Linking exposure to per- and polyfluoroalkyl substances (PFAS) in house dust and biomonitoring data in eight impacted communities.

Per- and polyfluoroalkyl substances (PFAS) are widely used in industry and have been linked to various adverse health effects. Communities adjacent to sites where PFAS are manufactured, stored, or used may be at elevated risk. In these impacted communities, significant exposure often occurs through contaminated drinking water, yet less is known about the role of other pathways such as residential exposure through house dust. We analyzed a paired serum and house dust dataset from the Agency for Toxic Substances and Disease Registry's PFAS Exposure Assessments, which sampled eight United States communities with a history of drinking water contamination due to aqueous film forming foam (AFFF) use at nearby military bases. We found that serum PFAS levels of residents were significantly positively associated with the dust PFAS levels in their homes, for three of seven PFAS analyzed, when accounting for site and participant age. We also found that increased dust PFAS levels were associated with a shift in the relative abundance of PFAS in serum towards those chemicals not strongly linked to AFFF contamination, which may suggest household sources. Additionally, we analyzed participant responses to exposure questionnaires to identify factors associated with dust PFAS levels. Dust PFAS levels for some analytes were significantly elevated in households where participants were older and had lived at the home longer, cleaned less frequently, used stain resistant products, and had carpeted living rooms. Our results suggest that residential exposure to PFAS via dust or other indoor pathways may contribute to overall exposure and body burden, even in communities impacted by AFFF contamination of drinking water, and the magnitude of this exposure may also be influenced by demographic, behavioral, and housing factors.

Systematic evidence mapping of potential correlates of exposure for per- and poly-fluoroalkyl substances (PFAS) based on measured occurrence in biomatrices and surveys of dietary consumption and product use.

Per- and poly-fluoroalkyl substances (PFAS) are widely observed in environmental media and often are found in indoor environments as well as personal-care and consumer products. Humans may be exposed through water, food, indoor dust, air, and the use of PFAS-containing products. Information about relationships between PFAS exposure sources and pathways and the amounts found in human biomatrices can inform source-contribution assessments and provide targets for exposure reduction. This work collected and collated evidence for correlates of PFAS human exposure as measured through sampling of biomatrices and surveys of dietary consumption and use of consumer products and articles. A systematic evidence mapping approach was applied to perform a literature search, conduct title-abstract and full-text screening, and to extract primary data into a comprehensive database for 16 PFAS. Parameters of interest included: sampling dates and locations, cohort descriptors, PFAS measured in a human biomatrix, information about food consumption in 11 categories, use of products/articles in 11 categories, and reported correlation values (and their statistical strength). The literature search and screening process yielded 103 studies with information for correlates of PFAS exposures. Detailed data were extracted and compiled on measures of PFAS correlations between biomatrix concentrations and dietary consumption and other product/article use. A majority of studies (61/103; 59%) were published after 2015 with few (8/103; 8%) prior to 2010. Studies were most abundant for dietary correlates (n = 94) with fewer publications reporting correlate assessments for product use (n = 56), while some examined both. PFOA and PFOS were assessed in almost all studies, followed by PFHxS, PFNA, and PFDA which were included in >50% of the studies. No relevant studies included PFNS or PFPeS. Among the 94 studies of dietary correlates, significant correlations were reported in 83% of the studies for one or more PFAS. The significant dietary correlations most commonly were for seafood, meats/eggs, and cereals/grains/pulses. Among the 56 studies of product/article correlates, significant correlations were reported in 70% of the studies. The significant product/article correlations most commonly were for smoking/tobacco, cosmetics/toiletries, non-stick cookware, and carpet/flooring/furniture and housing. Six of 11 product/article categories included five or fewer studies, including food containers and stain- and water-resistant products. Significant dietary and product/article correlations most commonly were positive. Some studies found a mix of positive and negative correlations depending on the PFAS, specific correlate, and specific response level, particularly for fats/oils, dairy consumption, food containers, and cosmetics/toiletries. Most of the significant findings for cereals/grains/pulses were negative correlations. Substantial evidence was found for correlations between dietary intake and biomatrix levels for several PFAS in multiple food groups. Studies examining product/article use relationships were relatively sparse, except for smoking/tobacco, and would benefit from additional research. The resulting database can inform further assessments of dietary and product use exposure relationships and can inform new research to better understand PFAS source-to-exposure relationships. The search strategy should be extended and implemented to support living evidence review in this rapidly advancing area.

