pesticides carbendazim, mancozeb, thiram and mandipropamide during the study period. In addition, high values of dermal exposure were found on the forearms, hands, chest and legs of study participants, indicating weaknesses in the overlapping areas of the personal protective equipment parts. These results show how the material flow analysis methodology can be applied in the field of human exposure for early recognition of the dispersion of pesticides and support the development of measures to improve operational safety during pesticide management. Furthermore, the model makes it possible to identify the status quo of the health risk faced by workers in the study area.

  4. Inhale while Dreaming: Human Exposure to Pollutants while Sleeping

    DEFF Research Database (Denmark)

    Corsi, Richard; Spilak, Michal; Boor, E., Brandon

    2012-01-01

    Humans spend approximately 1/3 of their total life asleep, typically on a mattress or other bedding. Despite the fact that there is no other location where most of humanity spends more time, this microenvironment has received little attention from the standpoint of human exposure to a wide range ...

  5. Wood smoke in a controlled exposure experiment with human volunteers

    DEFF Research Database (Denmark)

    Riddervold, Ingunn Skogstad; Bønløkke, Jakob Hjort; Mølhave, Lars

    2011-01-01

    Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung...... function and normal bronchial reactivity were randomly exposed for 3h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m3 (low) and 400 µg/m3 (high) under controlled environmental conditions.......0007), “irritative body perceptions” (p = 0.0127), “psychological/neurological effects” (p = 0.0075) and “weak inflammatory responses” (p = 0.0003). Furthermore, significant effects (p = 0.0192) on self-reported general mucosa irritation were found. In conclusion, exposure to wood smoke affected symptom rating...

  6. Evaluation of Pharmacokinetic Models for the Disposition of Lead (Pb) in Humans, in Support of Application to Occupational Exposure Limit Derivation

    Science.gov (United States)

    2015-11-09

    human model (received from Dr. Gary Diamond , SRC) was consistent with the code provided in O’Flaherty (2000). Simulations were conducted using...perfused tissues other than bone. In contrast, the tissue:plasma partition coefficients in the model code received from Dr. Diamond and in O’Flaherty...10, or 0 µg Pb/kg/day as necessary to sustain the BLL at or above 40 µg/dl until the end of the 49-day experiment. O’Flaherty (1993) simulated

  7. Environmental chemical exposures and human epigenetics

    Science.gov (United States)

    Hou, Lifang; Zhang, Xiao; Wang, Dong; Baccarelli, Andrea

    2012-01-01

    Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes. PMID:22253299

  8. Evaluation of perturbations in serum thyroid hormones during human pregnancy due to dietary iodide and perchlorate exposure using a biologically based dose-response model.

    Science.gov (United States)

    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.

  9. Human Health Effects Associated with Exposure to Toxic Cyanobacteria

    Science.gov (United States)

    Reports of toxic cyanobacteria blooms are increasing worldwide. Warming and eutrophic surface water systems support the development of blooms. We examine the evidence for adverse human health effects associated with exposure to toxic blooms in drinking water, recreational water a...

  10. Knowledge of human immunodeficiency virus post-exposure ...

    African Journals Online (AJOL)

    Knowledge of human immunodeficiency virus post-exposure prophylaxis among doctors in a Nigerian tertiary hospital. ... of PEP policy in the hospital. The level of knowledge concerning the high-risk fluid and three drugs used in PEP is high.

  11. Human Health Effects Associated with Exposure to Toxic Cyanobacteria

    Science.gov (United States)

    Reports of toxic cyanobacteria blooms are increasing worldwide. Warming and eutrophic surface water systems support the development of blooms. We examine the evidence for adverse human health effects associated with exposure to toxic blooms in drinking water, recreational water a...

  12. Parameterization Models for Pesticide Exposure via Crop Consumption

    DEFF Research Database (Denmark)

    Fantke, Peter; Wieland, Peter; Juraske, Ronnie

    2012-01-01

    An approach for estimating human exposure to pesticides via consumption of six important food crops is presented that can be used to extend multimedia models applied in health risk and life cycle impact assessment. We first assessed the variation of model output (pesticide residues per kg applied......) as a function of model input variables (substance, crop, and environmental properties) including their possible correlations using matrix algebra. We identified five key parameters responsible for between 80% and 93% of the variation in pesticide residues, namely time between substance application and crop......-specific models by parametrizing a complex fate and exposure assessment framework. The parametric models thereby reflect the framework’s physical and chemical mechanisms and predict pesticide residues in harvest using linear combinations of crop, crop surface, and soil compartments. Parametric model results...

  13. Modeling Cadmium Exposures in Low- and High-Exposure Areas in Thailand

    OpenAIRE

    Satarug, Soisungwan; Swaddiwudhipong, Witaya; Ruangyuttikarn, Werawan; Nishijo, Muneko; Ruiz, Patricia

    2013-01-01

    Background: Previous U.S. population modeling studies have reported that urinary cadmium (Cd) excretion patterns differ with age, sex, and dietary exposure; associations between Cd exposures and health outcomes also have differed by age and sex. Therefore, it is important to test models used to estimate Cd exposures across an expanded Cd-exposure range. Objectives: We estimated relative Cd exposures from both diet and smoking in low- and high-exposure scenarios to provide data for improving r...

  14. Parabens as Urinary Biomarkers of Exposure in Humans

    OpenAIRE

    Ye, Xiaoyun; Bishop, Amber M.; Reidy, John A; Needham, Larry L.; Calafat, Antonia M

    2006-01-01

    Background Parabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure. Objectives Assessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In ani...

  15. Developing, Applying, and Evaluating Models for Rapid Screening of Chemical Exposures

    DEFF Research Database (Denmark)

    Arnot, J.; Shin, H.; Ernstoff, Alexi;

    2015-01-01

    to limited exposure data there is limited information on chemical use patterns and production and emission quantities. These data gaps require the application of mass balance, statistical and quantitative structure-activity relationship (QSAR) models to predict exposure and exposure potential for humans...

  16. Structural change of human hair induced by mercury exposure.

    Science.gov (United States)

    Xing, Xueqing; Du, Rong; Li, Yufeng; Li, Bai; Cai, Quan; Mo, Guang; Gong, Yu; Chen, Zhongjun; Wu, Zhonghua

    2013-10-01

    Mercury is one of the most hazardous pollutants in the environment. In this paper, the structural change of human hair induced by mercury exposure was studied. Human hair samples were, respectively, collected from the normal Beijing area and the Hg-contaminated Wanshan area of the Guizhou Province, China. Inductively coupled plasma mass spectroscopy was used to detect the element contents. A small angle X-ray scattering technique was used to probe the structural change. Three reflections with 8.8, 6.7, and 4.5 nm spacing were compared between the normal and the Hg-contaminated hair samples. The results confirm that the 4.5 nm reflection is from the ordered fibrillar structure of glycosaminoglycan (GAG) in proteoglycan (PG) that composes the matrix around the intermediate filaments. The increase of Ca content makes the regular oriented fibrillar structure of GAG transform to a random oriented one, broadening the angular extent of the reflection with 4.5 nm spacing. However, overdose Hg makes the core proteins where the ordered fibrils of GAG are attached become coiled, which destroys the ordered arrangements of fibrillar GAG in PG, resulting in the disappearance of the reflections with 4.5 nm spacing. The disappearance of the 4.5 nm reflection can be used as a bioindicator of overdose Hg contamination to the human body. A supercoiled-coil model of hair nanoscale structure and a possible mechanism of mercury effect in human hair are proposed in this paper.

  17. A Theoretical Model for Selective Exposure Research.

    Science.gov (United States)

    Roloff, Michael E.; Noland, Mark

    This study tests the basic assumptions underlying Fishbein's Model of Attitudes by correlating an individual's selective exposure to types of television programs (situation comedies, family drama, and action/adventure) with the attitudinal similarity between individual attitudes and attitudes characterized on the programs. Twenty-three college…

  18. Parameterization models for pesticide exposure via crop consumption.

    Science.gov (United States)

    Fantke, Peter; Wieland, Peter; Juraske, Ronnie; Shaddick, Gavin; Itoiz, Eva Sevigné; Friedrich, Rainer; Jolliet, Olivier

    2012-12-04

    An approach for estimating human exposure to pesticides via consumption of six important food crops is presented that can be used to extend multimedia models applied in health risk and life cycle impact assessment. We first assessed the variation of model output (pesticide residues per kg applied) as a function of model input variables (substance, crop, and environmental properties) including their possible correlations using matrix algebra. We identified five key parameters responsible for between 80% and 93% of the variation in pesticide residues, namely time between substance application and crop harvest, degradation half-lives in crops and on crop surfaces, overall residence times in soil, and substance molecular weight. Partition coefficients also play an important role for fruit trees and tomato (Kow), potato (Koc), and lettuce (Kaw, Kow). Focusing on these parameters, we develop crop-specific models by parametrizing a complex fate and exposure assessment framework. The parametric models thereby reflect the framework's physical and chemical mechanisms and predict pesticide residues in harvest using linear combinations of crop, crop surface, and soil compartments. Parametric model results correspond well with results from the complex framework for 1540 substance-crop combinations with total deviations between a factor 4 (potato) and a factor 66 (lettuce). Predicted residues also correspond well with experimental data previously used to evaluate the complex framework. Pesticide mass in harvest can finally be combined with reduction factors accounting for food processing to estimate human exposure from crop consumption. All parametric models can be easily implemented into existing assessment frameworks.

  19. Chronic boron exposure and human semen parameters.

    Science.gov (United States)

    Robbins, Wendie A; Xun, Lin; Jia, Juan; Kennedy, Nola; Elashoff, David A; Ping, Liu

    2010-04-01

    Boron found as borates in soil, food, and water has important industrial and medical applications. A panel reviewing NTP reproductive toxicants identified boric acid as high priority for occupational studies to determine safe versus adverse reproductive effects. To address this, we collected boron exposure/dose measures in workplace inhalable dust, dietary food/fluids, blood, semen, and urine from boron workers and two comparison worker groups (n=192) over three months and determined correlations between boron and semen parameters (total sperm count, sperm concentration, motility, morphology, DNA breakage, apoptosis and aneuploidy). Blood boron averaged 499.2 ppb for boron workers, 96.1 and 47.9 ppb for workers from high and low environmental boron areas (pBoron concentrated in seminal fluid. No significant correlations were found between blood or urine boron and adverse semen parameters. Exposures did not reach those causing adverse effects published in animal toxicology work but exceeded those previously published for boron occupational groups.

  20. Exposure at Default Modeling with Default Intensities

    OpenAIRE

    Witzany, Jiří

    2011-01-01

    The paper provides an overview of the Exposure at Default (EAD) definition, requirements, and estimation methods as set by the Basel II regulation. A new methodology connected to the intensity of default modeling is proposed. The numerical examples show that various estimation techniques may lead to quite different results with intensity of default based model being recommended as the most faithful with respect to a precise probabilistic definition of the EAD parameter.

  1. Global climate change and contaminants--an overview of opportunities and priorities for modelling the potential implications for long-term human exposure to organic compounds in the Arctic.

    Science.gov (United States)

    Armitage, James M; Quinn, Cristina L; Wania, Frank

    2011-06-01

    This overview seeks to provide context and insight into the relative importance of different aspects related to global climate change for the exposure of Northern residents to organic contaminants. A key objective is to identify, from the perspective of researchers engaged in contaminant fate, transport and bioaccumulation modelling, the most useful research questions with respect to projecting the long-term trends in human exposure. Monitoring studies, modelling results, the magnitude of projected changes and simplified quantitative approaches are used to inform the discussion. Besides the influence of temperature on contaminant amplification and distribution, accumulation of organic contaminants in the Arctic is expected to be particularly sensitive to the reduction/elimination of sea-ice cover and also changes to the frequency and intensity of precipitation events (most notably for substances that are highly susceptible to precipitation scavenging). Changes to key food-web interactions, in particular the introduction of additional trophic levels, have the potential to exert a relatively high influence on contaminant exposure but the likelihood of such changes is difficult to assess. Similarly, changes in primary productivity and dynamics of organic matter in aquatic systems could be influential for very hydrophobic contaminants, but the magnitude of change that may occur is uncertain. Shifts in the amount and location of chemical use and emissions are key considerations, in particular if substances with relatively low long range transport potential are used in closer proximity to, or even within, the Arctic in the future. Temperature-dependent increases in emissions via (re)volatilization from primary and secondary sources outside the Arctic are also important in this regard. An increased frequency of boreal forest fires has relevance for compounds emitted via biomass burning and revolatilization from soil during/after burns but compound-specific analyses are

  2. Generation of infant anatomical models for evaluating electromagnetic field exposures.

    Science.gov (United States)

    Li, Congsheng; Chen, Zhiye; Yang, Lei; Lv, Bin; Liu, Jianzhe; Varsier, Nadège; Hadjem, Abdelhamid; Wiart, Joe; Xie, Yi; Ma, Lin; Wu, Tongning

    2015-01-01

    Realistic anatomical modeling is essential in analyzing human exposure to electromagnetic fields. Infants have significant physical and anatomical differences compared with other age groups. However, few realistic infant models are available. In this work, we developed one 12-month-old male whole body model and one 17-month-old male head model from magnetic resonance images. The whole body and head models contained 28 and 30 tissues, respectively, at spatial resolution of 1 mm × 1 mm × 1 mm. Fewer identified tissues in the whole body model were a result of the low original image quality induced by the fast imaging sequence. The anatomical and physical parameters of the models were validated against findings in published literature (e.g., a maximum deviation as 18% in tissue mass was observed compared with the data from International Commission on Radiological Protection). Several typical exposure scenarios were realized for numerical simulation. Dosimetric comparison with various adult and child anatomical models was conducted. Significant differences in the physical and anatomical features between adult and child models demonstrated the importance of creating realistic infant models. Current safety guidelines for infant exposure to radiofrequency electromagnetic fields may not be conservative.

  3. Modeling thermal protection outfits for fire exposures

    Science.gov (United States)

    Song, Guowen

    2002-01-01

    A numerical model has been developed that successfully predicts heat transfer through thermally protective clothing materials and garments exposed to intense heat. The model considers the effect of fire exposure to the thermophysical properties of materials as well as the air layers between the clothing material and skin surface. These experiments involved characterizing the flash fire surrounding the manikin by measuring the temperature of the flame above each thermal sensor in the manikin surface. An estimation method is used to calculate the heat transfer coefficient for each thermal sensor in a 4 second exposure to an average heat flux of 2.00cal/cm2sec. A parameter estimation method was used to estimate heat induced change in fabric thermophysical properties. The skin-clothe air gap distribution of different garments was determined using three-dimensional body scanning technology. Multi-layer skin model and a burn prediction method were used to predict second and third degree burns. The integrated generalized model developed was validated using the "Pyroman" Thermal Protective Clothing Analysis System with Kevlar/PBIRTM and NomexRTMIIIA coverall garments with different configuration and exposure time. A parametric study conducted using this numerical model indicated the influencing parameters on garment thermal protective performance in terms of skin burn damage subjected to 4 second flash fire exposure. The importance of these parameters is analyzed and distinguished. These parameters includes fabric thermophysical properties, PyromanRTM chamber flash fire characteristics, garment shrinkage and fit factors, as well as garment initial and test ambient temperature. Different skin models and their influence on burn prediction were also investigated using this model.

  4. Exposure Modeling of Residential Air Exchange Rates for NEXUS Participants.

    Science.gov (United States)

    Due to cost and participant burden of personal measurements, air pollution health studies often estimate exposures using local ambient air monitors. Since outdoor levels do not necessarily reflect personal exposures, we developed the Exposure Model for Individuals (EMI) to improv...

  5. Sampling strategy for estimating human exposure pathways to consumer chemicals

    Directory of Open Access Journals (Sweden)

    Eleni Papadopoulou

    2016-03-01

    Full Text Available Human exposure to consumer chemicals has become a worldwide concern. In this work, a comprehensive sampling strategy is presented, to our knowledge being the first to study all relevant exposure pathways in a single cohort using multiple methods for assessment of exposure from each exposure pathway. The selected groups of chemicals to be studied are consumer chemicals whose production and use are currently in a state of transition and are; per- and polyfluorinated alkyl substances (PFASs, traditional and “emerging” brominated flame retardants (BFRs and EBFRs, organophosphate esters (OPEs and phthalate esters (PEs. Information about human exposure to these contaminants is needed due to existing data gaps on human exposure intakes from multiple exposure pathways and relationships between internal and external exposure. Indoor environment, food and biological samples were collected from 61 participants and their households in the Oslo area (Norway on two consecutive days, during winter 2013-14. Air, dust, hand wipes, and duplicate diet (food and drink samples were collected as indicators of external exposure, and blood, urine, blood spots, hair, nails and saliva as indicators of internal exposure. A food diary, food frequency questionnaire (FFQ and indoor environment questionnaire were also implemented. Approximately 2000 samples were collected in total and participant views on their experiences of this campaign were collected via questionnaire. While 91% of our participants were positive about future participation in a similar project, some tasks were viewed as problematic. Completing the food diary and collection of duplicate food/drink portions were the tasks most frequent reported as “hard”/”very hard”. Nevertheless, a strong positive correlation between the reported total mass of food/drinks in the food record and the total weight of the food/drinks in the collection bottles was observed, being an indication of accurate performance

  6. Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.

    Science.gov (United States)

    Yoshizawa, Katsuhiko; Yuki, Michiko; Kinoshita, Yuichi; Emoto, Yuko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A; Tsubura, Airo

    2016-05-01

    The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans.

  7. Exposure Space: Integrating Exposure Data and Modeling with Toxicity Information

    Science.gov (United States)

    Recent advances have been made in high-throughput (HTP) toxicity testing, e.g. from ToxCast, which will ultimately be combined with HTP predictions of exposure potential to support next-generation chemical safety assessment. Rapid exposure methods are essential in selecting chemi...

  8. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.

    1996-01-01

    aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical......A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological...... for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers...

  9. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies dif

  10. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  11. Human reproductive system disturbances and pesticide exposure in Brazil

    OpenAIRE

    Sergio Koifman; Rosalina Jorge Koifman; Armando Meyer

    2002-01-01

    The observation of reproductive disturbances in humans and in the wildlife has been reported in the last decade in different countries. Exposure to different chemicals possibly acting in the endocrine system or endocrine disruptors, including pesticides, has been a hypothesis raised to explain the observed changes. This paper aimed to present results of an epidemiological ecologic study carried out to explore population data on pesticides exposure in selected Brazilian states in the eighties ...

  12. Developing human health exposure scenarios for petroleum substances under REACH

    Energy Technology Data Exchange (ETDEWEB)

    Carter, M.; De Wilde, P.; Maksimainen, K.; Margary, A.; Money, C.; Pizzella, G.; Svanehav, T.; Tsang, W.; Urbanus, J.; Rohde, A.

    2012-12-15

    This report describes the approaches that were adopted by CONCAWE to prepare the human exposure estimates in the chemical safety assessments of the REACH registration dossiers for petroleum substances based on all applicable regulatory guidance. Separate exposure estimates were developed for workers and for consumers and included inhalation and dermal routes. The complex nature of petroleum substances required various scientifically justified refinements of the regulatory guidance.

  13. Probabilistic integrated risk assessment of human exposure risk to environmental bisphenol A pollution sources.

    Science.gov (United States)

    Fu, Keng-Yen; Cheng, Yi-Hsien; Chio, Chia-Pin; Liao, Chung-Min

    2016-10-01

    Environmental bisphenol A (BPA) exposure has been linked to a variety of adverse health effects such as developmental and reproductive issues. However, establishing a clear association between BPA and the likelihood of human health is complex yet fundamentally uncertain. The purpose of this study was to assess the potential exposure risks from environmental BPA among Chinese population based on five human health outcomes, namely immune response, uterotrophic assay, cardiovascular disease (CVD), diabetes, and behavior change. We addressed these health concerns by using a stochastic integrated risk assessment approach. The BPA dose-dependent likelihood of effects was reconstructed by a series of Hill models based on animal models or epidemiological data. We developed a physiologically based pharmacokinetic (PBPK) model that allows estimation of urinary BPA concentration from external exposures. Here we showed that the daily average exposure concentrations of BPA and urinary BPA estimates were consistent with the published data. We found that BPA exposures were less likely to pose significant risks for infants (0-1 year) and adults (male and female >20 years) with human long-term BPA susceptibility in relation to multiple exposure pathways, and for informing the public of the negligible magnitude of environmental BPA pollution impacts on human health.

  14. Human solvent exposure. Factors influencing the pharmacokinetics and acute toxicity

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1991-01-01

    exposed to mixtures of solvents experience an increased frequency of work related irritative and neurological symptoms although the exposure has been far below the occupational exposure limits. A series of controlled human exposure studies was carried out. Different groups of persons were exposed...... to the most frequent solvent, toluene. Toluene in alveolar air and the urinary excretion of the metabolites were measured and the acute effects of toluene were assessed by the performance in a series of test of the perceptual and psychomotor functions as well as a standardized registration of annoyance...

  15. Human exposure to organic arsenic species from seafood.

    Science.gov (United States)

    Taylor, Vivien; Goodale, Britton; Raab, Andrea; Schwerdtle, Tanja; Reimer, Ken; Conklin, Sean; Karagas, Margaret R; Francesconi, Kevin A

    2017-02-15

    Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be non-toxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge.

  16. Human exposure to endocrine disruptors and breast milk.

    Science.gov (United States)

    Stefanidou, M; Maravelias, C; Spiliopoulou, C

    2009-09-01

    Endocrine system is one of the most sensitive communication networks of the human body which influences all aspects of human health and well-being, including reproductive potential, cognitive functions, thyroid and metabolism, digestion and hormonal balance. In recent years basic laboratory research has been focused on the potential relationship between environmental contaminants and cellular endocrine function. Environmental contaminants are ubiquitous in the environment, alter endocrine physiology and produce endocrine disruption without acting as classic toxicants. These endocrine disruptors (EDCs) are lipophilic and stored for long periods of time in the adipose tissue. Maternal exposure to EDCs during pregnancy and lactation has as a result the exposure of the fetus and neonate through placenta and breast milk. It has been recognized that human milk is the best natural food for neonates providing immunologic, developmental and practical advantages throughout childhood. However, contamination of human milk by the presence of environmental toxicants is widespread through the past decades due to inadequately controlled pollution. Persistent pesticides, chemical solvents and others tend to invade slowly the environment, to bioaccumulate in the food chain and to have long half-lives in animals and humans. During the past fifteen years, the scientific interest has been focused on xenoestrogens, i.e.,environmental chemicals with estrogen disrupting activity. Certain adverse health and reproductive outcomes are attributed to these chemicals in wildlife, in laboratory animals, as well as in humans. Although most toxic agents are hazardous in high doses, the human health risks associated with EDCs concern exposure to low doses. The human health risks that may be associated with these low-level but constant exposures are still largely unknown and highly controversial. In this paper, we review available data on environmental chemicals present in breast milk that may

  17. National Surveillance of Occupational Exposure to the Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Maura Ricketts

    1992-01-01

    Full Text Available In September 1985, a prospective study was initiated to monitor the occurrence of occupational exposures to human immunodeficiency virus (HIV-infected blood and body fluids in Canada. This program was coordinated by the Federal Centre for acquired immune deficiency syndrome (AIDS (now the Division of HIV/AIDS Epidemiology at the Laboratory Centre for Disease Control. The objective was to determine the risk to workers of acquiring HIV infection as a result of exposure to HIV-infected blood and other body fluids. To be eligible, a worker must have sustained a documented parenteral, mucous membrane or skin contact exposure to blood or body fluids from an HIV-infected person. A baseline specimen was collected within a week of the exposure and then at six weeks, 12 weeks, six months and 12 months. Information concerning the type of exposure, precautions used and post exposure treatment was submitted to the Federal Centre for AIDS on standard data collection forms. All information was anonymous, identified only by a code number. Guidelines for counselling an exposed employee were provided with enrollment material. As of July 29, 1991, 414 employees have been included in the study. Two hundred and thirty-seven of the 414 exposures (57% were needlestick injuries of which 167 (70% were sustained by nurses. Other exposures consisted of open wound contamination, eye splashes, scalpel wounds and skin contact with blood and body fluids. To date, there have been no seroconversions among workers enrolled in the surveillance program.

  18. Operation of the computer model for microenvironment atomic oxygen exposure

    Science.gov (United States)

    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.

  19. Controlled human exposures to ambient pollutant particles in susceptible populations

    Directory of Open Access Journals (Sweden)

    Ghio Andrew J

    2009-07-01

    Full Text Available Abstract Epidemiologic studies have established an association between exposures to air pollution particles and human mortality and morbidity at concentrations of particles currently found in major metropolitan areas. The adverse effects of pollution particles are most prominent in susceptible subjects, including the elderly and patients with cardiopulmonary diseases. Controlled human exposure studies have been used to confirm the causal relationship between pollution particle exposure and adverse health effects. Earlier studies enrolled mostly young healthy subjects and have largely confirmed the capability of particles to cause adverse health effects shown in epidemiological studies. In the last few years, more studies involving susceptible populations have been published. These recent studies in susceptible populations, however, have shown that the adverse responses to particles appear diminished in these susceptible subjects compared to those in healthy subjects. The present paper reviewed and compared control human exposure studies to particles and sought to explain the "unexpected" response to particle exposure in these susceptible populations and make recommendations for future studies. We found that the causes for the discrepant results are likely multifactorial. Factors such as medications, the disease itself, genetic susceptibility, subject selection bias that is intrinsic to many controlled exposure studies and nonspecificity of study endpoints may explain part of the results. Future controlled exposure studies should select endpoints that are more closely related to the pathogenesis of the disease and reflect the severity of particle-induced health effects in the specific populations under investigation. Future studies should also attempt to control for medications and genetic susceptibility. Using a different study design, such as exposing subjects to filtered air and ambient levels of particles, and assessing the improvement in

  20. Analysis of the local worst-case SAR exposure caused by an MRI multi-transmit body coil in anatomical models of the human body

    Science.gov (United States)

    Neufeld, Esra; Gosselin, Marie-Christine; Murbach, Manuel; Christ, Andreas; Cabot, Eugenia; Kuster, Niels

    2011-08-01

    Multi-transmit coils are increasingly being employed in high-field magnetic resonance imaging, along with a growing interest in multi-transmit body coils. However, they can lead to an increase in whole-body and local specific absorption rate (SAR) compared to conventional body coils excited in circular polarization for the same total incident input power. In this study, the maximum increase of SAR for three significantly different human anatomies is investigated for a large 3 T (128 MHz) multi-transmit body coil using numerical simulations and a (generalized) eigenvalue-based approach. The results demonstrate that the increase of SAR strongly depends on the anatomy. For the three models and normalization to the sum of the rung currents squared, the whole-body averaged SAR increases by up to a factor of 1.6 compared to conventional excitation and the peak spatial SAR (averaged over any 10 cm3 of tissue) by up to 13.4. For some locations the local averaged SAR goes up as much as 800 times (130 when looking only at regions where it is above 1% of the peak spatial SAR). The ratio of the peak spatial SAR to the whole-body SAR increases by a factor of up to 47 and can reach values above 800. Due to the potentially much larger power deposition, additional, preferably patient-specific, considerations are necessary to avoid injuries by such systems.

  1. Analysis of the local worst-case SAR exposure caused by an MRI multi-transmit body coil in anatomical models of the human body

    Energy Technology Data Exchange (ETDEWEB)

    Neufeld, Esra; Gosselin, Marie-Christine; Murbach, Manuel; Christ, Andreas; Cabot, Eugenia; Kuster, Niels, E-mail: neufeld@itis.ethz.ch [Foundation for Research on Information Technologies in Society (IT' IS), Zeughausstr. 43, 8004 Zuerich (Switzerland)

    2011-08-07

    Multi-transmit coils are increasingly being employed in high-field magnetic resonance imaging, along with a growing interest in multi-transmit body coils. However, they can lead to an increase in whole-body and local specific absorption rate (SAR) compared to conventional body coils excited in circular polarization for the same total incident input power. In this study, the maximum increase of SAR for three significantly different human anatomies is investigated for a large 3 T (128 MHz) multi-transmit body coil using numerical simulations and a (generalized) eigenvalue-based approach. The results demonstrate that the increase of SAR strongly depends on the anatomy. For the three models and normalization to the sum of the rung currents squared, the whole-body averaged SAR increases by up to a factor of 1.6 compared to conventional excitation and the peak spatial SAR (averaged over any 10 cm{sup 3} of tissue) by up to 13.4. For some locations the local averaged SAR goes up as much as 800 times (130 when looking only at regions where it is above 1% of the peak spatial SAR). The ratio of the peak spatial SAR to the whole-body SAR increases by a factor of up to 47 and can reach values above 800. Due to the potentially much larger power deposition, additional, preferably patient-specific, considerations are necessary to avoid injuries by such systems.

  2. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  3. EXPOSURE ANALYSIS MODELING SYSTEM (EXAMS): USER MANUAL AND SYSTEM DOCUMENTATION

    Science.gov (United States)

    The Exposure Analysis Modeling System, first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals - pesticides, ...

  4. Determinants of Dermal Exposure Relevant for Exposure Modelling in Regulatory Risk Assessment

    NARCIS (Netherlands)

    Marquart, J.; Brouwer, D.H.; Gijsbers, J.H.J.; Links, I.H.M.; Warren, N.; Hemmen, J.J. van

    2003-01-01

    Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European

  5. Outdoor and indoor cadmium distributions near an abandoned smelting works and their relations to human exposure

    Energy Technology Data Exchange (ETDEWEB)

    Spurgeon, David J., E-mail: dasp@ceh.ac.uk [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Crowmarsh Gifford, Wallingford, Oxon, OX10 8BB (United Kingdom); Lawlor, Alan [Centre for Ecology and Hydrology, Lancaster, Bailrigg, Lancaster LA1 4AP (United Kingdom); Hooper, Helen L. [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Crowmarsh Gifford, Wallingford, Oxon, OX10 8BB (United Kingdom); Wadsworth, Richard [Centre for Ecology and Hydrology, Lancaster, Bailrigg, Lancaster LA1 4AP (United Kingdom); Svendsen, Claus [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Crowmarsh Gifford, Wallingford, Oxon, OX10 8BB (United Kingdom); Thomas, Laura D.K. [MRC-HPA Centre for Environment and Health, Department of Epidemiology and Public health, Imperial College London (United Kingdom); Ellis, James K.; Bundy, Jacob G.; Keun, Hector C. [Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ (United Kingdom); Jarup, Lars [MRC-HPA Centre for Environment and Health, Department of Epidemiology and Public health, Imperial College London (United Kingdom)

    2011-12-15

    The relationship of measured or modelled Cd concentrations in soil, house dust and available to plants with human urinary Cd concentrations were assessed in a population living around a Cd/Pb/Zn smelter in the UK. Modelled air concentrations explained 35% of soil Cd variation indicating the smelter contributed to soil Cd loads. Multi-variate analysis confirmed a significant role of biological and life-style factors in determining urinary Cd levels. Significant correlations of urinary Cd with soil, house dust and modelled plant available Cd concentrations were not, however, found. Potential reasons for the absence of clear relationships include limited environmental contact in urban populations; the role of undefined factors in determining exposure; and the limited spatial scope of the survey which did not sample from the full pollution gradient. Further, the absence of any significant relationship indicates that environmental measures provide limited advantage over atmospheric model outputs for first stage human exposure assessment. - Highlights: > Environmental measurements indicate smelter pollution of a surrounding urban area. > Life-style and biology influenced U-Cd more than measured environmental levels. > Limited contact with outdoor environments may limit Cd uptake in urban populations. > Better life-style data could improve the attribution of human Cd exposure routes. > Measured Cd levels provide limited added exposure insight over dispersion models. - Measured and modelled environmental cadmium concentrations provide limited additional explanation of human urinary cadmium concentrations.

  6. Human disease resulting from exposure to electromagnetic fields.

    Science.gov (United States)

    Carpenter, David O

    2013-01-01

    Electromagnetic fields (EMFs) include everything from cosmic rays through visible light to the electric and magnetic fields associated with electricity. While the high frequency fields have sufficient energy to cause cancer, the question of whether there are human health hazards associated with communication radiofrequency (RF) EMFs and those associated with use of electricity remains controversial. The issue is more important than ever given the rapid increase in the use of cell phones and other wireless devices. This review summarizes the evidence stating that excessive exposure to magnetic fields from power lines and other sources of electric current increases the risk of development of some cancers and neurodegenerative diseases, and that excessive exposure to RF radiation increases risk of cancer, male infertility, and neurobehavioral abnormalities. The relative impact of various sources of exposure, the great range of standards for EMF exposure, and the costs of doing nothing are also discussed.

  7. Human convective boundary layer and its impact on personal exposure

    DEFF Research Database (Denmark)

    Licina, Dusan

    People spend most of their time indoors and they are constantly exposed to pollution that affects their health, comfort and productivity. Due to strong economic and environmental pressures to reduce building energy consumption, low air velocity design is gaining popularity; hence buoyancy flows...... differences in pollution concentration mean that personal exposure, rather than average space concentration, determines the risk of elevated exposure. Current room air distribution design practice does not take into account the air movement induced by the thermal flows from occupants, which often results...... in inaccurate exposure prediction. This highlights the importance of a detailed understanding of the complex air movements that take place in the vicinity of the human body and their impact on personal exposure. The two objectives of the present work are: (i) to examine the extent to which the room air...

  8. Modeling Impaired Hippocampal Neurogenesis after Radiation Exposure.

    Science.gov (United States)

    Cacao, Eliedonna; Cucinotta, Francis A

    2016-03-01

    Radiation impairment of neurogenesis in the hippocampal dentate gyrus is one of several factors associated with cognitive detriments after treatment of brain cancers in children and adults with radiation therapy. Mouse models have been used to study radiation-induced changes in neurogenesis, however the models are limited in the number of doses, dose fractions, age and time after exposure conditions that have been studied. The purpose of this study is to develop a novel predictive mathematical model of radiation-induced changes to neurogenesis using a system of nonlinear ordinary differential equations (ODEs) to represent the time, age and dose-dependent changes to several cell populations participating in neurogenesis as reported in mouse experiments exposed to low-LET radiation. We considered four compartments to model hippocampal neurogenesis and, consequently, the effects of radiation treatment in altering neurogenesis: (1) neural stem cells (NSCs), (2) neuronal progenitor cells or neuroblasts (NB), (3) immature neurons (ImN) and (4) glioblasts (GB). Because neurogenesis is decreasing with increasing mouse age, a description of the age-related dynamics of hippocampal neurogenesis is considered in the model, which is shown to be an important factor in comparisons to experimental data. A key feature of the model is the description of negative feedback regulation on early and late neuronal proliferation after radiation exposure. The model is augmented with parametric descriptions of the dose and time after irradiation dependences of activation of microglial cells and a possible shift of NSC proliferation from neurogenesis to gliogenesis reported at higher doses (∼10 Gy). Predictions for dose-fractionation regimes and for different mouse ages, and prospects for future work are then discussed.

  9. Human reproductive system disturbances and pesticide exposure in Brazil

    Directory of Open Access Journals (Sweden)

    Koifman Sergio

    2002-01-01

    Full Text Available The observation of reproductive disturbances in humans and in the wildlife has been reported in the last decade in different countries. Exposure to different chemicals possibly acting in the endocrine system or endocrine disruptors, including pesticides, has been a hypothesis raised to explain the observed changes. This paper aimed to present results of an epidemiological ecologic study carried out to explore population data on pesticides exposure in selected Brazilian states in the eighties and human reproductive outcomes in the nineties. Pearson correlation coefficients were ascertained between available data pesticides sales in eleven states in Brazil in 1985 and selected further reproductive outcomes or their surrogates. Moderate to high correlations were observed to infertility, testis, breast, prostate and ovarian cancer mortality. Despite the restrains of ecologic studies to establish cause-effect relationships, the observed results are in agreement with evidence supporting a possible association between pesticides exposure and the analyzed reproductive outcomes.

