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Chemical-induced alteration of maternal thyroid hormone levels may increase the risk of adverse neurodevelopmental outcomes in offspring. US federal risk assessments rely almost exclusively on apical endpoints in animal models for deriving points of departure (PODs). New approach methodologies (NAMs) such as high-throughput screening (HTS) and mechanistically informative in vitro human cell-based systems, combined with in vitro to in vivo extrapolation (IVIVE), supplement in vivo studies and provide an alternative approach to calculate/determine PODs. We examine how parameterization of IVIVE models impacts the comparison between IVIVE-derived equivalent administered doses (EADs) from thyroid-relevant in vitro assays and the POD values that serve as the basis for risk assessments. Pesticide chemicals with thyroid-based in vitro bioactivity data from the US Tox21 HTS program were included (

Purpose of Review Our comparative analysis sought to understand the factors which drive differences in fish consumption advisories across the USA — including exposure scenarios (acute and chronic health risk, non-cancer and cancer health endpoints), toxicity values (reference dose, cancer slope factor, acute tolerance level), and meal size and bodyweight assumptions. Recent Findings Fish consumption provides essential nutrients but also results in exposure to contaminants such as PCBs and methylmercury. To protect consumers from the risks of fish contaminants, fish consumption advisories are established, most often by state jurisdictions, to estimate the amount of a certain fish species a person could consume throughout their lifetime without harm. However, inconsistencies in advisories across the USA confuse consumers and undermine the public health goals of fish advisory programs. To date, no rigorous comparison of state and national fish consumption advisories has been reported. Summary Our work identifies discrepancies in key assumptions used to derive risk-based advisories between US states, reflecting differences in the interpretation of toxicity science. We also address the implications for these differences by reviewing advisories issued by contiguous states bordering two waterbodies: Lake Michigan and the Lower Mississippi River. Our findings highlight the importance of regional collaboration when issuing advisories, so that consumers of self-caught fish are equipped with clear knowledge to make decisions to protect their health.

Human exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous, with mixtures of PFAS detected in drinking water, food, household dust, and other exposure sources. Animal toxicity studies and human epidemiology indicate that PFAS may act through shared mechanisms including activation of peroxisome proliferator activated receptor α (PPARα). However, the effect of PFAS mixtures on human relevant molecular initiating events remains an important data gap in the PFAS literature. Here, we tested the ability of modeling approaches to predict the effect of diverse PPARα ligands on receptor activity using Cos7 cells transiently transfected with a full length human PPARα (hPPARα) expression construct and a peroxisome proliferator response element-driven luciferase reporter. Cells were treated for 24 hours with two full hPPARα agonists (pemafibrate and GW7647), a full and a partial hPPARα agonist (pemafibrate and mono(2-ethylhexyl) phthalate), or a full hPPARα agonist and a competitive antagonist (pemafibrate and GW6471). Receptor activity was modeled with three additive approaches: effect summation, relative potency factors (RPF), and generalized concentration addition (GCA). While RPF and GCA accurately predicted activity for mixtures of full hPPARα agonists, only GCA predicted activity for full and partial hPPARα agonists and a full agonist and antagonist. We then generated concentration response curves for seven PFAS, which were well-fit with three-parameter Hill functions. The four perfluorinated carboxylic acids (PFCA) tended to act as full hPPARα agonists while the three perfluorinated sulfonic acids (PFSA) tended to act as partial agonists that varied in efficacy between 28-67% of the full agonist, positive control level. GCA and RPF performed equally well at predicting the effects of mixtures with three PFCAs, but only GCA predicted experimental activity with mixtures of PFSAs and a mixture of PFCAs and PFSAs at ratios found in the general population. We conclude that of the three approaches, GCA most accurately models the effect of PFAS mixtures on hPPARα activity in vitro. Understanding the differences in efficacy with which PFAS activate hPPARα is essential for accurately predicting the effects of PFAS mixtures. As PFAS can activate multiple nuclear receptors, future analyses should examine mixtures effects in intact cells where multiple molecular initiating events contribute to proximate effects and functional changes.