Separating Measurement Error and Signal in Environmental Data: Use of Replicates to Address Uncertainty.

Measurement uncertainty has long been a concern in the characterizing and interpreting environmental and toxicological measurements. We compared statistical analysis approaches when there are replicates: a Naïve approach that omits replicates, a Hybrid approach that inappropriately treats replicates as independent samples, and a Measurement Error Model (MEM) approach in a random effects analysis of variance (ANOVA) model that appropriately incorporates replicates. A simulation study assessed the effects of sample size and levels of replication, signal variance, and measurement error on estimates from the three statistical approaches. MEM results were superior overall with confidence intervals for the observed mean narrower on average than those from the Naïve approach, giving improved characterization. The MEM approach also featured an unparalleled advantage in estimating signal and measurement error variance separately, directly addressing measurement uncertainty. These MEM estimates were approximately unbiased on average with more replication and larger sample sizes. Case studies illustrated analyzing normally distributed arsenic and log-normally distributed chromium concentrations in tap water and calculating MEM confidence intervals for the true, latent signal mean and latent signal geometric mean (i.e., with measurement error removed). MEM estimates are valuable for study planning; we used simulation to compare various sample sizes and levels of replication.

Assessing lead exposure in U.S. pregnant women using biological and residential measurements.

There is strong scientific evidence for multiple pathways of human exposure to lead (Pb) in residential settings, particularly for young children; however, less is known about maternal exposure during pregnancy and children's exposure during early lifestages. A robust, multi-faceted secondary analysis was conducted using data collected by the National Institute of Child Health and Human Development in the 2009-2014 National Children's Study Vanguard Studies. Descriptive statistics summarized Pb concentrations of maternal blood, maternal urine, and house dust vacuum samples collected during pregnancy and residence surface wipes collected both during pregnancy and six months post-partum. The maternal blood Pb level geometric mean was 0.44 µg/dL (n = 426), with no women having values ≥ 5 µg/dL; creatinine-adjusted maternal urinary Pb geometric mean was 0.43 µg/g (n = 366). These blood and urine concentrations are similar to those observed for females in the general U.S. population in the National Health and Nutrition Examination Survey 2010-2011 cycle. A modest correlation between maternal blood Pb and surface wipe measurements during pregnancy was observed (Spearman r = 0.35, p < 0.0001). Surface wipe Pb loadings obtained in mother's homes during pregnancy (n = 640) and from areas where children spent the most time at roughly 6 months of age (n = 99) ranged from 0.02 to 71.8 ng/cm2, with geometric means of 0.47 and 0.49 ng/cm2, respectively, which were relatively low compared to other national studies. Survey responses of demographic, lifestyle, and residence characteristics were assessed for associations with blood concentration and surface wipe loading. Demographic (e.g., race/ethnicity, income, education, marital status) and housing characteristics (e.g., year home built, paint condition, own or rent home, attached garage) were associated with both maternal blood and surface wipe loadings during pregnancy. The availability of residential environmental media and extensive survey data provided enhanced understanding of Pb exposure during pregnancy and early life.

Advancing Methodologies Used in Trace Element-Based Mass Balance Studies to Separately Estimate Soil and Dust Ingestion Rates for Children.

Historically, soil ingestion rate estimates were based on trace element-based mass balance (MB) study results. These were used in assessing exposures and health risks for children residing in Superfund or chemically contaminated communities. However, soil and dust can have considerable differences with respect to their sources, chemical, physical, and toxicological characteristics. Unfortunately, the MB approach is incapable of disentangling dust ingestion rates from soil ingestion rates. Alternative methods, such as activity pattern and biokinetic modeling techniques, have also been used to predict soil and dust ingestion rates. The results from these studies differed from those obtained from the MB studies. This research evaluated the MB methodology and formulated a physical model which characterized the environmental and behavioral determinants of soil and dust ingestion exposures by children. This new approach explicitly separates outdoor soil exposures from the indoor tracked-in soil portion of the dust and total dust exposures by utilizing information from five key MB studies along with new information derived from the SHEDS-Soil/Dust time-activity pattern-based modeling runs. Application of this new hybrid methodology showed that the predicted mean soil ingestion rates are 30%-70% less than the "total soil" ingestion rates obtained from the selected MB studies. In contrast, most of the predicted dust ingestion rate estimates were typically greater than the predicted soil ingestion rates. Moreover, the predicted total soil plus dust ingestion rates were found to be mostly higher (by ≤ 60%) than the MB-based "total soil" ingestion rates. Except for one study these results were higher than the results produced by the stand-alone SHEDS-Soil/Dust model runs. Across the MB studies analyzed, predicted outdoor soil ingestion rate contributions to "total soil" ingestion rates varied between 29% and 70% while the tracked-in soil portion of the indoor dust ingestion rates varied between 30% and 71%.