  10. Traditional goat husbandry may substantially contribute to human toxoplasmosis exposure

    Science.gov (United States)

    Raising goats in settings that are highly contaminated with oocysts of Toxoplasma gondii may contribute significantly to human exposure to this zoonotic parasite. Increasing consumption of young goats in Romania, where goats are typically reared in backyards that are also home to cats (the definitiv...

  11. Biocides Steering Group on human exposure assessment: A preliminary report

    NARCIS (Netherlands)

    Hemmen, J.J. van

    1999-01-01

    In a project granted by DG XI of the European Commission, it is attempted to collate experimental and theoretical data on human (workers and consumers) exposure assessment to biocidal products, and to outline the methodology for sampling and measurement. On the basis of the available evidence, appro

  12. Geographical modeling of exposure risk to cyanobacteria for epidemiological purposes.

    Science.gov (United States)

    Serrano, Tania; Dupas, Rémi; Upegui, Erika; Buscail, Camille; Grimaldi, Catherine; Viel, Jean François

    2015-08-01

    The cyanobacteria-derived neurotoxin β-methylamino-L-alanine (BMAA) represents a plausible environmental trigger for amyotrophic lateral sclerosis (ALS), a debilitating and fatal neuromuscular disease. With the eutrophication of water bodies, cyanobacterial blooms and their toxins are becoming increasingly prevalent in France, especially in the Brittany region. Cyanobacteria are monitored at only a few recreational sites, preventing an estimation of exposure of the human population. By contrast, phosphorus, a limiting nutrient for cyanobacterial growth and thus considered a good proxy for cyanobacteria exposure, is monitored in many but not all surface water bodies. Our goal was to develop a geographic exposure indicator that could be used in epidemiological research. We considered the total phosphorus (TP) concentration (mg/L) of samples collected between October 2007 and September 2012 at 179 monitoring stations distributed throughout the Brittany region. Using readily available spatial data, we computed environmental descriptors at the watershed level with a Geographic Information System. Then, these descriptors were introduced into a backward stepwise linear regression model to predict the median TP concentration in unmonitored surface water bodies. TP concentrations in surface water follow an increasing gradient from West to East and inland to coast. The empirical concentration model included five predictor variables with a fair coefficient of determination (R(2) = 0.51). The specific total runoff and the watershed slope correlated negatively with the TP concentrations (p = 0.01 and pcyanobacteria exposure that can be used along with other risk factors in further ALS epidemiologic case-control studies.

  13. Assessment of human exposure effects of nitrous acid

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, T.R.; Kjaergaard, S.K. (University of Aarhus. Institute of Environmental and Occupational Medicine (Denmark)); Brauer, M. (Harvard School of Public Health. Department of Environmental Health, Exposure Assessment and Engineering Program (United States))

    1993-01-01

    The study aimed at an estimation of the relative contribution of nitrous acid to measurable human exposure effects in relation to indoor environments with unvented gas combustion. Fifteen medically examined totally healthy non-smoker adults aged between 22 and 57 years were exposed in a double-blind, balanced design (3x3 latin square) to clean air and nitrous acid (HONO) concentration in an empty 74 m[sup 3] climate chamber. 3 teams of 5 subjects each were randomly exposed and the latin square was selected at random. Each exposure period was 3.5 hours and preceded by a 1 hour base-line pre-exposure measurement period. After 1 hr 40 minutes the subjects exercised for ten minutes on bicycle ergometers in order to increase the uptake of HONO by increasing ventilatory rate 3-4 fold. Workloads were calculated individually and ranged from 21800-34600 kpm/h. During the 10 minutes the test subjects were mouth-breathing to encourage deeper penetration of nitrous acid in the respiratory system so as to induce a mild cooling which would increase their responsiveness to irritants. The amount of deliverable H[sup +] was estimated at 16.350 nmoles with exposure to 395 ppb HONO with subjects breathing at the rate of 5 L min[sup -1]. It was assumed that HONO is efficiently absorbed into the respiratory system. Details are given of the results. Findings were highly variable, largely negative effects of exposure to nitrous acid which appear similiar to results seen in nitrogen dioxide exposure studies. It is concluded to be unlikely that HONO exposures alone can be responsible for exposure misclassification in NO[sub 2] exposure studies. (AB) (52 refs.).

  14. Assessment of human exposure effects of nitrous acid

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, T.R.; Kjaergaard, S.K. [University of Aarhus. Institute of Environmental and Occupational Medicine (Denmark); Brauer, M. [Harvard School of Public Health. Department of Environmental Health, Exposure Assessment and Engineering Program (United States)

    1993-01-01

    The study aimed at an estimation of the relative contribution of nitrous acid to measurable human exposure effects in relation to indoor environments with unvented gas combustion. Fifteen medically examined totally healthy non-smoker adults aged between 22 and 57 years were exposed in a double-blind, balanced design (3x3 latin square) to clean air and nitrous acid (HONO) concentration in an empty 74 m{sup 3} climate chamber. 3 teams of 5 subjects each were randomly exposed and the latin square was selected at random. Each exposure period was 3.5 hours and preceded by a 1 hour base-line pre-exposure measurement period. After 1 hr 40 minutes the subjects exercised for ten minutes on bicycle ergometers in order to increase the uptake of HONO by increasing ventilatory rate 3-4 fold. Workloads were calculated individually and ranged from 21800-34600 kpm/h. During the 10 minutes the test subjects were mouth-breathing to encourage deeper penetration of nitrous acid in the respiratory system so as to induce a mild cooling which would increase their responsiveness to irritants. The amount of deliverable H{sup +} was estimated at 16.350 nmoles with exposure to 395 ppb HONO with subjects breathing at the rate of 5 L min{sup -1}. It was assumed that HONO is efficiently absorbed into the respiratory system. Details are given of the results. Findings were highly variable, largely negative effects of exposure to nitrous acid which appear similiar to results seen in nitrogen dioxide exposure studies. It is concluded to be unlikely that HONO exposures alone can be responsible for exposure misclassification in NO{sub 2} exposure studies. (AB) (52 refs.).

  15. Preimplantation Exposure to Bisphenol A and Triclosan May Lead to Implantation Failure in Humans

    Directory of Open Access Journals (Sweden)

    Mu Yuan

    2015-01-01

    Full Text Available Endocrine disrupting chemicals (EDCs are chemicals that have the capacity to interfere with normal endocrine systems. Two EDCs, bisphenol A (BPA and triclosan (TCS, are mass-produced and widespread. They both have estrogenic properties and similar chemical structures and pharmacokinetic features and have been detected in human fluids and tissues. Clinical evidence has suggested a positive association between BPA exposure and implantation failure in IVF patients. Studies in mouse models have suggested that preimplantation exposure to BPA and TCS can lead to implantation failure. This paper reviews the relationship between preimplantation exposure to BPA and TCS and implantation failure and discusses the remaining problems and possible solutions.

  16. Quantitative assessment of human and pet exposure to Salmonella associated with dry pet foods.

    Science.gov (United States)

    Lambertini, Elisabetta; Buchanan, Robert L; Narrod, Clare; Ford, Randall M; Baker, Robert C; Pradhan, Abani K

    2016-01-04

    Recent Salmonella outbreaks associated with dry pet foods and treats highlight the importance of these foods as previously overlooked exposure vehicles for both pets and humans. In the last decade efforts have been made to raise the safety of this class of products, for instance by upgrading production equipment, cleaning protocols, and finished product testing. However, no comprehensive or quantitative risk profile is available for pet foods, thus limiting the ability to establish safety standards and assess the effectiveness of current and proposed Salmonella control measures. This study sought to develop an ingredients-to-consumer quantitative microbial exposure assessment model to: 1) estimate pet and human exposure to Salmonella via dry pet food, and 2) assess the impact of industry and household-level mitigation strategies on exposure. Data on prevalence and concentration of Salmonella in pet food ingredients, production process parameters, bacterial ecology, and contact transfer in the household were obtained through literature review, industry data, and targeted research. A probabilistic Monte Carlo modeling framework was developed to simulate the production process and basic household exposure routes. Under the range of assumptions adopted in this model, human exposure due to handling pet food is null to minimal if contamination occurs exclusively before extrusion. Exposure increases considerably if recontamination occurs post-extrusion during coating with fat, although mean ingested doses remain modest even at high fat contamination levels, due to the low percent of fat in the finished product. Exposure is highly variable, with the distribution of doses ingested by adult pet owners spanning 3Log CFU per exposure event. Child exposure due to ingestion of 1g of pet food leads to significantly higher doses than adult doses associated with handling the food. Recontamination after extrusion and coating, e.g., via dust or equipment surfaces, may also lead to

  17. Assessing hazardous risks of human exposure to temple airborne polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Chiang, Kuo-Chih; Chio, Chia-Pin; Chiang, Yu-Hui; Liao, Chung-Min

    2009-07-30

    We proposed an integrated probabilistic risk assessment framework based on reported data to quantify human health risks of temple goers/workers to airborne polycyclic aromatic hydrocarbons (PAHs) from incense burning in typical Taiwanese temples. The framework probabilistically integrates exposure, human respiratory tract, and incremental lifetime cancer risk (ILCR) models to quantitatively estimate size-dependent PAHs exposure in human lung regions and cancer risks for temple goers (moderate and high exposures) and temple workers (extreme exposure). Our results show that the ILCRs are greater than the acceptable level of 10(-6) for extreme and high exposure groups through inhalation route. The result also indicates that the higher ILCRs (10(-6) to 10(-4)) are found in ingestion and dermal contact routes for temple goers/workers. For personal extreme exposure to carcinogenic PAH in the temple, 95% probability total ILCR (TILCR) (9.87 x 10(-4) to 1.13 x 10(-3)) is much greater than the range of 10(-6) to 10(-4), indicating high potential health risk to temple workers. For temple goers with high and moderate exposure groups, however, the 95% probability TILCRs were estimated from 6.44 x 10(-5) to 7.50 x 10(-5) and 5.75 x 10(-6) to 6.99 x 10(-6), respectively. This study successfully offers a scientific basis for risk analysis due to incense burning to enhance broad risk management strategies for temple indoor air quality.

  18. A review of models for near-field exposure pathways of chemicals in consumer products

    DEFF Research Database (Denmark)

    Huang, Lei; Ernstoff, Alexi; Fantke, Peter;

    2017-01-01

    Exposure to chemicals in consumer products has been gaining increasing attention, with multiple studies showing that near-field exposures from products is high compared to far-field exposures. Regarding the numerous chemical-product combinations, there is a need for an overarching review of models...... able to quantify the multiple transfers of chemicals from products used near-field to humans. The present review therefore aims at an in-depth overview of modeling approaches for near-field chemical release and human exposure pathways associated with consumer products. It focuses on lower...... in a “human receptor compartment”. We first focus on models of physical mass transfers from the product to ‘near-field’ compartments. For transfers of chemicals from article interior, adequate modeling of in-article diffusion and of partitioning between article surface and air/skin/food is key. Modeling...

  19. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  20. Asbestos exposure increases human bronchial epithelial cell fibrinolytic activity.

    Science.gov (United States)

    Gross, T J; Cobb, S M; Gruenert, D C; Peterson, M W

    1993-03-01

    Chronic exposure to asbestos fibers results in fibrotic lung disease. The distal pulmonary epithelium is an early target of asbestos-mediated injury. Local plasmin activity may be important in modulating endoluminal inflammatory responses in the lung. We studied the effects of asbestos exposure on cell-mediated plasma clot lysis as a marker of pericellular plasminogen activation. Exposing human bronchial epithelial (HBE) cells to 100 micrograms/ml of asbestos fibers for 24 h resulted in increased plasma clot lysis. Fibrinolytic activity was augmented in a dose-dependent fashion, was not due to secreted protease, and occurred only when there was direct contact between the plasma clot and the epithelial monolayer. Further analysis showed that asbestos exposure increased HBE cell-associated urokinase-type plasminogen activator (uPA) activity in a time-dependent manner. The increased cell-associated PA activity could be removed by acid washing. The increase in PA activity following asbestos exposure required new protein synthesis because it was abrogated by treatment with either cycloheximide or actinomycin D. Therefore, asbestos exposure increases epithelial-mediated fibrinolysis by augmenting expression of uPA activity at the cell surface by mechanisms that require new RNA and protein synthesis. These observations suggest a novel mechanism whereby exposure of the distal epithelium to inhaled particulates may result in a chronic inflammatory response that culminates in the development of fibrotic lung disease.

  1. Human arsenic exposure and risk assessment at the landscape level: a review.

    Science.gov (United States)

    Khan, Nasreen Islam; Owens, Gary; Bruce, David; Naidu, Ravi

    2009-04-01

    Groundwater contaminated with arsenic (As), when extensively used for irrigation, causes potentially long term detrimental effects to the landscape. Such contamination can also directly affect human health when irrigated crops are primarily used for human consumption. Therefore, a large number of humans are potentially at risk worldwide due to daily As exposure. Numerous previous studies have been severely limited by small sample sizes which are not reliably extrapolated to large populations or landscapes. Human As exposure and risk assessment are no longer simple assessments limited to a few food samples from a small area. The focus of more recent studies has been to perform risk assessment at the landscape level involving the use of biomarkers to identify and quantify appropriate health problems and large surveys of human dietary patterns, supported by analytical testing of food, to quantify exposure. This approach generates large amounts of data from a wide variety of sources and geographic information system (GIS) techniques have been used widely to integrate the various spatial, demographic, social, field, and laboratory measured datasets. With the current worldwide shift in emphasis from qualitative to quantitative risk assessment, it is likely that future research efforts will be directed towards the integration of GIS, statistics, chemistry, and other dynamic models within a common platform to quantify human health risk at the landscape level. In this paper we review the present and likely future trends of human As exposure and GIS application in risk assessment at the landscape level.

  2. Parabens as Urinary Biomarkers of Exposure in Humans

    Science.gov (United States)

    Ye, Xiaoyun; Bishop, Amber M.; Reidy, John A.; Needham, Larry L.; Calafat, Antonia M.

    2006-01-01

    Background Parabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure. Objectives Assessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In animals, parabens are mostly hydrolyzed to p-hydroxybenzoic acid and excreted in the urine as conjugates. Still, monitoring urinary concentrations of p-hydroxybenzoic acid is not necessarily the best way to assess exposure to parabens. p-Hydroxybenzoic acid is a nonspecific biomarker, and the varying estrogenic bioactivities of parabens require specific biomarkers. Therefore, we evaluated the use of free and conjugated parent parabens as new biomarkers for human exposure to these compounds. Results We measured the urinary concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl parabens in a demographically diverse group of 100 anonymous adults. We detected methyl and n-propyl parabens at the highest median concentrations (43.9 ng/mL and 9.05 ng/mL, respectively) in nearly all (> 96%) of the samples. We also detected other parabens in more than half of the samples (ethyl, 58%; butyl, 69%). Most important, however, we found that parabens in urine appear predominantly in their conjugated forms. Conclusions The results, demonstrating the presence of urinary conjugates of parabens in humans, suggest that such conjugated parabens could be used as exposure biomarkers. Additionally, the fact that conjugates appear to be the main urinary products of parabens may be important for risk assessment. PMID:17185273

  3. WEMo (Wave Exposure Model): Formulation, Procedures and Validation

    OpenAIRE

    Malhotra, Amit; Mark S. Fonseca

    2007-01-01

    This report describes the working of National Centers for Coastal Ocean Service (NCCOS) Wave Exposure Model (WEMo) capable of predicting the exposure of a site in estuarine and closed water to local wind generated waves. WEMo works in two different modes: the Representative Wave Energy (RWE) mode calculates the exposure using physical parameters like wave energy and wave height, while the Relative Exposure Index (REI) empirically calculates exposure as a unitless index. Detailed working of th...

  4. Conceptual Framework To Extend Life Cycle Assessment Using Near-Field Human Exposure Modeling and High-Throughput Tools for Chemicals

    Science.gov (United States)

    Life Cycle Assessment (LCA) is a decision-making tool that accounts for multiple impacts across the life cycle of a product or service. This paper presents a conceptual framework to integrate human health impact assessment with risk screening approaches to extend LCA to include n...

  5. Modeling repeated measurement data for occupational exposure assessment and epidemiology

    NARCIS (Netherlands)

    Peretz, Chava

    2004-01-01

    Repeated measurements designs, occur frequently in the assessment of exposure to toxic chemicals. This thesis deals with the possibilities of using mixed effects models for occupational exposure assessment and in the analysis of exposure response relationships. The model enables simultaneous estima

  6. Chronic exposure to chlorpyrifos triggered body weight increase and memory impairment depending on human apoE polymorphisms in a targeted replacement mouse model.

    Science.gov (United States)

    Peris-Sampedro, Fiona; Basaure, Pia; Reverte, Ingrid; Cabré, Maria; Domingo, José L; Colomina, Maria Teresa

    2015-05-15

    Despite restrictions on their use, humans are still constantly exposed to organophosphates (OPs). A huge number of studies have ratified the neurotoxic effects of chlorpyrifos (CPF) and suggested its association with neurodegenerative diseases, but data are still scarce. Human apolipoprotein E (apoE) plays an important role in lipid transport and distribution. In humans, the apoE4 isoform has been linked to an increased risk of Alzheimer's disease (AD). ApoE3 is the most prevalent isoform worldwide, and has been often established as the healthful one. The current study, performed in targeted replacement (TR) adult male mice, aimed to inquire whether genetic variations of the human apoE respond differently to a chronic dietary challenge with CPF. At four/five months of age, mice carrying apoE2, apoE3 or apoE4 were pair-fed a diet supplemented with CPF at 0 or 2mg/kg body weight/day for 13weeks. Cholinergic signs were monitored daily and body weight changes weekly. In the last week of treatment, learning and memory were assessed in a Barnes maze task. Dietary CPF challenge increased body weight only in apoE3 mice. Differences in the acquisition and retention of the Barnes maze were attributed to apoE genetic differences. Our results showed that apoE4 mice performed worse than apoE2 and apoE3 carriers in the acquisition period of the spatial task, and that apoE2 mice had poorer retention than the other two genotypes. On the other hand, CPF increased the search velocity of apoE2 subjects during the acquisition period. Retention was impaired only in CPF-exposed apoE3 mice. These results underline that gene×environment interactions need to be taken into account in epidemiological studies. Given that apoE3, the most common polymorphism in humans, has proved to be the most sensitive to CPF, the potential implications for human health merit serious thought.

  7. Comparison of the use of a physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments.

    Science.gov (United States)

    Emond, Claude; Michalek, Joel E; Birnbaum, Linda S; DeVito, Michael J

    2005-12-01

    In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Recent data suggest a dose-dependent elimination rate for TCDD. A physiologically based pharmacokinetic (PBPK) model, which uses a body-burden-dependent elimination rate, was developed previously in rodents to describe the pharmacokinetics of TCDD and has been extrapolated to human exposure for this study. Optimizations were performed using data from a random selection of veterans from the Ranch Hand cohort and data from a human volunteer who was exposed to TCDD. Assessment of this PBPK model used additional data from the Ranch Hand cohort and a clinical report of two women exposed to TCDD. This PBPK model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in potential exposure misclassifications. Application of a PBPK model that incorporates an inducible elimination of TCDD may improve the exposure assessments in epidemiologic studies of TCDD.

  8. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    Science.gov (United States)

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary

  9. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    Science.gov (United States)

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration.

  10. Human health risk assessment from exposure to trihalomethanes in Canadian cities.

    Science.gov (United States)

    Chowdhury, Shakhawat; Hall, Kevin

    2010-07-01

    Lifetime exposure to trihalomethanes (THMs) through ingestion, inhalation and dermal contacts may pose risks to human health. Current approaches may under predict THMs exposure by using THMs in cold water during showering and bathing. Warming of chlorinated water during showering may increase THMs formation through reactions between organics and residual chlorine, which can increase human health risks. In this study, THMs concentrations in shower water were estimated using THMs rate increase model. Using cold water THMs, exposure through ingestion was estimated, while THMs exposure during showering was estimated using THMs in warm water. Human health cancer risks and additional expenses for 20 most populated Canadian cities from exposure to THMs were estimated. Inhalation and dermal contact during showering contributed 30% to 50% of total cancer risks, while risks from inhalation and dermal contacts were comparable for all cities. Overall cancer risks were estimated between 7.2 x 10(-6) and 6.4 x 10(-5) for these cities. Cancer incidents were estimated highest for Montreal (94/year) followed by Toronto (53/year), which may require additional medical expenses of 18.8 and 10.7 million dollars/year for Montreal and Toronto respectively. Cancer risks from exposure to THMs can be controlled by reducing THMs in water supply and varying shower stall volume, shower duration and air exchange rate in shower stall. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Risk of human exposure to polycyclic aromatic hydrocarbons: A case study in Beijing, China.

    Science.gov (United States)

    Yu, Yanxin; Li, Qi; Wang, Hui; Wang, Bin; Wang, Xilong; Ren, Aiguo; Tao, Shu

    2015-10-01

    Polycyclic aromatic hydrocarbons (PAHs) can cause adverse effects on human health. The relative contributions of their two major intake routes (diet and inhalation) to population PAH exposure are still unclear. We modeled the contributions of diet and inhalation to the overall PAH exposure of the population of Beijing in China, and assessed their human incremental lifetime cancer risks (ILCR) using a Mont Carlo simulation approach. The results showed that diet accounted for about 85% of low-molecular-weight PAH (L-PAH) exposure, while inhalation accounted for approximately 57% of high-molecular-weight PAH (H-PAH) exposure of the Beijing population. Meat and cereals were the main contributors to dietary PAH exposure. Both gaseous- and particulate-phase PAHs contributed to L-PAH exposure through inhalation, whereas exposure to H-PAHs was mostly from the particulate-phase. To reduce the cancer incidence of the Beijing population, more attention should be given to inhaled particulate-phase PAHs with considerable carcinogenic potential.

  12. Arsenic Exposure and the Induction of Human Cancers

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez

    2011-01-01

    Full Text Available Arsenic is a metalloid, that is, considered to be a human carcinogen. Millions of individuals worldwide are chronically exposed through drinking water, with consequences ranging from acute toxicities to development of malignancies, such as skin and lung cancer. Despite well-known arsenic-related health effects, the molecular mechanisms involved are not fully understood; however, the arsenic biotransformation process, which includes methylation changes, is thought to play a key role. This paper explores the relationship of arsenic exposure with cancer development and summarizes current knowledge of the potential mechanisms that may contribute to the neoplastic processes observed in arsenic exposed human populations.

  13. Exposure-response modeling methods and practical implementation

    CERN Document Server

    Wang, Jixian

    2015-01-01

    Discover the Latest Statistical Approaches for Modeling Exposure-Response RelationshipsWritten by an applied statistician with extensive practical experience in drug development, Exposure-Response Modeling: Methods and Practical Implementation explores a wide range of topics in exposure-response modeling, from traditional pharmacokinetic-pharmacodynamic (PKPD) modeling to other areas in drug development and beyond. It incorporates numerous examples and software programs for implementing novel methods.The book describes using measurement

  14. Pesticides: an update of human exposure and toxicity.

    Science.gov (United States)

    Mostafalou, Sara; Abdollahi, Mohammad

    2017-02-01

    Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity. A huge body of evidence exists on the possible role of pesticide exposures in the elevated incidence of human diseases such as cancers, Alzheimer, Parkinson, amyotrophic lateral sclerosis, asthma, bronchitis, infertility, birth defects, attention deficit hyperactivity disorder, autism, diabetes, and obesity. Most of the disorders are induced by insecticides and herbicides most notably organophosphorus, organochlorines, phenoxyacetic acids, and triazine compounds.

  15. Air Pollution Exposure Modeling for Health Studies | Science ...

    Science.gov (United States)

    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

  16. Biomonitoring studies should be used by regulatory agencies to assess human exposure levels and safety of bisphenol A.

    Science.gov (United States)

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

    2010-08-01

    Within the past 3 years, four major evaluations of bisphenol A (BPA) safety have been undertaken. However, these assessments have arrived at quite different conclusions regarding the safety of BPA at current human exposure levels. We compared the reasons provided by the European Food Safety Authority (EFSA) BPA risk assessment panel for their conclusion that human exposures are negligible with the conclusions reached by the other panels, with all panels having the same body of literature at their disposal. The EFSA panel dismissed > or = 80 biomonitoring studies that documented significant levels of BPA exposure in humans, including internal exposures to unconjugated BPA, on the basis that they did not match a model of BPA metabolism. Instead, the EFSA panel relied on two toxicokinetic studies-conducted in 15 adults administered BPA-to draw conclusions about exposure levels in the population, including exposures of neonates. As with all exposure assessments, models should be developed to explain actual data that are collected. In the case of BPA, samples from a large number of human subjects clearly indicate that humans are internally exposed to unconjugated BPA. The dismissal of these biomonitoring studies simply because their results do not conform to a model violates scientific principles. Expert panels should evaluate all data-including human biomonitoring studies-to make informed risk assessments.

  17. Evaluating environmental modeling and sampling data with biomarker data to identify sources and routes of exposure

    Science.gov (United States)

    Shin, Hyeong-Moo; McKone, Thomas E.; Bennett, Deborah H.

    2013-04-01

    Exposure to environmental chemicals results from multiple sources, environmental media, and exposure routes. Ideally, modeled exposures should be compared to biomonitoring data. This study compares the magnitude and variation of modeled polycyclic aromatic hydrocarbons (PAHs) exposures resulting from emissions to outdoor and indoor air and estimated exposure inferred from biomarker levels. Outdoor emissions result in both inhalation and food-based exposures. We modeled PAH intake doses using U.S. EPA's 2002 National Air Toxics Assessment (NATA) county-level emissions data for outdoor inhalation, the CalTOX model for food ingestion (based on NATA emissions), and indoor air concentrations from field studies for indoor inhalation. We then compared the modeled intake with the measured urine levels of hydroxy-PAH metabolites from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) survey as quantifiable human intake of PAH parent-compounds. Lognormal probability plots of modeled intakes and estimated intakes inferred from biomarkers suggest that a primary route of exposure to naphthalene, fluorene, and phenanthrene for the U.S. population is likely inhalation from indoor sources. For benzo(a)pyrene, the predominant exposure route is likely from food ingestion resulting from multi-pathway transport and bioaccumulation due to outdoor emissions. Multiple routes of exposure are important for pyrene. We also considered the sensitivity of the predicted exposure to the proportion of the total naphthalene production volume emitted to the indoor environment. The comparison of PAH biomarkers with exposure variability estimated from models and sample data for various exposure pathways supports that both indoor and outdoor models are needed to capture the sources and routes of exposure to environmental contaminants.

  18. Circulating factors induce coronary endothelial ceIl activation foIlowing exposure to inhaled diesel exhaust and nitrogen dioxide in humans :Evidence from a novel translational in vitro model

    Science.gov (United States)

    The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

  19. USEtox human exposure and toxicity factors for comparative assessment of toxic emissions in life cycle analysis: sensitivity to key chemical properties

    DEFF Research Database (Denmark)

    Rosenbaum, Ralph K.; Huijbregts, Mark; Henderson, Andrew D.

    2011-01-01

    Purpose The aim of this paper is to provide science-based consensus and guidance for health effects modelling in comparative assessments based on human exposure and toxicity. This aim is achieved by i) describing the USEtoxTM exposure and toxicity models representing consensus and recommended...... modelling practice, ii) identifying key mechanisms influencing human exposure and toxicity effects of chemical emissions, iii) extending substance coverage. Methods The methods section of this paper contains a detailed documentation of both the human exposure and toxic effects models of USEtox......TM, to determine impacts on human health per kg substance emitted in different compartments. These are considered as scientific consensus and therefore recommended practice for comparative toxic impact assessment. The framework of the exposure model is described in details including the modelling of each exposure...

  20. Advanced REACH tool: A Bayesian model for occupational exposure assessment

    NARCIS (Netherlands)

    McNally, K.; Warren, N.; Fransman, W.; Entink, R.K.; Schinkel, J.; Van Tongeren, M.; Cherrie, J.W.; Kromhout, H.; Schneider, T.; Tielemans, E.

    2014-01-01

    This paper describes a Bayesian model for the assessment of inhalation exposures in an occupational setting; the methodology underpins a freely available web-based application for exposure assessment, the Advanced REACH Tool (ART). The ART is a higher tier exposure tool that combines disparate sourc

  1. Chapter three: methodology of exposure modeling

    CSIR Research Space (South Africa)

    Moschandreas, DJ

    2002-12-01

    Full Text Available (particles due to smoking, hobbies or other activities that impact the subject but not other people in the same microenvironment). This expression of inhalation exposure to particles can be readily used if the concentration of particles of ambient origin... in the exposure measurement (USEPA, 1997). D.J. Moschandreas et al. / Chemosphere 49 (2002) 923?946 925 The indirect method estimates exposures by measur- ing or estimating pollutant concentrations at different microenvironments where people spend their time...

  2. Validation of the dermal exposure model in ECETOC TRA.

    Science.gov (United States)

    Marquart, Hans; Franken, Remy; Goede, Henk; Fransman, Wouter; Schinkel, Jody

    2017-08-01

    The ECETOC TRA model (presently version 3.1) is often used to estimate worker inhalation and dermal exposure in regulatory risk assessment. The dermal model in ECETOC TRA has not yet been validated by comparison with independent measured exposure levels. This was the goal of the present study. Measured exposure levels and relevant contextual information were gathered via literature search, websites of relevant occupational health institutes and direct requests for data to industry. Exposure data were clustered in so-called exposure cases, which are sets of data from one data source that are expected to have the same values for input parameters in the ECETOC TRA dermal exposure model. For each exposure case, the 75th percentile of measured values was calculated, because the model intends to estimate these values. The input values for the parameters in ECETOC TRA were assigned by an expert elicitation and consensus building process, based on descriptions of relevant contextual information.From more than 35 data sources, 106 useful exposure cases were derived, that were used for direct comparison with the model estimates. The exposure cases covered a large part of the ECETOC TRA dermal exposure model. The model explained 37% of the variance in the 75th percentiles of measured values. In around 80% of the exposure cases, the model estimate was higher than the 75th percentile of measured values. In the remaining exposure cases, the model estimate may not be sufficiently conservative.The model was shown to have a clear bias towards (severe) overestimation of dermal exposure at low measured exposure values, while all cases of apparent underestimation by the ECETOC TRA dermal exposure model occurred at high measured exposure values. This can be partly explained by a built-in bias in the effect of concentration of substance in product used, duration of exposure and the use of protective gloves in the model. The effect of protective gloves was calculated to be on average a

  3. Physiologically based pharmacokinetic toolkit to evaluate environmental exposures: Applications of the dioxin model to study real life exposures.

    Science.gov (United States)

    Emond, Claude; Ruiz, Patricia; Mumtaz, Moiz

    2017-01-15

    Chlorinated dibenzo-p-dioxins (CDDs) are a series of mono- to octa-chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well-known, and persistent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of translational research to make computerized models accessible to health risk assessors, we present a Berkeley Madonna recoded version of the human physiologically based pharmacokinetic (PBPK) model used by the U.S. Environmental Protection Agency (EPA) in the recent dioxin assessment. This model incorporates CYP1A2 induction, which is an important metabolic vector that drives dioxin distribution in the human body, and it uses a variable elimination half-life that is body burden dependent. To evaluate the model accuracy, the recoded model predictions were compared with those of the original published model. The simulations performed with the recoded model matched well with those of the original model. The recoded model was then applied to available data sets of real life exposure studies. The recoded model can describe acute and chronic exposures and can be useful for interpreting human biomonitoring data as part of an overall dioxin and/or dioxin-like compounds risk assessment. Copyright © 2016. Published by Elsevier Inc.

  4. Exposure-Based Cat Modeling, Available data, Advantages, & Limitations

    Science.gov (United States)

    Michel, Gero; Hosoe, Taro; Schrah, Mike; Saito, Keiko

    2010-05-01

    This paper discusses the advantages and disadvantages of exposure data for cat-modeling and considers concepts of scale as well as the completeness of data and data scoring using field/model examples. Catastrophe modeling based on exposure data has been considered the panacea for insurance-related cat modeling since the late 1980's. Reasons for this include: • The ability to extend risk modeling to consider data beyond historical losses, • Usability across many relevant scales, • Flexibility in addressing complex structures and policy conditions, and • Ability to assess dependence of risk results on exposure-attributes and exposure-modifiers, such as lines of business, occupancy types, and mitigation features, at any given scale. In order to calculate related risk, monetary exposure is correlated to vulnerabilities that have been calibrated with historical results, plausibility concepts, and/or physical modeling. While exposure based modeling is widely adopted, we also need to be aware of its limitations which include: • Boundaries in our understanding of the distribution of exposure, • Spatial interdependence of exposure patterns and the time-dependence of exposure, • Incomplete availability of loss information to calibrate relevant exposure attributes/structure with related vulnerabilities and losses, • The scale-dependence of vulnerability, • Potential for missing or incomplete communication of assumptions made during model calibration, • Inefficiencies in the aggregation or disaggregation of vulnerabilities, and • Factors which can influence losses other than exposure, vulnerability, and hazard. Although we might assume that the higher the resolution the better, regional model calibration is often limited to lower than street level resolution with higher resolution being achieved by disaggregating results using topographic/roughness features with often loosely constrained and/or varying effects on losses. This suggests that higher accuracy

  5. DUAL ION EXPOSURE VS. SPLIT-DOSE EXPOSURES IN HUMAN CELL NEOPLASTIC TRANSFORMATION.

    Energy Technology Data Exchange (ETDEWEB)

    BENNETT, P.V.; CUTTER, N.C.; SUTHERLAND, B.M.

    2006-06-05

    Since radiation fields of space contain many-fold more protons than high atomic number, high energy (HZE) particles, cells in astronaut crews will experience on average several proton hits before an HZE hit. Thus radiation regimes of proton exposure before HZE particle exposure simulate space radiation exposure, and measurement of the frequency of neoplastic transformation of human primary cells to anchorage-independent growth simulates in initial step in cancer induction. Previously our group found that exposure to 20 cGy 1 GeV/n protons followed within about 1 hr by a HZE ion (20 cGy 1 GeV/n Fe or Ti ions) hit gave about a 3-fold increase in transformation frequency ([1]). To provide insight into the H-HZE induced increased transformation frequencies, we asked if split doses of the same ion gave similar increased transformation frequencies. However, the data show that the split dose of 20 cGy plus 20 cGy of either H or HZE ions gave about the same effect as the 40 cGy uninterrupted dose, quite different from the effect of the mixed ion H + HZE irradiation. We also asked if lower proton doses than 20 cGy followed 15 minutes later by 20 cGy of HZE ions gave greater than additive transformation frequencies. Substantial increases in transformation levels were observed for all proton doses tested, including 1 cGy. These results point to the signal importance of protons in affecting the effect of space radiation on human cells.

  6. Biological exposure models for oil spill impact analysis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico-chemieal fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle-based exposure model for migratory adult fish populations, a particle-based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over-wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surrace oil of wildlife (bird and marine mammal ) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.

