Multipathway Exposures Research Articles

Evaluation of High-Throughput Chemical Exposure Models: Case Study of Matched Environmental and Biological Measurements

U.S. EPA, under its ExpoCast program, is developing high-throughput near-field modeling methods to estimate chemical exposure and to provide real-world context to high-throughput screening (HTS) data. These novel modeling methods include reverse methods, which infer parent chemical exposures from biomonitoring measurements, and forward models to predict multi-pathway exposures from chemical use information and/or residential media concentrations. Both modeling methods were used to characterize the relationship between near-field environmental and biomarker measurements. Indoor air, house dust, and urine samples of 120 females (aged 60 to 80 years) were analyzed. In the measured data, 78% of the residential media measurements and 54% of the urine measurements were below the limit of quantification. Due to the degree of censoring in both air and dust data, we applied a latent variable estimation approach based on an expected relationship between air and dust concentrations. Using the partitioning model of Weschler and Nazaroff (Atmos. Env., 2010) and assumptions about the variance in concentrations within homes, we jointly estimated chemical-specific geometric mean air and dust concentrations from the observed measurements. This resulted in 14 chemicals with matched air, dust, and urine metabolite data. The indoor air and dust concentrations were compared to population median exposures inferred from urine metabolite concentrations using a reverse-dosimetry approach. Median air and dust concentrations were found to be correlated with inferred exposures; forward model predictions were used to characterize pathway contributions to aggregate exposures. These results demonstrate that the forward and reverse methods being developed in ExpoCast can predict intake amounts and routes of exposure, and that these models can also identify exposure pathways that contribute to biomarker concentrations in the general population. This abstract does not reflect EPA policy.

Human health risk assessment from exposure of heavy metals in soil samples of Jammu district of Jammu and Kashmir, India

Contamination in soil can directly pose significant health risks through oral ingestion, particle inhalation, and dermal contact. Here, we studied the contamination level of heavy metals in soil samples to assess the carcinogenic and non-carcinogenic doses through multi-pathway exposures for health hazard point of view. The concentration of metals viz. zinc, iron, chromium, cadmium, copper, and manganese were measured in the collected soil samples of Jammu district, Jammu and Kashmir, India by using atomic absorption spectrometry (AAS). The average contents of the metals studied were as follows: Zn, 112 mg kg−1; Fe, 7403 mg kg−1; Cr, 92 mg kg−1; Cu, 37 mg kg−1; Cd, 0.4 mg kg−1; and Mn, 350 mg kg−1, respectively and metal decreased in the order Fe > Mn > Zn > Cr > Cu > Cd. The contamination factor, pollution load index, and index of geo-accumulation were also calculated to assess the quality of soil. Carcinogenic risk also has been calculated for Cr and Cd and carcinogenic doses for different exposure routes follow the order doses for ingestion (CDIing-ca) > > doses for inhalation (CDIinh-ca) > > doses for dermal absorption (CDIdermal-ca). Our results showed that the average values of Zn and Cd in the soil were within the acceptable limits, whereas the average values of Fe, Cr, Cu, and Mn in the soil samples were higher than the USEPA (1999) guidelines. The hazard index for both children and adults is less than unity, indicating no non-carcinogenic risk for both children and adults.

Multi-pathway exposure modeling of chemicals in cosmetics with application to shampoo

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 presented PiF based framework offers a novel and critical advancement for life cycle assessments and high-throughput exposure screening of chemicals in cosmetic products demonstrating the importance of consistent consideration of near- and far-field multi-pathway exposures.

Carcinogenic polycyclic aromatic hydrocarbons: an analysis of screening values, guidelines, and standards in the Northeast.