Background Characterizing retrospective exposure to toxicants during multiple early-life developmental periods is challenging, yet critical for understanding developmental effects. Objective To characterize early-life metal exposure using deciduous teeth in a community concerned about past exposures. Methods Naturally shed teeth were collected from 30 children ages 5–13 years who resided in Holliston, Massachusetts since conception. We estimated weekly prenatal and postnatal (up to 1 year of age) exposure to 12 metals by measuring dentine concentrations using laser ablation-inductively coupled plasma-mass spectrometry. Multivariable linear mixed models were used to explore sociodemographic, dietary, and behavioral correlates of dentine metal concentrations. Results Temporal trends in dentine levels differed by metal. Source of milk during the first year of life was associated with dentine barium (Ba) levels, where being fed predominantly breastmilk was associated with 39% (95% CI: –57%, –13%) lower dentine Ba compared to predominantly formula use. Females had higher prenatal and postnatal dentine Mn and Pb, compared to males (e.g., % difference, postnatal Mn: 122% (17%, 321%); postnatal Pb: 60% (95% CI: –8%, 178%)). Significance Deciduous teeth provide retrospective information on dose and timing of early-life metals exposure at high resolution. We demonstrate their utility in a community-based study with known past contamination of drinking water. Impact statement We conducted a community-initiated pilot study in a community concerned with historical exposure to multiple metals. Using deciduous teeth, a novel noninvasive biomarker, we characterized early-life exposure to 12 metals in approximately weekly increments during sensitive developmental periods, thus demonstrating the utility of this biomarker in communities concerned with past exposures.

Elevated red blood cell distribution width (RDW), traditionally an indicator of anemia, has now been recognized as a risk marker for cardiovascular disease incidence and mortality. Experimental and acute exposure studies suggest that cadmium and lead individually affect red blood cell production; however, associations between environmental exposures and RDW have not been explored. We evaluated relationships of environmental cadmium and lead exposures to RDW. We used data from 24,607 participants aged ≥20 years in the National Health and Nutrition Examination Survey (2003–2016) with information on blood concentrations of cadmium and lead, RDW and socio-demographic factors. In models adjusted for age, sex, race/ethnicity, education, poverty income ratio, BMI, alcohol consumption, smoking status and serum cotinine, RDW was increasingly elevated across progressively higher quartiles of blood cadmium concentration. A doubling of cadmium concentration was associated with 0.16 higher RDW (95% CI: 0.14, 0.18) and a doubling of lead concentration with 0.04 higher RDW (95% CI: 0.01, 0.06). Also, higher cadmium and lead concentrations were associated with increased odds of high RDW (RDW>14.8%). The associations were more pronounced in women and those with low-to-normal mean corpuscular volume (MCV) and held even after controlling for iron, folate or vitamin B12 deficiencies. In analysis including both metals, cadmium remained associated with RDW, whereas the corresponding association for lead was substantially attenuated. In this general population sample, blood cadmium and lead exposures were positively associated with RDW. The associations may indicate hemolytic or erythropoietic mechanisms by which exposure increases mortality risk.

Concentration/dose addition is widely used for compounds that act by similar mechanisms. But it cannot make predictions for mixtures of full and partial agonists for effect levels above that of the least efficacious component. As partial agonists are common, we developed generalized concentration addition, which has been successfully applied to systems in which ligands compete for a single binding site. Here, we applied a pharmacodynamic model for a homodimer receptor system with 2 binding sites, the androgen receptor, that acts according to the classic homodimer activation model: Each cytoplasmic monomer protein binds ligand, undergoes a conformational change that relieves inhibition of dimerization, and binds to DNA response elements as a dimer. We generated individual dose-response data for full (dihydroxytestosterone, BMS564929) and partial (TFM-4AS-1) agonists and a competitive antagonist (MDV3100) using reporter data generated in the MDA-kb2 cell line. We used the Schild method to estimate the binding affinity of MDV3100. Data for individual compounds fit the homodimer pharmacodynamic model well. In the presence of a full agonist, the partial agonist had agonistic effects at low effect levels and antagonistic effects at high levels, as predicted by pharmacological theory. The generalized concentration addition model fits the empirical mixtures data—full/full agonist, full/partial agonist, and full agonist/antagonist—as well or better than relative potency factors or effect summation. The ability of generalized concentration addition to predict the activity of mixtures of different types of androgen receptor ligands is important as a number of environmental compounds act as partial androgen receptor agonists or antagonists.