  7. Human Exposure and Health Effects of Inorganic and Elemental Mercury

    Science.gov (United States)

    Zheng, Wei

    2012-01-01

    Mercury is a toxic and non-essential metal in the human body. Mercury is ubiquitously distributed in the environment, present in natural products, and exists extensively in items encountered in daily life. There are three forms of mercury, i.e., elemental (or metallic) mercury, inorganic mercury compounds, and organic mercury compounds. This review examines the toxicity of elemental mercury and inorganic mercury compounds. Inorganic mercury compounds are water soluble with a bioavailability of 7% to 15% after ingestion; they are also irritants and cause gastrointestinal symptoms. Upon entering the body, inorganic mercury compounds are accumulated mainly in the kidneys and produce kidney damage. In contrast, human exposure to elemental mercury is mainly by inhalation, followed by rapid absorption and distribution in all major organs. Elemental mercury from ingestion is poorly absorbed with a bioavailability of less than 0.01%. The primary target organs of elemental mercury are the brain and kidney. Elemental mercury is lipid soluble and can cross the blood-brain barrier, while inorganic mercury compounds are not lipid soluble, rendering them unable to cross the blood-brain barrier. Elemental mercury may also enter the brain from the nasal cavity through the olfactory pathway. The blood mercury is a useful biomarker after short-term and high-level exposure, whereas the urine mercury is the ideal biomarker for long-term exposure to both elemental and inorganic mercury, and also as a good indicator of body burden. This review discusses the common sources of mercury exposure, skin lightening products containing mercury and mercury release from dental amalgam filling, two issues that happen in daily life, bear significant public health importance, and yet undergo extensive debate on their safety. PMID:23230464

  8. Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans.

    Science.gov (United States)

    Reinisch, June M; Mortensen, Erik Lykke; Sanders, Stephanie A

    2017-07-01

    Prenatal sex hormone levels affect physical and behavioral sexual differentiation in animals and humans. Although prenatal hormones are theorized to influence sexual orientation in humans, evidence is sparse. Sexual orientation variables for 34 prenatally progesterone-exposed subjects (17 males and 17 females) were compared to matched controls (M age = 23.2 years). A case-control double-blind design was used drawing on existing data from the US/Denmark Prenatal Development Project. Index cases were exposed to lutocyclin (bioidentical progesterone = C21H30O2; M W : 314.46) and no other hormonal preparation. Controls were matched on 14 physical, medical, and socioeconomic variables. A structured interview conducted by a psychologist and self-administered questionnaires were used to collect data on sexual orientation, self-identification, attraction to the same and other sex, and history of sexual behavior with each sex. Compared to the unexposed, fewer exposed males and females identified as heterosexual and more of them reported histories of same-sex sexual behavior, attraction to the same or both sexes, and scored higher on attraction to males. Measures of heterosexual behavior and scores on attraction to females did not differ significantly by exposure. We conclude that, regardless of sex, exposure appeared to be associated with higher rates of bisexuality. Prenatal progesterone may be an underappreciated epigenetic factor in human sexual and psychosexual development and, in light of the current prevalence of progesterone treatment during pregnancy for a variety of pregnancy complications, warrants further investigation. These data on the effects of prenatal exposure to exogenous progesterone also suggest a potential role for natural early perturbations in progesterone levels in the development of sexual orientation.

  9. Large organic aerosols in a human exposure chamber : Applications in occupational dermatology and lung medicine

    OpenAIRE

    Lundgren, Lennart

    2006-01-01

    Exposure to large organic aerosol particles may cause respiratory and skin reactions. The use of human exposure chambers offers possibilities for experimental exposure challenges carried out with patients, in research and for investigations of the effects of exposure on the skin and in the respiratory tract. The present aim was to study the performance of modern human whole-body exposure chambers during generation of large organic particles, and to develop and test new me...

  10. Soil is an important pathway of human lead exposure.

    OpenAIRE

    Mielke, H W; Reagan, P L

    1998-01-01

    This review shows the equal or greater importance of leaded gasoline-contaminated dust compared to lead-based paint to the child lead problem, and that soil lead, resulting from leaded gasoline and pulverized lead-based paint, is at least or more important than lead-based paint (intact and not pulverized) as a pathway of human lead exposure. Because lead-based paint is a high-dose source, the biologically relevant dosage is similar to lead in soil. Both lead-based paint and soil lead are asso...

  11. Soil is an important pathway of human lead exposure.

    OpenAIRE

    Mielke, H W; Reagan, P L

    1998-01-01

    This review shows the equal or greater importance of leaded gasoline-contaminated dust compared to lead-based paint to the child lead problem, and that soil lead, resulting from leaded gasoline and pulverized lead-based paint, is at least or more important than lead-based paint (intact and not pulverized) as a pathway of human lead exposure. Because lead-based paint is a high-dose source, the biologically relevant dosage is similar to lead in soil. Both lead-based paint and soil lead are asso...

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

    Science.gov (United States)

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

    2012-01-01

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

  13. Operation of the computer model for microenvironment solar exposure

    Science.gov (United States)

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

    1995-01-01

    A computer model for microenvironmental solar exposure was developed to predict solar exposure to satellite surfaces which may shadow or reflect on one another. This document describes the technical features of the model as well as instructions for the installation and use of the program.

  14. Integration of Air Quality & Exposure Models for Health Studies

    Science.gov (United States)

    The presentation describes a new community-scale tool called exposure model for individuals (EMI), which predicts five tiers of individual-level exposure metrics for ambient PM using outdoor concentrations, questionnaires, weather, and time-location information. In this modeling ...

  15. Data Sources Available for Modeling Environmental Exposures in Older Adults

    Science.gov (United States)

    This report, “Data Sources Available for Modeling Environmental Exposures in Older Adults,” focuses on information sources and data available for modeling environmental exposures in the older U.S. population, defined here to be people 60 years and older, with an emphasis on those...

  16. Environmental pathways and human exposure to manganese in southern Brazil

    Directory of Open Access Journals (Sweden)

    NADIR HERMES

    2013-01-01

    Full Text Available The study of environmental pathways and human exposure to Manganese (Mn in Southern Brazil was performed using two steps. The first step consisted of taking water samples from the surface of the Pardinho River. The average results from this technique showed a significant increase of pollutants, including increased levels of Mn, above the environmentally acceptable standard recommended by the Brazilian National Environment Council. Additionally, 64 soil samples were taken from areas with and without agricultural activity. Many results were above the mean crust and did not indicate significant differences of Mn levels between the sampled areas. For the second step, 12 families were selected and assessed for exposure to Mn in a region with high levels of Mn in the soil. Most of the analyzed foods contained amounts of Mn above the reference values, indicating that food can be an important source of exposure. The Mn content from the hair of most subjects studied was also high compared to reference values from non-exposed populations. Although the contamination appeared to come from a natural origin, the results found in the present study showed that the Mn levels present in the Pardinho River Basin are a relevant public health issue.

  17. New approach for assessing human perfluoroalkyl exposure via hair.

    Science.gov (United States)

    Alves, Andreia; Jacobs, Griet; Vanermen, Guido; Covaci, Adrian; Voorspoels, Stefan

    2015-11-01

    In the recent years hair has been increasingly used as alternative matrix in human biomonitoring (HBM) of environmental pollutants. Sampling advantages and time integration of exposure assessment seems the most attractive features of hair matrix. In the current study, a novel miniaturized method was developed and validated for measuring 15 perfluoroalkyl substances (PFAS), including perfluoro n-butanoic acid (PFBA), perfluoro n-pentanoic acid (PFPeA), perfluoro n-hexanoic acid (PFHxA), perfluoro n-heptanoic acid (PFHpA), perfluor n-octanoic acid (PFOA), perfluoro n-nonanoic acid (PFNA), perfluoro tetradecanoic acid (PFTeDA), perfluorobutane sulfonic acid (PFBS), perfluoro pentane sulfonic acid (PFPeS), perfluorohexane sulfonic acid (PFHxS), perfluoroheptane sulfonic acid (PFHpS), perfluorooctane sulfonic acid (PFOS), perfluorononane sulfonic acid (PFNS), perfluorodecane sulfonic acid (PFDS) and perfluorododecane sulfonic acid (PFDoS) in human hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). After extraction using ethyl acetate, dispersive ENVI-Carb was used for clean-up. Good intra- and inter-day precision for low (LQ 5 ng/g hair) and high spike (HQ 15n g/g) levels were achieved (in general RSD hair and 3-13 pg/g hair, respectively. The method limit of quantification (LOQm) ranged between 6 and 301 pg/g hair. The PFAS levels were measured in 30 human hair samples indicating that the levels are low (14-1534 pg/g hair). Some PFAS were not present in any hair sample (e.g. PFHpA, PFTeDA, PFNA, PFPeS, PFHpS, PFOS and PFNS), while other PFAS were frequently detected (PFBA, PFPeA, PFHxA, PFOA, PFBS, PFHxS, PFOS, PFDS and PFDoS) in human hair. Although levels in general were low, there is evidence of higher human exposure to some analytes, such as PFBA, PFPeA, PFHxA, PFOA, PFBS, PFHxS, and PFDoS. The current study shows that hair is a suitable alternative non-invasive matrix for exposure assessment of PFAS.

  18. Modeling/GIS, Risk Assessment, Economic Impact: Seasonal Patterns for Entomological Measures of Risk for Exposure to Culex Vectors and West Nile Virus in Relation to Human Disease Cases in Northeastern Colorado

    OpenAIRE

    Bolling, Bethany G.; Barker, Christopher M.; Moore, Chester G.; Pape, W. John; Eisen, Lars

    2009-01-01

    We examined seasonal patterns for entomological measures of risk for exposure to Culex vectors and West Nile virus (family Flaviviridae, genus Flavivirus, WNV) in relation to human WNV disease cases in a five-county area of northeastern Colorado during 2006–2007. Studies along habitat/elevation gradients in 2006 showed that the seasonal activity period is shortened and peak numbers occur later in the summer for Culex tarsalis Coquillett females in foothills-montane areas >1,600 m compared wit...

  19. Human exposure to arsenic in groundwater from Lahore district, Pakistan.

    Science.gov (United States)

    Bibi, Mehwish; Hashmi, Muhammad Zaffar; Malik, Riffat Naseem

    2015-01-01

    In the present study we determined As concentrations in healthy volunteers from three different age groups (children, adults and old age) residing in Lahore, Pakistan to gain insight into arsenic exposure to humans via drinking water. The results revealed that the concentrations of As were significantly (p<0.05) different among different sites, while non significant trends were observed among different age classes. As concentrations in blood and nails samples showed a significant (p<0.05) positive correlation. The mean concentrations of As were higher in nails samples (1.43μg/g) followed by blood samples (1.15μg/L); urine samples (0.82μg/l) and hair samples (0.74μg/g) based on all sites. The antioxidants enzyme activities in blood samples showed a significant (p<0.01) decrease with the increase in As concentrations. The result suggests that urgent action is needed to prevent further human exposure to As.

  20. Human exposure to soil contaminants in subarctic Ontario, Canada

    Directory of Open Access Journals (Sweden)

    Ellen Stephanie Reyes

    2015-05-01

    Full Text Available Background: Chemical contaminants in the Canadian subarctic present a health risk with exposures primarily occurring via the food consumption. Objective: Characterization of soil contaminants is needed in northern Canada due to increased gardening and agricultural food security initiatives and the presence of known point sources of pollution. Design: A field study was conducted in the western James Bay Region of Ontario, Canada, to examine the concentrations of polychlorinated biphenyls, dichlorodiphenyltrichloroethane and its metabolites (ΣDDT, other organochlorines, and metals/metalloids in potentially contaminated agriculture sites. Methods: Exposure pathways were assessed by comparing the estimated daily intake to acceptable daily intake values. Ninety soil samples were collected at random (grid sampling from 3 plots (A, B, and C in Fort Albany (on the mainland, subarctic Ontario, Canada. The contaminated-soil samples were analysed by gas chromatography with an electron capture detector or inductively coupled plasma mass spectrometer. Results: The range of ΣDDT in 90 soil samples was below the limit of detection to 4.19 mg/kg. From the 3 soil plots analysed, Plot A had the highest ΣDDT mean concentration of 1.12 mg/kg, followed by Plot B and Plot C which had 0.09 and 0.01 mg/kg, respectively. Concentrations of other organic contaminants and metals in the soil samples were below the limit of detection or found in low concentrations in all plots and did not present a human health risk. Conclusions: Exposure analyses showed that the human risk was below regulatory thresholds. However, the ΣDDT concentration in Plot A exceeded soil guidelines set out by the Canadian Council of Ministers of the Environment of 0.7 mg/kg, and thus the land should not be used for agricultural or recreational purposes. Both Plots B and C were below threshold limits, and this land can be used for agricultural purposes.

  1. The response of human nasal and bronchial organotypic tissue cultures to repeated whole cigarette smoke exposure.

    Science.gov (United States)

    Talikka, Marja; Kostadinova, Radina; Xiang, Yang; Mathis, Carole; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Merg, Celine; Geertz, Marcel; Martin, Florian; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2014-01-01

    Exposure to cigarette smoke (CS) is linked to the development of respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. Although animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. We report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures that mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Despite the similar cellular staining and cytokine secretion in both tissue types, the transcriptomic analyses in the context of biological network models identified similar and diverse biological processes that were impacted by CS-exposed nasal and bronchial cultures. Our results demonstrate that nasal and bronchial tissue cultures are appropriate in vitro models for the assessment of CS-induced adverse effects in the respiratory system and promising alternative to animal experimentation.

  2. Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection.

    Directory of Open Access Journals (Sweden)

    Matthew J Kesic

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

  3. International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

    Directory of Open Access Journals (Sweden)

    European Food Safety Authority

    2013-07-01

    Full Text Available The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures” is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation to tier 3 (full probabilistic models. This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area.

  4. In-residence, multiple route exposures to chlorpyrifos and diazinon estimated by indirect method models

    Science.gov (United States)

    Moschandreas, D. J.; Kim, Y.; Karuchit, S.; Ari, H.; Lebowitz, M. D.; O'Rourke, M. K.; Gordon, S.; Robertson, G.

    One of the objectives of the National Human Exposure Assessment Survey (NHEXAS) is to estimate exposures to several pollutants in multiple media and determine their distributions for the population of Arizona. This paper presents modeling methods used to estimate exposure distributions of chlorpyrifos and diazinon in the residential microenvironment using the database generated in Arizona (NHEXAS-AZ). A four-stage probability sampling design was used for sample selection. Exposures to pesticides were estimated using the indirect method of exposure calculation by combining measured concentrations of the two pesticides in multiple media with questionnaire information such as time subjects spent indoors, dietary and non-dietary items they consumed, and areas they touched. Most distributions of in-residence exposure to chlorpyrifos and diazinon were log-normal or nearly log-normal. Exposures to chlorpyrifos and diazinon vary by pesticide and route as well as by various demographic characteristics of the subjects. Comparisons of exposure to pesticides were investigated among subgroups of demographic categories, including gender, age, minority status, education, family income, household dwelling type, year the dwelling was built, pesticide use, and carpeted areas within dwellings. Residents with large carpeted areas within their dwellings have higher exposures to both pesticides for all routes than those in less carpet-covered areas. Depending on the route, several other determinants of exposure to pesticides were identified, but a clear pattern could not be established regarding the exposure differences between several subpopulation groups.

  5. The effect of dust emissions from open storage piles to particle ambient concentration and human exposure.

    Science.gov (United States)

    Chalvatzaki, E; Aleksandropoulou, V; Glytsos, T; Lazaridis, M

    2012-12-01

    The current study focus on the determination of dust emissions from piles in open storage yards of a municipal solid waste (MSW) composting site and the subsequent atmospheric dust dispersion. The ISC3-ST (Industrial Source Complex Version 3 - Short Term) model was used for the evaluation of the PM(10) ambient concentrations associated with the dispersion of MSW compost dust emissions in air. Dust emission rates were calculated using the United States Environmental Protection Agency proposed dust resuspension formulation from open storage piles using local meteorological data. The dispersion modelling results on the spatial distribution of PM(10) source depletion showed that the maximum concentrations were observed at a distance 25-75 m downwind of the piles in the prevailing wind direction. Sensitivity calculations were performed also to reveal the effect of the compost pile height, the friction velocity and the receptor height on the ambient PM(10) concentration. It was observed that PM(10) concentrations (downwind in the prevailing wind direction) increased with increasing the friction velocity, increasing the pile height (for distances greater than 125 m from the source) and decreasing the receptor height (for distances greater than 125 m from the source). Furthermore, the results of ISC3-ST were analysed with the ExDoM (Exposure Dose Model) human exposure model. The ExDoM is a model for calculating the human exposure and the deposition dose, clearance, and finally retention of aerosol particles in the human respiratory tract (RT). PM(10) concentration at the composting site was calculated as the sum of the concentration from compost pile dust resuspension and the background concentration. It was found that the exposure to PM(10) and deposited lung dose for an adult Caucasian male who is not working at the composting site is less by 20-74% and 29-84%, respectively, compared to those for a worker exposed to PM concentrations at the composting site.

  6. Media Exposure: How Models Simplify Sampling

    DEFF Research Database (Denmark)

    Mortensen, Peter Stendahl

    1998-01-01

    In media planning, the distribution of exposures to more ad spots in more media (print, TV, radio) is crucial to the evaluation of the campaign. If such information should be sampled, it would only be possible in expensive panel-studies (eg TV-meter panels). Alternatively, the distribution of exp...

  7. Media Exposure: How Models Simplify Sampling

    DEFF Research Database (Denmark)

    Mortensen, Peter Stendahl

    1998-01-01

    In media planning, the distribution of exposures to more ad spots in more media (print, TV, radio) is crucial to the evaluation of the campaign. If such information should be sampled, it would only be possible in expensive panel-studies (eg TV-meter panels). Alternatively, the distribution of exp...

  8. Simulation of longitudinal exposure data with variance-covariance structures based on mixed models.

    Science.gov (United States)

    Song, Peng; Xue, Jianping; Li, Zhilin

    2013-03-01

    Longitudinal data are important in exposure and risk assessments, especially for pollutants with long half-lives in the human body and where chronic exposures to current levels in the environment raise concerns for human health effects. It is usually difficult and expensive to obtain large longitudinal data sets for human exposure studies. This article reports a new simulation method to generate longitudinal data with flexible numbers of subjects and days. Mixed models are used to describe the variance-covariance structures of input longitudinal data. Based on estimated model parameters, simulation data are generated with similar statistical characteristics compared to the input data. Three criteria are used to determine similarity: the overall mean and standard deviation, the variance components percentages, and the average autocorrelation coefficients. Upon the discussion of mixed models, a simulation procedure is produced and numerical results are shown through one human exposure study. Simulations of three sets of exposure data successfully meet above criteria. In particular, simulations can always retain correct weights of inter- and intrasubject variances as in the input data. Autocorrelations are also well followed. Compared with other simulation algorithms, this new method stores more information about the input overall distribution so as to satisfy the above multiple criteria for statistical targets. In addition, it generates values from numerous data sources and simulates continuous observed variables better than current data methods. This new method also provides flexible options in both modeling and simulation procedures according to various user requirements.

  9. Human dermal exposure to galaxolide from personal care products.

    Science.gov (United States)

    Correia, P; Cruz, A; Santos, L; Alves, A

    2013-06-01

    Musks are synthetic fragrances applied on personal care and household products as fixatives, by retarding the release of other fragrances with higher volatility. Galaxolide is the most used polycyclic musk since the 90th decade, and it has been detected in several environmental and biological matrices, particularly in human tissues and fluids. For exposure assessment purposes, large-monitoring data need to be obtained and rapid but reliable analytical techniques are requested. The main objective of this study is to develop and validate a new and fast analytical methodology to quantify galaxolide in personal care products and to apply this method to real matrices like skin care products (creams and lotions), shower products (soap bar), hair care products (shampoo and hair conditioner) and oral care products (toothpaste), to evaluate the human dermal exposure risk. A dispersive solid-phase extraction is proposed, using QuEChERS methodology, followed by HPLC with fluorescence detection. Some extraction parameters were studied, like the ratio of sample/solvent amounts, the homogenization time, the salt addition effect and the used sorbents. The validation parameters of the developed method were the following: a linearity range of 0.005-1.002 mg kg⁻¹ sample, a limit of detection of 0.001 mg kg⁻¹ sample, repeatability between 0.7% and 11.3% (variation coefficient of six standard injections), an intermediate precision of 2.5% (variation coefficient of six independent analysis of the same sample), mean recoveries ranging from 65% (soap bar) to 95% (body cream) and 3% of global uncertainty in most of the working range. The time of analysis, including the extraction steps, is 60 min, allowing a throughput of 4 samples h⁻¹ . Galaxolide was detected in all of the seven analysed products in concentrations ranging from 0.04 ± 0.01 mg kg⁻¹ sample (toothpaste) to 280.78 ± 8.19 mg kg⁻¹ sample (perfumed body cream), which may correspond to a significant estimated

  10. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  11. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  12. Stochastic modelling of human exposure to food chemicals and nutrients within the "Montecarlo" project: an exploration of the influence of brand loyalty and market share on intake estimates of intense sweeteners from sugar-free soft drinks.

    Science.gov (United States)

    Leclercq, Catherine; Arcella, Davide; Le Donne, Cinzia; Piccinelli, Raffaela; Sette, Stefania; Soggiu, Maria Eleonora

    2003-04-11

    To get a more realistic view of exposure to food chemicals, risk managers are getting more interested in stochastic modelling as an alternative to deterministic approaches based on conservative assumptions. It allows to take into account all the available information in the concentration of the chemical present in foods and in food consumption patterns. Within the EC-funded "Montecarlo" project, a comprehensive set of mathematical algorithms was developed to take into account all the necessary components for stochastic modelling of a variety of food chemicals, nutrients and ingredients. An appropriate computer software is being developed. Since the concentration of food chemicals may vary among different brands of the same product, consumer behaviour with respect to brands may have an impact on exposure assessments. Numeric experiments were carried out on different ways of incorporating indicators of market share and brand loyalty in the mathematical algorithms developed within the stochastic model of exposure to intense sweeteners from sugar-free beverages. The 95th percentiles of intake were shown to vary according to the inclusion/exclusion of these indicators. The market share should be included in the model especially if the market is not equitably distributed between brands. If brand loyalty data are not available, the model may be run under theoretical scenarios.

  13. Mercury Human Exposure in Populations Living Around Lake Tana (Ethiopia).

    Science.gov (United States)

    Habiba, G; Abebe, G; Bravo, Andrea G; Ermias, D; Staffan, Ǻ; Bishop, K

    2017-02-01

    A survey carried out in Lake Tana in 2015 found that Hg levels in some fish species exceeded internationally accepted safe levels for fish consumption. The current study assesses human exposure to Hg through fish consumption around the Lake Tana. Of particular interest was that a dietary intake of fishes is currently a health risk for Bihar Dar residents and anglers. Hair samples were collected from three different groups: anglers, college students and teachers, and daily laborers. A questionary includes gender, age, weight, activity. Frequency of fish consumption and origin of the eaten fish were completed by each participant. Mercury concentrations in hair were significantly higher (P value mercury and age associated with mercury concentration in scalp hair. Mercury concentrations in the hair of men were on average twice the value of the women. Also, users of skin lightening soap on a daily basis had 2.5 times greater mercury in scalp hair than non-users. Despite the different sources of mercury exposure mentioned above, the mercury concentrations of the scalp hair of participants of this study were below levels deemed to pose a threat to health.

  14. Exposure assessment modeling for volatiles--towards an Australian indoor vapor intrusion model.

    Science.gov (United States)

    Turczynowicz, Leonid; Robinson, Neville I

    2007-10-01

    Human health risk assessment of sites contaminated by volatile hydrocarbons involves site-specific evaluations of soil or groundwater contaminants and development of Australian soil health-based investigation levels (HILs). Exposure assessment of vapors arising from subsurface sources includes the use of overseas-derived commercial models to predict indoor air concentrations. These indoor vapor intrusion models commonly consider steady-state assumptions, infinite sources, limited soil biodegradation, negligible free phase, and equilibrium partitioning into air and water phases to represent advective and diffusive processes. Regional model construct influences and input parameters affect model predictions while steady-state assumptions introduce conservatism and jointly highlight the need for Australian-specific indoor vapor intrusion assessment. An Australian non-steady-state indoor vapor intrusion model has been developed to determine cumulative indoor human doses (CIHDs) and to address these concerns by incorporating Australian experimental field data to consider mixing, dilution, ventilation, sink effects and first-order soil and air degradation. It was used to develop provisional HILs for benzene, toluene, ethylbenzene, and xylene (BTEX), naphthalene, and volatile aliphatic and aromatic total petroleum hydrocarbons (TPH) < or = EC16 fractions for crawl space dwellings. This article summarizes current state of knowledge and discusses proposed research for differing exposure scenarios based on Australian dwelling and subsurface influences, concurrent with sensitivity analyses of input parameters and in-field model validation.

  15. Human Bronchial Epithelial Cell Response to Heavy Particle Exposure

    Science.gov (United States)

    Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Peyton, Michael; Larsen, Jill

    2012-07-01

    A battery of non-oncogenically immortalized human bronchial epithelial cells (HBECs) are being used to examine the molecular changes that lead to lung carcinogenesis after exposure to heavy particles found in the free space environment. The goal is to ultimately identify biomarkers of radioresponse that can be used for prediction of carcinogenic risk for fatal lung cancer. Our initial studies have focused on the cell line HBEC3 KT and the isogenic variant HBEC3 KTR53, which overexpresses the RASv12 mutant and where p53 has been knocked down by shRNA, and is considered to be a more oncogenically progressed variant. We have previously described the response of HBEC3 KT at the cellular and molecular level, however, the focus here is on the rate of cellular transformation after HZE radiation exposure and the molecular changes in transformed cells. When comparing the two cell lines we find that there is a maximum rate of cellular transformation at 0.25 Gy when cells are exposed to 1 GeV Fe particles, and, for the HBEC3 KTR53 there are multiple pathways upregulated that promote anchorage independent growth including the mTOR pathway, the TGF-1 pathway, RhoA signaling and the ERK/MAPK pathway as early as 2 weeks after radiation. This does not occur in the HBEC3 KT cell line. Transformed HBEC3 KT cells do not show any morphologic or phenotypic changes when grown as cell cultures. HBEC3 KTR53 cells on the other hand show substantial changes in morphology from a cobblestone epithelial appearance to a mesenchymal appearance with a lack of contact inhibition. This epithelial to mesenchymal change in morphology is accompanied by the expression of vimentin and a reduction in the expression of E-cadherin, which are hallmarks of epithelial to mesenchymal transition. Interestingly, for HBEC3 KT transformed cells there are no mutations in the p53 gene, 2 of 15 clones were found to be heterozygous for the RASV12 mutation, and 3 of 15 clones expressed high levels of BigH3, a TGFB

  16. Human exposure to fipronil from dogs treated with frontline.

    Science.gov (United States)

    Jennings, K A; Canerdy, T D; Keller, R J; Atieh, B H; Doss, R B; Gupta, R C

    2002-10-01

    This investigation determined fipronil residues on gloves worn while petting dogs after Frontline application. Frontline contains 9.8% fipronil, which controls fleas and ticks on dogs for at least 30 d. Frontline (1.34 ml) was applied topically on adult household dogs and gloves worn for 5 min during pettingwere collected 24 hr and 1, 2, 3, 4 and 5 w post-Frontline application for fipronil residue determinations using GC/MS. The highest concentration of fipronil (589.3 +/- 205.7ppm) was detected 24 h after Frontline application and was undetectable in the gloves collected at 5w. Repeated exposure to such contamination can pose human health risks.

  17. LIPOPOLYSACCHARIDE INDUCES EXPOSURE OF FIBRINOGEN RECEPTORS ON HUMAN PLATELETS

    Institute of Scientific and Technical Information of China (English)

    于希春; 吴其夏

    1995-01-01

    The effect of lipopolysaccharide (LPS) on the exposure of platelet fibrinogen receptors was investigated.The results showed that:1)LPS increased the binding of fibrinogen-gold complexes to platelets and the labels were primarily limited to shape-changed platelets;2)LPS caused a dose-dependent rise in intracellular Ca2+ concentration in platelets;3)LPS induced the activation of platelet protein kinase C(PKC) and the phosphorylation of glycoprotein llla (GP llla) which was inhibited by H-7.All these results suggest that stimulation of platelets with LPS causes a conformational change in glycoprotein llb/Illa (GPllb/llla) through platelet shape change and/or phosphorylation of GPllla via PKC,which serves to expose the fibrinogen binding sites of GPllb/llla on human platelets.

  18. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  19. Probability-summation model of multiple laser-exposure effects.

    Science.gov (United States)

    Menendez, A R; Cheney, F E; Zuclich, J A; Crump, P

    1993-11-01

    A probability-summation model is introduced to provide quantitative criteria for discriminating independent from interactive effects of multiple laser exposures on biological tissue. Data that differ statistically from predictions of the probability-summation model indicate the action of sensitizing (synergistic/positive) or desensitizing (hardening/negative) biophysical interactions. Interactions are indicated when response probabilities vary with changes in the spatial or temporal separation of exposures. In the absence of interactions, probability-summation parsimoniously accounts for "cumulative" effects. Data analyzed using the probability-summation model show instances of both sensitization and desensitization of retinal tissue by laser exposures. Other results are shown to be consistent with probability-summation. The relevance of the probability-summation model to previous laser-bioeffects studies, models, and safety standards is discussed and an appeal is made for improved empirical estimates of response probabilities for single exposures.

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

    Science.gov (United States)

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

    2012-01-01

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

  1. Quantifying human exposure to air pollution - moving from static monitoring to spatio-temporally resolved personal exposure assessment

    DEFF Research Database (Denmark)

    Steinle, Susanne; Reis, Stefan; Sabel, Clive E

    2013-01-01

    results from multifaceted relationships and interactions between environmental and human systems, adding complexity to the assessment process. Traditionally, approaches to quantify human exposure have relied on pollutant concentrations from fixed air quality network sites and static population...... distributions. New developments in sensor technology now enable us to monitor personal exposure to air pollutants directly while people are moving through their activity spaces and varying concentration fields. The literature review on which this paper is based on reflects recent developments in the assessment...... for the integrated assessment of human exposure to air pollutants taking into account latest technological capabilities and contextual information. Highlights ? We review and discuss recent developments and advances of research into personal exposure to air pollution. ? We emphasise the importance of personal...

  2. Conceptual model for assessment of inhalation exposure to manufactured nanoparticles

    NARCIS (Netherlands)

    Schneider, T.; Brouwer, D.H.; Koponen, I.K.; Jensen, K.A.; Fransman, W.; Duuren-Stuurman, B. van; Tongeren, M. van; Tielemans, E.

    2011-01-01

    As workplace air measurements of manufactured nanoparticles are relatively expensive to conduct, models can be helpful for a first tier assessment of exposure. A conceptual model was developed to give a framework for such models. The basis for the model is an analysis of the fate and underlying

  3. A test chamber for experimental hydrogen fluoride exposure in humans.

    Science.gov (United States)

    Søstrand, P; Kongerud, J; Eduard, W; Nilsen, T; Skogland, M; Boe, J

    1997-07-01

    An inhalation chamber was built to perform experimental studies with hydrogen fluoride (HF), other gases, and particulate matter. The present study sought to describe a new gas delivery system and the distribution and concentration of HF gas in the chamber. The aluminum chamber has a volume of 19.2 m3 and a variable ventilation rate of about 1 to 10 air changes per hour. The negative pressure difference between the chamber and outside air can be regulated from 0 to 300 Pa. HF was fed at concentrations of up to 4000 mg/m3 directly into the ventilation duct feeding the chamber through openings with diameters as small as 50 microns, oriented opposite to the airflow. Gas flow was varied from about 0.1 dm3/min at a pressure of 4 atm. The dilution factor of HF concentration from cylinder to chamber was on the order of 10(3) to 10(4). The standard deviation (SD) of the HF concentrations at a fixed measurement point during a 1-hour test was typically 0.05 mg/m3 at a time-weighted average (TWA) concentration of 2.66 mg/m3. The SD of the TWA HF concentrations at six locations in the chamber was typically 0.05 mg/m3 and 0.29 mg/m3 at 0.61 and 3.46 mg/m3, respectively. Human exposure could be predicted from calculations based on ventilation data, gas flow, and observed ratio between calculated and measured concentrations. When the target exposure concentration was 1.5 mg/m3, the measured mean exposure concentration was typically 1.54 mg/m3 (range: 1.4-1.7 mg/m3, SD 0.09 mg/m3, n = 8). The chamber is well-suited for inhalation studies in humans. Chamber atmosphere was controlled and has proved to be stable and homogeneous, even in tests with HF, a highly reactive gas in the class of superacids.

  4. Guide to the evaluation of human exposure to noise from large wind turbines

    Science.gov (United States)

    Stephens, D. G.; Shepherd, K. P.; Hubbard, H. H.; Grosveld, F.

    1982-01-01

    Guidance for evaluating human exposure to wind turbine noise is provided and includes consideration of the source characteristics, the propagation to the receiver location, and the exposure of the receiver to the noise. The criteria for evaluation of human exposure are based on comparisons of the noise at the receiver location with the human perception thresholds for wind turbine noise and noise-induced building vibrations in the presence of background noise.

  5. Numerical compliance testing of human exposure to electromagnetic radiation from smart-watches

    Science.gov (United States)

    Hong, Seon-Eui; Lee, Ae-Kyoung; Kwon, Jong-Hwa; Pack, Jeong-Ki

    2016-10-01

    In this study, we investigated the electromagnetic dosimetry for smart-watches. At present, the standard for compliance testing of body-mounted and handheld devices specifies the use of a flat phantom to provide conservative estimates of the peak spatial-averaged specific absorption rate (SAR). This means that the estimated SAR using a flat phantom should be higher than the SAR in the exposure part of an anatomical human-body model. To verify this, we numerically calculated the SAR for a flat phantom and compared it with the numerical calculation of the SAR for four anatomical human-body models of different ages. The numerical analysis was performed using the finite difference time domain method (FDTD). The smart-watch models were used in the three antennas: the shorted planar inverted-F antenna (PIFA), loop antenna, and monopole antenna. Numerical smart-watch models were implemented for cellular commutation and wireless local-area network operation at 835, 1850, and 2450 MHz. The peak spatial-averaged SARs of the smart-watch models are calculated for the flat phantom and anatomical human-body model for the wrist-worn and next to mouth positions. The results show that the flat phantom does not provide a consistent conservative SAR estimate. We concluded that the difference in the SAR results between an anatomical human-body model and a flat phantom can be attributed to the different phantom shapes and tissue structures.

  6. CEM-Consumer Exposure Model Download and Install Instructions

    Science.gov (United States)

    CEM contains a combination of models and default parameters which are used to estimate inhalation, dermal, and oral exposures to consumer products and articles for a wide variety of product and article use categories.

  7. Bisphenol-A exposure and gene expression in human luteinized membrana granulosa cells in vitro.

    Science.gov (United States)

    Mansur, Abdallah; Israel, Ariel; Combelles, Catherine M H; Adir, Michal; Racowsky, Catherine; Hauser, Russ; Baccarelli, Andrea A; Machtinger, Ronit

    2017-02-01

    Does bisphenol-A (BPA) affect gene expression in human membrana granulosa cells (MGC)? In vitro, short exposure to supra-physiological concentrations of BPA alters human MGC gene expression. Exposure to BPA may interfere with reproductive endocrine signaling. In vitro studies, mostly in animal models, have shown an inverse correlation between exposure to BPA and follicular growth, meiosis, and steroid hormone production in granulosa cells. Primary cultures of MGC obtained from 24 patients undergoing IVF (for PGD, male factor infertility or unexplained infertility) were exposed to various concentrations of BPA (0, 0.02, 0.2, 2 or 20 µg/ml) for 48 h. The study was conducted in a university-affiliated hospital. Microarray analysis was used to identify genes exhibiting expression changes following BPA exposure. Genes significantly altered were identified based on changes greater than 2-fold relative to the control group (not treated by BPA) and a Student's t-test P-value <0.05. Statistical significance was adjusted for multiple comparisons using the Benjamini-Hochberg method. Alterations in the expression of genes that are involved in the enriched functional annotations altered by BPA at the concentration of 20 µg/ml were confirmed by real-time PCR. A distinct pattern of gene expression was observed in primary cultures of MGC exposed to the highest BPA concentration compared with untreated cells. We identified 652 genes that exhibited at least 2-fold differences in expression after BPA exposure (all P < 0.05 versus untreated). These genes were significantly enriched for annotations related to cell cycle progression, segregation of chromosomes, steroid metabolism, apoptosis, lipid synthesis, oocyte maturation and chromosomal alignment. No significant changes in gene expression were found at the lower doses of BPA most relevant to human exposure. N/A. Human exposure to BPA in vivo occurs over long periods of time. In this in vitro model, cells were exposed to the

  8. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.