Risk-based, background, and laboratory quantitation limit-derived standards for carcinogenic polycyclic aromatic hydrocarbons (cPAHs) in residential and nonresidential soils vary across the northeast region of the United States. The magnitude and extent of this variation, however, have not been systematically studied. This article examines the technical basis and methodology used by eight northeastern states in the development of risk-based screening values, guidelines, and standards for cPAHs in soils. Exposure pathways, human receptors, algorithms, and input variables used by each state in the calculation of acceptable human health risks are identified and reviewed within the context of environmental policy and regulatory impacts. Emphasis is placed on a comparative analysis of multipathway exposures (incidental ingestion, dermal contact, and particulate inhalation) and key science-policy decisions that have led to the promulgation and adoption of different exposure criteria for cPAHs in the Northeast. More than 425 data points and 20 distinct exposure factors across eight state programs, 18 age subgroups, six activity scenarios, and three exposure pathways were systematically evaluated. Risk-based values for one state varied either above or below risk-based, background or laboratory quantitation limit-derived standards of another state for the same cPAH and receptor. Standards for cPAHs in soils were found to differ significantly across the northeast region--in some cases, by one or two orders of magnitude. While interstate differences can be expected to persist, future changes in federal guidance could mean a shift in risk drivers, compliance status, or calculated cumulative risks for individual properties impacted by PAH releases.

Golfer Exposure to Chlorpyrifos and Carbaryl Following Application to Turfgrass

Exposure of golfers to pesticides following their application to turfgrass is of concern to regulators, turfgrass professionals, and consumers. Multipathway exposures were evaluated for golfers on turfgrass treated with chlorpyrifos and carbaryl. Air concentrations and transferable foliar residues (TFRs) were measured to assess potential respiratory and dermal exposures, respectively. At the same time, exposure to individuals simulating the play of golf was determined by dosimetry and urinary biomonitoring. Individual golfer exposure was determined in 76 rounds of golf following eight applications of chlorpyrifos and two applications of carbaryl. Estimated exposures to golfers following full course and full rate applications of chlorpyrifos and carbaryl were 19-68 times below current U.S. EPA acute reference dose (Rfd) values, indicating safe exposures under U.S. EPA hazard quotient criteria. Dermal exposure was determined to be the dominant exposure pathway to golfers, accounting for approximately 60% of the chlorpyrifos absorbed dose and 100% of the carbaryl absorbed dose. This study also provides a set of transfer factors (TFs) that may be used to determine dermal exposure of golfers to pesticides using transferable residue data.

Assessing Human Exposure to Animal Neurocarcinogens: A Pilot Study

MAB4-O-04 Introduction: The assessment of multimedia and multipathway exposures to known and suspected animal neurocarcinogens (ANCs) in an epidemiologic investigation of brain cancer has not been attempted previously. We hypothesize that the poor associations or absence of causal links between exposure to a chemical agent and brain tumors may be due to inadequate exposure data underlying the analysis and/or exposure data nonspecific to chemicals, which have been demonstrated to cause neurocarcinogenicity in animal models. Methods: We present new human exposure assessment tools and methods used in support of a case-control study of brain tumors, with a focus on known and/or suspected animal neurocarcinogens. We initially reviewed the toxicity literature and compiled a list of 27 known ANCs and 15 suspected ANCs. Subsequently, we performed a comprehensive review of the physical, chemical, toxicological, environmental fate, and transport information for each compound to determine exposure media and pathway(s) of concern for each chemical of interest. Results: A neurocarcinogen-specific questionnaire was developed using occupational, environmental, and dietary exposure questions pertaining to specific exposure scenarios to assess overall human ANC exposure with consideration for the expected environmental media (air, water, and soil) and expected pathways of exposure (ingestion, inhalation, dermal). Data were obtained on approximately 200 cases from brain tumor clinics 180 friend and 180 sibling controls. Exposure specific indices created from these responses provide variation in human exposure for epidemiologic analysis. Preliminary results suggest exposures to selected ANCs in the breathing zone may increase the risk of brain tumors. Discussion and Conclusions: A neurocarcinogen questionnaire and detailed exposure matrix are essential for estimation of cumulative exposure index across pathway(s), across media, and across multiple chemicals. This exposure matrix links each compound to relevant questions in the questionnaire and allows calculation of an exposure score as a relative indicator of pathway-specific or cumulative exposure of an individual within the study population. These data, combined with biomarkers of exposure, will eventually provide a comprehensive assessment of ANCs and brain cancer.