In the midst of the COVID-19 pandemic, United States (U.S.) educational institutions must weigh incomplete scientific evidence to inform decisions about how best to re-open schools without sacrificing public health. While many communities face surging case numbers, others are experiencing case plateaus or even decreasing numbers. Simultaneously, some U.S. school systems face immense infrastructure challenges and resource constraints, while others are better positioned to resume face-to-face instruction. In this review, we first examine potential engineering controls to reduce SARS-CoV-2 exposures; we then present processes whereby local decision-makers can identify and partner with scientists, faculty, students, parents, public health officials, and others to determine the controls most appropriate for their communities. While no solution completely eliminates risks of SARS-CoV-2 exposure and illness, this mini-review discusses engaged decision and communication processes that incorporate current scientific knowledge, school district constraints, local tolerance for health risk, and community priorities to help guide schools in selecting and implementing re-opening strategies that are acceptable, feasible, and context-specific.

This chapter will help you appreciate: environmental health in the rapidly changing context of health protection; the utility of having a framework for environmental health risk assessment; the process for conducting an environmental health risk assessment; the major strengths and limitations of risk assessment; the process of identifying, evaluating, and planning a response to an environmental health threat.

Humans are exposed to per- and polyfluoroalkyl substances (PFAS) in their drinking water, food, air, dust in their homes, and by direct use of consumer products. Increased concentrations of serum total cholesterol and low density lipoprotein cholesterol are among the endpoints best supported by epidemiology. The objectives of this study were to generate a new model for examining PFAS-induced dyslipidemia and to conduct molecular studies to better define mechanism(s) of action. We tested the hypothesis that PFOA exposure at a human-relevant level dysregulates expression of genes controlling cholesterol homeostasis in livers of mice expressing human PPARα (hPPARα). Female and male hPPARα and PPARα null mice were fed a diet based on the “What we eat in America” analysis and exposed to perfluorooctanoic acid (PFOA) in drinking water (8 µM) for 6 weeks. This resulted in a serum PFOA concentration of 48 μg/ml. PFOA increased liver mass, which was associated with histologically-evident lipid accumulation. PFOA induced PPARα and constitutive androstane receptor target gene expression in liver. Expression of genes in four pathways regulating cholesterol homeostasis were also measured. PFOA decreased expression ofHmgcrin a PPARα-dependent manner. PFOA decreased expression ofLdlrandCyp7a1in a PPARα-independent manner.Apobexpression was not changed. Gene expression in females appeared to be more sensitive to PFOA exposure than in males. This novel study design (hPPARα mice, American diet, long term exposure) generated new insight on the effects of PFOA on cholesterol regulation in the liver and the role of hPPARα.

In response to concerns raised by communities surrounding the New Bedford Harbor Superfund site, we completed a field and modeling study that concluded the harbor is the primary source of polychlorinated biphenyls (PCBs) in air around the harbor. The follow-up question from residents was whether the PCBs measured in air pose a risk to their health. The US Environmental Protection Agency focuses their site-specific, risk-based decisions for site clean-up on cancers. We focused our assessment on the non-cancer effects on the thyroid based on the congener specific patterns and concentrations of PCBs measured in air near and distant to the harbor. Human and animal studies of PCB-induced effects on the thyroid provide evidence to support our analysis. Drawing from the published toxicological data, we used a Margin of Exposure (MOE) approach to derive a human-equivalent concentration in air associated with human health effects on the thyroid. Based on the MOEs calculated herein, evaluation of the MOE indicates that changes in thyroid hormone levels are possible among people living adjacent to the Harbor. Changes in thyroid hormone levels are more likely among people who live near the harbor compared to residents living in areas distant from the harbor. This risk assessment documents potential health risks associated with proximity to a marine Superfund Site using site-specific ambient air PCB congener data.