    Directory of Open Access Journals (Sweden)

    Helen Budworth

    Full Text Available DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS. Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06human blood ex vivo dataset, and 100% accuracy for discriminating patients who received total body radiation. Three genes of this panel (CDKN1A, FDXR and BBC3 were also highly sensitive to LPS treatment in the absence of radiation exposure, and LPS co-treatment significantly affected their radiation responses. At the protein level, BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68 response was significantly decreased in the presence of LPS. Our combined panel yields an estimated 4-group accuracy of ∼90% to discriminate between radiation alone, inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

  9. Comprehensive European dietary exposure model (CEDEM) for food additives.

    Science.gov (United States)

    Tennant, David R

    2016-05-01

    European methods for assessing dietary exposures to nutrients, additives and other substances in food are limited by the availability of detailed food consumption data for all member states. A proposed comprehensive European dietary exposure model (CEDEM) applies summary data published by the European Food Safety Authority (EFSA) in a deterministic model based on an algorithm from the EFSA intake method for food additives. The proposed approach can predict estimates of food additive exposure provided in previous EFSA scientific opinions that were based on the full European food consumption database.

  10. PAH exposure through soil ingestion: Combining digestion models and bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Wiele, T.R. van de; Verstraete, W. [Ghent University (BE).Laboratory Microbial Ecology and Technology (LabMET); Siciliano, S.D. [University of Saskatchewan (Canada). Department of Soil Science

    2003-07-01

    Exposure to environmental contaminants through soil ingestion is an important issue in current health risk assessment. Polycyclic aromatic hydrocarbons (PAH) or their metabolites pose risks to humans due to their toxic, mutagenic, carcinogenic or even (anti)estrogenic properties. PAH mobilization from a soil matrix (49.1{+-}1.5 mg PAH/kg DW) was assessed using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME). PAH GC-MS analysis was performed on the pellet and supernatant of SHIME digests and gave 101, 92, 89 and 97% recovery for water, stomach, duodenal and colon digests, respectively. PAH release was highest for the water extract (0.51%) and the stomach digestion (0.44%). Lower mobilized fractions in the duodenum (0.13%) and colon (0.30%) digests could be attributed to PAH complexation with bile salts, dissolved organic matter or colon microbiota. The digestion model provides us with relevant information to what extent soil bound PAHs are mobilized in the gastrointestinal tract and thus reach the gut wall, prior to absorption. (orig.)

  11. Comparing the ecological relevance of four wave exposure models

    Science.gov (United States)

    Sundblad, G.; Bekkby, T.; Isæus, M.; Nikolopoulos, A.; Norderhaug, K. M.; Rinde, E.

    2014-03-01

    Wave exposure is one of the main structuring forces in the marine environment. Methods that enable large scale quantification of environmental variables have become increasingly important for predicting marine communities in the context of spatial planning and coastal zone management. Existing methods range from cartographic solutions to numerical hydrodynamic simulations, and differ in the scale and spatial coverage of their outputs. Using a biological exposure index we compared the performance of four wave exposure models ranging from simple to more advanced techniques. All models were found to be related to the biological exposure index and their performance, measured as bootstrapped R2 distributions, overlapped. Qualitatively, there were differences in the spatial patterns indicating higher complexity with more advanced techniques. In order to create complex spatial patterns wave exposure models should include diffraction, especially in coastal areas rich in islands. The inclusion of wind strength and frequency, in addition to wind direction and bathymetry, further tended to increase the amount of explained variation. The large potential of high-resolution numerical models to explain the observed patterns of species distribution in complex coastal areas provide exciting opportunities for future research. Easy access to relevant wave exposure models will aid large scale habitat classification systems and the continuously growing field of marine species distribution modelling, ultimately serving marine spatial management and planning.

  12. Human exposure to piroplasms in Central and Northern Italy

    Directory of Open Access Journals (Sweden)

    Simona Gabrielli

    2014-03-01

    Full Text Available A serosurvey has been conducted in Northern and Central Italy to investigate the presence in humans of antibodies against zoonotic Babesia and Theileria species. The study focused on a total of 432 volunteers, of which 290 were persistently exposed to tick bites because of their jobs (forester employees, livestock keepers, veterinary practitioners, farmers and hunters and 142 resident in the same area less frequently exposed. An indirect fluorescent antibody test (IFAT for humans was used to detect antibodies to Babesia microti, IFAT tests for veterinary use were modified to detect reactivity to Babesia bovis, Babesia canis and Theileria equi. A laboratory-derived ELISA was employed to detect antibodies to Babesia divergens. Both reactive and 10 negative sera were analysed against plasmodial antigens to evaluate possible aspecificity. A high reactivity to piroplasm antigens was found, showing significant difference between the sera of the two groups of volunteers (24% vs 7.0%; p<0.001. No cross-reactivity was observed, while each professional group showed reactivity that would fit with the professional risk exposure. In particular, a high reactivity to B. microti and B. divergens antigens was observed in foresters and hunters (32% and 12%, respectively. This is the first report on the human seroreactivity to piroplasms in Italy; it also provides additional epidemiological information on these tick-borne zoonoses in Europe. Our findings suggest the possible occurrence of piroplasm infections in Italy and alert physicians to consider these otherwise neglected parasitic diseases when dealing with any febrile illness, especially in subjects exposed to tick bites.

  13. Conceptual model for assessment of inhalation exposure: Defining modifying factors

    NARCIS (Netherlands)

    Tielemans, E.; Schneider, T.; Goede, H.; Tischer, M.; Warren, N.; Kromhout, H.; Tongeren, M. van; Hemmen, J. van; Cherrie, J.W.

    2008-01-01

    The present paper proposes a source-receptor model to schematically describe inhalation exposure to help understand the complex processes leading to inhalation of hazardous substances. The model considers a stepwise transfer of a contaminant from the source to the receptor. The conceptual model is c

  14. A model of food reward learning with dynamic reward exposure

    Directory of Open Access Journals (Sweden)

    Ross A Hammond

    2012-10-01

    Full Text Available The process of conditioning via reward learning is highly relevant to the study of food choice and obesity. Learning is itself shaped by environmental exposure, with the potential for such exposures to vary substantially across individuals and across place and time. In this paper, we use computational techniques to extend a well-validated standard model of reward learning, introducing both substantial heterogeneity and dynamic reward exposures. We then apply the extended model to a food choice context. The model produces a variety of individual behaviors and population-level patterns which are not evident from the traditional formulation, but which offer potential insights for understanding food reward learning and obesity. These include a lock-in effect, through which early exposure can strongly shape later reward valuation. We discuss potential implications of our results for the study and prevention of obesity, for the reward learning field, and for future experimental and computational work.

  15. International issues on human health effects of exposure to chemical mixtures.

    Science.gov (United States)

    Feron, Victor J; Cassee, Flemming R; Groten, John P; van Vliet, Petronella W; van Zorge, Job A

    2002-12-01

    In this article, we highlight new developments and recent studies concerning adverse human health effects related to chemical mixtures. One group of activities comprises the development of a new computer program for analyzing mixture studies and a mathematical model as a basis for combination rules that predict the toxicity of mixtures. Other new activities in the area of experimental studies are the application of gene expression technologies in mixture research, and pattern recognition as a tool in safety evaluation of complex mixtures. A "bottom-up" approach for chemosensory detection of mixtures has recently been presented. Other topics include a method for the safety evaluation of natural flavoring complexes, and an evaluation of the possible health effects of the simultaneous intake of food additives. Examples of issues related to mixtures of airborne chemicals are potential interaction of fine particles and gaseous pollutants in ambient air, nasal cancer associated with inhaled chemical mixtures, and the recommendation of a limit value for volatile organic compounds. Topics of a more strategic nature include studies concerning the public health effects of large airports, and the development of criteria for a harmonized classification of chemical mixtures. This overview illustrates that strategies to tackle the safety evaluation of combined exposures and complex mixtures as well as models facilitating the interpretation of findings in the context of risk assessment of mixtures have become increasingly important. It is true that exposure of humans to chemical mixtures is the rule rather than the exception, and therefore health risk assessments should focus on mixtures and not on single chemicals. It is also true, however, that humans have learned to cope with exposure to huge numbers of chemicals simultaneously (food, water, air, soil, and consumer products). Therefore, in view of limited resources for toxicological research, the focus in toxicology should be

  16. Evaluation of the Modeling of Exposure to Environmental Tobacco Smoke (ETS) in the SHEDS-PM Model.

    Science.gov (United States)

    Cao, Ye; Frey, H Christopher; Liu, Xiaozhen; Deshpande, Bela K

    2009-06-01

    Environmental tobacco smoke (ETS) is estimated to be a major contributor to indoor PM concentration and human exposures to fine particulate matter of 2.5 microns or smaller (PM2.5). The Stochastic Human Exposure and Dose Simulation for Particulate Matter (SHEDS-PM) model developed by the US Environmental Protection Agency estimates distributions of outdoor and indoor PM2.5 exposure for a specified population based on ambient concentrations and indoor emissions sources. Because indoor exposures to ETS can be high, especially in indoor residential microenvironments, a critical assessment was conducted of the methodology and data used in SHEDS-PM for estimation of indoor exposure to ETS. For the residential microenvironment, SHEDS uses a mass-balance approach which is comparable to best practices. The default inputs in SHEDS-PM were reviewed and more recent and extensive data sources were identified. Sensitivity analysis was used to determine which inputs should be prioritized for updating. Data regarding the cigarette emission rate was found to be the most important. SHEDS-PM does not currently account for in-vehicle ETS exposure; however, in-vehicle ETS-related PM2.5 levels can exceed those in residential microenvironments by a factor of 10 or more. Therefore, a mass-balance based methodology for estimating in-vehicle ETS PM2.5 concentration is evaluated. Recommendations are made regarding updating of input data and algorithms related to ETS exposure in the SHEDS-PM model.

  17. Polybrominated diphenyl ethers (PBDEs) in the indoor dust in China: levels, spatial distribution and human exposure.

    Science.gov (United States)

    Zhu, Ning-Zheng; Liu, Li-Yan; Ma, Wan-Li; Li, Wen-Long; Song, Wei-Wei; Qi, Hong; Li, Yi-Fan

    2015-01-01

    Indoor environment is an important source of human exposure to several toxicants, such as brominated flame retardants. Indoor dust samples were collected in winter season in 2010, which covered 23 provinces across China, for the analysis of polybrominated diphenyl ethers (PBDEs). Concentrations of PBDEs (Σ14PBDEs) ranged from 8.92 to 37,500 ng/g, with the mean of 3520 ng/g. BDE-209 was the most dominate congener, followed by BDE-183, BDE-47 and BDE-99. PBDE concentrations and the longitude were significantly correlated (pPBDEs through dust ingestion and dermal absorption indicated that the toddlers had the highest exposure dose, with the median value of 6.0 ng/kg-bw/day. According to the hazard quotients, health risk of PBDEs via dust ingestion in China is currently acceptable. Monte Carlo simulation was implemented to quantify the uncertainty and sensitivity of exposure models for determining the most influential variables. The results suggested that more specific and accurate parameters should be used for dust ingestion and dermal absorption exposure models in future.

  18. ASSESSING HUMAN EXPOSURE TO GRASS POLLEN IN DENMARK

    DEFF Research Database (Denmark)

    Peel, Robert George; Hertel, Ole; Herbert, Rob

    Objectives: Exposure to pollen is typically assessed using data collected at fixed roof-top monitoring stations, which give a general picture of airborne pollen concentrations over a wide region. Actual exposure levels can be obtained through personal exposure monitoring. This is typically done u...

  19. Simplified pregnant woman models for the fetus exposure assessment

    Science.gov (United States)

    Jala, Marjorie; Conil, Emmanuelle; Varsier, Nadège; Wiart, Joe; Hadjem, Abdelhamid; Moulines, Éric; Lévy-Leduc, Céline

    2013-05-01

    In this paper, we introduce a study that we carried out in order to validate the use of a simplified pregnant woman model for the assessment of the fetus exposure to radio frequency waves. This simplified model, based on the use of a homogeneous tissue to replace most of the inner organs of the virtual mother, would allow us to deal with many issues that are raised because of the lack of pregnant woman models for numerical dosimetry. Using specific absorption rate comparisons, we show that this model could be used to estimate the fetus exposure to plane waves.

  20. Modeling Air Pollution Exposure Metrics for the Diabetes and Environment Panel Study (DEPS)

    Science.gov (United States)

    Air pollution health studies of fine particulate matter (PM) often use outdoor concentrations as exposure surrogates. To improve exposure assessments, we developed and evaluated an exposure model for individuals (EMI), which predicts five tiers of individual-level exposure metric...

  1. Computational strategy for quantifying human pesticide exposure based upon a saliva measurement

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Charles; Weber, Thomas J.; Smith, Jordan N.

    2015-05-27

    The National Research Council of the National Academies report, Toxicity Testing in the 21st Century: A Vision and Strategy, highlighted the importance of quantitative exposure data for evaluating human toxicity risk and noted that biomonitoring is a critical tool for quantitatively evaluating exposure from both environmental and occupational settings. Direct measurement of chemical exposures using personal monitoring provides the most accurate estimation of a subject’s true exposure, and non-invasive methods have also been advocated for quantifying the pharmacokinetics and bioavailability of drugs and xenobiotics. In this regard, there is a need to identify chemicals that are readily cleared in saliva at concentrations that can be quantified to support the implementation of this approach.. The current manuscript describes the use of computational modeling approaches that are closely coupled to in vivo and in vitro experiments to predict salivary uptake and clearance of xenobiotics. The primary mechanism by which xenobiotics leave the blood and enter saliva is thought to involve paracellular transport, passive transcellular diffusion, or trancellular active transport with the majority of drugs and xenobiotics cleared from plasma into saliva by passive diffusion. The transcellular or paracellular diffusion of unbound chemicals in plasma to saliva has been computational modeled using a combination of compartmental and physiologically based approaches. Of key importance for determining the plasma:saliva partitioning was the utilization of a modified Schmitt algorithm that calculates partitioning based upon the tissue composition, pH, chemical pKa and plasma protein-binding. Sensitivity analysis of key model parameters specifically identified that both protein-binding and pKa (for weak acids and bases) had the most significant impact on the determination of partitioning and that there were clear species dependent differences based upon physiological variance between

  2. Elderly Exposure to Air Pollutants: Measuring, assessing and modelling

    NARCIS (Netherlands)

    Almeida-Silva, M.A.

    2016-01-01

    This Thesis focuses on the estimation of the human exposure to air pollutants, and gives special attention to one of the most susceptible groups in the general population - elders. To fulfil the goal the work was conducted following the risk assessment paradigm and, consequently, was divided into 5

  3. Animal Model Selection for Inhalational HCN Exposure

    Science.gov (United States)

    2016-08-01

    the medullary respiratory center is believed to regulate the respiratory system of the rat with the carotid bodies playing a role. The carotid...dogs do not sweat through the skin, the respiratory system also plays an important role in regulation of temperature . Rapid breaths, termed panting...identify the similarities and differences between human and animal species exposed orally to cyanide and provide documentation and justification for

  4. Dermal permeation data and models for the prioritization and screening-level exposure assessment of organic chemicals

    Science.gov (United States)

    High throughput screening (HTS) models are being developed and applied to prioritize chemicals for more comprehensive exposure and risk assessment. Dermal pathways are possible exposure routes to humans for thousands of chemicals found in personal care products and the indoor env...

  5. Computational Strategy for Quantifying Human Pesticide Exposure based upon a Saliva Measurement

    Directory of Open Access Journals (Sweden)

    Charles eTimchalk

    2015-05-01

    Full Text Available Quantitative exposure data is important for evaluating toxicity risk and biomonitoring is a critical tool for evaluating human exposure. Direct personal monitoring provides the most accurate estimation of a subject’s true dose, and non-invasive methods are advocated for quantifying exposure to xenobiotics. In this regard, there is a need to identify chemicals that are cleared in saliva at concentrations that can be quantified to support the implementation of this approach. This manuscript reviews the computational modeling approaches that are coupled to in vivo and in vitro experiments to predict salivary uptake and clearance of xenobiotics and provides additional insight on species-dependent differences in partitioning that are of key importance for extrapolation. The primary mechanism by which xenobiotics leave the blood and enter saliva involves paracellular transport, passive transcellular diffusion, or trancellular active transport with the majority of xenobiotics transferred by passive diffusion. The transcellular or paracellular diffusion of unbound chemicals in plasma to saliva has been computationally modeled using compartmental and physiologically based approaches. Of key importance for determining the plasma:saliva partitioning was the utilization of the Schmitt algorithm that calculates partitioning based upon the tissue composition, pH, chemical pKa and plasma protein-binding. Sensitivity analysis identified that both protein-binding and pKa (for weak acids and bases have significant impact on determining partitioning and species dependent differences based upon physiological variance. Future strategies are focused on an in vitro salivary acinar cell based system to experimentally determine and computationally predict salivary gland uptake and clearance for xenobiotics. It is envisioned that a combination of salivary biomonitoring and computational modeling will enable the non-invasive measurement of chemical exposures in human

  6. Computational strategy for quantifying human pesticide exposure based upon a saliva measurement.

    Science.gov (United States)

    Timchalk, Charles; Weber, Thomas J; Smith, Jordan N

    2015-01-01

    Quantitative exposure data is important for evaluating toxicity risk and biomonitoring is a critical tool for evaluating human exposure. Direct personal monitoring provides the most accurate estimation of a subject's true dose, and non-invasive methods are advocated for quantifying exposure to xenobiotics. In this regard, there is a need to identify chemicals that are cleared in saliva at concentrations that can be quantified to support the implementation of this approach. This manuscript reviews the computational modeling approaches that are coupled to in vivo and in vitro experiments to predict salivary uptake and clearance of xenobiotics and provides additional insight on species-dependent differences in partitioning that are of key importance for extrapolation. The primary mechanism by which xenobiotics leave the blood and enter saliva involves paracellular transport, passive transcellular diffusion, or transcellular active transport with the majority of xenobiotics transferred by passive diffusion. The transcellular or paracellular diffusion of unbound chemicals in plasma to saliva has been computationally modeled using compartmental and physiologically based approaches. Of key importance for determining the plasma:saliva partitioning was the utilization of the Schmitt algorithm that calculates partitioning based upon the tissue composition, pH, chemical pKa, and plasma protein-binding. Sensitivity analysis identified that both protein-binding and pKa (for weak acids and bases) have significant impact on determining partitioning and species dependent differences based upon physiological variance. Future strategies are focused on an in vitro salivary acinar cell based system to experimentally determine and computationally predict salivary gland uptake and clearance for xenobiotics. It is envisioned that a combination of salivary biomonitoring and computational modeling will enable the non-invasive measurement of chemical exposures in human populations.

  7. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived......, thereby implying that interactions between spreading processes are driving forces of attention dynamics. Overall, the thesis contributes to a quantitative understanding of a wide range of different human behaviors by applying mathematical modeling to behavioral data. There can be no doubt......During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...

  8. Impact of Hot and Cold Exposure on Human Skeletal Muscle Gene Expression

    Science.gov (United States)

    Zak, Roksana B.; Shute, Robert J.; Heesch, Matthew W.S.; La Salle, D. Taylor; Bubak, Matthew P.; Dinan, Nicholas E.; Laursen, Terence L.; Slivka, Dustin R.

    2017-01-01

    Many human diseases lead to a loss of skeletal muscle metabolic function and mass. Local and environmental temperature can modulate the exercise-stimulated response of several genes involved in mitochondrial biogenesis and skeletal muscle function in a human model. However, the impact of environmental temperature, independent of exercise, has not been addressed in a human model. Thus, the purpose of this study was to compare the effects of exposure to hot, cold, and room temperature conditions on skeletal muscle gene expression related to mitochondrial biogenesis and muscle mass. METHODS Recreationally trained male subjects (n=12) had muscle biopsies taken from the vastus lateralis before and after 3 h exposure to hot (33 °C), cold (7 °C), or room temperature (20 °C) conditions. RESULTS Temperature had no effect on most of the genes related to mitochondrial biogenesis, myogenesis, or proteolysis (p > 0.05). Core temperature was significantly higher in hot and cold environments compared to room temperature (37.2 ± 0.1 °C, p = 0.001; 37.1 ± 0.1 °C, p = 0.013; 36.9 ± 0.1 °C, respectively). Whole body oxygen consumption was also significantly higher in hot and cold compared to room temperature (0.38 ± 0.01 L·min−1, p < 0.001; 0.52 ± 0.03 L·min−1, p < 0.001; 0.35 ± 0.01 L·min−1, respectively). CONCLUSIONS These data show that acute temperature exposure alone does not elicit significant changes in skeletal muscle gene expression. When considered in conjunction with previous research, exercise appears to be a necessary component to observe gene expression alterations between different environmental temperatures in humans. PMID:28177744

  9. The art of occupational exposure modelling - development and evaluation of generic inhalation exposure models

    NARCIS (Netherlands)

    Schinkel, J.M.

    2013-01-01

    When working with chemical substances, workers might be exposed to chemical contaminants. In a risk assessment the exposure is compared with a toxicological limit value. In a risk assessment the toxicological effect of a chemical substance is compared with the exposure to the chemical in order to

  10. Relevance of animal models to human tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Blanchet Pierre J

    2012-03-01

    Full Text Available Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.

  11. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov

    2013-12-01

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the

  12. Relationship between vapor intrusion and human exposure to trichloroethylene.

    Science.gov (United States)

    Archer, Natalie P; Bradford, Carrie M; Villanacci, John F; Crain, Neil E; Corsi, Richard L; Chambers, David M; Burk, Tonia; Blount, Benjamin C

    2015-01-01

    Trichloroethylene (TCE) in groundwater has the potential to volatilize through soil into indoor air where it can be inhaled. The purpose of this study was to determine whether individuals living above TCE-contaminated groundwater are exposed to TCE through vapor intrusion. We examined associations between TCE concentrations in various environmental media and TCE concentrations in residents. For this assessment, indoor air, outdoor air, soil gas, and tap water samples were collected in and around 36 randomly selected homes; blood samples were collected from 63 residents of these homes. Additionally, a completed exposure survey was collected from each participant. Environmental and blood samples were analyzed for TCE. Mixed model multiple linear regression analyses were performed to determine associations between TCE in residents' blood and TCE in indoor air, outdoor air, and soil gas. Blood TCE concentrations were above the limit of quantitation (LOQ; ≥ 0.012 µg L(-1)) in 17.5% of the blood samples. Of the 36 homes, 54.3%, 47.2%, and >84% had detectable concentrations of TCE in indoor air, outdoor air, and soil gas, respectively. Both indoor air and soil gas concentrations were statistically significantly positively associated with participants' blood concentrations (P = 0.0002 and P = 0.04, respectively). Geometric mean blood concentrations of residents from homes with indoor air concentrations of >1.6 µg m(-3) were approximately 50 times higher than geometric mean blood TCE concentrations in participants from homes with no detectable TCE in indoor air (P < .0001; 95% CI 10.4-236.4). This study confirms the occurrence of vapor intrusion and demonstrates the magnitude of exposure from vapor intrusion of TCE in a residential setting.

  13. Assessing human exposure risk to cadmium through inhalation and seafood consumption

    Energy Technology Data Exchange (ETDEWEB)

    Ju, Yun-Ru; Chen, Wei-Yu [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei10617, Taiwan, ROC (China); Liao, Chung-Min, E-mail: cmliao@ccms.ntu.edu.tw [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei10617, Taiwan, ROC (China)

    2012-08-15

    Highlights: Black-Right-Pointing-Pointer Trophically available fraction in seafood and bioaccessibility is linked. Black-Right-Pointing-Pointer Human health risk to Cd can via inhalation and seafood consumption. Black-Right-Pointing-Pointer Female had the higher Cd accumulation in urine and blood than male. Black-Right-Pointing-Pointer Cigarette smoking is a major determinant of human Cd intake. - Abstract: The role of cadmium (Cd) bioaccessibility in risk assessment is less well studied. The aim of this study was to assess human health risk to Cd through inhalation and seafood consumption by incorporating bioaccessibility. The relationships between trophically available Cd and bioaccessibility were constructed based on available experimental data. We estimated Cd concentrations in human urine and blood via daily intake from seafood consumption and inhalation based on a physiologically-based pharmacokinetic (PBPK) model. A Hill-based dose-response model was used to assess human renal dysfunction and peripheral arterial disease risks for long-term Cd exposure. Here we showed that fish had higher bioaccessibility ({approx}83.7%) than that of shellfish ({approx}73.2%) for human ingestion. Our results indicated that glomerular and tubular damage among different genders and smokers ranged from 18.03 to 18.18%. Our analysis showed that nonsmokers had 50% probability of peripheral arterial disease level exceeding from 3.28 to 8.80%. Smoking populations had 2-3 folds higher morbidity risk of peripheral arterial disease than those of nonsmokers. Our study concluded that the adverse effects of Cd exposure are exacerbated when high seafood consumption coincides with cigarette smoking. Our work provides a framework that could more accurately address risk dose dependency of Cd hazard.

  14. Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations.

    Science.gov (United States)

    Fowler, Paul A; Abramovich, David R; Haites, Neva E; Cash, Phillip; Groome, Nigel P; Al-Qahtani, Ahmed; Murray, Tessa J; Lea, Richard G

    2007-11-01

    Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis. Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10-1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated. Exposure to dieldrin reduced LH-induced testosterone secretion (P Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH-induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals. Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity.

  15. Dose conversion coefficients for neutron exposure to the lens of the human eye

    Energy Technology Data Exchange (ETDEWEB)

    Manger, Ryan P [ORNL; Bellamy, Michael B [ORNL; Eckerman, Keith F [ORNL

    2011-01-01

    Dose conversion coefficients for the lens of the human eye have been calculated for neutron exposure at energies from 1 x 10{sup -9} to 20 MeV and several standard orientations: anterior-to-posterior, rotational and right lateral. MCNPX version 2.6.0, a Monte Carlo-based particle transport package, was used to determine the energy deposited in the lens of the eye. The human eyeball model was updated by partitioning the lens into sensitive and insensitive volumes as the anterior portion (sensitive volume) of the lens being more radiosensitive and prone to cataract formation. The updated eye model was used with the adult UF-ORNL mathematical phantom in the MCNPX transport calculations.

  16. Modelling of skin exposure from distributed sources

    DEFF Research Database (Denmark)

    Fogh, C.L.; Andersson, Kasper Grann

    2000-01-01

    A simple model of indoor air pollution concentrations was used together with experimental results on deposition velocities to skin to calculate the skin dose from an outdoor plume of contaminants, The primary pathway was considered to be direct deposition to the skin from a homogeneously distribu...... distributed air source. The model has been used to show that skin deposition was a significant dose contributor for example when compared to inhalation dose. (C) 2000 British Occupational Hygiene Society, Published by Elsevier Science Ltd. All rights reserved....

  17. Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs).

    Science.gov (United States)

    Sharma, Monita; Nikota, Jake; Halappanavar, Sabina; Castranova, Vincent; Rothen-Rutishauser, Barbara; Clippinger, Amy J

    2016-07-01

    The increased production and use of multi-walled carbon nanotubes (MWCNTs) in a diverse array of consumer, medical, and industrial applications have raised concerns about potential human exposure to these materials in the workplace and ambient environments. Inhalation is a primary route of exposure to MWCNTs, and the existing data indicate that they are potentially hazardous to human health. While a 90-day rodent inhalation test (e.g., OECD Test No. 413: subchronic inhalation toxicity: 90-day study or EPA Health Effects Test Guidelines OPPTS 870.3465 90-day inhalation toxicity) is recommended by the U.S. Environmental Protection Agency Office of Pollution Prevention and Toxics for MWCNTs (and other CNTs) if they are to be commercially produced (Godwin et al. in ACS Nano 9:3409-3417, 2015), this test is time and cost-intensive and subject to scientific and ethical concerns. As a result, there has been much interest in transitioning away from studies on animals and moving toward human-based in vitro and in silico models. However, given the multiple mechanisms of toxicity associated with subchronic exposure to inhaled MWCNTs, a battery of non-animal tests will likely be needed to evaluate the key endpoints assessed by the 90-day rodent study. Pulmonary fibrosis is an important adverse outcome related to inhalation exposure to MWCNTs and one that the non-animal approach should be able to assess. This review summarizes the state-of-the-science regarding in vivo and in vitro toxicological methods for predicting MWCNT-induced pulmonary fibrosis.

  18. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on obs

  19. Modelling survival: exposure pattern, species sensitivity and uncertainty

    NARCIS (Netherlands)

    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.; Brink, Van Den 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

  20. ASSESSING HUMAN EXPOSURE TO GRASS POLLEN IN DENMARK

    DEFF Research Database (Denmark)

    Peel, Robert George; Hertel, Ole; Herbert, Rob

    Objectives: Exposure to pollen is typically assessed using data collected at fixed roof-top monitoring stations, which give a general picture of airborne pollen concentrations over a wide region. Actual exposure levels can be obtained through personal exposure monitoring. This is typically done...... using a suction sampler worn on the chest or lapel that measures breathing zone concentration; a more useful exposure parameter for pollen allergy sufferers is the amount of pollen inhaled, i.e. the dose. The objective of this study was to investigate how well monitoring station data reflect actual...... exposure, something that is currently not well understood. Methods: Exposure samples were collected during the 2011 grass pollen season in an area of abundant unmaintained grass coverage close to the centre of Aarhus, Denmark. Sampling was performed at two-hourly intervals between 12:00 and 20:00 on 14...

  1. Metabolomic Response of Human Embryonic Stem Cell Derived Germ-like Cells after Exposure to Steroid Hormones

    Science.gov (United States)

    To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC ...

  2. Human intake fraction of toxic pollutants: a model comparison between caltox and uses-lca

    OpenAIRE

    Huijbregts, Mark A J; Geelen, Loes M.J.; Edgar G. Hertwich; McKone, Thomas E.; Meent, Dik van de

    2004-01-01

    In Life Cycle Assessment and Comparative Risk Assessment potential human exposure to toxic pollutants can be expressed as the human intake fraction (iF), representing the fraction of the quantity emitted that enters the human population. To assess model uncertainty in the human intake fraction, ingestion and inhalation iFs of 367 substances emitted to air and freshwater were calculated with two commonly applied multi-media fate and exposure models, CalTOX and USES-LCA. Comparison of the ...

  3. Climate Change Impacts on Environmental and Human Exposure to Mercury in the Arctic

    Science.gov (United States)

    Sundseth, Kyrre; Pacyna, Jozef M.; Banel, Anna; Pacyna, Elisabeth G.; Rautio, Arja

    2015-01-01

    This paper reviews information from the literature and the EU ArcRisk project to assess whether climate change results in an increase or decrease in exposure to mercury (Hg) in the Arctic, and if this in turn will impact the risks related to its harmful effects. It presents the state-of-the art of knowledge on atmospheric mercury emissions from anthropogenic sources worldwide, the long-range transport to the Arctic, and it discusses the likely environmental fate and exposure effects on population groups in the Arctic under climate change conditions. The paper also includes information about the likely synergy effects (co-benefits) current and new climate change polices and mitigation options might have on mercury emissions reductions in the future. The review concludes that reductions of mercury emission from anthropogenic sources worldwide would need to be introduced as soon as possible in order to assure lowering the adverse impact of climate change on human health. Scientific information currently available, however, is not in the position to clearly answer whether climate change will increase or decrease the risk of exposure to mercury in the Arctic. New research should therefore be undertaken to model the relationships between climate change and mercury exposure. PMID:25837201

  4. Human Rights Engagement and Exposure: New Scales to Challenge Social Work Education

    Science.gov (United States)

    McPherson, Jane; Abell, Neil

    2012-01-01

    Objectives: Advancing human rights is a core competency of U.S. social work education; yet, human rights attitudes and behaviors have never been measured in the social work literature. Thus, this article describes the development and initial validation of two scales, Human Rights Engagement in Social Work (HRESW) and Human Rights Exposure in…

  5. Human Rights Engagement and Exposure: New Scales to Challenge Social Work Education

    Science.gov (United States)

    McPherson, Jane; Abell, Neil

    2012-01-01

    Objectives: Advancing human rights is a core competency of U.S. social work education; yet, human rights attitudes and behaviors have never been measured in the social work literature. Thus, this article describes the development and initial validation of two scales, Human Rights Engagement in Social Work (HRESW) and Human Rights Exposure in…

  6. Consumer exposure modelling under REACH: Assessing the defaults.

    Science.gov (United States)

    Oltmanns, J; Neisel, F; Heinemeyer, G; Kaiser, E; Schneider, K

    2015-07-01

    Consumer exposure to chemicals from products and articles is rarely monitored. Since an assessment of consumer exposure has become particularly important under the European REACH Regulation, dedicated modelling approaches with exposure assessment tools are applied. The results of these tools are critically dependent on the default input values embedded in the tools. These inputs were therefore compiled for three lower tier tools (ECETOC TRA (version 3.0), EGRET and REACT)) and benchmarked against a higher tier tool (ConsExpo (version 4.1)). Mostly, conservative input values are used in the lower tier tools. Some cases were identified where the lower tier tools used less conservative values than ConsExpo. However, these deviations only rarely resulted in less conservative exposure estimates compared to ConsExpo, when tested in reference scenarios. This finding is mainly due to the conservatism of (a) the default value for the thickness of the product layer (with complete release of the substance) used for the prediction of dermal exposure and (b) the complete release assumed for volatile substances (i.e. substances with a vapour pressure ⩾10Pa) for inhalation exposure estimates. The examples demonstrate that care must be taken when changing critical defaults in order to retain conservative estimates of consumer exposure to chemicals.

  7. Modelling exposure of mammalian predators to anticoagulant rodenticide

    Directory of Open Access Journals (Sweden)

    Christopher John Topping

    2016-12-01

    Full Text Available Anticoagulant rodenticides (AR are a widespread and effective method of rodent control but there is concern about the impact these may have on non-target organisms, in particular secondary poisoning of rodent predators. Incidence and concentration of AR in free-living predators in Denmark is very high. We postulate that this is caused by widespread exposure due to widespread use of AR in Denmark in and around buildings. To investigate this theory a spatio-temporal model of AR use and mammalian predator distribution was created. This model was supported by data from an experimental study of mice as vectors of AR, and was used to evaluate likely impacts of restrictions imposed on AR use in Denmark banning the use of rodenticides for plant protection in woodlands and tree-crops. The model uses input based on frequencies and timings of baiting for rodent control for urban, rural and woodland locations and creates an exposure map based on spatio-temporal modelling of movement of mice-vectored AR (based on Apodemus flavicollis. Simulated predator territories are super-imposed over this exposure map to create an exposure index. Predictions from the model concur with field studies of AR prevalence both before and after the change in AR use. In most cases incidence of exposure to AR is predicted to be greater than 90%, although cessation of use in woodlots and Christmas tree plantations should reduce mean exposure concentrations. Model results suggest that the driver of high AR incidence in non-target small mammal predators is likely to be the pattern of use and not the distance AR is vectored. Reducing baiting frequency by 75% had different effects depending on the landscape simulated, but having a maximum of 12% reduction in exposure incidence, and in one landscape a maximum reduction of <2%. We discuss sources of uncertainty in the model and directions for future development of predictive models for environmental impact assessment of rodenticides. The

  8. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...... studies have considered data sets with just one behavioral variable such as email communication. The Social Fabric interdisciplinary research project is an attempt to collect a more complete data set on human behavior by providing 1000 smartphones with pre-installed data collection software to students...... data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived...