Systematic Evidence Mapping of Potential Exposure Pathways for Per- and Polyfluoroalkyl Substances Based on Measured Occurrence in Multiple Media.

Given that human biomonitoring surveys show per- and polyfluoroalkyl substances (PFAS) to be ubiquitous, humans can be exposed to PFAS through various sources, including drinking water, food, and indoor environmental media. Data on the nature and level of PFAS in residential environments are required to identify important pathways for human exposure. This work investigated important pathways of exposure to PFAS by reviewing, curating, and mapping evidence for the measured occurrence of PFAS in exposure media. Real-world occurrence for 20 PFAS was targeted primarily in media commonly related to human exposure (outdoor and indoor air, indoor dust, drinking water, food, food packaging, articles, and products, and soil). A systematic-mapping process was implemented to conduct title-abstract and full-text screening and to extract PECO-relevant primary data into comprehensive evidence databases. Parameters of interest included the following: sampling dates and locations, numbers of collection sites and participants, detection frequencies, and occurrence statistics. Detailed data were extracted on PFAS occurrence in indoor and environmental media from 229 references and on PFAS occurrence in human matrices where available from those references. Studies of PFAS occurrence became numerous after 2005. Studies were most abundant for PFOA (80% of the references) and PFOS (77%). Many studies analyzed additional PFAS, particularly, PFNA and PFHxS (60% of references each). Food (38%) and drinking water (23%) were the commonly studied media. Most studies found detectable levels of PFAS, and detectable levels were reported in a majority of states in the United States. Half or more of the limited studies for indoor air and products detected PFAS in 50% or more of the collected samples. The resulting databases can inform problem formulation for systematic reviews to address specific PFAS exposure queries and questions, support prioritization of PFAS sampling, and inform PFAS exposure measurement studies. The search strategy should be extended and implemented to support living evidence review in this rapidly advancing area.

Geographic and demographic variability in serum PFAS concentrations for pregnant women in the United States.

BACKGROUND: While major pathways of human PFAS exposure are thought to be drinking water and diet, other pathways and sources have also been shown to contribute to a person's cumulative exposure. However, the degree of contribution of these other sources to PFAS body burdens is still not well understood and occurrence data for PFAS in conssumer products and household materials are sparse. Questionnaire data concordant with biomonitoring may improve understanding of associations between other PFAS exposure pathways and exposure in human populations. OBJECTIVE: This study aims to better understand maternal and early-life exposures to PFAS from various potential sources and pathways in the context of household and community level characteristics. METHODS: PFAS data from the National Children's Study (NCS) Vanguard Data and Sample Archive Access System were analyzed from serum of 427 pregnant women residing in 7 counties throughout the United States. Location and self-reported questionnaire responses were used to analyze variability in serum concentrations based on demographics, housing characteristics, behaviors, and geography. Spatial mapping analyses incorporated publicly available data to further hypothesize potential sources of exposure in two NCS counties. RESULTS: Location was associated with serum concentrations for all PFAS chemicals measured. Questionnaire responses for race/ethnicity, income, education level, number of household members, drinking water source, home age, and fast-food consumption were associated with PFAS levels. Statistical differences were observed between participants with the same questionnaire responses but in different locations. Spatial mapping analyses suggested that participants' proximity to local point sources can overshadow expected trends with demographic information. SIGNIFICANCE: By increasing understanding of maternal and early-life PFAS exposures from various potential sources and pathways, as well as highlighting the importance of proximity to potential sources in identifying vulnerable populations and locations, this work reveals environmental justice considerations and contributes to risk management strategies that maximize public health protection. IMPACT: This work increases understanding of maternal and early-life PFAS exposures, reveals environmental justice considerations, and contributes to study design and risk management strategies.

Model-based predictions of soil and dust ingestion rates for U.S. adults using the stochastic human exposure and dose simulation soil and dust model.