In this manuscript, we describe the process of establishing partnerships for community-based environmental exposure research, the tools and methods implemented for data report-back to community members, and the results of evaluations of these efforts. Data discovery and report-back materials developed by Statistics for Action (SFA) were employed as the framework to communicate the environmental data to community members and workshops. These data communication and research translation efforts are described in detail and evaluated for effectiveness based on feedback provided from community members who attended the workshops. Overall, the methods were mostly effective for the intended data communication.

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor α (hPPARα)-expressing mice fed an American diet. Mice were exposed to PFOA (3.3 mg/l) in drinking water for 6 weeks resulting in a serum concentration of 48 ± 9 μg/ml. In male and female hPPARα mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of hPPARα alone also increased total liver TG, and PFOA treatment had little effect on liver TG in null mice. In hPPARα mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Across studies, a non-monotonic effect of PFOA on serum TG is evident, with the serum PFOA concentration in this study falling near the “null point” between increasing and decreasing serum TG. Intriguingly, in female PPARα null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPARα-dependent manner, but not in adipose. The results reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.

Qualitatively and quantitatively, we have demonstrated that airborne polychlorinated biphenyl (PCB) concentrations in the air surrounding New Bedford Harbor (NBH) are caused by its water PCB emissions. We measured airborne PCBs at 18 homes and businesses near NBH in 2015, with values ranging from 0.4 to 38 ng m–3, with a very strong Aroclor 1242/1016 signal that is most pronounced closest to the harbor and reproducible over three sampling rounds. Using U.S. Environmental Protection Agency (U.S. EPA) water PCB data from 2015 and local meteorology, we predicted gas-phase fluxes of PCBs from 160 to 1200 μg m–2 day–1. Fluxes were used as emissions for AERMOD, a widely applied U.S. EPA atmospheric dispersion model, to predict airborne PCB concentrations. The AERMOD predictions were within a factor of 2 of the field measurements. PCB emission from NBH (110 kg year–1, average 2015) is the largest reported source of airborne PCBs from natural waters in North America, and the source of high ambient air PCB concentrations in locations close to NBH. It is likely that NBH has been an important source of airborne PCBs since it was contaminated with Aroclors more than 60 years ago.

Tributyltin (TBT) and dioxin-like polychlorinated biphenyls (PCBs) are environmental contaminants that are highly toxic to fish and co-occur in New Bedford Harbor (NBH), an estuarine Superfund site located in Massachusetts, USA. Atlantic killifish (Fundulus heteroclitus) that reside in NBH (and other highly contaminated sites along the east coast of the United States) have developed resistance to activation of the aryl hydrocarbon receptor (AHR) pathway and the toxicity of dioxin-like chemicals, such as 3,3′,4,4′,5-pentachlorobiphenyl, PCB126. In many biological systems, TBT disregulates adipose and bone development via the PPARγ-RXR pathway; AHR activation also disrupts adipose and bone homeostasis, potentially through molecular crosstalk between AHR and PPARγ. However, little is known about how co-exposure and the interaction of these pathways modulate the toxicological effects of these contaminants. Here, we tested the hypotheses that TBT would induce teratogenesis in killifish via activation of PPARγ and that PCB126 co-exposure would suppress PPARγ pathway activation in PCB-sensitive killifish from a reference site (Scorton Creek, SC, PCB-sensitive) but not in PCB-tolerant NBH killifish. Killifish embryos from both populations exposed to TBT (50 and 100 nM) displayed caudal fin deformities. TBT did not change the expression of pparg or its target genes related to adipogenesis (fabp11a and fabp1b) in either population. However, expression of osx/sp7, an osteoblast marker gene, and col2a1b, a chondroblast marker gene, was significantly suppressed by TBT only in SC killifish. An RXR-specific agonist, but not a PPARγ-specific agonist, induced caudal fin deformities like those observed in TBT-treated embryos. PCB126 did not induce caudal fin deformities and did not exacerbate TBT-induced fin deformities. Further, PCB126 increased expression of pparg in SC embryos and not NBH embryos, but did not change the expression of fabp1b. Taken together, these results suggest that in killifish embryos the PPARγ pathway is regulated in part by AHR, but is minimally active at least in this early life stage. In killifish, RXR activation, rather than PPARγ activation, appears to be the mechanism by which TBT induces caudal fin teratogenicity, which is not modulated by AHR responsiveness.