  9. Physiological responses to exposure to carbon dioxide and human bioeffluents

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2015-01-01

    Present paper describes physiological responses as a result of exposures to CO2 (between 500 ppm to 3,000 ppm) with and without bioeffluents. Twenty-five subjects participated. They were exposed in the climate chamber for 255 minutes in groups of five at a time. During exposure, they performed di...

  10. Limiting criteria for human exposure to low humidity indoors

    DEFF Research Database (Denmark)

    Wyon, David; Fang, Lei; Meyer, H.;

    2002-01-01

    % RH. The subjects performed simulated office work throughout each exposure. Building Related Symptom (BRS) intensity was reported on visual-analogue scales. Tests of eye, nose and skin function were applied. In these short exposures subjective discomfort, though significantly increased by low humidity...

  11. Modeling exposure to depleted uranium in support of decommissioning at Jefferson Proving Ground, Indiana

    Energy Technology Data Exchange (ETDEWEB)

    Ebinger, M.H. [Los Alamos National Lab., NM (United States); Oxenburg, T.P. [Army Test and Evaluation Command, Aberdeen Proving Ground, MD (United States)

    1997-02-01

    Jefferson Proving Ground was used by the US Army Test and Evaluation Command for testing of depleted uranium munitions and closed in 1995 under the Base Realignment and Closure Act. As part of the closure of JPG, assessments of potential adverse health effects to humans and the ecosystem were conducted. This paper integrates recent information obtained from site characterization surveys at JPG with environmental monitoring data collected from 1983 through 1994 during DU testing. Three exposure scenarios were evaluated for potential adverse effects to human health: an occasional use scenario and two farming scenarios. Human exposure was minimal from occasional use, but significant risk were predicted from the farming scenarios when contaminated groundwater was used by site occupants. The human health risk assessments do not consider the significant risk posed by accidents with unexploded ordnance. Exposures of white-tailed deer to DU were also estimated in this study, and exposure rates result in no significant increase in either toxicological or radiological risks. The results of this study indicate that remediation of the DU impact area would not substantially reduce already low risks to humans and the ecosystem, and that managed access to JPG is a reasonable model for future land use options.

  12. Nonthermal Effects of Radar Exposure on Human: A Review Article

    Directory of Open Access Journals (Sweden)

    vida zaroushani

    2014-01-01

    Full Text Available ABSTRACT Microwave is part of the electromagnetic spectrum that has different application such as communications, military, air-traffic Control and etc... Previous studies showed that radar frequency could be a health hazard agent. This review article mentioned some of the studies that investigated non-thermal effects of radar frequencies. Reproductive effects, cancers, blood effects, genetic, adverse immune effects and mental effects are non-thermal effects that presented in this report. There are many unknown aspects of the biological effects and many of them did not determined very well such as oxidative stress and mental effects. Compliance with permissible exposure limits, reduction in exposure, and shielding are some of the controlling methods to protect workers from the exposure of microwave and among them, The use of shielding is a superior method for prevention of microwave exposure and among them, electromagnetic Nano composites shields is appropriate for protection of workers from radar exposure.

  13. Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure

    Science.gov (United States)

    Laakso, Ilkka; Hirata, Akimasa

    2011-12-01

    Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core-temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters—some of which may be subject to considerable uncertainty—that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body-core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg-1.

  14. Model of spacecraft atomic oxygen and solar exposure microenvironments

    Science.gov (United States)

    Bourassa, R. J.; Pippin, H. G.

    1993-01-01

    Computer models of environmental conditions in Earth orbit are needed for the following reasons: (1) derivation of material performance parameters from orbital test data, (2) evaluation of spacecraft hardware designs, (3) prediction of material service life, and (4) scheduling spacecraft maintenance. To meet these needs, Boeing has developed programs for modeling atomic oxygen (AO) and solar radiation exposures. The model allows determination of AO and solar ultraviolet (UV) radiation exposures for spacecraft surfaces (1) in arbitrary orientations with respect to the direction of spacecraft motion, (2) overall ranges of solar conditions, and (3) for any mission duration. The models have been successfully applied to prediction of experiment environments on the Long Duration Exposure Facility (LDEF) and for analysis of selected hardware designs for deployment on other spacecraft. The work on these models has been reported at previous LDEF conferences. Since publication of these reports, a revision has been made to the AO calculation for LDEF, and further work has been done on the microenvironments model for solar exposure.

  15. Human exposure to per- and polyfluoroalkyl substances (PFASs) via house dust in Korea: Implication to exposure pathway.

    Science.gov (United States)

    Tian, Zhexi; Kim, Seung-Kyu; Shoeib, Mahiba; Oh, Jeong-Eun; Park, Jong-Eun

    2016-05-15

    A wide range of per- and polyfluoroalkyl substances (PFASs), including fluorotelomer alcohols (FTOHs), perfluorooctane sulfonamidoethanols (FOSEs), perfluoroalkyl carboxylic acids (PFCAs), and perfluoroalkane sulfonic acids (PFSAs), were measured in fifteen house dust and two nonresidential indoor dust of Korea. Total concentrations of PFASs in house dust ranged from 29.9 to 97.6 ng g(-1), with a dominance of perfluorooctane sulfonic acid (PFOS), followed by 8:2 FTOH, N-Ethyl perfluorooctane sulfonamidoethanol (EtFOSE), perfluoroctanoic acid (PFOA). In a typical exposure scenario, the estimated daily intakes (EDIs) of total PFASs via house dust ingestion were 2.83 ng d(-1) for toddlers and 1.13 ng d(-1) for adults, which were within the range of the mean EDIs reported from several countries. For PFOA and PFOS exposure via house dust ingestion, indirect exposure (via precursors) was a minor contributor, accounting for 5% and 12%, respectively. An aggregated exposure (hereafter, overall-EDIs) of PFOA and PFOS occurring via all pathways, estimated using data compiled from the literature, were 53.6 and 14.8 ng d(-1) for toddlers, and 20.5 and 40.6 ng d(-1) for adults, respectively, in a typical scenario. These overall-EDIs corresponded to 82% (PFOA) and 92% (PFOS) of a pharmacokinetic model-based EDIs estimated from adults' serum data. Direct dietary exposure was a major contributor (>89% of overall-EDI) to PFOS in both toddlers and adults, and PFOA in toddlers. As for PFOA exposure of adults, however direct exposure via tap water drinking (37%) and indirect exposure via inhalation (22%) were as important as direct dietary exposure (41%). House dust-ingested exposure (direct+indirect) was responsible for 5% (PFOS in toddlers) and house-dust ingestion was a minor contributor in this study, but should not be ignored for toddlers' PFOS exposure due to its significance in the worst-case scenario.

  16. Mechanistic Modeling to Predict Midazolam Metabolite Exposure from In Vitro Data.

    Science.gov (United States)

    Nguyen, Hoa Q; Kimoto, Emi; Callegari, Ernesto; Obach, R Scott

    2016-05-01

    Methods to predict the pharmacokinetics of drugs in humans from in vitro data have been established, but corresponding methods to predict exposure to circulating metabolites are unproven. The objective of this study was to use in vitro methods combined with static and dynamic physiologically based pharmacokinetic (PBPK) models to predict metabolite exposures, using midazolam and its major metabolites as a test system. Intrinsic clearances (CLint) of formation of individual metabolites were determined using human liver microsomes. Metabolic CLintof hydroxymidazolam metabolites via oxidation and glucuronidation were also determined. Passive diffusion intrinsic clearances of hydroxymidazolam metabolites were determined using sandwich cultured human hepatocytes and the combination of this term along with the metabolic CLint, and liver blood flow was used to estimate the fraction of the metabolite that can enter the systemic circulation after formation in the liver. The metabolite/parent drug area under the plasma concentration-time curve ratio (AUCm/AUCp) was predicted using a static model relating the fraction of midazolam clearance to each metabolite, the clearance rates of midazolam and hydroxymidazolam metabolites, and the availability of the metabolites. Additionally, the human disposition of midazolam metabolites was simulated using a SimCYP PBPK model. Both approaches yielded AUCm/AUCpratios that were in agreement with the in vivo ratios. This study shows that in vivo midazolam metabolite exposure can be predicted from in vitro data and PBPK modeling. This study emphasized the importance of metabolite systemic availability from its tissue of formation, which remains a challenge to quantitative prediction.

  17. FDTD assessment of human exposure to electromagnetic fields from WiFi and bluetooth devices in some operating situations.

    Science.gov (United States)

    Martínez-Búrdalo, M; Martín, A; Sanchis, A; Villar, R

    2009-02-01

    In this work, the numerical dosimetry in human exposure to the electromagnetic fields from antennas of wireless devices, such as those of wireless local area networks (WLAN) access points or phone and computer peripherals with Bluetooth antennas, is analyzed with the objective of assessing guidelines compliance. Several geometrical configurations are considered to simulate possible exposure situations of a person to the fields from WLAN or Bluetooth antennas operating at 2400 MHz. The exposure to radiation from two sources of different frequencies when using a 1800 MHz GSM mobile phone connected via Bluetooth with a hands-free car kit is also considered. The finite-difference time-domain (FDTD) method is used to calculate electric and magnetic field values in the vicinity of the antennas and specific absorption rates (SAR) in a high-resolution model of the human head and torso, to be compared with the limits from the guidelines (reference levels and basic restrictions, respectively). Results show that the exposure levels in worst-case situations studied are lower than those obtained when analyzing the exposure to mobile phones, as could be expected because of the low power of the signals and the distance between the human and the antennas, with both field and SAR values being far below the limits established by the guidelines, even when considering the combined exposure to both a GSM and a Bluetooth antenna.

  18. Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model for aldicarb and its metabolites in rats and human using exposure-related dose Estimating Model (ERDEM)%应用ERDEM模型为涕灭威及其代谢物构建大鼠和人的PBPK/PD模型研究

    Institute of Scientific and Technical Information of China (English)

    巢迎妍; 张辉; 张晓菲

    2012-01-01

    Objective To construct the PBPK/PD models for aldicarb in rats and humans to help understandits disposition in both species in order to use the models for risk assessment purposes due to aldicarb exposure. MethodsThe PBPK/PD models were constructed using the ERDEM ( Exposure-related dose estimating model ) platform. Themodel structures for both species included a full gastrointestinal compartment, liver metabolism, urinary excretion, fecalelimination,and bimolecular acetylcholinesterase ( AChE ) inhibition by aldicarb and its two oxidized metabolites, aldi-carb sulfoxide and aldicarb sulfone. Experimentally reported values or estimation of physiological, biochemical, and physicochemical parameters were obtained from the open literature or optimized by fitting to the experimental data. Results The rat model simulation of oral exposure of 0. 4 mg/kg aldicarb indicated that aldicarb had an overall half-life of 1. 35 h,and 96. 6% of the dose was excreted in urine compared to the measured 91. 6% at 144 h after oral exposure. AChE activity in blood was inhibited to 31 % of the control level at 0. 35 h in the rat model compared to the measured 42. 5% at 0. 5 h after oral exposure of 0. 33 mg/kg aldicarb. In the human model,the simulation showed that the minimum blood AChE activity was 76. 9% at 1 h compared to the measured 75. 3% after a 0. 05 mg/kg dose of aldicarb. Conclusion The ERDEM model simulations for both species were consistent with the experimental data. Therefore, the models constructed in the ERDEM platform may be helpful in evaluating human health risk due to aldicarb exposure.%目的 为构建涕灭威在大鼠和人的生理药代动力学/药效学(PBPK/PD)模型,以进一步了解涕灭威在两物种体内的转化过程,从而用于其风险评估.方法 采用暴露相关的剂量估算模型(Exposure-related dose estimating model,ERDEM)的构建平台进行模型构建.两个物种的模型结构均包括完整的胃肠道、肝脏代谢、尿排泄

  19. Current issues in human lead exposure and regulation of lead.

    Science.gov (United States)

    Davis, J M; Elias, R W; Grant, L D

    1993-01-01

    Concern about lead as a significant public health problem has increased as epidemiological and experimental evidence has mounted regarding adverse health effects at successively lower levels of lead exposure. This concern has led to downward revision of criteria for acceptable blood lead concentrations to the 10 micrograms/dL mark now designated by EPA as a target level for regulatory development and enforcement/clean-up purposes. Much progress has been made in reducing lead exposures during the past 10-15 years, with marked declines evident both in air lead and blood lead concentrations in parallel to the phase-down of lead in gasoline and notable decreases in food lead exposure due to elimination of lead soldered cans by U.S. food processors. With the lessening of exposure from these sources, the importance of other components of multimedia exposure pathways has grown and stimulated increasing regulatory attention and abatement efforts to reduce health risks associated with lead exposure from drinking water, from lead-based paint, and from household dust and soil contaminated by deteriorating paint, smelter emissions, or various other sources. Increasing attention is also being accorded to reduction of occupational lead exposures (including those related to lead abatement activities), with particular concern for protection of men and women during their reproductive years.

  20. CalTOX, a multimedia total exposure model for hazardous-waste sites; Part 1, Executive summary

    Energy Technology Data Exchange (ETDEWEB)

    McKone, T.E.

    1993-06-01

    CalTOX has been developed as a spreadsheet model to assist in health-risk assessments that address contaminated soils and the contamination of adjacent air, surface water, sediments, and ground water. The modeling effort includes a multimedia transport and transformation model, exposure scenario models, and efforts to quantify and reduce uncertainty in multimedia, multiple-pathway exposure models. This report provides an overview of the CalTOX model components, lists the objectives of the model, describes the philosophy under which the model was developed, identifies the chemical classes for which the model can be used, and describes critical sensitivities and uncertainties. The multimedia transport and transformation model is a dynamic model that can be used to assess time-varying concentrations of contaminants introduced initially to soil layers or for contaminants released continuously to air or water. This model assists the user in examining how chemical and landscape properties impact both the ultimate route and quantity of human contact. Multimedia, multiple pathway exposure models are used in the CalTOX model to estimate average daily potential doses within a human population in the vicinity of a hazardous substances release site. The exposure models encompass twenty-three exposure pathways. The exposure assessment process consists of relating contaminant concentrations in the multimedia model compartments to contaminant concentrations in the media with which a human population has contact (personal air, tap water, foods, household dusts soils, etc.). The average daily dose is the product of the exposure concentrations in these contact media and an intake or uptake factor that relates the concentrations to the distributions of potential dose within the population.

  1. Tetrabromobisphenol-A, hexabromocyclododecane and its degradation products in UK human milk: relationship to external exposure.

    Science.gov (United States)

    Abdallah, Mohamed Abou-Elwafa; Harrad, Stuart

    2011-02-01

    Tetrabromobisphenol-A (TBBP-A), hexabromocyclododecane (HBCD) and its degradation products were determined in 34 human milk samples from Birmingham, UK. TBBP-A was detected in 36% of samples (average=0.06 ng g(-1) lw), with HBCDs detected in all samples (average ΣHBCDs=5.95 ng g(-1) lw). α-HBCD comprised 62-95% ΣHBCDs while β- and γ-HBCD constituted 2-18% and 3-33% respectively. Enantioselective enrichment of (-)-α-HBCD (average enantiomer fraction=0.29) was observed indicating potential enantioselectivity associated with HBCD absorption, metabolism and/or excretion. The degradation products pentabromocyclododecenes (average=0.04 ng g(-1) lw; n=9) and tetrabromocyclododecadienes (average=0.15 ng g(-1) lw; n=25) were detected for the first time in human tissues. Average exposures of a nursing infant to ΣHBCDs and TBBP-A (35 and 1 ng kg(-1) bw day(-1) respectively) via breast milk exceeded upper-bound dietary intakes of both UK adults and toddlers. Using a simple pharmacokinetic model, intakes of UK adults via inhalation, diet and dust ingestion were converted to predicted body burdens. Predictions compared well with those observed for HBCDs but observed body burdens of TBBP-A exceeded predictions. This may indicate the human half-life of TBBP-A is greater than observed previously, that intakes may be underestimated, or that concentrations reported here reflect recent elevated episodic exposure.

  2. Probabilistic modeling of financial exposure to flood in France

    Science.gov (United States)

    Moncoulon, David; Quantin, Antoine; Leblois, Etienne

    2014-05-01

    CCR is a French reinsurance company which offers natural catastrophe covers with the State guarantee. Within this framework, CCR develops its own models to assess its financial exposure to floods, droughts, earthquakes and other perils, and thus the exposure of insurers and the French State. A probabilistic flood model has been developed in order to estimate the financial exposure of the Nat Cat insurance market to flood events, depending on their annual occurrence probability. This presentation is organized in two parts. The first part is dedicated to the development of a flood hazard and damage model (ARTEMIS). The model calibration and validation on historical events are then described. In the second part, the coupling of ARTEMIS with two generators of probabilistic events is achieved: a stochastic flow generator and a stochastic spatialized precipitation generator, adapted from the SAMPO model developed by IRSTEA. The analysis of the complementary nature of these two generators is proposed: the first one allows generating floods on the French hydrological station network; the second allows simulating surface water runoff and Small River floods, even on ungauged rivers. Thus, the simulation of thousands of non-occured, but possible events allows us to provide for the first time an estimate of the financial exposure to flooding in France at different scales (commune, department, country) and from different points of view (hazard, vulnerability and damages).

  3. Human exposure to acrolein: Time-dependence and individual variation in eye irritation.

    Science.gov (United States)

    Claeson, Anna-Sara; Lind, Nina

    2016-07-01

    The aim of the study was to examine the time dependence on sensory irritation detection following exposure to threshold levels of acrolein, in humans. The exposures occurred in an exposure chamber and the subjects were breathing fresh air through a mask that covered the nose and mouth. All participants participated in four exposure conditions, of which three consisted of a mixture of acrolein and heptane and one of only heptane. Exposure to acrolein at a concentration half of the TLV-C lead to sensory irritation. The perceived sensory irritation resulted in both increased detectability and sensory irritation after about 6.8min of exposure in 58% of the participants. The study confirm the previously suggested LOAEL of about 0.34mg/m(3) for eye irritation due to acrolein exposure. The sensory irritation was still significant 10min after exposure. These results have implications for risk assessment and limit setting in occupational hygiene.

  4. Human exposure to unconventional natural gas development: A public health demonstration of periodic high exposure to chemical mixtures in ambient air.

    Science.gov (United States)

    Brown, David R; Lewis, Celia; Weinberger, Beth I

    2015-01-01

    hydraulic fracturing stage. Over one year, compressor station emissions created 118 peak exposure levels and a gas processing plant produced 99 peak exposures over one year. The screening model identified the periods during the day and the specific weather conditions when the highest potential exposures would occur. The periodicity of occurrence of extreme exposures is similar to the episodic nature of the health complaints reported in Washington County and in the literature. This study demonstrates the need to determine the aggregate quantitative impact on health when multiple facilities are placed near residences, schools, daycare centers and other locations where people are present. It shows that understanding the influence of air stability and wind direction is essential to exposure assessment at the residential level. The model can be applied to other emissions and similar sites. Profiles such as this will assist health providers in understanding the frequency and intensity of the human exposures when diagnosing and treating patients living near unconventional natural gas development.

  5. Human anthrax outbreak associated with livestock exposure: Georgia, 2012.

    Science.gov (United States)

    Navdarashvili, A; Doker, T J; Geleishvili, M; Haberling, D L; Kharod, G A; Rush, T H; Maes, E; Zakhashvili, K; Imnadze, P; Bower, W A; Walke, H T; Shadomy, S V

    2016-01-01

    Human anthrax cases reported in the country of Georgia increased 75% from 2011 (n = 81) to 2012 (n = 142). This increase prompted a case-control investigation using 67 culture- or PCR-confirmed cases and 134 controls matched by residence and gender to investigate risk factor(s) for infection during the month before case onset. Independent predictors most strongly associated with disease in the multivariable modelling were slaughtering animals [odds ratio (OR) 7·3, 95% confidence interval (CI) 2·9-18·1, P 1 km; 15 (12%) of 125 had sick livestock; and 11 (9%) of 128 respondents reported finding dead livestock. We recommend joint public health and veterinary anthrax case investigations to identify areas of increased risk for livestock anthrax outbreaks, annual anthrax vaccination of livestock in those areas, and public awareness education.

  6. Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Megumi [Department of Biofunctional Chemistry, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530 (Japan); Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Yamamoto, Shoko [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Chen, Ying [Division of Pneumoconiosis, School of Public Health, China Medical University, 92 North 2nd, Heping District, Shenyang 110001 (China); Kumagai-Takei, Naoko [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Hayashi, Hiroaki [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Department of Dermatology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Matsuzaki, Hidenori; Lee, Suni; Hatayama, Tamayo; Miyahara, Naomi; Katoh, Minako [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Hiratsuka, Juni-ichi [Department of Radiation Oncology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Nishimura, Yasumitsu [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Otsuki, Takemi, E-mail: takemi@med.kawasaki-m.ac.jp [Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan)

    2012-07-01

    We have been investigating the immunological effects of asbestos. The establishment of a low-dose and continuously exposed human T cell line, HTLV-1 immortalized MT-2, to chrysotile (CB) revealed reduction of CXCR3 chemokine receptor and production of IFN-{gamma} that caused a decline of tumor immunity. These effects were coupled with upregulation of IL-10, TGF-{beta}, and BCL-2 in asbestos-exposed patients. To observe the immunological effects of crocidolite (CR) on human T cells, a trial to establish a low-dose and continuously exposed model was conducted and compared with a previously reported CB-exposed model (MT-2CB). Transient exposure of MT-2 original cells to CB or CR induced a similar level of apoptosis and growth inhibition. The establishment of a continuously exposed subline to CR (MT-2CR) revealed resistance against CR-induced apoptosis and upregulation of the BCL-2/BAX ratio similar to that recorded for MT-2CB. Both sublines showed reduced production of IFN-{gamma}, TNF-{alpha}, and IL-6 with increased IL-10. cDNA microarray with network/pathway analyses focusing on transcription factors revealed that many similar factors related to cell proliferation were involved following continuous exposure to asbestos in both MT-2CB and MT-2CR. These results indicate that both CB and CR fibers affect human T cells with similar degrees even though the carcinogenic activity of these substances differs due to their chemical and physical forms. Trials to identify early detection markers for asbestos exposure or the occurrence of asbestos-inducing malignancies using these findings may lead to the development of clinical tools for asbestos-related diseases and chemoprevention that modifies the reduced tumor immunity. - Highlights: Black-Right-Pointing-Pointer Comparison of effects of chrysotile and crocidolite on human T cell was done. Black-Right-Pointing-Pointer Both fibers caused apoptosis of T cells by transient exposure. Black-Right-Pointing-Pointer T cells

  7. Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans.

    Science.gov (United States)

    Lerchl, Alexander; Klose, Melanie; Grote, Karen; Wilhelm, Adalbert F X; Spathmann, Oliver; Fiedler, Thomas; Streckert, Joachim; Hansen, Volkert; Clemens, Markus

    2015-04-17

    The vast majority of in vitro and in vivo studies did not find cancerogenic effects of exposure to electromagnetic fields (RF-EMF), i.e. emitted by mobile phones and base stations. Previously published results from a pilot study with carcinogen-treated mice, however, suggested tumor-promoting effects of RF-EMF (Tillmann et al., 2010). We have performed a replication study using higher numbers of animals per group and including two additional exposure levels (0 (sham), 0.04, 0.4 and 2 W/kg SAR). We could confirm and extend the originally reported findings. Numbers of tumors of the lungs and livers in exposed animals were significantly higher than in sham-exposed controls. In addition, lymphomas were also found to be significantly elevated by exposure. A clear dose-response effect is absent. We hypothesize that these tumor-promoting effects may be caused by metabolic changes due to exposure. Since many of the tumor-promoting effects in our study were seen at low to moderate exposure levels (0.04 and 0.4 W/kg SAR), thus well below exposure limits for the users of mobile phones, further studies are warranted to investigate the underlying mechanisms. Our findings may help to understand the repeatedly reported increased incidences of brain tumors in heavy users of mobile phones.

  8. Campylobacter fetus infections in humans : exposure and disease

    NARCIS (Netherlands)

    Wagenaar, Jaap A; van Bergen, Marcel A P; Blaser, Martin J; Tauxe, Robert V; Newell, Diane G; van Putten, Jos P M

    2014-01-01

    Campylobacter fetus can cause intestinal illness and, occasionally, severe systemic infections. Infections mainly affect persons at higher risk, including elderly and immunocompromised individuals and those with occupational exposure to infected animals. Outbreaks are infrequent but have provided in

  9. Physiological responses to exposure to carbon dioxide and human bioeffluents

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2015-01-01

    different cognitive tasks and assessed their comfort and acute health symptoms. Besides, the following were determined: heart rate, blood pressure, oxygen saturation of blood, respiration rate, minute ventilation rate, nasal peak flow, forced expiratory volume, and the end-tidal CO2 pressure (ETCO2). Saliva...... with bioeffluents, the performance of Tsai-Partington test was reduced, and diastolic blood pressure and alpha-amylase increased after exposure compared with their levels before exposure, which may suggest higher arousal/stress. During exposure to CO2 without bioeffluents, the performance of Tsai-Partington test...... also was lower, which may suggest higher stress/arousal, too. However, no effects on blood pressure and alpha-amylase were seen for this exposure....

  10. Climate change impacts on human exposures to air pollution

    Science.gov (United States)

    This is an abstract for a presentations at the Annual Conference of the International Society on Exposure Science and Environmental Epidemiology. This presentation will serve as an introduction to the symposium.

  11. Flexible Bayesian Human Fecundity Models.

    Science.gov (United States)

    Kim, Sungduk; Sundaram, Rajeshwari; Buck Louis, Germaine M; Pyper, Cecilia

    2012-12-01

    Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis.

  12. The Shigella human challenge model.

    Science.gov (United States)

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  13. Efficacy of CMX001 as a Post Exposure Antiviral in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans

    Directory of Open Access Journals (Sweden)

    Scott Foster

    2011-01-01

    Full Text Available CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxypropan-1-ol to cidofovir (CDV, is being developed as a treatment for smallpox. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the efficacy of CMX001 in protecting New Zealand White rabbits from mortality following intradermal infection with rabbitpox virus as a model for smallpox, monkeypox and for treatment of adverse reactions to smallpox vaccination. Here we extend these studies by exploring different dosing regimens and performing randomized, blinded, placebo-controlled studies. In addition, because rabbitpox virus can be transmitted via naturally generated aerosols (animal to animal transmission, we report on studies to test the efficacy of CMX001 in protecting rabbits from lethal rabbitpox virus disease when infection occurs by animal to animal transmission. In all cases, CMX001 treatment was initiated at the onset of observable lesions in the ears to model the use of CMX001 as a treatment for symptomatic smallpox. The results demonstrate that CMX001 is an effective treatment for symptomatic rabbitpox virus infection. The rabbitpox model has key similarities to human smallpox including an incubation period, generalized systemic disease, the occurrence of lesions which may be used as a trigger for initiating therapy, and natural animal to animal spread, making it an appropriate model.

  14. Retention modeling of refractory ceramic fibers (RCF) in humans.

    Science.gov (United States)

    Yu, C P; Ding, Y J; Zhang, L; Oberdörster, G; Mast, R W; Maxim, L D; Utell, M J

    1997-02-01

    A mathematical retention model has been developed to predict the lung burden and size distribution of kaolin refractory ceramic fibers (RCF) in the pulmonary region of the human lung during exposure. Fiber dissolution, breakage, and differential clearance are considered in this model; rates for these processes are obtained by extrapolation from available data on laboratory rats. The lung burden predicted by this model is in general agreement with fiber counts from three factory workers. An important prediction from this study is that clearance of RCF is not significantly impaired at a fiber concentration beneath 10 f/cm3 during occupational exposure.

  15. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of ne

  16. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of

  17. Assessment of human body influence on exposure measurements of electric field in indoor enclosures.

    Science.gov (United States)

    de Miguel-Bilbao, Silvia; García, Jorge; Ramos, Victoria; Blas, Juan

    2015-02-01

    Personal exposure meters (PEMs) used for measuring exposure to electromagnetic fields (EMF) are typically used in epidemiological studies. As is well known, these measurement devices cause a perturbation of real EMF exposure levels due to the presence of the human body in the immediate proximity. This paper aims to model the alteration caused by the body shadow effect (BSE) in motion conditions and in indoor enclosures at the Wi-Fi frequency of 2.4 GHz. For this purpose, simulation techniques based on ray-tracing have been carried out, and their results have been verified experimentally. A good agreement exists between simulation and experimental results in terms of electric field (E-field) levels, and taking into account the cumulative distribution function (CDF) of the spatial distribution of amplitude. The Kolmogorov-Smirnov (KS) test provides a P-value greater than 0.05, in fact close to 1. It has been found that the influence of the presence of the human body can be characterized as an angle of shadow that depends on the dimensions of the indoor enclosure. The CDFs show that the E-field levels in indoor conditions follow a lognormal distribution in the absence of the human body and under the influence of BSE. In conclusion, the perturbation caused by BSE in PEMs readings cannot be compensated for by correction factors. Although the mean value is well adjusted, BSE causes changes in CDF that would require improvements in measurement protocols and in the design of measuring devices to subsequently avoid systematic errors.

  18. Environmental exposure to asbestos and other inorganic fibres using animal lung model

    Energy Technology Data Exchange (ETDEWEB)

    Fornero, Elisa [Dipartimento di Scienze dell' Ambiente e della Vita, Universita del Piemonte Orientale ' A. Avogadro' , Via Bellini 25/g, 15100 Alessandria (Italy); Centro Interdipartimentale per lo Studio degli Amianti e di altri Particolati Nocivi ' Giovanni Scansetti' , Universita degli Studi di Torino, Torino (Italy)], E-mail: elisa.fornero@mfn.unipmn.it; Belluso, Elena [Dipartimento di Scienze Mineralogiche e Petrologiche, Universita degli Studi di Torino, Via V. Caluso 35, 10125 Torino (Italy); Istituto di Geoscienze e Georisorse, CNR-Unita di Torino, Via V. Caluso 35, 10125 Torino (Italy); Centro Interdipartimentale per lo Studio degli Amianti e di altri Particolati Nocivi ' Giovanni Scansetti' , Universita degli Studi di Torino, Torino (Italy); Capella, Silvana [Dipartimento di Scienze Mineralogiche e Petrologiche, Universita degli Studi di Torino, Via V. Caluso 35, 10125 Torino (Italy); Centro Interdipartimentale per lo Studio degli Amianti e di altri Particolati Nocivi ' Giovanni Scansetti' , Universita degli Studi di Torino, Torino (Italy); Bellis, Donata [Servizio di Anatomia, Istologia Patologica e Citodiagnostica, Azienda Ospedaliera San Giovanni Bosco, ASLTO2 Piazza Donatori del Sangue 3, 10154 Torino (Italy); Centro Interdipartimentale per lo Studio degli Amianti e di altri Particolati Nocivi ' Giovanni Scansetti' , Universita degli Studi di Torino, Torino (Italy)

    2009-01-15

    Professional exposure to asbestos fibres is widely recognized as very dangerous to human health and for this reason many countries have banned their commercial uses. People, nevertheless, continue to be exposed to low dose of asbestos from natural and anthropogenic sources still in loco, for which the potential hazard is unknown. The aim of this research is to assess environmental exposure in an area with outcropping serpentinite rocks, which bear asbestos mineralizations, using sentinel animals which are a non-experimental animal model. We studied the burden of inorganic fibres in cattle lungs which come from two areas in Italy's Western Alps bearing serpentinitic outcrops: Susa Valley with a heavy anthropization and Lanzo Valleys, with a minor human impact. The identification and quantification of inorganic fibres were performed by Scanning Electron Microscope (SEM) and Energy Dispersive Spectrometer (EDS). In comparison to humans, studies of animals have some advantages, such as no occupational exposure or history of smoking and, in the case of cattle, a sedentary life restricted to one region. Results spotlight that over than 35% of inorganic fibres found both in Susa and Lanzo valleys, belong to asbestos mineralogical species (asbestos tremolite/actinolite, chrysotile s.s., asbestos grunerite, crocidolite). We also observed a higher concentration of artificial fibrous products in Susa samples showing a correlation with the level of anthropization. These results confirm that sentinel animals are an excellent model to assess breathable environmental background because it is possible to eliminate some variables, such as unknown occupational exposure.

  19. Potential genotoxic effects of GSM-1800 exposure on human cutaneous and nerve cells

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, S.; Poulletier De Gannes, F.; Haro, E.; Ruffie, G.; Lagroye, I.; Billaudel, B.; Veyret, B. [PIOM laboratory, UMR 5501 CNRS, ENSCPB, 33 -Pessac (France)

    2006-07-01

    Introduction The GSM-1800 signal has been in use for several years in Europe and questions raised about its potential biological effects, in view of the fact that, with respect to GSM-900, the increase in the carrier frequency corresponds to a more superficial absorption in the tissues. Consequently, the skin becomes an even more important target for the absorption of the radiofrequency radiation (R.F.R.) emitted by mobile phones. Nevertheless, brain tissues remain a critical target. Cells In order to determine whether R.F.R. at 1800 MHz could behave as a genotoxic agent, skin and brain cells were exposed to a 217-Hz-modulated GSM-1800 signal and assayed using the comet assay: (1) normal human epidermal keratinocytes (N.H.E.K.) and dermal fibroblasts (N.H.D.F.) which are cutaneous cells from epidermis and dermis respectively, and (2) the S.H. -S.Y.5.Y. and C.H.M.E.-5 human cell lines, which are neuroblastoma and micro-glial cells, respectively. Exposure The R.F.R. exposure system that was used in these experiments was manufactured by I.T. I.S. (Zurich, Switzerland). It consists in two shorted waveguides allowing to run exposed and sham conditions at the same time in the same culture incubator, at 37 Celsius degrees, 5% CO{sub 2}. It is controlled by a software, which provides blind conditions until completion of data analysis. The specific absorption rate (S.A.R.) used was 2 W/kg, corresponding to the public exposure limit recommended by I.C.N.I.R.P. and the exposure duration was 48 hours. Comet assay At the end of the exposure, cells were removed from their Petri dish by trypsin/EDTA treatment, counted and 5 x 10{sup 4} cells were used to detect DNA damage including single DNA breaks. Positive controls were performed using hydrogen peroxidase (1%, 1 hour). The genotoxic effects were detected using the alkaline comet assay kit (Trevigen slides) following the supplier procedure. Under these conditions, 6 independent experiments were performed for each cell type (2

  20. Polycyclic Aromatic Hydrocarbon (PAH Exposure and DNA Adduct Semi-Quantitation in Archived Human Tissues

    Directory of Open Access Journals (Sweden)

    M. Margaret Pratt

    2011-06-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products, considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS. These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies.

  1. Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013

    OpenAIRE

    Memish, Ziad A.; Cotten, Matthew; Meyer, Benjamin; Simon J Watson; Alsahafi, Abdullah J.; Al Rabeeah, Abdullah A.; Corman, Victor Max; Sieberg, Andrea; Makhdoom, Hatem Q.; Assiri, Abdullah; Al Masri, Malaki; Aldabbagh, Souhaib; Bosch, Berend-Jan; Beer, Martin; Müller, Marcel A.

    2014-01-01

    We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species transmission. Camels may act as a direct source of human MERS-CoV infection.

  2. Effects of subchronic exposures to concentrated ambient particles in mice. IX. Integral assessment and human health implications of subchronic exposures of mice to CAPs.