BACKGROUND: Adults can be exposed to chemicals through incidental ingestion of soil and dust, either through hobbies, occupations, or behaviors that increase contact with soil or dust (e.g., cleaning or renovating). However, few data describing these ingestion rates are available. OBJECTIVE: Our objective was to use the Stochastic Human Exposure and Dose Simulation Soil and Dust (SHEDS-Soil/Dust) model to estimate distributions of soil and dust ingestion rates for adults (≥21 years old) with varying degrees of soil and dust contact. METHODS: We parameterized SHEDS-Soil/Dust to estimate soil and dust ingestion rates for several categories of adults: adults in the general population; adults with moderate (higher) soil exposure (represented by hobbyists, such as gardeners, with increased soil contact); adults with high soil exposure (represented by occupationally exposed individuals, such as landscapers); and individuals who have high dust exposure (e.g., are in contact with very dusty indoor environments). RESULTS: Total soil plus dust ingestion for adults in the general population was 7 mg/day. Hobbyists or adults with moderate soil exposure averaged 33 mg/day and occupationally exposed individuals averaged 123 mg/day. Total soil plus dust ingestion for adults in the high dust exposure scenario was 25 mg/day. Results were driven by time spent in contact with soil and, thus, warmer seasons (e.g., summer) were associated with higher ingestion rates than colder seasons (e.g., winter). SIGNIFICANCE: These results provide modeled estimates of soil and dust ingestion rates for adults for use in decision making using real-world exposure considerations. These modeled estimates suggest that soil and dust ingestion is a potential concern for adults who spend a higher amount of time interacting with either soil or dusty environments. IMPACT STATEMENT: The parameterization of real-world scenarios within the application of SHEDS-Soil/Dust model to predict soil and dust ingestion rates for adults provides estimates of soil and dust ingestion rates useful for refining population-based risk assessments. These data illuminate drivers of exposure useful for both risk management decisions and designing future studies to improve existing tracer methodologies.

Model based prediction of age-specific soil and dust ingestion rates for children.

BACKGROUND: Soil and dust ingestion can be a primary route of environmental exposures. Studies have shown that young children are more vulnerable to incidental soil and dust ingestion. However, available data to develop soil and dust ingestion rates for some child-specific age groups are either lacking or uncertain. OBJECTIVE: Our objective was to use the Stochastic Human Exposure and Dose Simulation Soil and Dust (SHEDS-Soil/Dust) model to estimate distributions of soil and dust ingestion rates for ten age ranges from infancy to late adolescents (birth to 21 years). METHODS: We developed approaches for modeling age groups previously not studied, including a new exposure scenario for infants to capture exposures to indoor dust via pacifier use and accounting for use of blankets that act as a barrier to soil and dust exposure. RESULTS: Overall mean soil and dust ingestion rates ranged from ~35 mg/day (infants, 0-<6 m) to ~60 mg/day (toddlers and young children, 6m-<11 yr) and were considerably lower (about 20 mg/day) for teenagers and late adolescents (16-<21 y). The pacifier use scenario contributed about 20 mg/day to the median dust ingestion rate for young infants. Except for the infant age groups, seasonal analysis showed that the modeled estimates of average summer mean daily total soil plus dust ingestion rates were about 50% higher than the values predicted for the winter months. Pacifier use factors and carpet dust loading values were drivers of exposure for infants and younger children. For older children, influential variables included carpet dust loading, soil adherence, and factors that capture the frequency and intensity of hand-to-mouth behaviors. SIGNIFICANCE: These results provide modeled estimates of children's soil and dust ingestion rates for use in decision making using real-world exposure considerations. IMPACT STATEMENT: The parameterization of scenarios to capture infant soil and dust ingestion and the application of SHEDS-Soil/Dust to a broader age range of children provides additional estimates of soil and dust ingestion rates that are useful in refining population-based risk assessments. These data illuminate drivers of exposure that are useful to both risk management applications and for designing future studies that improve upon existing tracer methodologies.

Censoring Trace-Level Environmental Data: Statistical Analysis Considerations to Limit Bias.