Electrical manufacturing near New Bedford Harbor (NBH), MA in the mid-1900s led to severe polychlorinated biphenyl (PCB) contamination, which resulted in the harbor’s designation as a Superfund Site. Restrictions on the harvest of seafood from NBH have been in effect since 1979. Efforts to reduce the overall mass of PCBs in NBH by dredging PCB-contaminated sediments have been ongoing since the late 1980s. One goal of dredging is to reduce PCB concentrations in NBH seafood, monitored annually by Massachusetts Department of Environmental Protection (DEP) and Massachusetts Division of Marine Fisheries (MDMF). We used PCB concentrations in quahogs (2003-2016) and scup (2003-2014) to evaluate PCB distribution across seafood management areas and over time. Seafood PCB concentrations were used to evaluate improvements in environmental quality by examining total PCBs and patterns of PCB congeners within homolog groups, and by assessing human cancer risk from seafood consumption in the past (1980) and present (2012-2016). PCB concentrations in quahogs generally declined with increased time and distance from the PCB source, as does the cancer risk associated with their consumption. PCB concentrations in scup follow similar spatial patterns but show high annual variability. We conclude that quahogs are a reliable proxy for in-situ conditions, environmental quality, and human health risk.

Sentinel species such as the Atlantic killifish (Fundulus heteroclitus) living in urban waterways can be used as toxicological models to understand impacts of environmental metabolism disrupting compound (MDC) exposure on both wildlife and humans. Exposure to MDCs is associated with increased risk of metabolic syndrome, including impaired lipid and glucose homeostasis, adipogenesis, appetite control, and basal metabolism. MDCs are ubiquitous in the environment, including in aquatic environments. New Bedford Harbor (NBH), Massachusetts is polluted with polychlorinated biphenyls (PCBs), and, as we show for the first time, tin (Sn). PCBs and organotins are ligands for two receptor systems known to regulate lipid homeostasis, the aryl hydrocarbon receptor (AHR) and the peroxisome proliferator-activated receptors (PPARs), respectively. In the current study, we compared lipid homeostasis in laboratory-reared killifish from NBH (F2) and a reference location (Scorton Creek, Massachusetts; F1 and F2) to evaluate how adaptation to local conditions may influence responses to MDCs. Adult killifish from each population were exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126, dioxin-like), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153, non-dioxin-like), or tributyltin (TBT, a PPARγ ligand) by a single intraperitoneal injection and analyzed after 3 days. AHR activation was assessed by measuring cyp1a mRNA expression. Lipid homeostasis was evaluated phenotypically by measuring liver triglycerides and organosomatic indices, and at the molecular level by measuring the mRNA expression of pparg and ppara and a target gene for each receptor. Acute MDC exposure did not affect phenotypic outcomes. However, overall NBH killifish had higher liver triglycerides and adiposomatic indices than SC killifish. Both season and population were significant predictors of the lipid phenotype. Acute MDC exposure altered hepatic gene expression only in male killifish from SC. PCB126 exposure induced cyp1a and pparg, whereas PCB153 exposure induced ppara. TBT exposure did not induce ppar-dependent pathways. Comparison of lipid homeostasis in two killifish populations extends our understanding of how MDCs act on fish and provides a basis to infer adaptive benefits of these differences in the wild.

Flame retardants are widely used in polyurethane foam materials including gymnastics safety equipment such as pit cubes and landing mats. We previously reported elevated concentrations of flame retardants in the air and dust of a U.S. gymnastics training facility and elevated PentaBDE in the serum of collegiate gymnasts. Our objective in this pilot study was to compare urinary biomarkers of exposure to other flame retardants and additives of polyurethane foam including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), triphenyl phosphate (TPHP) and 2-ethylhexyl- 2,3,4,5-tetrabromobenzoate (EH-TBB) in samples collected from 11 collegiate gymnasts before and after a gymnastics practice (n = 53 urine samples total). We identified a 50% increase in the TPHP biomarker (p = 0.03) from before to after practice, a non-significant 22% increase in the TDCIPP biomarker (p = 0.14) and no change for the EH-TBB biomarker. These preliminary results indicate that the gymnastics training environment can be a source of recreational exposure to flame retardants. Such exposures are likely widespread, as we identified flame retardants in 89% of foam samples collected from gyms across the U.S. Keywords: Flame retardants, Gymnastics