    Science.gov (United States)

    Lippmann, Morton; Gordon, Terry; Chen, Lung Chi

    2005-04-01

    In order to examine the biologic plausibility of adverse chronic cardiopulmonary effects in humans associated with ambient particulate matter (PM) exposure, we exposed groups of normal mice (C57) and knockout mice that develop atherosclerotic plaque (ApoE-/- and ApoE-/- LDLr-/-) for 6 h/day, 5 days/wk for 5 or 6 mo during the spring/summer of 2003 to either filtered air or 10-fold concentrated ambient particles (CAPs) in Tuxedo, NY (average PM2.5 concentration during exposure = 110 microg/m3). Some of the mice had implanted electrocardiographic monitors. We demonstrated that: (1) this complex interdisciplinary study was technically feasible in terms of daily exposure, collection of air quality monitoring data, the collection, analysis, and interpretation of continuous data on cardiac function, and the collection and analyses of tissues of the animals sacrificed at the end of the study; (2) the daily variations in CAPs were significantly associated, in ApoE-/- mice, with daily variations in cardiac functions; (3) there were significant differences between CAPs and sham-exposed ApoE-/- mice in terms of cardiac function after the end of exposure period, as well as small differences in atherosclerotic plaque density, coronary artery disease, and cell density in the substantia nigra in the brain in the ApoE-/- mice; (4) there are suggestive indications of gene expression changes for genes associated with the control of circadian rhythm in the ApoE-/- LDLr-/- double knockout (DK) mice. These various CAPs-related effects on cardiac function and the development of histological evidence of increased risk of clinically significant disease at the end of exposures in animal models of atherosclerosis provide biological plausibility for the premature mortality associated with PM2.5 exposure in human subjects and provide suggestive evidence for neurogenic disease as well.

  3. Human internal and external exposure to PBDEs - A review of levels and sources

    DEFF Research Database (Denmark)

    Frederiksen, Marie; Vorkamp, Katrin; Thomsen, Marianne

    2009-01-01

    ingest more dust than adults. Infants are also exposed to PBDEs via breast milk. Internal human exposure has generally been found to be one order of magnitude larger in North America than in Europe and Asia. These differences cannot solely be explained by the dietary intake as meat products are the only......This paper reviews the existing literature on human exposure to polybrominated diphenyl ethers (PBDEs), with particular focus on external exposure routes (e.g. dust, diet, and air) and the resulting internal exposure to PBDEs (e.g. breast milk and blood). Being lipophilic and persistent organic...... compounds, PBDEs accumulate in lipid-rich tissues. Consequently, food items like fish from high trophic levels or lipid-rich oils have been found to contain relatively high concentrations of PBDEs, thus presenting an important exposure pathway to humans. The presence of PBDEs in various products of everyday...

  4. Groundwater: Quality Levels and Human Exposure, SW Nigeria

    Directory of Open Access Journals (Sweden)

    Olusola Adeyemi

    2017-04-01

    Full Text Available Groundwater serves as a source of freshwater for agricultural, industrial and domestic purposes and it accounts for about 42%, 27% and 36% respectively. As it remains the only source of all-year-round supply of freshwater globally, it is of vital importance as regards water security, human survival and sustainable agriculture. The main goal of this study is to identify the main cause-effect relationship between human activities and the state of groundwater quality using a communication tool (the DPSIR Model; Drivers, Pressures, State, Impact and Response. A total of twenty-one samples were collected from ten peri-urban communities scattered across three conterminous Local Government Areas in Southwestern Nigeria. Each of the groundwater samples was tested for twelve parameters - total dissolved solids, pH, bicarbonate, chloride, lead, electrical conductivity, dissolved oxygen, nitrate, sulphate, magnesium and total suspended solids. The study revealed that the concentrations of DO and Pb were above threshold limits, while pH and N were just below the threshold and others elements were within acceptable limits based on Guidelines for Drinking Water Quality and Nigeria Standard for Drinking Water Quality. The study revealed that groundwater quality levels from the sampled wells are under pressure leading to reduction in the amount of freshwater availability. This is a first-order setback in achieving access to freshwater as a sustainable development goal across Less Developed Communities (LDCs globally. To combat this threat, there is the need for an integrated approach in response towards groundwater conservation and sustainability by all stakeholders.

  5. Overview of ozone human exposure and health risk analyses used in the U.S. EPA's review of the ozone air quality standard.

    Energy Technology Data Exchange (ETDEWEB)

    Whitfield, R. G.

    1999-03-04

    This paper presents an overview of the ozone human exposure and health risk analyses developed under sponsorship of the U.S. Environmental Protection Agency (EPA). These analyses are being used in the current review of the national ambient air quality standards (NAAQS) for ozone. The analyses consist of three principal steps: (1) estimating short-term ozone exposure for particular populations (exposure model); (2) estimating population response to exposures or concentrations (exposure-response or concentration-response models); and (3) integrating concentrations or exposure with concentration-response or exposure-response models to produce overall risk estimates (risk model). The exposure model, called the probabilistic NAAQS exposure model for ozone (pNEM/03), incorporates the following factors: hourly ambient ozone concentrations; spatial distribution of concentrations; ventilation state of individuals at time of exposure; and movement of people through various microenvironments (e.g., outdoors, indoors, inside a vehicle) of varying air quality. Exposure estimates are represented by probability distributions. Exposure-response relationships have been developed for several respiratory symptom and lung function health effects, based on the results of controlled human exposure studies. These relationships also are probabilistic and reflect uncertainties associated with sample size and variability of response among subjects. The analyses also provide estimates of excess hospital admissions in the New York City area based on results from an epidemiology study. Overall risk results for selected health endpoints and recently analyzed air quality scenarios associated with alternative 8-hour NAAQS and the current 1-hour standard for outdoor children are used to illustrate application of the methodology.

  6. 40 CFR 26.1203 - Prohibition of research involving intentional exposure of any human subject who is a pregnant...

    Science.gov (United States)

    2010-07-01

    ... intentional exposure of any human subject who is a pregnant woman (and therefore her fetus), a nursing woman... Exposure of Human Subjects who are Children or Pregnant or Nursing Women § 26.1203 Prohibition of research involving intentional exposure of any human subject who is a pregnant woman (and therefore her fetus),...

  7. A dermal model for spray painters, part I : subjective exposure modelling of spray paint deposition

    NARCIS (Netherlands)

    Brouwer, D.H.; Semple, S.; Marquart, J.; Cherrie, J.W.

    2001-01-01

    The discriminative power of existing dermal exposure models is limited. Most models only allow occupational hygienists to rank workers between and within workplaces according to broad bands of dermal exposure. No allowance is made for the work practices of different individuals. In this study a

  8. Probabilistic modeling of percutaneous absorption for risk-based exposure assessments and transdermal drug delivery.

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Clifford Kuofei

    2004-06-01

    Chemical transport through human skin can play a significant role in human exposure to toxic chemicals in the workplace, as well as to chemical/biological warfare agents in the battlefield. The viability of transdermal drug delivery also relies on chemical transport processes through the skin. Models of percutaneous absorption are needed for risk-based exposure assessments and drug-delivery analyses, but previous mechanistic models have been largely deterministic. A probabilistic, transient, three-phase model of percutaneous absorption of chemicals has been developed to assess the relative importance of uncertain parameters and processes that may be important to risk-based assessments. Penetration routes through the skin that were modeled include the following: (1) intercellular diffusion through the multiphase stratum corneum; (2) aqueous-phase diffusion through sweat ducts; and (3) oil-phase diffusion through hair follicles. Uncertainty distributions were developed for the model parameters, and a Monte Carlo analysis was performed to simulate probability distributions of mass fluxes through each of the routes. Sensitivity analyses using stepwise linear regression were also performed to identify model parameters that were most important to the simulated mass fluxes at different times. This probabilistic analysis of percutaneous absorption (PAPA) method has been developed to improve risk-based exposure assessments and transdermal drug-delivery analyses, where parameters and processes can be highly uncertain.

  9. Subtleties of human exposure and response to chemical mixtures from spills.

    Science.gov (United States)

    Phetxumphou, Katherine; Dietrich, Andrea M; Shanaiah, Narasimhamurthy; Smiley, Elizabeth; Gallagher, Daniel L

    2016-07-01

    Worldwide, chemical spills degrade drinking water quality and threaten human health through ingestion and inhalation. Spills are often mixtures of chemicals; thus, understanding the interaction of chemical and biological properties of the major and minor components is critical to assessing human exposure. The crude (4-methylcyclohexyl)methanol (MCHM) spill provides an opportunity to assess such subtleties. This research determined the relative amounts, volatilization, and biological odor properties of minor components cis- and trans-methyl-4-methylcyclohexanecarboxylate (MMCHC) isomers and major components cis- and trans-4-MCHM, then compared properties and human exposure differences among them. (1)H nuclear magnetic resonance and chromatography revealed that the minor MMCHC isomers were about 1% of the major MCHM isomers. At typical showering temperature of 40 °C, Henry's law constants were 1.50 × 10(-2) and 2.23 × 10(-2) for cis- and trans-MMCHC, respectively, which is 20-50 fold higher than for 4-MCHM isomers. The odor thresholds were 1.83 and 0.02 ppb-v air for cis- and trans-MMCHC, which were both described as predominantly sweet. These data are compared to the higher 120 ppb-v air and 0.06 ppb-v odor thresholds for cis- and trans-4-MCHM, for which the trans-isomer had a dominant licorice descriptor. Application of a shower model demonstrated that while MMCHC isomers are only about 1% of the MCHM isomers, during showering, the MMCHC isomers are 13.8% by volume (16.3% by mass) because of their higher volatility. Trans-4-MCHM contributed about 82% of the odor because of higher volatility and lower odor threshold, trans-MMCHC, which represents 0.3% of the mass, contributed 18% of the odor. This study, with its unique human sensory component to assess exposure, reaffirmed that hazard assessment must not be based solely on relative concentration, but also consider the chemical fate, transport, and biological properties to determine the actual levels of

  10. Evaluating biomarkers to model cancer risk post cosmic ray exposure.

    Science.gov (United States)

    Sridharan, Deepa M; Asaithamby, Aroumougame; Blattnig, Steve R; Costes, Sylvain V; Doetsch, Paul W; Dynan, William S; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D; Peterson, Leif E; Plante, Ianik; Ponomarev, Artem L; Saha, Janapriya; Snijders, Antoine M; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M

    2016-06-01

    Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing

  11. Evaluating biomarkers to model cancer risk post cosmic ray exposure

    Science.gov (United States)

    Sridharan, Deepa M.; Asaithamby, Aroumougame; Blattnig, Steve R.; Costes, Sylvain V.; Doetsch, Paul W.; Dynan, William S.; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D.; Peterson, Leif E.; Plante, Ianik; Ponomarev, Artem L.; Saha, Janapriya; Snijders, Antoine M.; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M.

    2016-06-01

    Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing

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

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Jacobsen, Ulrik Plesner; Kalhauge, Christian Gram

    2013-01-01

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

  13. Developing a Salivary Antibody Multiplex Immunoassay to Measure Human Exposure to Environmental Pathogens

    Science.gov (United States)

    The etiology and impacts of human exposure to environmental pathogens are of major concern worldwide and, thus, the ability to assess exposure and infections using cost effective, high-throughput approaches would be indispensable. The principal objective of this work is to devel...

  14. Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis.

    Science.gov (United States)

    Williams, Amy Lavin; Watson, Rebecca E; DeSesso, John M

    2012-01-01

    Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.

  15. Modeling Burns for Pre-Cooled Skin Flame Exposure

    Directory of Open Access Journals (Sweden)

    Torgrim Log

    2017-09-01

    Full Text Available On a television show, a pre-cooled bare-skinned person (TV host passed through engulfing kerosene flames. The assumption was that a water film should protect him during 0.74 s flame exposure in an environment of 86 kW/m2 heat flux. The TV host got light burn inflammation on the back, arms and legs. The present work studies skin temperatures and burn damage integral of such dangerous flame exposure. The skin temperature distribution during water spray pre-cooling, transport to the flames, flame exposure, transport to the water pool, and final water pool cooling is modelled numerically. Details of the temperature development of the skin layers are presented, as well as the associated damage integral. It is shown that 5 °C water spray applied for a 30 s period pre-cooled the skin sufficiently to prevent severe skin injury. Soot marks indicate that the water layer evaporated completely in some areas resulting in skin flame contact. This exposed dry skin directly to the flames contributing significantly to the damage integral. It is further analyzed how higher water temperature, shorter pre-cooling period or longer flame exposure influence the damage integral. It is evident that minor changes in conditions could lead to severe burns and that high heat flux levels at the end of the exposure period are especially dangerous. This flame stunt should never be repeated.

  16. Exposure to perfluorinated compounds and human semen quality in arctic and European populations

    DEFF Research Database (Denmark)

    Toft, Gunnar; Jönsson, B A G; Lindh, C H

    2012-01-01

    Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality....

  17. In vivo plasma concentration for lindane after 6 hour exposure in human skin

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dataset is a time course description of lindane disappearance in blood plasma after dermal exposure in human volunteers. This dataset is associated with the...

  18. A SIMPLE COLORIMETRIC METHOD TO DETECT BIOLOGICAL EVIDENCE OF HUMAN EXPOSURE TO MICROCYSTINS

    Science.gov (United States)

    Toxic cyanobacteria are contaminants of surface waters worldwide. Microcystins are some of the most commonly detected toxins. Biological evidence of human exposure may be difficult to obtain due to limitations associated with cost, laboratory capacity, analytic support, and exp...

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

    Science.gov (United States)

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

  20. Application of pharmacokinetic modelling for 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure assessment.

    Science.gov (United States)

    Ruiz, P; Aylward, L L; Mumtaz, M

    2014-01-01

    Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (dioxin-like PCBs) are identified as a family or group of organic compounds known as 'dioxins' or dioxin-like chemicals (DLCs). The most toxic member of this group is 2,3,7,8-tetrachlorodibenzo-(p)-dioxin (TCDD). Historically, DLCs have caused a variety of negative human health effects, but a disfiguring skin condition known as chloracne is the only health effect reported consistently. As part of translational research to make computerized models accessible to health risk assessors, the Concentration- and Age-Dependent Model (CADM) for TCDD was recoded in the Berkeley Madonna simulation language. The US Agency for Toxic Substances and Disease Registry's computational toxicology laboratory used the recoded model to predict TCDD tissue concentrations at different exposure levels. The model simulations successfully reproduced the National Health and Nutrition Examination Survey (NHANES) 2001-2002 TCDD data in age groups from 6 to 60 years and older, as well as in other human datasets. The model also enabled the estimation of lipid-normalized serum TCDD concentrations in breastfed infants. The model performed best for low background exposures over time compared with a high acute poisoning case that could due to the large dose and associated liver toxicity. Hence, this model may be useful for interpreting human biomonitoring data as a part of an overall DLC risk assessment.

  1. The human placenta--an alternative for studying foetal exposure

    DEFF Research Database (Denmark)

    Myren, Maja; Mose, Tina; Mathiesen, Line;

    2007-01-01

    , and though its main task is to act as a barrier and transport nutrients and oxygen to the foetus, many foreign compounds are transported across the placenta to some degree and may therefore influence the unborn child. Foetal exposures to environmental and medicinal products may have impact on the growth...

  2. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth

    Directory of Open Access Journals (Sweden)

    Emily F. Winterbottom

    2015-06-01

    Full Text Available Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

  3. 18. Adduct detection in human monitoring for carcinogen exposure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Determination of the covalently bound products (adducts) of carcinogens with DNA or proteins may be used for the monitoring of exposure to these compounds. Protein adducts are generally stable and are not enzymatically repaired, and the use of these for cxposure monitoring is normally carried out with globin or albumin, because

  4. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth.

    Science.gov (United States)

    Winterbottom, Emily F; Fei, Dennis L; Koestler, Devin C; Giambelli, Camilla; Wika, Eric; Capobianco, Anthony J; Lee, Ethan; Marsit, Carmen J; Karagas, Margaret R; Robbins, David J

    2015-06-01

    Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

  5. Changes in human pluripotent stem cell gene expression after genotoxic stress exposures

    Science.gov (United States)

    Sokolov, Mykyta V; Neumann, Ronald D

    2014-01-01

    Human pluripotent stem cells (hPSCs) represent heterogeneous populations, including induced pluripotent stem cells (iPSCs), endogenous plastic somatic cells, and embryonic stem cells (ESCs). Human ESCs are derived from the inner cell mass of the blastocyst, and they are characterized by the abilities to self-renew indefinitely, and to give rise to all cell types of embryonic lineage (pluripotency) under the guidance of the appropriate chemical, mechanical and environmental cues. The combination of these critical features is unique to hESCs, and set them apart from other human cells. The expectations are high to utilize hESCs for treating injuries and degenerative diseases; for modeling of complex illnesses and development; for screening and testing of pharmacological products; and for examining toxicity, mutagenicity, teratogenicity, and potential carcinogenic effects of a variety of environmental factors, including ionizing radiation (IR). Exposures to genotoxic stresses, such as background IR, are unavoidable; moreover, IR is widely used in diagnostic and therapeutic procedures in medicine on a routine basis. One of the key outcomes of cell exposures to IR is the change in gene expression, which may underlie the ultimate hESCs fate after such a stress. However, gaps in our knowledge about basic biology of hESCs impose a serious limitation to fully realize the potential of hESCs in practice. The purpose of this review is to examine the available evidence of alterations in gene expression in human pluripotent stem cells after genotoxic stress, and to discuss strategies for future research in this important area. PMID:25426256

  6. Changes in human pluripotent stem cell gene expression after genotoxic stress exposures

    Institute of Scientific and Technical Information of China (English)

    Mykyta; V; Sokolov; Ronald; D; Neumann

    2014-01-01

    Human pluripotent stem cells(h PSCs) represent heterogeneous populations, including induced pluripotent stem cells(i PSCs), endogenous plastic somatic cells, and embryonic stem cells(ESCs). Human ESCs are derived from the inner cell mass of the blastocyst, and they are characterized by the abilities to self-renew indefinitely, and to give rise to all cell types of embryonic lineage(pluripotency) under the guidance of the appropriate chemical, mechanical and environmental cues. The combination of these critical features is unique to h ESCs, and set them apart from other human cells. The expectations are high to utilize h ESCs for treating injuries and degenerative diseases; for modeling of complex illnesses and development; for screening and testing of pharmacological products; and for examining toxicity, mutagenicity, teratogenicity, and potential carcinogenic effects of a variety of environmental factors, including ionizing radiation(IR). Exposures to genotoxic stresses, such as background IR, are unavoidable; moreover, IR is widely used in diagnostic and therapeutic procedures in medicine on a routine basis. One of the key outcomes of cell exposures to IR is the change in gene expression, which may underlie the ultimate h ESCs fate after such a stress. However, gaps in our knowledge about basic biology of h ESCs impose a serious limitation to fully realize the potential of h ESCs in practice. The purpose of this review is to examine the available evidence of alterations in gene expression in human pluripotent stem cells after genotoxic stress, and to discuss strategies for future research in this important area.

  7. Inhalation Exposure Input Parameters for the Biosphere Model

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2006-06-05

    This analysis is one of the technical reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), referred to in this report as the biosphere model. ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. ''Inhalation Exposure Input Parameters for the Biosphere Model'' is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the biosphere model is presented in Figure 1-1 (based on BSC 2006 [DIRS 176938]). This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and how this analysis report contributes to biosphere modeling. This analysis report defines and justifies values of atmospheric mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of the biosphere model to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception. This

  8. Modeling of Human Joint Structures.

    Science.gov (United States)

    1982-09-01

    Radial Lateral " epicondyle Olecranon Radius Ulna Figure 3. Lateral aspect of the right elbow joint. -17- Annular Ligament This strong band encircles... elbow joint, knee joint, human joints, shoulder joint, ankle joint, joint models, hip joint, ligaments. 20. ABSTRACT (Continue on reverse side If...ligaments. -A rather extended discussion of the articulations and anatomical descriptions of the elbow , shoulder, hip, knee and ankle joints are

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

    Science.gov (United States)

    Song, Qingbin; Li, Jinhui

    2014-07-01

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

  10. Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

    Directory of Open Access Journals (Sweden)

    Annamaria Morelli

    2013-01-01

    Full Text Available Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins, along with glucose transporters (GLUT1, GLUT3, and GLUT4. High glucose exposure (22 mM; 40 mM significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM. Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.

  11. Modelling of aircrew radiation exposure during solar particle events

    Energy Technology Data Exchange (ETDEWEB)

    Al Anid, H.; Lewis, B.J.; Bennett, L.G.I. [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada); Takada, M. [National Inst. of Radiological Science, International Space Radiation Lab., anagawa, Inage-Ku, Chiba (Japan)

    2010-07-01

    A transport code analysis using the Monte Carlo N-Particle eXtended code, MCNPX, has been used to propagate an extrapolated particle spectrum based on satellite measurements through the atmosphere to estimate radiation exposure during solar storms at high altitudes. Neutron monitor count rate data from stations around the world were used to benchmark the model calculations during a Ground Level Event. A comparison was made between the model predictions and actual flight measurements taken with various types of instruments used to measure the mixed radiation field during GLE 60. A computer-code has been developed to implement the model for routine analysis. (author)

  12. Modelling of aircrew radiation exposure during solar particle events

    Energy Technology Data Exchange (ETDEWEB)

    Al Anid, H.; Lewis, B.J.; Bennett, L.G.I. [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada); Takada, M. [National Inst. of Radiological Science, International Space Radiation Lab., Anagawa, Inage-Ku, Chiba (Japan)

    2011-03-15

    A transport code analysis using the Monte Carlo N-Particle eXtended code, MCNPX, has been used to propagate an extrapolated particle spectrum based on satellite measurements through the atmosphere to estimate radiation exposure during solar storms at high altitudes. Neutron monitor count rate data from stations around the world were used to benchmark the model calculations during a Ground Level Event. A comparison was made between the model predictions and actual flight measurements taken with various types of instruments used to measure the mixed radiation field during GLE 60. A computer-code has been developed to implement the model for routine analysis. (author)

  13. Modelling of aircrew radiation exposure from solar particle events

    Energy Technology Data Exchange (ETDEWEB)

    Al Anid, H.; Lewis, B.J.; Bennett, L.G.I. [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2008-07-01

    A transport code analysis using the Monte Carlo code, MCNPX, has been used to propagate an extrapolated particle spectrum based on GOES satellite measurements through the atmosphere to estimate aircrew radiation exposure due to solar particle events. Neutron monitor count rate data from ground stations around the world were used to benchmark the model calculations during several Ground Level Events (GLEs). In addition, a comparison was made between the model predictions and actual flight measurements made by some European investigators with various types of instrument used to measure the mixed radiation field during GLE 60 and 65. A computer-code has been further developed to implement the model for routine analysis. (author)

  14. Human brain derived cells respond in a type-specific manner after exposure to urban particulate matter (PM).

    Science.gov (United States)

    Campbell, Arezoo; Daher, Nancy; Solaimani, Parrisa; Mendoza, Kriscelle; Sioutas, Constantinos

    2014-10-01

    Exposure to particulate matter (PM), a component of urban air pollution, may cause adverse effects in the brain. Although the exact mechanisms involved are unknown, both oxidative and inflammatory responses have been reported. Since the main route of exposure to particulate matter is through inhalation, there is a potential for compounds to directly enter the brain and alter normal cellular function. Enhancement in both oxidative stress and neuroinflammatory markers has been observed in neurodegenerative disorders and PM-induced potentiation of these events may accelerate the disease process. The objective of this pilot study was to use normal human brain cells, a model system which has not been previously used, to assess cell-type-specific responses after exposure to ultrafine particles (UFP). Human microglia, neurons, and astrocytes were grown separately or as co-cultures and then exposed to aqueous UFP suspensions. Reactive Oxygen Species (ROS) formation and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) were measured as markers of oxidative stress or inflammation respectively. Our results revealed that after exposure to 2 μg/ml of particles, normal human neurons exhibit a decrease in ROS formation and an increase in TNF-α. The observed decrease in ROS formation persisted in the presence of glial cells, which contrasts previous studies done in rodent cells reporting that PM-induced microglial activation modulates neuronal responses. Our study indicates that human CNS cells may respond differently compared to rodent cells and that their use may be more predictive in risk assessment.

  15. Induction of apoptosis in human myeloid leukemia cells by remote exposure of resistive barrier cold plasma.

    Science.gov (United States)

    Thiyagarajan, Magesh; Anderson, Heather; Gonzales, Xavier F

    2014-03-01

    Cold atmospheric plasma (CAP), an ambient temperature ionized gas, is gaining extensive interest as a promising addition to anti-tumor therapy primarily due to the ability to generate and control delivery of electrons, ions, excited molecules, UV photons, and reactive species such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) to a specific site. The heterogeneous composition of CAP offers the opportunity to mediate several signaling pathways that regulate tumor cells. Consequently, the array of CAP generated products has limited the identification of the mechanisms of action on tumor cells. The aim of this work is to assess the cell death response of human myeloid leukemia cells by remote exposure to CAP generated RNS by utilizing a novel resistive barrier discharge system that primarily produces RNS. The effect of variable treatments of CAP generated RNS was tested in THP-1 cell (human monocytic leukemia cell line), a model for hematological malignancy. The number of viable cells was evaluated with erythrosine-B staining, while apoptosis and necrosis was assessed by endonuclease cleavage observed by agarose gel electrophoresis and detection of cells with the exclusionary dye propidium iodide and fluorescently labeled annexin-V by flow cytometry and fluorescent microscopy. Our observations indicate that treatment dosage levels of 45 s of exposure to CAP emitted RNS-induced apoptotic cell death and for higher dosage conditions of ≥50 s of exposure to CAP induced necrosis. Overall the results suggest that CAP emitted RNS play a significant role in the anti-tumor potential of CAP.

  16. Personal exposure to particulate PAHs and anthraquinone and oxidative DNA damages in humans.

    Science.gov (United States)

    Wei, Yongjie; Han, In-Kyu; Hu, Min; Shao, Min; Zhang, Junfeng Jim; Tang, Xiaoyan

    2010-11-01

    Recent studies suggest that DNA oxidative damage be related to the chemical constituents of ambient particles. The purpose of this study was to examine whether particulate polycyclic aromatic hydrocarbons (PAHs) and quinone-structure chemicals increase body burden of oxidative stress in human exposed to heavy traffic volume. We recruited two nonsmoking security guards who worked at a university campus gate near a heavily trafficked road. Each subject wore a personal air sampler for 24h per day to estimate exposures to 24 PAHs and anthraquinone (AnQ) in PM(2.5). Daily pre- and post-work shift spot urines were collected for 29d from each subject. Urine samples were analyzed for 8-hydroxy-2'-deoxyguanosine (8-OHdG). Additionally, using 19 organic tracers other than 24 PAHs and AnQ, a receptor source apportionment model of chemical mass balance was applied to determine the contributions of sources on the PM: gasoline vehicle, diesel vehicle, coal burning, vegetable debris, cooking, natural gas and biomass burning. The relationship among urinary 8-OHdG, individual PAH, and AnQ was demonstrated as follows: the average urinary concentration of 8-OHdG was increased more than three times after 8-h work-shift than those before the work shift. All the 24 PAH and AnQ levels were positively and significantly associated with the post-work urinary 8-OHdG. The results from source apportionment suggest vehicular emission to be the dominant source of personal exposure to PM(2.5). Our finding indicates that personal air exposures to 24 individual PAHs and AnQ originating from traffic emissions are important in increasing oxidative burdens in human body.

  17. Additional human exposure information for gasoline substance risk assessment (period 2002-2007)

    Energy Technology Data Exchange (ETDEWEB)

    Bomer, R.; Carter, M.; Dmytrasz, B.; Mulari, M.; Pizzella, G.; Roth, S.; Van de Sandt, P.

    2009-06-15

    This report provides an update on human exposure information for gasoline-related activities for which previous assessments had suggested that exposure was either elevated or highly variable or available data were considered out-of-date. In addition data are presented for several activities for which no information had been available previously. The occupational exposures activities described in this report include railcar loading, refinery maintenance, laboratory operations, aviation gasoline refuelling, gasoline pump maintenance and repair, gasoline pump calibration, and the operation of gasoline-powered gardening equipment. In addition, general public exposure levels are described, particularly relating to residency near service stations.

  18. Mobile phone model with metamaterials to reduce the exposure

    Science.gov (United States)

    Pinto, Yenny; Begaud, Xavier

    2016-04-01

    This work presents a terminal mobile model where an Inverted-F Antenna (IFA) is associated with three different kinds of metamaterials: artificial magnetic conductor (AMC), electromagnetic band gap (EBG) and resistive high-impedance surface (RHIS). The objective was to evaluate whether some metamaterials may be used to reduce exposure while preserving the antenna performances. The exposure has been evaluated using a simplified phantom model. Two configurations, antenna in front of the phantom and antenna hidden by the ground plane, have been evaluated. Results show that using an optimized RHIS, the SAR 10 g is reduced and the antenna performances are preserved. With RHIS solution, the SAR 10 g peak is reduced by 8 % when the antenna is located in front of the phantom and by 6 % when the antenna is hidden by ground plane.

  19. In vitro and in vivo models of acute alcohol exposure

    Institute of Scientific and Technical Information of China (English)

    Angela Dolganiuc; Gyongyi Szabo

    2009-01-01

    Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse,and identifies their suitability for biomedical research.

  20. Assessment of human exposure to fumonisin B1

    NARCIS (Netherlands)

    Nijs, M. de; Egmond, H.P. van; Nauta, M.; Rombouts, F.M.; Notermans, S.H.W.

    1998-01-01

    Fumonisin B1 is currently regarded as the most significant mycotoxin produced by Fusarium spp. It has carcinogenic properties and may play a role in the etiology of human esophageal cancer. The human population is exposed to fumonisin B1 primarily by intake of fumonisin B1-contaminated maize. Maize

  1. Human Exposure to Herpesvirus B–Seropositive Macaques, Bali, Indonesia

    Science.gov (United States)

    Engel, Gregory A.; Schillaci, Michael A.; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-01-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a “monkey forest” (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B. PMID:12141963

  2. Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

    Science.gov (United States)

    Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-08-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

  3. Critical elements for human health risk assessment of less than lifetime exposures.

    Science.gov (United States)

    Geraets, Liesbeth; Nijkamp, Monique M; Ter Burg, Wouter

    2016-11-01

    Less than lifetime exposure has confronted risk assessors as to how to interpret the risks for human health in case a chronic health-based limit is exceeded. Intermittent, fluctuating and peak exposures do not match with the basis of the chronic limit values possibly leading to conservative outcomes. This paper presents guidance on how to deal with human risk assessment of less than lifetime exposure. Important steps to be considered are characterization of the human exposure situation, evaluation whether the human less than lifetime exposure scenario corresponds to a non-chronic internal exposure: toxicokinetic and toxicodynamic considerations, and, finally, re-evaluation of the risk assessment. Critical elements for these steps are the mode of action, Haber's rule, and toxicokinetics (ADME) amongst others. Previous work for the endpoints non-genotoxic carcinogenicity and developmental toxicity is included in the guidance. The guidance provides a way to consider the critical elements, without setting default factors to correct for the less than lifetime exposure in risk assessment.

  4. Mercury in human brain, blood, muscle and toenails in relation to exposure: an autopsy study

    Directory of Open Access Journals (Sweden)

    Morild Inge

    2007-10-01

    Full Text Available Abstract Background The main forms of mercury (Hg exposure in the general population are methylmercury (MeHg from seafood, inorganic mercury (I-Hg from food, and mercury vapor (Hg0 from dental amalgam restorations. While the distribution of MeHg in the body is described by a one compartment model, the distribution of I-Hg after exposure to elemental mercury is more complex, and there is no biomarker for I-Hg in the brain. The aim of this study was to elucidate the relationships between on the one hand MeHg and I-Hg in human brain and other tissues, including blood, and on the other Hg exposure via dental amalgam in a fish-eating population. In addition, the use of blood and toenails as biological indicator media for inorganic and organic mercury (MeHg in the tissues was evaluated. Methods Samples of blood, brain (occipital lobe cortex, pituitary, thyroid, abdominal muscle and toenails were collected at autopsy of 30 deceased individuals, age from 47 to 91 years of age. Concentrations of total-Hg and I-Hg in blood and brain cortex were determined by cold vapor atomic fluorescence spectrometry and total-Hg in other tissues by sector field inductively coupled plasma-mass spectrometry (ICP-SFMS. Results The median concentrations of MeHg (total-Hg minus I-Hg and I-Hg in blood were 2.2 and 1.0 μg/L, and in occipital lobe cortex 4 and 5 μg/kg, respectively. There was a significant correlation between MeHg in blood and occipital cortex. Also, total-Hg in toenails correlated with MeHg in both blood and occipital lobe. I-Hg in both blood and occipital cortex, as well as total-Hg in pituitary and thyroid were strongly associated with the number of dental amalgam surfaces at the time of death. Conclusion In a fish-eating population, intake of MeHg via the diet has a marked impact on the MeHg concentration in the brain, while exposure to dental amalgam restorations increases the I-Hg concentrations in the brain. Discrimination between mercury species is

  5. Lead Exposure Induces Telomere Instability in Human Cells.

    Directory of Open Access Journals (Sweden)

    Géraldine Pottier

    Full Text Available Lead (Pb is an important environmental contaminant due to its widespread use over many centuries. While it affects primarily every organ system of the body, the most pernicious effects of Pb are on the central nervous system leading to cognitive and behavioral modification. Despite decades of research, the mechanisms responsible for Pb toxicity remain poorly understood. Recent work has suggested that Pb exposure may have consequences on chromosomal integrity as it was shown that Pb exposure leads to the generation of γH2Ax foci, a well-established biomarker for DNA double stranded break (DSB formation. As the chromosomal localization of γH2Ax foci plays an important role in determining the molecular mechanism responsible for their formation, we examined the localization of Pb-induced foci with respect to telomeres. Indeed, short or dysfunctional telomeres (uncapped or damaged telomeres may be recognized as DSB by the DNA repair machinery, leading to "telomere-Induced Foci" (TIFs. In the current study, we show that while Pb exposure did not increase intra-chromosomal foci, it significantly induced TIFs, leading in some cases, to chromosomal abnormalities including telomere loss. The evidence suggests that these chromosomal abnormalities are likely due to perturbation of telomere replication, in particular on the lagging DNA strand. We propose a mechanism by which Pb exposure leads to the loss of telomere maintenance. As numerous studies have demonstrated a role for telomere maintenance in brain development and tissue homeostasis, our results suggest a possible mechanism for lead-induced neurotoxicity.

  6. Novel Human Radiation Exposure Biomarker Panel Applicable for Population Triage

    Energy Technology Data Exchange (ETDEWEB)

    Bazan, Jose G. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Chang, Polly; Balog, Robert; D' Andrea, Annalisa; Shaler, Thomas; Lin, Hua; Lee, Shirley; Harrison, Travis [SRI International, Menlo Park, California (United States); Shura, Lei; Schoen, Lucy; Knox, Susan J. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Cooper, David E., E-mail: david.cooper@sri.com [SRI International, Menlo Park, California (United States)

    2014-11-01

    Purpose: To identify a panel of radiation-responsive plasma proteins that could be used in a point-of-care biologic dosimeter to detect clinically significant levels of ionizing radiation exposure. Methods and Materials: Patients undergoing preparation for hematopoietic cell transplantation using radiation therapy (RT) with either total lymphoid irradiation or fractionated total body irradiation were eligible. Plasma was examined from patients with potentially confounding conditions and from normal individuals. Each plasma sample was analyzed for a panel of 17 proteins before RT was begun and at several time points after RT exposure. Paired and unpaired t tests between the dose and control groups were performed. Conditional inference trees were constructed based on panels of proteins to compare the non-RT group with the RT group. Results: A total of 151 patients (62 RT, 41 infection, 48 trauma) were enrolled on the study, and the plasma from an additional 24 healthy control individuals was analyzed. In comparison with to control individuals, tenascin-C was upregulated and clusterin was downregulated in patients receiving RT. Salivary amylase was strongly radiation responsive, with upregulation in total body irradiation patients and slight downregulation in total lymphoid irradiation patients compared with control individuals. A panel consisting of these 3 proteins accurately distinguished between irradiated patients and healthy control individuals within 3 days after exposure: 97% accuracy, 0.5% false negative rate, 2% false positive rate. The accuracy was diminished when patients with trauma, infection, or both were included (accuracy, 74%-84%; false positive rate, 14%-33%, false negative rate: 8%-40%). Conclusions: A panel of 3 proteins accurately distinguishes unirradiated healthy donors from those exposed to RT (0.8-9.6 Gy) within 3 days of exposure. These findings have significant implications in terms of triaging individuals in the case of nuclear or other

  7. Modelling of aircrew radiation exposure during solar particle events

    Science.gov (United States)

    Al Anid, Hani Khaled

    show a very different response during anisotropic events, leading to variations in aircrew radiation doses that may be significant for dose assessment. To estimate the additional exposure due to solar flares, a model was developed using a Monte-Carlo radiation transport code, MCNPX. The model transports an extrapolated particle spectrum based on satellite measurements through the atmosphere using the MCNPX analysis. This code produces the estimated flux at a specific altitude where radiation dose conversion coefficients are applied to convert the particle flux into effective and ambient dose-equivalent rates. A cut-off rigidity model accounts for the shielding effects of the Earth's magnetic field. Comparisons were made between the model predictions and actual flight measurements taken with various types of instruments used to measure the mixed radiation field during Ground Level Enhancements 60 and 65. An anisotropy analysis that uses neutron monitor responses and the pitch angle distribution of energetic solar particles was used to identify particle anisotropy for a solar event in December 2006. In anticipation of future commercial use, a computer code has been developed to implement the radiation dose assessment model for routine analysis. Keywords: Radiation Dosimetry, Radiation Protection, Space Physics.