Trace-level environmental data typically include values near or below detection and quantitation thresholds where health effects may result from low-concentration exposures to one chemical over time or to multiple chemicals. In a cook stove case study, bias in dibenzo[a,h]anthracene concentration means and standard deviations (SDs) was assessed following censoring at thresholds for selected analysis approaches: substituting threshold/2, maximum likelihood estimation, robust regression on order statistics, Kaplan-Meier, and omitting censored observations. Means and SDs for gas chromatography-mass spectrometry-determined concentrations were calculated after censoring at detection and calibration thresholds, 17% and 55% of the data, respectively. Threshold/2 substitution was the least biased. Measurement values were subsequently simulated from two log-normal distributions at two sample sizes. Means and SDs were calculated for 30%, 50%, and 80% censoring levels and compared to known distribution counterparts. Simulation results illustrated (1) threshold/2 substitution to be inferior to modern after-censoring statistical approaches and (2) all after-censoring approaches to be inferior to including all measurement data in analysis. Additionally, differences in stove-specific group means were tested for uncensored samples and after censoring. Group differences of means tests varied depending on censoring and distributional decisions. Investigators should guard against censoring-related bias from (explicit or implicit) distributional and analysis approach decisions.

An algorithm for quantitatively estimating non-occupational pesticide exposure intensity for spouses in the Agricultural Health Study.

Residents of agricultural areas experience pesticide exposures from sources other than direct agricultural work. We developed a quantitative, active ingredient-specific algorithm for cumulative (adult, married lifetime) non-occupational pesticide exposure intensity for spouses of farmers who applied pesticides in the Agricultural Health Study (AHS). The algorithm addressed three exposure pathways: take-home, agricultural drift, and residential pesticide use. Pathway-specific equations combined (i) weights derived from previous meta-analyses of published pesticide exposure data and (ii) information from the questionnaire on frequency and duration of pesticide use by applicators, home proximity to treated fields, residential pesticide usage (e.g., termite treatments), and spouse's off-farm employment (proxy for time at home). The residential use equation also incorporated a published probability matrix that documented the likelihood active ingredients were used in home pest treatment products. We illustrate use of these equations by calculating exposure intensities for the insecticide chlorpyrifos and herbicide atrazine for 19,959 spouses. Non-zero estimates for ≥1 pathway were found for 78% and 77% of spouses for chlorpyrifos and atrazine, respectively. Variability in exposed spouses' intensity estimates was observed for both pesticides, with 75th to 25th percentile ratios ranging from 7.1 to 7.3 for take-home, 6.5 to 8.5 for drift, 2.4 to 2.8 for residential use, and 3.8 to 7.0 for the summed pathways. Take-home and drift estimates were highly correlated (≥0.98), but were not correlated with residential use (0.01‒0.02). This algorithm represents an important advancement in quantifying non-occupational pesticide relative exposure differences and will facilitate improved etiologic analyses in the AHS spouses. The algorithm could be adapted to studies with similar information.

Chemical and non-chemical stressors affecting childhood obesity: a systematic scoping review.

Childhood obesity in the United States has doubled over the last three decades and currently affects 17% of children and adolescents. While much research has focused on individual behaviors impacting obesity, little research has emphasized the complex interactions of numerous chemical and non-chemical stressors found in a child's environment and how these interactions affect a child's health and well-being. The objectives of this systematic scoping review were to (1) identify potential chemical stressors in the context of non-chemical stressors that impact childhood obesity; and, (2) summarize our observations for chemical and non-chemical stressors in regards to child-specific environments within a community setting. A review was conducted to identify chemical and non-chemical stressors related to childhood obesity for the childhood life stages ranging from prenatal to adolescence. Stressors were identified and grouped into domains: individual behaviors, family/household behaviors, community stressors, and chemical exposures. Stressors were related to the child and the child's everyday environments and used to characterize child health and well-being. This review suggests that the interactions of chemical and non-chemical stressors are important for understanding a child's overall health and well-being. By considering these relationships, the exposure science research community can better design and implement strategies to reduce childhood obesity.

Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study.

BACKGROUND: Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence. OBJECTIVE: We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina. METHODS: Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking (smoking status and pack-years), sex, and lifetime days of use of any pesticides. RESULTS: Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p = 0.049) and borderline for lifetime days (p = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence. CONCLUSIONS: These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted.

Relative Contributions of Agricultural Drift, Para-Occupational, and Residential Use Exposure Pathways to House Dust Pesticide Concentrations: Meta-Regression of Published Data.