BACKGROUND: Residential combustion (RC) and electricity generating unit (EGU) emissions adversely impact air quality and human health by increasing ambient concentrations of fine particulate matter (PM2.5) and ozone (O3). Studies to date have not isolated contributing emissions by state of origin (source-state), which is necessary for policy makers to determine efficient strategies to decrease health impacts. OBJECTIVES: In this study, we aimed to estimate health impacts (premature mortalities) attributable to PM2.5 and O3 from RC and EGU emissions by precursor species, source sector, and source-state in the continental United States for 2005. METHODS: We used the Community Multiscale Air Quality model employing the decoupled direct method to quantify changes in air quality and epidemiological evidence to determine concentration-response functions to calculate associated health impacts. RESULTS: We estimated 21,000 premature mortalities per year from EGU emissions, driven by sulfur dioxide emissions forming PM2.5. More than half of EGU health impacts are attributable to emissions from eight states with significant coal combustion and large downwind populations. We estimate 10,000 premature mortalities per year from RC emissions, driven by primary PM2.5 emissions. States with large populations and significant residential wood combustion dominate RC health impacts. Annual mortality risk per thousand tons of precursor emissions (health damage functions) varied significantly across source-states for both source sectors and all precursor pollutants. CONCLUSIONS: Our findings reinforce the importance of pollutant-specific, location-specific, and source-specific models of health impacts in design of health-risk minimizing emissions control policies. Citation: Penn SL, Arunachalam S, Woody M, Heiger-Bernays W, Tripodis Y, Levy JI. 2017. Estimating state-specific contributions to PM2.5- and O3-related health burden from residential combustion and electricity generating unit emissions in the United States. Environ Health Perspect 125:324-332; http://dx.doi.org/10.1289/EHP550.

USEPA recommends a multiple lines of evidence approach to make informed decisions at vapor intrusion sites because the vapor intrusion pathway is notoriously difficult to characterize. Our study uses this approach by incorporating groundwater, soil gas, indoor air field measurements and numerical models to evaluate vapor intrusion exposure risks in a Metro-Boston neighborhood known to exhibit lower than anticipated indoor air concentrations based on groundwater concentrations. We collected and evaluated five rounds of field sampling data over the period of one year. Field data results show a steep gradient in soil gas concentrations near the groundwater surface; however as the depth decreases, soil gas concentration gradients also decrease. Together, the field data and the numerical model results suggest that a subsurface feature is limiting vapor transport into indoor air spaces at the study site and that groundwater concentrations are not appropriate indicators of vapor intrusion exposure risks in this neighborhood. This research also reveals the importance of including relevant physical models when evaluating vapor intrusion exposure risks using the multiple lines of evidence approach. Overall, the findings provide insight about how the multiple lines of evidence approach can be used to inform decisions by using field data collected using regulatory-relevant sampling techniques, and a well-established 3-D vapor intrusion model.

Water recycling is one potential solution to meeting the growing global demand for water in an age of dwindling freshwater supplies. However, public opposition has played a key role historically in blunting the broad implementation of water recycling technologies across the United States. Addressing public concerns and overcoming this opposition is critical to the political viability of water recycling programs as a response to growing water insecurity. This analysis builds on existing research on Americans’ attitudes toward water recycling in three ways. First, it explores public understanding of basic elements of water recycling and identifies important gaps in public knowledge. Second, it examines the factors that most concern Americans about water recycling. Finally, it investigates how knowledge, specific concerns, and a range of other factors, including Americans’ environmental priorities, local context, partisan leanings, and demographic characteristics, combine to influence attitudes toward recycled water. The results identify several promising targets for future educational outreach efforts to build public support for water recycling projects. Policy-relevant knowledge is the single most important predictor of support for water recycling. Yet, there is a stark knowledge gap between a highly informed few and an unaware majority. Bridging this gap could greatly increase support for water recycling. Concerns about sewage contamination were most corrosive to support for water recycling, making them a prime target for further outreach. Finally, our results suggest that future educational campaigns may seek to decouple water scarcity and climate change in the public mind to avoid exacerbating existing cleavages.