  8. Electromagnetic absorption in a multilayered slab model of tissue under near-field exposure conditions

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, I.; Hagmann, M.J.; Gandhi, O.P.

    1980-01-01

    The electromagnetic energy deposited in a semi-infinite slab model consisting of skin, fat, and muscle layers is calculated for both plane-wave and near-field exposures. The plane-wave spectrum (PWS) approach is used to calculate the energy deposited in the model by fields present due to leakage from equipment using electromagnetic energy. This analysis applies to near-field exposures where coupling of the target to the leakage source can be neglected. Calculations were made for 2,450 MHz, at which frequency the layered slab adequately models flat regions of the human body. Resonant absorption due to layering is examined as a function of the skin and fat thicknesses for plane-wave exposure and as a function of the physical extent of the near-field distribution. Calculations show that for fields that are nearly constant over at least a free-space wavelength, the energy deposition (for skin, fat, and muscle combination that gives resonant absorption) is equal to or less than that resulting from plane-wave exposure, but is appreciably greater than that obtained for a homogeneous muscle slab model.

  9. Multi-pathway exposure modelling of chemicals in cosmetics ...

    Science.gov (United States)

    We present a novel multi-pathway, mass balance based, fate and exposure model compatible with life cycle and high-throughput screening assessments of chemicals in cosmetic products. The exposures through product use as well as post-use emissions and environmental media were quantified based on the chemical mass originally applied via a product, multiplied by the product intake fractions (PiF, the fraction of a chemical in a product that is taken in by exposed persons) to yield intake rates. The average PiFs for the evaluated chemicals in shampoo ranged from 3 × 10− 4 up to 0.3 for rapidly absorbed ingredients. Average intake rates ranged between nano- and micrograms per kilogram bodyweight per day; the order of chemical prioritization was strongly affected by the ingredient concentration in shampoo. Dermal intake and inhalation (for 20% of the evaluated chemicals) during use dominated exposure, while the skin permeation coefficient dominated the estimated uncertainties. The fraction of chemical taken in by a shampoo user often exceeded, by orders of magnitude, the aggregated fraction taken in by the population through post-use environmental emissions. Chemicals with relatively high octanol-water partitioning and/or volatility, and low molecular weight tended to have higher use stage exposure. Chemicals with low intakes during use (< 1%) and subsequent high post-use emissions, however, may yield comparable intake for a member of the general population. The pre

  10. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    Science.gov (United States)

    Bue, Grant; Makinen, Janice; Cognata, Thomas

    2012-01-01

    Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

  11. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B₁ exposure in rats and humans.

    Science.gov (United States)

    Robinson, A; Johnson, N M; Strey, A; Taylor, J F; Marroquin-Cardona, A; Mitchell, N J; Afriyie-Gyawu, E; Ankrah, N A; Williams, J H; Wang, J S; Jolly, P E; Nachman, R J; Phillips, T D

    2012-01-01

    Fumonisin B₁ (FB₁) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF's carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB₁ (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB₁ in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either FB₁ control, FB₁ + 2% NS or absolute control group. FB₁ alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3 g day⁻¹) or placebo (1.5 g day⁻¹) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB₁ biomarker by 20% in 24 h and 50% after 48 h compared to controls. In the humans, 56% of the urine samples analysed (n = 186) had detectable levels of FB₁. Median urinary FB₁ levels were significantly (p 90% in the high dose NS group (3 g day⁻¹) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB₁ (in addition to AFs) from the diet. Moreover, earlier studies have shown conclusively that NS reduces the bioavailability of AF and the findings from this study suggest that NS clay also reduces the bioavailability FB₁. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB₁ is suspected to be a dietary risk factor for HCC and oesophageal cancer in humans.

  12. Insulin and GH Signaling in Human Skeletal Muscle In Vivo following Exogenous GH Exposure: Impact of an Oral Glucose Load

    OpenAIRE

    Thomas Krusenstjerna-Hafstrøm; Michael Madsen; Vendelbo, Mikkel H.; Pedersen, Steen B.; Christiansen, Jens S.; Niels Møller; Niels Jessen; Jørgensen, Jens O.L.

    2011-01-01

    INTRODUCTION: GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load. METHODS: Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1) after an int...

  13. Modeling Forces on the Human Body.

    Science.gov (United States)

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-01-01

    Presents five models of the human body as a mechanical system which can be used in introductory physics courses: human arms as levers, humans falling from small heights, a model of the human back, collisions during football, and the rotating gymnast. Gives ideas for discussions and activities, including Interactive Physics (TM) simulations. (WRM)

  14. Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

    Science.gov (United States)

    1979-01-01

    parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

  15. Human Infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013

    NARCIS (Netherlands)

    Memish, Ziad A.; Cotten, Matthew; Meyer, Benjamin; Watson, Simon J.; Alsahafi, Abdullah J.; Al Rabeeah, Abdullah A.; Corman, Victor Max; Sieberg, Andrea; Makhdoom, Hatem Q.; Assiri, Abdullah; Al Masri, Malaki; Aldabbagh, Souhaib; Bosch, Berend Jan; Beer, Martin; Müller, Marcel A.; Kellam, Paul; Drosten, Christian

    2014-01-01

    We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species trans

  16. Ochratoxin A in Portugal: A Review to Assess Human Exposure

    Directory of Open Access Journals (Sweden)

    Sofia C. Duarte

    2010-06-01

    Full Text Available In Portugal, the climate, dietary habits, and food contamination levels present the characteristics for higher population susceptibility to ochratoxin A (OTA, one of the known mycotoxins with the greatest public health and agro-economic importance. In this review, following a brief historical insight on OTA research, a summary of the available data on OTA occurrence in food (cereals, bread, wine, meat and biological fluids (blood, urine is made. With this data, an estimation of intake is made to ascertain and update the risk exposure estimation of the Portuguese population, in comparison to previous studies and other populations.

  17. Effects of acute exercise on fear extinction in rats and exposure therapy in humans: Null findings from five experiments.

    Science.gov (United States)

    Jacquart, Jolene; Roquet, Rheall F; Papini, Santiago; Powers, Mark B; Rosenfield, David; Smits, Jasper A J; Monfils, Marie-H

    2017-08-01

    Exposure therapy is an established learning-based intervention for the treatment of anxiety disorders with an average response rate of nearly 50%, leaving room for improvement. Emerging strategies to enhance exposure therapy in humans and fear extinction retention in animal models are primarily pharmacological. These approaches are limited as many patients report preferring non-pharmacological approaches in therapy. With general cognitive enhancement effects, exercise has emerged as a plausible non-pharmacological augmentation strategy. The present study tested the hypothesis that fear extinction and exposure therapy would be enhanced by a pre-training bout of exercise. We conducted four experiments with rats that involved a standardized conditioning and extinction paradigm and a manipulation of exercise. In a fifth experiment, we manipulated vigorous-intensity exercise prior to a standardized virtual reality exposure therapy session among adults with fear of heights. In experiments 1-4, exercise did not facilitate fear extinction, long-term memory, or fear relapse tests. In experiment 5, human participants showed an overall reduction in fear of heights but exercise did not enhance symptom improvement. Although acute exercise prior to fear extinction or exposure therapy, as operationalized in the present 5 studies, did not enhance outcomes, these results must be interpreted within the context of a broader literature that includes positive findings. Taken all together, this suggests that more research is necessary to identify optimal parameters and key individual differences so that exercise can be implemented successfully to treat anxiety disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The calculation of dose from external photon exposures using reference human phantoms and Monte Carlo methods. Pt. 7. Organ doses due to parallel and environmental exposure geometries

    Energy Technology Data Exchange (ETDEWEB)

    Zankl, M. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenschutz; Drexler, G. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenschutz; Petoussi-Henss, N. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenschutz; Saito, K. [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan)

    1997-03-01

    This report presents a tabulation of organ and tissue equivalent dose as well as effective dose conversion coefficients, normalised to air kerma free in air, for occupational exposures and environmental exposures of the public to external photon radiation. For occupational exposures, whole-body irradiation with idealised geometries, i.e. broad parallel beams and fully isotropic radiation incidence, is considered. The directions of incidence for the parallel beams are anterior-posterior, posterior-anterior, left lateral, right lateral and a full 360 rotation around the body`s longitudinal axis. The influence of beam divergence on the body doses is also considered as well as the dependence of effective dose on the angle of radiation incidence. Regarding exposure of the public to environmental sources, three source geometries are considered: exposure from a radioactive cloud, from ground contamination and from the natural radionuclides distributed homogeneously in the ground. The precise angular and energy distributions of the gamma rays incident on the human body were taken into account. The organ dose conversion coefficients given in this catalogue were calculated using a Monte Carlo code simulating the photon transport in mathematical models of an adult male and an adult female, respectively. Conversion coefficients are given for the equivalent dose of 23 organs and tissues as well as for effective dose and the equivalent dose of the so-called `remainder`. The organ equivalent dose conversion coefficients are given separately for the adult male and female models and - as arithmetic mean of the conversion coefficients of both - for an average adult. Fitted data of the coefficients are presented in tables; the primary raw data as resulting from the Monte Carlo calculation are shown in figures together with the fitted data. (orig.)

  19. Exposure measurement of aflatoxins and aflatoxin metabolites in human body fluids. A short review.

    Science.gov (United States)

    Leong, Yin-Hui; Latiff, Aishah A; Ahmad, Nurul Izzah; Rosma, Ahmad

    2012-05-01

    Aflatoxins are highly toxic secondary fungal metabolites mainly produced by Aspergillus flavus and A. parasiticus. Human exposure to aflatoxins may result directly from ingestion of contaminated foods, or indirectly from consumption of foods from animals previously exposed to aflatoxins in feeds. This paper focuses on exposure measurement of aflatoxins and aflatoxin metabolites in various human body fluids. Research on different metabolites present in blood, urine, breast milk, and other human fluids or tissues including their detection techniques is reviewed. The association between dietary intake of aflatoxins and biomarker measurement is also highlighted. Finally, aspects related to the differences between aflatoxin determination in food versus the biomarker approach are discussed.

  20. Bisphenol a induces steatosis in HepaRG cells using a model of perinatal exposure.

    Science.gov (United States)

    Bucher, Simon; Jalili, Pégah; Le Guillou, Dounia; Begriche, Karima; Rondel, Karine; Martinais, Sophie; Zalko, Daniel; Corlu, Anne; Robin, Marie-Anne; Fromenty, Bernard

    2017-03-01

    Human exposure to bisphenol A (BPA) could favor obesity and related metabolic disorders such as hepatic steatosis. Investigations in rodents have shown that these deleterious effects are observed not only when BPA is administered during the adult life but also with different protocols of perinatal exposure. Whether perinatal BPA exposure could pose a risk in human is currently unknown, and thus appropriate in vitro models could be important to tackle this major issue. Accordingly, we determined whether long-term BPA treatment could induce steatosis in human HepaRG cells by using a protocol mimicking perinatal exposure. To this end, the kinetics of expression of seven proteins differentially expressed during liver development was determined during a 4-week period of cell culture required for proliferation and differentiation. By analogy with data reported in rodents and humans, our results indicated that the period of cell culture around day 15 and day 18 after seeding could be considered as the "natal" period. Consequently, HepaRG cells were treated for 3 weeks with BPA (from 0.2 to 2000 nM), with a treatment starting during the proliferating period. BPA was able to induce steatosis with a nonmonotonic dose response profile, with significant effects on neutral lipids and triglycerides observed for the 2 nM concentration. However, the expression of many enzymes involved in lipid and carbohydrate homeostasis was unchanged in exposed HepaRG cells. The expression of other potential BPA targets and enzymes involved in BPA biotransformation was also determined, giving answers as well as new questions regarding the mechanisms of action of BPA. Hence, HepaRG cells provide a valuable model that can prove useful for the toxicological assessment of endocrine disruptors on hepatic metabolisms, in particular in the developing liver. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1024-1036, 2017. © 2016 Wiley Periodicals, Inc.

  1. Application of a source-to-outcome model for the assessment of health impacts from dietary exposures to insecticide residues.

    Science.gov (United States)

    Price, Paul S; Schnelle, Karl D; Cleveland, Cheryl B; Bartels, Michael J; Hinderliter, Paul M; Timchalk, Charles; Poet, Torka S

    2011-10-01

    The paper presents a case study of the application of a "source-to-outcome" model for the evaluation of the health outcomes from dietary exposures to an insecticide, chlorpyrifos, in populations of adults (age 30) and children (age 3). The model is based on publically-available software programs that characterize the longitudinal dietary exposure and anthropometry of exposed individuals. These predictions are applied to a validated PBPK/PD model to estimate interindividual and longitudinal variation in brain and RBC AChE inhibition (key events) and chlorpyrifos concentrations in blood and TCPy in urine (biomarkers of exposure). The predicted levels of chlorpyrifos and TCPy are compared to published measurements of the biomarkers. Predictions of RBC AChE are compared to levels of inhibition associated with reported exposure-related effects in humans to determine the potential for the occurrence of adverse cholinergic effects. The predicted distributions of chlorpyrifos in blood and TCPy in urine were found to be reasonably consistent with published values, supporting the predictive value of the exposure and PBPK portions of the source-to-outcome model. Key sources of uncertainty in predictions of dietary exposures were investigated and found to have a modest impact on the model predictions. Future versions of this source-to-outcome model can be developed that consider advances in our understanding of metabolism, to extend the approach to other age groups (infants), and address intakes from other routes of exposure.

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

    Science.gov (United States)

    Laffon, Blanca; Pásaro, Eduardo; Valdiglesias, Vanessa

    2016-01-01

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

  3. In vitro exposure of human chondrocytes to pulsed electromagnetic fields

    Directory of Open Access Journals (Sweden)

    V Nicolin

    2009-08-01

    Full Text Available The effect of pulsed electromagnetic fields (PEMFs on the proliferation and survival of matrix-induced autologous chondrocyte implantation (MACI®-derived cells was studied to ascertain the healing potential of PEMFs. MACI-derived cells were taken from cartilage biopsies 6 months after surgery and cultured. No dedifferentiation towards the fibroblastic phenotype occurred, indicating the success of the surgical implantation. The MACI-derived cultured chondrocytes were exposed to 12 h/day (short term or 4 h/day (long term PEMFs exposure (magnetic field intensity, 2 mT; frequency, 75 Hz and proliferation rate determined by flow cytometric analysis. The PEMFs exposure elicited a significant increase of cell number in the SG2M cell cycle phase. Moreover, cells isolated from MACI® scaffolds showed the presence of collagen type II, a typical marker of chondrocyte functionality. The results show that MACI® membranes represent an optimal bioengineering device to support chondrocyte growth and proliferation in surgical implants. The surgical implant of MACI® combined with physiotherapy is suggested as a promising approach for a faster and safer treatment of cartilage traumatic lesions.

  4. Novel biomarkers of prenatal methamphetamine exposure in human meconium

    Science.gov (United States)

    Gray, Teresa R.; Kelly, Tamsin; LaGasse, Linda L.; Smith, Lynne M.; Derauf, Chris; Haning, William; Grant, Penny; Shah, Rizwan; Arria, Amelia; Strauss, Arthur; Lester, Barry M.; Huestis, Marilyn A.

    2008-01-01

    Meconium analysis can detect fetal exposure to drugs taken by the mother during pregnancy. Methamphetamine and amphetamine have previously been observed in meconium of methamphetamine-exposed neonates; the presence of other metabolites has not been investigated. Detection of such analytes may lead to more sensitive identification and, thus improved medical treatment of affected infants. Methods and Materials Forty-three methamphetamine-positive meconium specimens were analyzed for newly identified methamphetamine biomarkers, p-hydroxymethamphetamine, p-hydroxyamphetamine, and norephedrine. Due to methamphetamine adulteration in illicit ecstasy and to simultaneously monitor 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine prenatal exposure, MDMA, its metabolites and related sympathomimetic amines were assayed. Results Methamphetamine, amphetamine and unconjugated p-hydroxymethamphetamine were the most prevalent and abundant analytes present in meconium; however, unconjugated p-hydroxyamphetamine and norephedrine also were identified. Discussion It is possible that one of these additional analytes could be important for predicting toxicity or maternal or neonatal outcome measures in fetuses exposed to methamphetamine at specific gestational ages or with different metabolic capabilities. Although these new biomarkers were present in lower concentrations than methamphetamine and amphetamine in the meconium of previously confirmed specimens, additional research will determine if inclusion of these analytes can increase identification of methamphetamine-exposed neonates. Conclusion Novel methamphetamine biomarker concentrations were characterized in meconium of infants exposed in utero to methamphetamine. PMID:19125148

  5. Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides

    Science.gov (United States)

    Kubicek-Sutherland, Jessica Z.; Lofton, Hava; Vestergaard, Martin; Hjort, Karin; Ingmer, Hanne; Andersson, Dan I.

    2017-01-01

    Background The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the human innate immune system and the ramifications of prolonged bacterial exposure to AMPs are not fully understood. Objectives We show that in vitro serial passage of a clinical USA300 MRSA strain in a host-mimicking environment containing host-derived AMPs results in the selection of stable AMP resistance. Methods Serial passage experiments were conducted using steadily increasing concentrations of LL-37, PR-39 or wheat germ histones. WGS and proteomic analysis by MS were used to identify the molecular mechanism associated with increased tolerance of AMPs. AMP-resistant mutants were characterized by measuring in vitro fitness, AMP and antibiotic susceptibility, and virulence in a mouse model of sepsis. Results AMP-resistant Staphylococcus aureus mutants often displayed little to no fitness cost and caused invasive disease in mice. Further, this phenotype coincided with diminished susceptibility to both clinically prescribed antibiotics and human defence peptides. Conclusions These findings suggest that therapeutic use of AMPs could select for virulent mutants with cross-resistance to human innate immunity as well as antibiotic therapy. Thus, therapeutic use of AMPs and the implications of cross-resistance need to be carefully monitored and evaluated. PMID:27650186

  6. Predictive modeling of terrestrial radiation exposure from geologic materials

    Science.gov (United States)

    Haber, Daniel A.

    Aerial gamma ray surveys are an important tool for national security, scientific, and industrial interests in determining locations of both anthropogenic and natural sources of radioactivity. There is a relationship between radioactivity and geology and in the past this relationship has been used to predict geology from an aerial survey. The purpose of this project is to develop a method to predict the radiologic exposure rate of the geologic materials in an area by creating a model using geologic data, images from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), geochemical data, and pre-existing low spatial resolution aerial surveys from the National Uranium Resource Evaluation (NURE) Survey. Using these data, geospatial areas, referred to as background radiation units, homogenous in terms of K, U, and Th are defined and the gamma ray exposure rate is predicted. The prediction is compared to data collected via detailed aerial survey by our partner National Security Technologies, LLC (NSTec), allowing for the refinement of the technique. High resolution radiation exposure rate models have been developed for two study areas in Southern Nevada that include the alluvium on the western shore of Lake Mohave, and Government Wash north of Lake Mead; both of these areas are arid with little soil moisture and vegetation. We determined that by using geologic units to define radiation background units of exposed bedrock and ASTER visualizations to subdivide radiation background units of alluvium, regions of homogeneous geochemistry can be defined allowing for the exposure rate to be predicted. Soil and rock samples have been collected at Government Wash and Lake Mohave as well as a third site near Cameron, Arizona. K, U, and Th concentrations of these samples have been determined using inductively coupled mass spectrometry (ICP-MS) and laboratory counting using radiation detection equipment. In addition, many sample locations also have

  7. Impact of cigarette smoke exposure on innate immunity: a Caenorhabditis elegans model.

    Directory of Open Access Journals (Sweden)

    Rebecca M Green

    Full Text Available BACKGROUND: Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD and lung cancer. Respiratory bacterial infections have been shown to be involved in the development of COPD along with impaired airway innate immunity. METHODOLOGY/PRINCIPAL FINDINGS: To address the in vivo impact of cigarette smoke (CS exclusively on host innate defense mechanisms, we took advantage of Caenorhabditis elegans (C. elegans, which has an innate immune system but lacks adaptive immune function. Pseudomonas aeruginosa (PA clearance from intestines of C. elegans was dampened by CS. Microarray analysis identified 6 candidate genes with a 2-fold or greater reduction after CS exposure, that have a human orthologue, and that may participate in innate immunity. To confirm a role of CS-down-regulated genes in the innate immune response to PA, RNA interference (RNAi by feeding was carried out in C. elegans to inhibit the gene of interest, followed by PA infection to determine if the gene affected innate immunity. Inhibition of lbp-7, which encodes a lipid binding protein, resulted in increased levels of intestinal PA. Primary human bronchial epithelial cells were shown to express mRNA of human Fatty Acid Binding Protein 5 (FABP-5, the human orthologue of lpb-7. Interestingly, FABP-5 mRNA levels from human smokers with COPD were significantly lower (p = 0.036 than those from smokers without COPD. Furthermore, FABP-5 mRNA levels were up-regulated (7-fold after bacterial (i.e., Mycoplasma pneumoniae infection in primary human bronchial epithelial cell culture (air-liquid interface culture. CONCLUSIONS: Our results suggest that the C. elegans model offers a novel in vivo approach to specifically study innate immune deficiencies resulting from exposure to cigarette smoke, and that results from the nematode may provide insight into human airway epithelial cell biology and cigarette smoke exposure.

  8. Gene expression signatures that predict radiation exposure in mice and humans.

    Directory of Open Access Journals (Sweden)

    Holly K Dressman

    2007-04-01

    Full Text Available BACKGROUND: The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation. METHODS AND FINDINGS: We have made use of gene expression analysis of peripheral blood (PB mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans. CONCLUSIONS: We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.

  9. Effects of ozone exposure on lipid metabolism in human alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, M.; Madden, M.C.; Samet, J.M.; Koren, H.S.

    1991-01-01

    Alveolar macrophages (AM) store arachidonic acid (AA) which is esterified in cellular phospholipids until liberated by phospholipase A2 or C after exposure to inflammatory stimuli. Following release, there can be subsequent metabolism of AA into various potent, biological active mediators including prostaglandins and platelet activating factor (PAF). To examine the possibility that these mediators may account for some of the pathophysiologic alterations seen in the lung following O3 exposure, human AM were collected by bronchoalveolar lavage of normal subjects, plated into tissue culture dishes, and the adherent cells were incubated with 3H-AA or 3H-lysoPAF. Human AM exposed 1.0 ppm O3 for 2 hr released 65 + or - 12% more tritium, derived from 3H-AA, than paired air-exposed controls into media supernatants. In other studies using a similar O3 exposure protocol, there was also a significant increase in human AM PGE2 production (2.0 + or - 0.5 fold-increase above air-exposure values, p<0.01, n=17). In additional studies, using a similar O3 exposure protocol (1.0 ppm for 1 hr), there was also a significant increase in human AM PAF content (1.7 + or - 0.2 fold-increase above air-exposure values, p<0.02, n=5).

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

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

  12. Modeling emission rates and exposures from outdoor cooking

    Science.gov (United States)

    Edwards, Rufus; Princevac, Marko; Weltman, Robert; Ghasemian, Masoud; Arora, Narendra K.; Bond, Tami

    2017-09-01

    Approximately 3 billion individuals rely on solid fuels for cooking globally. For a large portion of these - an estimated 533 million - cooking is outdoors, where emissions from cookstoves pose a health risk to both cooks and other household and village members. Models that estimate emissions rates from stoves in indoor environments that would meet WHO air quality guidelines (AQG), explicitly don't account for outdoor cooking. The objectives of this paper are to link health based exposure guidelines with emissions from outdoor cookstoves, using a Monte Carlo simulation of cooking times from Haryana India coupled with inverse Gaussian dispersion models. Mean emission rates for outdoor cooking that would result in incremental increases in personal exposure equivalent to the WHO AQG during a 24-h period were 126 ± 13 mg/min for cooking while squatting and 99 ± 10 mg/min while standing. Emission rates modeled for outdoor cooking are substantially higher than emission rates for indoor cooking to meet AQG, because the models estimate impact of emissions on personal exposure concentrations rather than microenvironment concentrations, and because the smoke disperses more readily outdoors compared to indoor environments. As a result, many more stoves including the best performing solid-fuel biomass stoves would meet AQG when cooking outdoors, but may also result in substantial localized neighborhood pollution depending on housing density. Inclusion of the neighborhood impact of pollution should be addressed more formally both in guidelines on emissions rates from stoves that would be protective of health, and also in wider health impact evaluation efforts and burden of disease estimates. Emissions guidelines should better represent the different contexts in which stoves are being used, especially because in these contexts the best performing solid fuel stoves have the potential to provide significant benefits.

  13. Human volunteer study with PGME: Eye irritation during vapour exposure

    NARCIS (Netherlands)

    Emmen, H.H.; Muijser, H.; Arts, J.H.E.; Prinsen, M.K.

    2003-01-01

    The objective of this study was to establish the possible occurrence of eye irritation and subjective symptoms in human volunteers exposed to propylene glycol monomethyl ether (PGME) vapour at concentrations of 0, 100 and 150 ppm. Testing was conducted in 12 healthy male volunteers using a repeated

  14. Human volunteer study with PGME: Eye irritation during vapour exposure

    NARCIS (Netherlands)

    Emmen, H.H.; Muijser, H.; Arts, J.H.E.; Prinsen, M.K.

    2003-01-01

    The objective of this study was to establish the possible occurrence of eye irritation and subjective symptoms in human volunteers exposed to propylene glycol monomethyl ether (PGME) vapour at concentrations of 0, 100 and 150 ppm. Testing was conducted in 12 healthy male volunteers using a repeated

  15. Human Resource Challenges to Integrating HIV Pre-Exposure ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    We documented consultation discussions through note taking. Human resource .... coordinators, and nursing officer in-charges. Interviews were ... shifting as playing an important role in PrEP .... counseling, and to high patient volume and longer wait times on the ... about the safety and efficacy of PrEP, which may influence ...

  16. Assessment of dietary exposure and effect in humans

    NARCIS (Netherlands)

    Duynhoven, Van John P.M.; Jacobs, Doris M.

    2016-01-01

    In human nutritional science progress has always depended strongly on analytical measurements for establishing relationships between diet and health. This field has undergone significant changes as a result of the development of NMR and mass spectrometry methods for large scale detection, identif

  17. Inhalation Exposure Input Parameters for the Biosphere Model

    Energy Technology Data Exchange (ETDEWEB)

    K. Rautenstrauch

    2004-09-10

    This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling, and the plan for development of the biosphere abstraction products for TSPA, as identified in the Technical Work Plan for Biosphere Modeling and Expert Support (BSC 2004 [DIRS 169573]). This analysis report defines and justifies values of mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of ERMYN to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception.

  18. Developing and evaluating distributions for probabilistic human exposure assessments

    Energy Technology Data Exchange (ETDEWEB)

    Maddalena, Randy L.; McKone, Thomas E.

    2002-08-01

    This report describes research carried out at the Lawrence Berkeley National Laboratory (LBNL) to assist the U. S. Environmental Protection Agency (EPA) in developing a consistent yet flexible approach for evaluating the inputs to probabilistic risk assessments. The U.S. EPA Office of Emergency and Remedial Response (OERR) recently released Volume 3 Part A of Risk Assessment Guidance for Superfund (RAGS), as an update to the existing two-volume set of RAGS. The update provides policy and technical guidance on performing probabilistic risk assessment (PRA). Consequently, EPA risk managers and decision-makers need to review and evaluate the adequacy of PRAs for supporting regulatory decisions. A critical part of evaluating a PRA is the problem of evaluating or judging the adequacy of input distributions PRA. Although the overarching theme of this report is the need to improve the ease and consistency of the regulatory review process, the specific objectives are presented in two parts. The objective of Part 1 is to develop a consistent yet flexible process for evaluating distributions in a PRA by identifying the critical attributes of an exposure factor distribution and discussing how these attributes relate to the task-specific adequacy of the input. This objective is carried out with emphasis on the perspective of a risk manager or decision-maker. The proposed evaluation procedure provides consistency to the review process without a loss of flexibility. As a result, the approach described in Part 1 provides an opportunity to apply a single review framework for all EPA regions and yet provide the regional risk manager with the flexibility to deal with site- and case-specific issues in the PRA process. However, as the number of inputs to a PRA increases, so does the complexity of the process for calculating, communicating and managing risk. As a result, there is increasing effort required of both the risk professionals performing the analysis and the risk manager

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

    Science.gov (United States)

    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.

  20. The potential utility of animal poisoning data to identify human exposure to environmental toxins.

    Science.gov (United States)

    Hungerford, L L; Trammel, H L; Clark, J M

    1995-04-01

    The database of the National Animal Poison Control Center (NAPCC) was evaluated as a source for animal poison data indicating human health hazards in indoor and outdoor environments. From 14,150 calls in the 1985 database, 259 cases were identified with histories suggesting human exposure. A subgroup of 25 cases with known human exposure was found. Dogs were the most common sentinel animal, but bird cases represented the highest proportional selection from the total 1985 call list. Indoor exposures represented 43.2% of cases; the most common toxicants were insecticides, lead and toxic fumes. Exposures associated with lawns were mainly due to insecticides and herbicides and constituted 25.5% of cases. Other outdoor exposures composed the remaining 31.7% of cases, with insecticides, herbicides and unidentified toxins the leading categories. Many of the specific agents identified, such as organophosphate insecticides, lead, gas and fume toxins, and phenoxy herbicides are also risk factors in human diseases. This study indicates that databases such as NAPCC could serve as sources of sentinel animal intoxications for followup studies to evaluate known and potential human health hazards.

  1. Mutagenic potential assessment associated with human exposure to natural radioactivity.

    Science.gov (United States)

    Marcon, Alexandre Endres; Navoni, Julio Alejandro; de Oliveira Galvão, Marcos Felipe; Garcia, Anuska Conde Fagundes Soares; do Amaral, Viviane Souza; Petta, Reinaldo Antônio; Campos, Thomas Ferreira da Costa; Panosso, Renata; Quinelato, Antônio Luiz; de Medeiros, Sílvia Regina Batistuzzo

    2017-01-01

    Lucrécia city, known to harbor a high cancer rate, is located in a semiarid region characterized by the presence of mineral reservoirs, facing a high exposure to metal and natural radioactivity. The present study aimed to assess the environmental scenario at a semiarid region located in Northeastern Brazil. Metal concentration, alpha and beta radiation, and cyanobacteria content in tap water along with indoor radon and gamma emitters (U, K and Th) concentrations were measured. In addition, mutagenic and nuclear instability effects were assessed using buccal micronucleus cytome assay. The study included five samplings corresponding to a period between 2007 and 2009. Drinking water from Lucrécia city presented levels of Mn, Ni and Cr along with cyanobacteria in concentrations one to four times higher than regulatory guidelines considered. Furthermore, high levels of all the tested radionuclides were found. A high percentage of the houses included in this study presented indoor radon concentrations over 100 Bq m(-3). The mean annual effective dose from Lucrécia houses was six times higher than observed in a control region. The levels of exposure in most of the Lucrécia houses were classified as middle to high. A significant mutagenic effect, represented as an increase of micronuclei (MN) frequency and nuclear abnormalities as nuclear buds (NB), binucleated cells (BN), and pyknotic cells (PYC) were found. The results obtained highlight the role of high background radioactivity on the observed mutagenic effect and could help to explain the exacerbated cancer rate reported in this locality.

  2. Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

    Science.gov (United States)

    2012-06-13

    daily low-dose Bacillus anthracis spore inhalation exposures in the rabbit model Roy E. Barnewall 1, Jason E. Comer 1, Brian D. Miller 1, BradfordW...multiple exposure days. Keywords: Bacillus anthracis , inhalation exposures, low-dose, subchronic exposures, spores, anthrax, aerosol system INTRODUCTION... Bacillus Anthracis Spore Inhalation Exposures In The Rabbit Model 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  3. Use of chromosome translocations for measuring prior environment exposures in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J. D.

    1997-05-01

    Recent advances in cytogenetic methodology are beginning to have a major impact upon our ability to provide assessments of environmental exposure in humans. The advent of fluorescent-based techniques for `painting` whole chromosomes has made the analysis of chromosome translocations rapid, specific, sensitive and routine. Chromosome painting has been used to address a wide variety of scientific questions, resulting in an increased understanding of the biological consequences of adverse environmental exposure. This paper describes the use of chromosome translocations as a biological marker of exposure and effect in humans. The relevance of translocations is discussed, as are the advantages and disadvantages of painting compared to classical cytogenetic methods for translocation evaluation. The factors to consider in the use of translocations as a retrospective indicator of exposure are then described. Several theoretical parameters that are important to the use of translocations are provided, and the paper concludes with a vision for the future of cytogenetic methodology.

  4. Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2004-04-15

    Nitrogen dioxide (NO2) is an environmental oxidant, known to be associated with lung epithelial injury. In the present study, cellular pro-inflammatory responses following exposure to a brief high concentration of NO2 (45 ppm) were assessed, using normal human bronchial epithelial (NHBE) cells as an in vitro model of inhalation injury. Generation and release of pro-inflammatory mediators such as nitric oxide (NO), IL-8, TNF-alpha, IFN-gamma and IL-1beta were assessed at different time intervals following NO2 exposure. Effects of a pre-existing inflammatory condition was tested by treating the NHBE cells with different inflammatory cytokines such as IFN-gamma, IL-8, TNF-alpha, IL-1beta, either alone or in combination, before exposing them to NO2. Immunofluorescence studies confirmed oxidant-induced formation of 3-nitrotyrosine in the NO2-exposed cells. A marked increase in the levels of nitrite (as an index of NO) and IL-8 were observed in the NO2-exposed cells, which were further enhanced in the presence of the cytokines. Effects of various NO inhibitors combined, with immunofluorescence and Western blotting data, indicated partial contribution of the nitric oxide synthases (NOSs) toward the observed increase in nitrite levels. Furthermore, a significant increase in IL-1beta and TNF-alpha generation was observed in the NO2-exposed cells. Although NO2 exposure alone did induce slight cytotoxicity (<12%), but presence of inflammatory cytokines such as TNF-alpha and IFN-gamma resulted in an increased cell death (28-36%). These results suggest a synergistic role of inflammatory mediators, particularly of NO and IL-8, in NO2-mediated early cellular changes. Our results also demonstrate an increased sensitivity of the cytokine-treated NHBE cells toward NO2, which may have significant functional implications in vivo.

  5. Human urinary biomarkers of dioxin exposure: analysis by metabolomics and biologically driven data dimensionality reduction.