From a Theoretical Framework of Human Exposure and Dose Assessment to Computational System Implementation: The Modeling ENvironment for TOtal Risk Studies (MENTOR)

Georgopoulos and Lioy (1994) presented a theoretical framework for exposure analysis, incorporating multiple levels of empirical and mechanistic information while characterizing/reducing uncertainties. The present review summarizes efforts towards implementing that framework, through the development of a mechanistic source-to-dose Modeling ENvironment for TOtal Risks studies (MENTOR), a computational toolbox that provides various modeling and data analysis tools to facilitate assessment of cumulative and aggregate (multipathway) exposures to contaminant mixtures. MENTOR adopts a “Person Oriented Modeling” (POM) approach that can be applied to either specific individuals or to populations/subpopulations of interest; the latter is accomplished by defining samples of “virtual” individuals that statistically reproduce the physiological, demographic, etc., attributes of the populations studied. MENTOR implementations currently incorporate and expand USEPA's SHEDS (Stochastic Human Exposure and Dose Simulation) approach and consider multiple exposure routes (inhalation, food, drinking water intake; non-dietary ingestion; dermal absorption). Typically, simulations involve: (1) characterizing background levels of contaminants by combining model predictions and measurement studies; (2) characterizing multimedia levels and temporal profiles of contaminants in various residential and occupational microenvironments; (3) selecting sample populations that statistically reproduce essential demographics (age, gender, race, occupation, education) of relevant population units (e.g., census tracts); (4) developing activity event sequences for each member of the sample by matching attributes to entries of USEPA's Consolidated Human Activity Database (CHAD); (5) calculating intake rates for the sample population members, reflecting physiological attributes and activities pursued; (6) combining intake rates from multiple routes to assess exposures; (7) estimating target tissue doses with physiologically based dosimetry/toxicokinetic modeling.

Distributions, associations, and partial aggregate exposure of pesticides and polynuclear aromatic hydrocarbons in the Minnesota Children's Pesticide Exposure Study (MNCPES).

The Minnesota Children's Pesticide Exposure Study (MNCPES) provides exposure, environmental, and biologic data relating to multipathway exposures of children for four primary pesticides (chlorpyrifos, malathion, diazinon, and atrazine), 14 secondary pesticides, and 13 polynuclear aromatic hydrocarbons (PAHs). Monitoring was performed on a probability-based sample of 102 children aged 3-12 in Minneapolis/St. Paul and in a nearby rural area (Goodhue and Rice counties). This paper provides estimated distributions of this population's exposures and exposure-related measurements and examines associations among the various measures via rank (Spearman) correlations. In addition, it provides some aggregate and cumulative exposure estimates for pesticides, and compares the relative intakes from inhalation and dietary ingestion. Intakes for the four primary pesticides appeared to come principally from the ingestion rather than the inhalation route; this was clearly true for chlorpyrifos but was less certain for the other three primary pesticides because of their higher degree of nondetects. Solid food rather than beverages was clearly the main contributor to the ingestion intake. Despite the dominance of the ingestion route, the urinary metabolite of chlorpyrifos exhibited a stronger association with the air measurements than with the dietary measures. Personal-air samples exhibited strong rank correlations with indoor air samples for chlorpyrifos, malathion, and diazinon (0.81, 0.51, and 0.62, respectively), while personal-air atrazine levels correlated well with outdoor levels (0.69); personal-air diazinon levels also correlated well with outdoor levels (0.67). For the PAHs, many significant associations were evident among the various air samples and for the air samples with the dust samples, especially for those compounds with consistently high percent measurable values (particularly fluoranthene, phenanthrene, and pyrene).

Measurement of multi-pollutant and multi-pathway exposures in a probability-based sample of children: practical strategies for effective field studies.

The purpose of this manuscript is to describe the practical strategies developed for the implementation of the Minnesota Children's Pesticide Exposure Study (MNCPES), which is one of the first probability-based samples of multi-pathway and multi-pesticide exposures in children. The primary objective of MNCPES was to characterize children's exposure to selected pesticides through a combination of questionnaires, personal exposure measurements (i.e., air, duplicate diet, hand rinse), and complementary monitoring of biological samples (i.e., pesticide metabolites in urine), environmental samples (i.e., residential indoor/outdoor air, drinking water, dust on residential surfaces, soil), and children's activity patterns. A cross-sectional design employing a stratified random sample was used to identify homes with age-eligible children and screen residences to facilitate oversampling of households with higher potential exposures. Numerous techniques were employed in the study, including in-person contact by locally based interviewers, brief and highly focused home visits, graduated subject incentives, and training of parents and children to assist in sample collection. It is not feasible to quantify increases in rates of subject recruitment, retention, or compliance that resulted from the techniques employed in this study. Nevertheless, results indicate that the total package of implemented procedures was instrumental in obtaining a high percentage of valid samples for targeted households and environmental media.