Backyard chicken ownership is rapidly increasing in urban areas in the United States, largely as a way to provide eggs for household consumption. Despite elevated levels of environmental lead contamination in many US cities, the role of backyard chicken eggs as a pathway for lead exposure, particularly for children, has received limited scrutiny. To characterize lead exposure from consumption of backyard chicken eggs for children and predict related effects on blood lead level (BLL), we conducted a cross-sectional study of backyard chicken owners in the Greater Boston area (n = 51). We interviewed participants regarding egg consumption by household members and collected backyard eggs (n = 201) and coop soil samples (n = 48) for analysis. Inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate lead concentration in homogenized eggs and an X-ray fluorescence (XRF) portable device was used to assess soil lead levels in the laboratory. We used the USEPA's Integrated Exposure Uptake Biokinetic Model for Lead in Children (IEUBK) to assess the relative contribution of backyard egg consumption to aggregate BLL in children. Four scenarios were developed in the IEUBK model to address variability in egg consumption rates and egg lead contamination. Lead was detected in egg samples from 98% of the households that provided egg samples. Mean household lead concentration was 0.10 μg/g (SD: 0.18). Egg lead concentrations ranged from below the limit of detection (0.0014 μg/g) to 1.798 μg/g (1.4-1198 ppb). Egg lead levels were strongly positively correlated with lead concentration in coop soil (r = 0.64; p 0.001). In modeled scenarios where a child 7 years frequently ate eggs highly contaminated with lead, BLLs are predicted to increase by 0.9-1.5 μg/dL. In three other scenarios reflecting more moderate egg lead contamination and consumption rates, BLLs were predicted to increase from 0.1 to 0.8 μg/dL. Consumption of backyard chicken eggs can contribute to lead exposure in children. Soil lead remediation prior to chicken ownership may reduce lead exposure from backyard eggs.

Existing regulations seek to protect the public from exposure to polychlorinated biphenyls (PCBs) in food, water, and soil. Exposure to PCBs in ambient air has recently been given explicit consideration in the human health risk assessments that form the basis of risk management decisions at contaminated sites. The objective of this paper is to examine how ambient air exposure to PCBs is regulated and monitored at five contaminated sites in the United States. We reviewed online accessible materials (including Environmental Protection Agency-site specific websites, data repositories, and other agency websites). Results indicate that the five sites vary in regard to the measured PCB concentrations in air, the sampling and monitoring methodologies, and the established site-specific guidelines/standards and their basis. We conclude that current practices may not adequately protect those living or working near these sites from airborne PCB exposure and that regulations should include recognition of exposure to indoor sources.

The presence of industrial chemicals, consumer product chemicals, and pharmaceuticals is well documented in waters in the U.S. and globally. Most of these chemicals lack health-protective guidelines and many have been shown to have endocrine bioactivity. There is currently no systematic or national prioritization for monitoring waters for chemicals with endocrine disrupting activity. We propose ambient water bioactivity concentrations (AWBCs) generated from high throughput data as a health-based screen for endocrine bioactivity of chemicals in water. The U.S. EPA ToxCast program has screened over 1800 chemicals for estrogen receptor (ER) and androgen receptor (AR) pathway bioactivity. AWBCs are calculated for 110 ER and 212 AR bioactive chemicals using high throughput ToxCast data from in vitro screening assays and predictive pathway models, high-throughput toxicokinetic data, and data-driven assumptions about consumption of water. Chemical-specific AWBCs are compared with measured water concentrations in data sets from the greater Denver area, Minnesota lakes, and Oregon waters, demonstrating a framework for identifying endocrine bioactive chemicals. This approach can be used to screen potential cumulative endocrine activity in drinking water and to inform prioritization of future monitoring, chemical testing and pollution prevention efforts.