    Science.gov (United States)

    Jeanneret, Fabienne; Boccard, Julien; Badoud, Flavia; Sorg, Olivier; Tonoli, David; Pelclova, Daniela; Vlckova, Stepanka; Rutledge, Douglas N; Samer, Caroline F; Hochstrasser, Denis; Saurat, Jean-Hilaire; Rudaz, Serge

    2014-10-15

    Untargeted metabolomic approaches offer new opportunities for a deeper understanding of the molecular events related to toxic exposure. This study proposes a metabolomic investigation of biochemical alterations occurring in urine as a result of dioxin toxicity. Urine samples were collected from Czech chemical workers submitted to severe dioxin occupational exposure in a herbicide production plant in the late 1960s. Experiments were carried out with ultra-high pressure liquid chromatography (UHPLC) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry. A chemistry-driven feature selection was applied to focus on steroid-related metabolites. Supervised multivariate data analysis allowed biomarkers, mainly related to bile acids, to be highlighted. These results supported the hypothesis of liver damage and oxidative stress for long-term dioxin toxicity. As a second step of data analysis, the information gained from the urine analysis of Victor Yushchenko after his poisoning was examined. A subset of relevant urinary markers of acute dioxin toxicity from this extreme phenotype, including glucuro- and sulfo-conjugated endogenous steroid metabolites and bile acids, was assessed for its ability to detect long-term effects of exposure. The metabolomic strategy presented in this work allowed the determination of metabolic patterns related to dioxin effects in human and the discovery of highly predictive subsets of biologically meaningful and clinically relevant compounds. These results are expected to provide valuable information for a deeper understanding of the molecular events related to dioxin toxicity. Furthermore, it presents an original methodology of data dimensionality reduction by using extreme phenotype as a guide to select relevant features prior to data modeling (biologically driven data reduction).

  6. UV exposure modulates hemidesmosome plasticity, contributing to long-term pigmentation in human skin

    Science.gov (United States)

    Coelho, Sergio G.; Valencia, Julio C.; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Miller, Sharon A.; Beer, Janusz Z.; Zhang, Guofeng; Tuma, Pamela L.; Hearing, Vincent J.

    2014-01-01

    Human skin color, i.e. pigmentation, differs widely among individuals as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer. In some individuals UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, e.g. solar lentigines or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. To investigate what UV-induced molecular changes may persist in individuals with LLP, clinical specimens from non-sunburn-inducing repeated UV exposures (UVA, UVB or UVA+UVB) at 4 months post-exposure (short-term LLP) were evaluated by microarray analysis and dataset mining. Validated targets were further evaluated in clinical specimens from 6 healthy individuals (3 LLP+ and 3 LLP-) followed for more than 9 months (long-term LLP) who initially received a single sunburn-inducing UVA+UVB exposure. The results support a UV-induced hyperpigmentation model in which basal keratinocytes have an impaired ability to remove melanin that leads to a compensatory mechanism by neighboring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated expression of SOX7 and other hemidesmosomal components (integrin α6β4 and plectin) leads to increased melanosome uptake by keratinocytes and points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes provides supporting evidence for plasticity at the epidermal-dermal junction. Altered hemidesmosome plasticity, and the sustained nature of LLP, may be mediated by the role of SOX7 in basal keratinocytes. The long-term sustained subtle changes detected are modest, but sufficient to create dramatic visual differences in skin color. These results suggest that the hyperpigmentation phenomenon leading to increased

  7. Modelling the exposure to chemicals for risk assessment: a comprehensive library of multimedia and PBPK models for integration, prediction, uncertainty and sensitivity analysis - the MERLIN-Expo tool.

    Science.gov (United States)

    Ciffroy, P; Alfonso, B; Altenpohl, A; Banjac, Z; Bierkens, J; Brochot, C; Critto, A; De Wilde, T; Fait, G; Fierens, T; Garratt, J; Giubilato, E; Grange, E; Johansson, E; Radomyski, A; Reschwann, K; Suciu, N; Tanaka, T; Tediosi, A; Van Holderbeke, M; Verdonck, F

    2016-10-15

    MERLIN-Expo is a library of models that was developed in the frame of the FP7 EU project 4FUN in order to provide an integrated assessment tool for state-of-the-art exposure assessment for environment, biota and humans, allowing the detection of scientific uncertainties at each step of the exposure process. This paper describes the main features of the MERLIN-Expo tool. The main challenges in exposure modelling that MERLIN-Expo has tackled are: (i) the integration of multimedia (MM) models simulating the fate of chemicals in environmental media, and of physiologically based pharmacokinetic (PBPK) models simulating the fate of chemicals in human body. MERLIN-Expo thus allows the determination of internal effective chemical concentrations; (ii) the incorporation of a set of functionalities for uncertainty/sensitivity analysis, from screening to variance-based approaches. The availability of such tools for uncertainty and sensitivity analysis aimed to facilitate the incorporation of such issues in future decision making; (iii) the integration of human and wildlife biota targets with common fate modelling in the environment. MERLIN-Expo is composed of a library of fate models dedicated to non biological receptor media (surface waters, soils, outdoor air), biological media of concern for humans (several cultivated crops, mammals, milk, fish), as well as wildlife biota (primary producers in rivers, invertebrates, fish) and humans. These models can be linked together to create flexible scenarios relevant for both human and wildlife biota exposure. Standardized documentation for each model and training material were prepared to support an accurate use of the tool by end-users. One of the objectives of the 4FUN project was also to increase the confidence in the applicability of the MERLIN-Expo tool through targeted realistic case studies. In particular, we aimed at demonstrating the feasibility of building complex realistic exposure scenarios and the accuracy of the

  8. Predictive modeling of nanomaterial exposure effects in biological systems

    Directory of Open Access Journals (Sweden)

    Liu X

    2013-09-01

    Full Text Available Xiong Liu,1 Kaizhi Tang,1 Stacey Harper,2 Bryan Harper,2 Jeffery A Steevens,3 Roger Xu1 1Intelligent Automation, Inc., Rockville, MD, USA; 2Department of Environmental and Molecular Toxicology, School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USA; 3ERDC Environmental Laboratory, Vicksburg, MS, USA Background: Predictive modeling of the biological effects of nanomaterials is critical for industry and policymakers to assess the potential hazards resulting from the application of engineered nanomaterials. Methods: We generated an experimental dataset on the toxic effects experienced by embryonic zebrafish due to exposure to nanomaterials. Several nanomaterials were studied, such as metal nanoparticles, dendrimer, metal oxide, and polymeric materials. The embryonic zebrafish metric (EZ Metric was used as a screening-level measurement representative of adverse effects. Using the dataset, we developed a data mining approach to model the toxic endpoints and the overall biological impact of nanomaterials. Data mining techniques, such as numerical prediction, can assist analysts in developing risk assessment models for nanomaterials. Results: We found several important attributes that contribute to the 24 hours post-fertilization (hpf mortality, such as dosage concentration, shell composition, and surface charge. These findings concur with previous studies on nanomaterial toxicity using embryonic zebrafish. We conducted case studies on modeling the overall effect/impact of nanomaterials and the specific toxic endpoints such as mortality, delayed development, and morphological malformations. The results show that we can achieve high prediction accuracy for certain biological effects, such as 24 hpf mortality, 120 hpf mortality, and 120 hpf heart malformation. The results also show that the weighting scheme for individual biological effects has a significant influence on modeling the overall impact of

  9. Modelling the scaling properties of human mobility

    Science.gov (United States)

    Song, Chaoming; Koren, Tal; Wang, Pu; Barabási, Albert-László

    2010-10-01

    Individual human trajectories are characterized by fat-tailed distributions of jump sizes and waiting times, suggesting the relevance of continuous-time random-walk (CTRW) models for human mobility. However, human traces are barely random. Given the importance of human mobility, from epidemic modelling to traffic prediction and urban planning, we need quantitative models that can account for the statistical characteristics of individual human trajectories. Here we use empirical data on human mobility, captured by mobile-phone traces, to show that the predictions of the CTRW models are in systematic conflict with the empirical results. We introduce two principles that govern human trajectories, allowing us to build a statistically self-consistent microscopic model for individual human mobility. The model accounts for the empirically observed scaling laws, but also allows us to analytically predict most of the pertinent scaling exponents.

  10. Human exposure to high natural background radiation: what can it teach us about radiation risks?

    OpenAIRE

    Jolyon H Hendry; Simon, Steven L.; Wojcik, Andrzej; Sohrabi, Mehdi; Burkart, Werner; Cardis, Elisabeth; Laurier, Dominique; Tirmarche, Margot; Hayata, Isamu

    2009-01-01

    Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations li...

  11. Human urinary mutagenicity after wood smoke exposure during traditional temazcal use

    OpenAIRE

    Long, Alexandra S.; Lemieux, Christine L.; Yousefi, Paul; Ruiz-Mercado, Ilse; Lam, Nicholas L.; Orellana, Carolina Romero; White, Paul A.; Smith, Kirk R.; Holland, Nina

    2014-01-01

    In Central America, the traditional temazcales or wood-fired steam baths, commonly used by many Native American populations, are often heated by wood fires with little ventilation, and this use results in high wood smoke exposure. Urinary mutagenicity has been previously employed as a non-invasive biomarker of human exposure to combustion emissions. This study examined the urinary mutagenicity in 19 indigenous Mayan families from the highlands of Guatemala who regularly use temazcales (N = 32...

  12. Immunomodulation of human monocytes following exposure to Lutzomyia intermedia saliva

    Directory of Open Access Journals (Sweden)

    Barral Aldina

    2008-04-01

    Full Text Available Abstract Background Sand fly saliva contains potent and complex pharmacologic molecules that are able to modulate the host's hemostatic, inflammatory, and immune systems. In this study, we evaluated the effects of salivary gland sonicate (SGS of Lutzomyia intermedia, the natural vector of Leishmania braziliensis, on monocytes obtained from the peripheral blood mononuclear cells (PBMC of healthy volunteers. We investigated the effects of sand fly saliva on cytokine production and surface molecule expression of LPS-stimulated human monocytes uninfected or infected with L. braziliensis. Results Pre-treatment of non-infected human monocytes with L. intermedia SGS followed by LPS-stimulation led to a significant decrease in IL-10 production accompanied by a significant increase in CD86, CD80, and HLA-DR expression. Pre-treatment with SGS followed by LPS stimulation and L. braziliensis infection led to a significant increase in TNF-α, IL-6, and IL-8 production without significant alterations in co-stimulatory molecule expression. However, pre-treatment with L. intermedia SGS did not result in significant changes in the infection rate of human monocytes. Conclusion Our data indicate that L. intermedia saliva is able to modulate monocyte response, and, although this modulation is dissociated from enhanced infection with L. braziliensis, it may be associated with successful parasitism.

  13. KREAM: Korean Radiation Exposure Assessment Model for Aviation Route Dose

    Science.gov (United States)

    Hwang, J.; Dokgo, K.; Choi, E. J.; Kim, K. C.; Kim, H. P.; Cho, K. S. F.

    2014-12-01

    Since Korean Air has begun to use the polar route from Seoul/ICN airport to New York/JFK airport on August 2006, there are explosive needs for the estimation and prediction against cosmic radiation exposure for Korean aircrew and passengers in South Korea from public. To keep pace with those needs of public, Korean government made the law on safety standards and managements of cosmic radiation for the flight attendants and the pilots in 2013. And we have begun to develop our own Korean Radiation Exposure Assessment Model (KREAM) for aviation route dose since last year funded by Korea Meteorological Administration (KMA). GEANT4 model and NRLMSIS 00 model are used for calculation of the energetic particles' transport in the atmosphere and for obtaining the background atmospheric neutral densities depending on altitude. For prediction the radiation exposure in many routes depending on the various space weather effects, we constructed a database from pre-arranged simulations using all possible combinations of R, S, and G, which are the space weather effect scales provided by the National Oceanic and Atmospheric Administration (NOAA). To get the solar energetic particles' spectrum at the 100 km altitude which we set as a top of the atmospheric layers in the KREAM, we use ACE and GOES satellites' proton flux observations. We compare the results between KREAM and the other cosmic radiation estimation programs such as CARI-6M which is provided by the Federal Aviation Agency (FAA). We also validate KREAM's results by comparison with the measurement from Liulin-6K LET spectrometer onboard Korean commercial flights and Korean Air Force reconnaissance flights.

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

    Science.gov (United States)

    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.

  15. Chromosome aberrations as biomarkers of radiation exposure: Modelling basic mechanisms

    Science.gov (United States)

    Ballarini, F.; Ottolenghi, A.

    The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).

  16. Sensory and Physiological Effects on Humans of Combined Exposures to Air Temperatures and Volatile Organic Compounds

    DEFF Research Database (Denmark)

    Mølhave, Lars; Liu, Zunyong; Jørgensen, Anne Hempel

    1993-01-01

    Ten healthy humans were exposed to combinations of volatile organic compounds (VOCs) and air temperature (0 mg/m3 and 10 mg/m3 of a mixture of 22 volatile organic compounds and 18, 22 and 26° C). Previously demonstrated effects of VOCs and thermal exposures were replicated. For the first time nasal...... cross-sectional areas and nasal volumes, as measured by acoustic rhinometry, were shown to decrease with decreasing temperature and increasing VOC exposure. Temperature and pollutant exposures affected air quality, the need for more ventilation, skin humidity on the forehead, sweating, acute sensory...

  17. A comprehensive assessment of human exposure to phthalates from environmental media and food in Tianjin, China.

    Science.gov (United States)

    Ji, Yaqin; Wang, Fumei; Zhang, Leibo; Shan, Chunyan; Bai, Zhipeng; Sun, Zengrong; Liu, Lingling; Shen, Boxiong

    2014-08-30

    A total of 448 samples including foodstuffs (rice, steamed bun, vegetables, meat, poultry, fish, milk and fruits), ambient PM10, drinking water, soil, indoor PM10 and indoor dust samples from Tianjin were obtained to determine the distribution of six priority phthalates (PAEs) and assess the human exposure to them. The results indicated that DBP and DEHP were the most frequently detected PAEs in these samples. The concentrations of PAEs in environmental media were higher than those in food. We estimated the daily intake (DI) of PAEs via ingestion, inhalation and dermal absorption from five sources (food, water, air, dust and soil). Dietary intake was the main exposure source to DEP, BBP, DEHP and DOP, whereas water ingestion/absorption was the major source of exposure to DBP, DEHP and DOP. Although food and water were the overwhelmingly predominant sources of PAEs intake by Tianjin population, contaminated air was another important source of DMP, DEP and DBP contributing to up to 45% of the exposure. The results of this study will help in understanding the major pathways of human exposure to PAEs. These findings also suggest that human exposure to phthalate esters via the environment should not be overlooked.

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

    Science.gov (United States)

    Kita, Ryosuke; Fraser, Hunter B.

    2016-01-01

    Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin. We then tested whether genetic variants may influence each individual’s gene expression response to sun-exposure. Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). The allele frequencies of the RASSF9 se-eQTL across diverse populations correlate with the magnitude of solar radiation experienced by these populations, suggesting local adaptation to varying levels of sunlight. These results provide the first examples of sun-exposure-dependent regulatory variation and suggest that this variation has contributed to recent human adaptation. PMID:27760139

  19. Exposure estimates using urban plume dispersion and traffic microsimulation models

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.J.; Mueller, C.; Bush, B.; Stretz, P.

    1997-12-01

    The goal of this research effort was to demonstrate a capability for analyzing emergency response issues resulting from accidental or mediated airborne toxic releases in an urban setting. In the first year of the program, the authors linked a system of fluid dynamics, plume dispersion, and vehicle transportation models developed at Los Alamos National Laboratory to study the dispersion of a plume in an urban setting and the resulting exposures to vehicle traffic. This research is part of a larger laboratory-directed research and development project for studying the relationships between urban infrastructure elements and natural systems.

  20. A review of human exposure to polybrominated diphenyl ethers (PBDEs) in China.

    Science.gov (United States)

    Ni, Kun; Lu, Yonglong; Wang, Tieyu; Kannan, Kurunthachalam; Gosens, Jorrit; Xu, Li; Li, Qiushuang; Wang, Lin; Liu, Shijie

    2013-11-01

    This paper reviews recent studies on human exposure to polybrominated diphenyl ethers (PBDEs) in China, with particular focus on external exposure routes (e.g. diet and dust ingestion, inhalation of air) and internal doses based on biomonitoring studies of PBDEs (e.g. breast milk, blood and hair). PBDE concentrations reported for fish samples collected from electronic waste (e-waste) recycling sites, PBDE manufacturing sites, local markets in selected cities and estuarine areas in China have been compiled. House dust has been a significant contributor to human exposure to PBDEs in many countries. This is especially true for toddlers, who are exposed to significantly higher doses of PBDEs than adults. Infants are also exposed to high levels of PBDEs via breast-feeding. The general population's inhalation exposure to PBDEs from household products is likely a less significant source into the indoor environment. In addition, the contribution of several exposure pathways to PBDEs among various age groups was analyzed. We found that house dust contributed most to the daily exposure to PBDEs for both toddlers and adults in urban areas of China. Furthermore, workers and residents in and around electronic recycling and PBDE manufacturing sites are exposed to the highest PBDE levels among all populations studied thus far. For the occupationally exposed populations, BDE209 was the dominant congener, in most cases. Rigorous pollution prevention and occupational protection measures are needed in China to mitigate potential health effects associated with PBDE exposures.

  1. Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans.

    Science.gov (United States)

    Solomon, Keith R; Wilks, Martin F; Bachman, Ammie; Boobis, Alan; Moretto, Angelo; Pastoor, Timothy P; Phillips, Richard; Embry, Michelle R

    2016-11-01

    When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

  2. Health Risk Evaluations for Ingestion Exposure of Humans to Polonium-210

    Science.gov (United States)

    Scott, Bobby R.

    2007-01-01

    The incident in London during November 2006 involving a lethal intake by Mr. Alexander Litvinenko of the highly-radioactive, alpha-particles-emitting polonium-210 (Po-210) isotope, presumably via ingestion, sparked renewed interest in the area of Po-210 toxicity to humans. This paper is the result of assembling and interpreting existing Po-210 data within the context of what is considered a reliable risk model (hazard-function [HF] model) for characterizing the risk of death from deterministic effects of high alpha radiation doses and dose rates to body organs. The HF model was developed to address radiation exposure scenarios involving combined exposures to alpha, beta, and gamma radiations and can be used in circumstances where only one type of radiation is involved. Under a plausible but not yet validated set of assumptions and using available megabecquerel (Po-210) to gray dose-conversion factors, acute lethality risk vs. dose curves were developed for circumstances of ingestion exposure to Po-210 by humans. Initial risk calculations were carried out for a reference adult male human (a hypothetical 70-kg person). Results were then modified for application to all ages (except the in utero child) via the use of systemic Po-210 burden. Because of the unavailability of acute lethality data derived from human ingestions of high levels of Po-210, plausibility of risk calculations were evaluated based on data from studies of Po-210 injections in animals. The animal data, although limited, were found to be consistent with the theoretical risk calculations. Key findings are as follows: (1) ingestion (or inhalation) of a few tents of a milligram of Po-210 will likely be fatal to all exposed persons. (2) Lethal intakes are expected to involve fatal damage to the bone marrow which is likely to be compounded by damage caused by higher doses to other organs including the kidneys and liver. (3) Lethal intakes are expected to cause severe damage to the kidney, spleen, stomach

  3. Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data.

    Science.gov (United States)

    Hinderliter, P M; Thrall, K D; Corley, R A; Bloemen, L J; Bogdanffy, M S

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13C1,13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1,13C2 vinyl acetate and the major metabolite 13C1,13C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

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

    Directory of Open Access Journals (Sweden)

    Luis A. Henríquez-Hernández

    2017-05-01

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

  5. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure.

    Science.gov (United States)

    Kosten, Ilona J; Spiekstra, Sander W; de Gruijl, Tanja D; Gibbs, Susan

    2015-08-15

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a(+) MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a(-)/CD14(+)/CD68(+) which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets.

  6. Prioritization of pesticides based on daily dietary exposure potential as determined from the SHEDS model

    Science.gov (United States)

    A major pathway for exposure to many pesticides is through diet. The objectives were to rank pesticides by comparing their calculated daily dietary exposure as determined by EPA's Stochastic Human Exposure and Dose Simulation (SHEDS) to single pesticides for different age groups ...

  7. Prioritization of pesticides based on daily dietary exposure potential as determined from the SHEDS model

    Science.gov (United States)

    A major pathway for exposure to many pesticides is through diet. The objectives were to rank pesticides by comparing their calculated daily dietary exposure as determined by EPA's Stochastic Human Exposure and Dose Simulation (SHEDS) to single pesticides for different age groups ...

  8. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory; Joe, Jeffrey Clark [Idaho National Laboratory; Mandelli, Diego [Idaho National Laboratory

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  9. Modelling human actions on lightweight structures: experimental and numerical developments

    Directory of Open Access Journals (Sweden)

    Živanović S.

    2015-01-01

    Full Text Available This paper presents recent, numerical and experimental, developments in modelling dynamic loading generated by humans. As modern structures with exposure to human-induced loading, such as footbridges, building floors and grandstands, are becoming ever lighter and more slender, they are increasingly susceptible to vibration under human-induced dynamic excitation, such as walking, jumping, running and bobbing, and their vibration serviceability assessment is often a deciding factor in the design process. While simplified modelling of the human using a harmonic force was sufficient for assessment of vibration performance of more robust structures a few decades ago, the higher fidelity models are required in the contemporary design. These models are expected not only to describe both temporal and spectral features of the force signal more accurately, but also to capture the influence, psychological and physiological, of human-structure and human-human interaction mechanisms on the human kinematics, and consequently on the force generated and the resulting vibration response. Significant advances have been made in both the research studies and design guidance. This paper reports the key developments and identifies the scope for further research.

  10. Steroids in marine aquaculture farms surrounding Hailing Island, South China: occurrence, bioconcentration, and human dietary exposure.

    Science.gov (United States)

    Liu, Shan; Chen, Hui; Xu, Xiang-Rong; Liu, Shuang-Shuang; Sun, Kai-Feng; Zhao, Jian-Liang; Ying, Guang-Guo

    2015-01-01

    The occurrence, bioconcentration, and human dietary exposure via seafood consumption of 24 steroids were investigated by rapid resolution liquid chromatography-tandem mass spectrometry (RRLC-MS/MS) in six typical marine aquaculture farms surrounding Hailing Island, South China. Ten, 9, 10, 15 of 24 steroids were detected at concentrations ranging from 18 years), respectively. Even though no significant risk from dietary exposure arises from individual steroid, elevated risk to humans can result from the occurrence of multiple steroids in the seafood raised in the aquaculture farms, especially for the sensitive populations, such as pregnant women and children.

  11. A proposed study on the transplacental transport of parabens in the human placental perfusion model

    DEFF Research Database (Denmark)

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H

    2013-01-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment......, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance......, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim...

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

    Science.gov (United States)

    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.

  13. Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, Mykyta V., E-mail: sokolovm@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Irina V., E-mail: ipanyutinv@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Igor G., E-mail: igorp@helix.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Neumann, Ronald D., E-mail: rneumann@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States)

    2011-05-10

    One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

  14. Agent Orange Exposure and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in Human Milk.

    Science.gov (United States)

    Scialli, Anthony R; Watkins, Deborah K; Ginevan, Michael E

    2015-06-01

    Agent Orange was sprayed in parts of southern Vietnam during the U.S.-Vietnam war and was a mixture of two chlorophenoxy herbicides. The mixture was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD and other dioxins and furans are measurable in the milk of Vietnamese women. We explored whether the TCDD in milk from these women was from Agent Orange and whether lactational exposure can be a mode of transgenerational effects of TCDD from Agent Orange. A review of the world's literature on milk concentrations of polychlorinated compounds showed the presence of TCDD and other dioxins and furans in all countries that have been assessed. The congener profile of these chemicals, that is, the proportion of different congeners in the sample, can be used to assess the source of milk contamination. Measurements in most countries, including contemporary measurements in Vietnam, are consistent with non-Agent Orange exposure sources, including industrial activities and incineration of waste. Models and supporting human data suggest that TCDD from breastfeeding does not persist in a child past adolescence and that the adult body burden of TCDD is independent of whether the individual was breast- or bottle-fed as a child. These findings suggest that exposure to Agent Orange in Vietnam did not result in persistent transgenerational exposure through human milk.

  15. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

  16. S-arylcysteine-keratin adducts as biomarkers of human dermal exposure to aromatic hydrocarbons.

    Science.gov (United States)

    Kang-Sickel, Juei-Chuan C; Fox, Donii D; Nam, Tae-Gyu; Jayaraj, Karupiah; Ball, Louise M; French, John E; Klapper, David G; Gold, Avram; Nylander-French, Leena A

    2008-04-01

    aromatic hydrocarbon) detected in the exposed intact human skin. Quantitation of naphthyl-keratin adducts in the skin of exposed individuals will allow us to investigate the importance of dermal penetration, metabolism, and adduction to keratin and to predict more accurately the contribution of dermal exposure to systemic dose for use in exposure and risk-assessment models.

  17. Effects of gasoline and ethanol-gasoline exhaust exposure on human bronchial epithelial and natural killer cells in vitro.

    Science.gov (United States)

    Roth, Michèle; Usemann, Jakob; Bisig, Christoph; Comte, Pierre; Czerwinski, Jan; Mayer, Andreas C R; Beier, Konstantin; Rothen-Rutishauser, Barbara; Latzin, Philipp; Müller, Loretta

    2017-08-24

    Air pollution exposure, including passenger car emissions, may cause substantial respiratory health effects and cancer death. In western countries, the majority of passenger cars are driven by gasoline fuel. Recently, new motor technologies and ethanol fuels have been introduced to the market, but potential health effects have not been thoroughly investigated. We developed and verified a coculture model composed of bronchial epithelial cells (ECs) and natural killer cells (NKs) mimicking the human airways to compare toxic effects between pure gasoline (E0) and ethanol-gasoline-blend (E85, 85% ethanol, 15% gasoline) exhaust emitted from a flexfuel gasoline car. We drove a steady state cycle, exposed ECs for 6h and added NKs. We assessed exhaust effects in ECs alone and in cocultures by RT-PCR, flow cytometry, and oxidative stress assay. We found no toxic effects after exposure to E0 or E85 compared to air controls. Comparison between E0 and E85 exposure showed a weak association for less oxidative DNA damage after E85 exposure compared to E0. Our results indicate that short-term exposure to gasoline exhaust may have no major toxic effects in ECs and NKs and that ethanol as part of fuel for gasoline cars may be favorable. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-02-21

    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.

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

    Science.gov (United States)

    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.

  20. Simulation of Longitudinal Exposure Data with Variance-Covariance Structures Based on Mixed Models

    Science.gov (United States)

    Longitudinal data are important in exposure and risk assessments, especially for pollutants with long half-lives in the human body and where chronic exposures to current levels in the environment raise concerns for human health effects. It is usually difficult and expensive to ob...

  1. Human aflatoxin exposure in Kenya, 2007: a cross-sectional study

    Science.gov (United States)

    Yard, Ellen E.; Daniel, Johnni H.; Lewis, Lauren S.; Rybak, Michael E.; Paliakov, Ekaterina M.; Kim, Andrea A.; Montgomery, Joel M.; Bunnell, Rebecca; Abudo, Mamo Umuro; Akhwale, Willis; Breiman, Robert F.; Sharif, Shahnaaz K.

    2013-01-01

    Aflatoxins contaminate approximately 25% of agricultural products worldwide. They can cause liver failure and liver cancer. Kenya has experienced multiple aflatoxicosis outbreaks in recent years, often resulting in fatalities. However, the full extent of aflatoxin exposure in Kenya has been unknown. Our objective was to quantify aflatoxin exposure across Kenya. We analysed aflatoxin levels in serum specimens from the 2007 Kenya AIDS Indicator Survey – a nationally representative, cross-sectional serosurvey. KAIS collected 15,853 blood specimens. Of the 3180 human immunodeficiency virus-negative specimens with ≥1 mL sera, we randomly selected 600 specimens stratified by province and sex. We analysed serum specimens for aflatoxin albumin adducts by using isotope dilution MS/MS to quantify aflatoxin B1-lysine, and normalised with serum albumin. Aflatoxin concentrations were then compared by demographic, socioeconomic and geographic characteristics. We detected serum aflatoxin B1-lysine in 78% of serum specimens (range = Aflatoxin exposure did not vary by sex, age group, marital status, religion or socioeconomic characteristics. Aflatoxin exposure varied by province (p aflatoxin exposure is a public health problem throughout Kenya, and it could be substantially impacting human health. Wide-scale, evidence-based interventions are urgently needed to decrease exposure and subsequent health effects. PMID:23767939

  2. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  3. Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders.

    Science.gov (United States)

    Burcham, Philip C

    2017-01-17

    Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.

  4. Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use and compulsive smoking

    Directory of Open Access Journals (Sweden)

    Ami eCohen

    2013-06-01

    Full Text Available Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake.

  5. C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.

    Science.gov (United States)

    Kanteti, Rajani; Dhanasingh, Immanuel; El-Hashani, Essam; Riehm, Jacob J; Stricker, Thomas; Nagy, Stanislav; Zaborin, Alexander; Zaborina, Olga; Biron, David; Alverdy, John C; Im, Hae Kyung; Siddiqui, Shahid; Padilla, Pamela A; Salgia, Ravi

    2016-01-01

    We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1981-05-01

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

  7. DNA adducts in human tissues:biomarkers of exposure to carcinogens in tobacco smoke

    OpenAIRE

    Phillips, D.H.

    1996-01-01

    Tobacco smoking causes millions of cancer deaths annually. Tobacco smoke is a complex mixture of thousands of chemicals including many known animal carcinogens. Because many carcinogens from DNA adducts in target animal or human tissues, the detection of the formation of adducts using such methods as postlabeling, immunoassay, fluorescence spectroscopy, and mass spectrometry is a means of monitoring human exposure to tobacco carcinogens. Smokers are at increased risk of cancer in many organs,...

  8. Companion animals symposium: humanized animal models of the microbiome.

    Science.gov (United States)

    Gootenberg, D B; Turnbaugh, P J

    2011-05-01

    Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.

  9. Setting safe acute exposure limits for halon replacement chemicals using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Vinegar, A; Jepson, G W; Cisneros, M; Rubenstein, R; Brock, W J

    2000-08-01

    Most proposed replacements for Halon 1301 as a fire suppressant are halogenated hydrocarbons. The acute toxic endpoint of concern for these agents is cardiac sensitization. An approach is described that links the cardiac endpoint as assessed in dogs to a target arterial concentration in humans. Linkage was made using a physiologically based pharmacokinetic (PBPK) model. Monte Carlo simulations, which account for population variability, were used to establish safe exposure times at different exposure concentrations for Halon 1301 (bromotrifluoromethane), CF(3)I (trifluoroiodomethane), HFC-125 (pentafluoroethane), HFC-227ea (1,1,1,2,3,3,3-heptafluoropropane), and HFC-236fa (1,1,1,3,3,3-hexafluoropropane). Application of the modeling technique described here not only makes use of the conservative cardiac sensitization endpoint, but also uses an understanding of the pharmacokinetics of the chemical agents to better establish standards for safe exposure. The combined application of cardiac sensitization data and physiologically based modeling provides a quantitative approach, which can facilitate the selection and effective use of halon replacement candidates.

  10. Accelerated 20-year sunlight exposure simulation of a photochromic foldable intraocular lens in a rabbit model

    Science.gov (United States)

    Werner, Liliana; Abdel-Aziz, Salwa; Peck, Carolee Cutler; Monson, Bryan; Espandar, Ladan; Zaugg, Brian; Stringham, Jack; Wilcox, Chris; Mamalis, Nick

    2011-01-01

    PURPOSE To assess the long-term biocompatibility and photochromic stability of a new photochromic hydrophobic acrylic intraocular lens (IOL) under extended ultraviolet (UV) light exposure. SETTING John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN Experimental study. METHODS A Matrix Aurium photochromic IOL was implanted in right eyes and a Matrix Acrylic IOL without photochromic properties (n = 6) or a single-piece AcrySof Natural SN60AT (N = 5) IOL in left eyes of 11 New Zealand rabbits. The rabbits were exposed to a UV light source of 5 mW/cm2 for 3 hours during every 8-hour period, equivalent to 9 hours a day, and followed for up to 12 months. The photochromic changes were evaluated during slitlamp examination by shining a penlight UV source in the right eye. After the rabbits were humanely killed and the eyes enucleated, study and control IOLs were explanted and evaluated in vitro on UV exposure and studied histopathologically. RESULTS The photochromic IOL was as biocompatible as the control IOLs after 12 months under conditions simulating at least 20 years of UV exposure. In vitro evaluation confirmed the retained optical properties, with photochromic changes observed within 7 seconds of UV exposure. The rabbit eyes had clinical and histopathological changes expected in this model with a 12-month follow-up. CONCLUSIONS The new photochromic IOL turned yellow only on exposure to UV light. The photochromic changes were reversible, reproducible, and stable over time. The IOL was biocompatible with up to 12 months of accelerated UV exposure simulation. PMID:21241924

  11. Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts

    Science.gov (United States)

    Fakhar-E-Alam, Muhammad; Akram, M. Waseem; Iqbal, Seemab; Alimgeer, K. S.; Atif, M.; Sultana, K.; Willander, M.; Wang, Zhiming M.

    2017-04-01

    Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

  12. Controlled exposures of human volunteers to sulfate aerosols. Health effects and aerosol characterization.

    Science.gov (United States)

    Avol, E L; Jones, M P; Bailey, R M; Chang, N M; Kleinman, M T; Linn, W S; Bell, K A; Hackney, J D

    1979-08-01

    Our laboratory has undertaken the study of possible acute adverse health effects of sulfate aerosols through controlled exposures of volunteer human subjects. Both healthy and asthmatic adult men were exposed for 2-hour periods (with intermittent exercise) to ammonium sulfate, ammonium bisulfate, and sulfuric acid of particle size distributions and concentrations intended to simulate "worst case" exposures during Los Angeles smog episodes. Lung function tests were performed by the subjects on entering and before exiting from a carefully controlled environmental chamber. Subject symptoms were evluated in a standardized manner. Aerosol concentrations and size distributions were determined by an on-line computer/aerometric monitoring system; gravimetric and chemical analyses were performed on impactor and total filter samples after test exposures. We found little or no evidence of adverse health effects from 2-hour multiple-day exposures to any of the compounds at "worst case" ambient concentrations.

  13. Biological effects on human health due to radiofrequency/microwave exposure

    DEFF Research Database (Denmark)

    Breckenkamp, Jürgen; Berg, Gabriele; Blettner, Maria

    2003-01-01

    electromagnetic pulses similar to those after a nuclear explosion. In all studies (except one that used a qualitative job-exposure-matrix) either the duration of occupational work as an approximation to actual exposure was determined or a simple yes/no differentiation was used based on a definition of high......We evaluated the methods and results of nine cohort studies dealing with the biological effects on human health from exposure to radiofrequencies/microwaves, published between 1980 and 2002. The size of the cohorts varied between 304 (3,362 person years) and nearly 200,000 persons (2.7 million...... person years). As exposures were defined: dielectric heaters in a plastic manufacturing plant, working with radio devices (professional and amateur), production of wireless communication technologies, radar devices of the Canadian police, radar units used by the military as well as artificially produced...

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Hepatitis B virus exposure in human immunodeficiency virus seropositive Cuban patients

    Directory of Open Access Journals (Sweden)

    Licel Rodríguez

    2000-04-01

    Full Text Available In order to estimate the prevalence of serological markers of exposure to Hepatitis B Virus (HBV, 295 subjects were selected at random from the National Registry of human immunodeficiency virus positive subjects. Evidence of exposure to HBV was defined as: testing Hepatitis B surface an