BACKGROUND: Increased pesticide concentrations in house dust in agricultural areas have been attributed to several exposure pathways, including agricultural drift, para-occupational, and residential use. OBJECTIVE: To guide future exposure assessment efforts, we quantified relative contributions of these pathways using meta-regression models of published data on dust pesticide concentrations. METHODS: From studies in North American agricultural areas published from 1995 to 2015, we abstracted dust pesticide concentrations reported as summary statistics [e.g., geometric means (GM)]. We analyzed these data using mixed-effects meta-regression models that weighted each summary statistic by its inverse variance. Dependent variables were either the log-transformed GM (drift) or the log-transformed ratio of GMs from two groups (para-occupational, residential use). RESULTS: For the drift pathway, predicted GMs decreased sharply and nonlinearly, with GMs 64% lower in homes 250 m versus 23 m from fields (interquartile range of published data) based on 52 statistics from seven studies. For the para-occupational pathway, GMs were 2.3 times higher [95% confidence interval (CI): 1.5, 3.3; 15 statistics, five studies] in homes of farmers who applied pesticides more recently or frequently versus less recently or frequently. For the residential use pathway, GMs were 1.3 (95% CI: 1.1, 1.4) and 1.5 (95% CI: 1.2, 1.9) times higher in treated versus untreated homes, when the probability that a pesticide was used for the pest treatment was 1-19% and ≥ 20%, respectively (88 statistics, five studies). CONCLUSION: Our quantification of the relative contributions of pesticide exposure pathways in agricultural populations could improve exposure assessments in epidemiologic studies. The meta-regression models can be updated when additional data become available. Citation: Deziel NC, Beane Freeman LE, Graubard BI, Jones RR, Hoppin JA, Thomas K, Hines CJ, Blair A, Sandler DP, Chen H, Lubin JH, Andreotti G, Alavanja MC, Friesen MC. 2017. Relative contributions of agricultural drift, para-occupational, and residential use exposure pathways to house dust pesticide concentrations: meta-regression of published data. Environ Health Perspect 125:296-305; http://dx.doi.org/10.1289/EHP426.

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

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 near-field chemical sources (e.g., those originating from consumer products and building materials) that have traditionally been excluded from LCA. A new generation of rapid human exposure modeling and high-throughput toxicity testing is transforming chemical risk prioritization and provides an opportunity for integration of screening-level risk assessment (RA) with LCA. The combined LCA and RA approach considers environmental impacts of products alongside risks to human health, which is consistent with regulatory frameworks addressing RA within a sustainability mindset. A case study is presented to juxtapose LCA and risk screening approaches for a chemical used in a consumer product. The case study demonstrates how these new risk screening tools can be used to inform toxicity impact estimates in LCA and highlights needs for future research. The framework provides a basis for developing tools and methods to support decision making on the use of chemicals in products.

The Biomarkers of Exposure and Effect in Agriculture (BEEA) Study: Rationale, Design, Methods, and Participant Characteristics.

Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. At least 1,600 male farmers over 50 years of age will be enrolled in the BEEA study. During a home visit, participants are asked to complete a detailed interview about recent agricultural exposures and provide samples of blood, urine, and (since 2013) house dust. As of mid-September 2014, in total, 1,233 participants have enrolled. Most of these participants (83%) were still farming at the time of interview. Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk.

A review of nonoccupational pathways for pesticide exposure in women living in agricultural areas.

BACKGROUND: Women living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities. OBJECTIVE: Our objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas. METHODS: We evaluated the following nonoccupational exposure pathways: paraoccupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal). RESULTS: Among 35 publications identified (published 1995-2013), several reported significant or suggestive (p < 0.1) associations between paraoccupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified. CONCLUSIONS: Evidence supported the importance of paraoccupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies.

Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study.

Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993-97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999-2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.

Lifetime organophosphorous insecticide use among private pesticide applicators in the Agricultural Health Study.

Organophosphorous insecticides (OPs) are the most commonly used insecticides in US agriculture, but little information is available regarding specific OP use by individual farmers. We describe OP use for licensed private pesticide applicators from Iowa and North Carolina in the Agricultural Health Study (AHS) using lifetime pesticide use data from 701 randomly selected male participants collected at three time periods. Of 27 OPs studied, 20 were used by >1%. Overall, 95% had ever applied at least one OP. The median number of different OPs used was 4 (maximum=13). Malathion was the most commonly used OP (74%) followed by chlorpyrifos (54%). OP use declined over time. At the first interview (1993-1997), 68% of participants had applied OPs in the past year; by the last interview (2005-2007), only 42% had. Similarly, median annual application days of OPs declined from 13.5 to 6 days. Although OP use was common, the specific OPs used varied by state, time period, and individual. Much of the variability in OP use was associated with the choice of OP, rather than the frequency or duration of application. Information on farmers' OP use enhances our ability to characterize and understand the potential health effects of multiple OP exposures.