Aggregate Exposures under the Food Quality Protection Act: An Approach Using Chlorpyrifos

The Food Quality Protection Act of 1996 (Public Law 104-170, August 3, 1996), which amended the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA), requires that the EPA evaluate pesticide safety in light of potential aggregate exposures from both nondietary and dietary routes. As with any new legislation, there has been considerable discussion and challenges presented within the regulatory and scientific communities regarding the effective implementation of this act as it relates to the determination of aggregate exposures. This paper describes a novel methodology incorporating personal exposure factors, route-specific exposure measurements, and usage information to characterize potential aggregate exposures to a widely used pesticide, chlorpyrifos. A calendar model framework has been developed to describe potential multipathway exposures to individuals. The model assimilates information regarding the typical use patterns of chlorpyrifos-containing pesticides in concert with quantitative exposure and dose measurements to estimate the probability and magnitude of exposures to members of the U.S. population. Studies measuring 3,5,6-trichloropyridinol, the primary metabolite of chlorpyrifos, in the urine of individuals within the United States show that aggregate exposures derived from this approach are consistent with actual population-based exposures to chlorpyrifos. According to this assessment, potential health risks attributed to exposure to chlorpyrifos are low when compared to relevant toxicological end points.

Targeting Lead in the Multimedia Environment in the Continental United States

ABSTRACT The U.S. Environmental Protection Agency’s (EPA) lead attainment strategy for air is being expanded to address geographic areas with the potential for multimedia, multipathway exposures to lead. Geographic Information Systems (GIS) technology is used to coordinate information from various databases to identify areas of potential concern. The data retrieval and decision processes used in identifying priority sources from each medium and in evaluating identified areas of concern are described in this paper. Only EPA databases with reliable locational information were used to facilitate accurate mapping and allow correlation with other data sources. The sources of lead loadings to air, water, and soils were mapped using either latitude and longitude or zip code, or county centroids for data lacking longitudinal and latitudinal coordinates (such as the drinking water data). A multimedia cluster of lead sources was identified at the county level, since all the facility data in the five databases could be mapped to this level. An impact factor and weighting system was devised to combine the information on the number of facilities and their relative size in developing a ranking of the multimedia lead clusters of concern in each region. The counties with the highest number of points were considered clusters of highest concern for multimedia lead sources. Two separate lists of the clusters were developed according to a point system. One identified 10 multimedia lead clusters in each of the 10 EPA regions, and the other identified the 100 clusters of highest concern in the country as a whole. The project is designed to be a first step in targeting future efforts to identify potential environmental problems associated with lead. The analyses presented in this paper provide a first look at the areas in the country where there is a potential for multimedia exposure to lead. A more refined analysis at the zip code level was subsequently developed to provide a good understanding of the issues pertaining to potential exposure at the neighborhood level. The results of this analysis will ultimately help the EPA and the states to target implementation and enforcement in areas of high potential lead exposures.

Assessment of Health Risks Due to Hazardous Air Pollutant Emissions from Electric Utilities

ABSTRACTHazardous air pollutant (HAP) emissions from electric utilities were evaluated. Cancer risks, as well as noncancer effects, due to inhalation exposure were assessed for 67 HAPs. Also, cancer risks due to multipathway exposure to radionuclide emissions were assessed. In addition, an assessment of the fate of mercury (Hg) through various environmental media was included. Results suggest arsenic, chromium, and nickel are the HAPs that present the highest cancer risk due to inhalation exposure. For noncancer effects due to inhalation exposure, hydrogen chloride appears to present the greatest potential concern. The risks due to multipathway exposure to radionuclides are estimated to be of similar magnitude to the risks posed by inhalation of arsenic and nickel. Mercury is of potential concern for multipathway exposures because it persists in the environment and bioaccumulates in the aquatic food web. The study suggests there is a plausible link between Hg emissions from utilities and the Hg found in soil, water, and freshwater fish.