In this manuscript, we describe the process of establishing partnerships for community-based environmental exposure research, the tools and methods implemented for data report-back to community members, and the results of evaluations of these efforts. Data discovery and report-back materials developed by Statistics for Action (SFA) were employed as the framework to communicate the environmental data to community members and workshops. These data communication and research translation efforts are described in detail and evaluated for effectiveness based on feedback provided from community members who attended the workshops. Overall, the methods were mostly effective for the intended data communication.

Aircraft activity and airport operations can increase combustion-related air pollutant concentrations, but it is difficult to distinguish aviation emissions from traffic and other local sources. Emission inventories are uncertain and dispersion models may not capture aircraft plume complexity; ambient monitoring data require detailed statistical analyses to extract aviation signals. The goal of this study is to compare two modeling approaches including monitoring-based regression models and the EDMS/AERMOD dispersion model, informing improvements and allowing quantitation of aviation impacts on air quality through multi-pollutant sensitivity and multi-monitor fate/transport analyses. Aggregate concentration comparisons are similar, though diurnal patterns show potential weaknesses in near-field dispersion, treatment of overnight conditions, and emission inventory accuracy.

Tetrabromobisphenol-A (TBBP-A) and hexabromocyclododecanes (HBCDs) are brominated flame retardants that have been found in human milk and serum throughout the world, but have received comparatively little attention in the United States. The objective of this study is to determine concentrations of these analytes in samples of breast milk collected from first-time mothers in the Greater Boston, Massachusetts area and to explore predictors of exposure. Human milk samples were analyzed by LC-ESI-MS/MS for TBBP-A, HBCDs (the α, β, and γ diastereomers), and HBCD degradation products: pentabromocyclododecanes (PBCDs) and tetrabromocyclododecadienes (TBCDs). HBCD diastereomers were detected in all samples with α-HBCD present in the highest proportion. TBBP-A, PBCDs, and TBCDs were detected in 35%, 42%, and 56% of the analyzed samples, respectively. Self-reported demographic, dietary and behavioral data were examined as predictors of HBCD levels. Levels of HBCD were significantly, positively associated with the number of stereo and video electronics in the home (17% increase/item; 95% Confidence Interval (CI) = 4-31%) and reduced in participants who regularly chose organic foods compared to those who did not (0.51, 95% CI = 0.32-0.82). These results suggest that lifestyle factors are related to body burdens of HBCD and that domestic electronics may be an important source of HBCD exposure in the indoor environment.

In this study, we modeled concentrations of fine particulate matter (PM 2.5 ) and ozone (O 3 ) attributable to precursor emissions from individual airports in the United States, developing airport-specific health damage functions (deaths per 1000 t of precursor emissions) and physically-interpretable regression models to explain variability in these functions. We applied the Community Multiscale Air Quality model using the Decoupled Direct Method to isolate PM 2.5 - or O 3 -related contributions from precursor pollutants emitted by 66 individual airports. We linked airport- and pollutant-specific concentrations with population data and literature-based concentration-response functions to create health damage functions. Deaths per 1000 t of primary PM 2.5 emissions ranged from 3 to 160 across airports, with variability explained by population patterns within 500 km of the airport. Deaths per 1000 t of precursors for secondary PM 2.5 varied across airports from 0.1 to 2.7 for NOx, 0.06 to 2.9 for SO 2 , and 0.06 to 11 for VOCs, with variability explained by population patterns and ambient concentrations influencing particle formation. Deaths per 1000 t of O 3 precursors ranged from −0.004 to 1.0 for NOx and 0.03 to 1.5 for VOCs, with strong seasonality and influence of ambient concentrations. Our findings reinforce the importance of location- and source-specific health damage functions in design of health-maximizing emissions control policies.

Background The oil-rich Niger Delta suffers from extensive petroleum contamination. A pilot study was conducted in the region of Ogoniland where one community, Ogale, has drinking water wells highly contaminated with a refined oil product. In a 2011 study, the United Nations Environment Programme (UNEP) sampled Ogale drinking water wells and detected numerous petroleum hydrocarbons, including benzene at concentrations as much as 1800 times higher than the USEPA drinking water standard. UNEP recommended immediate provision of clean drinking water, medical surveillance, and a prospective cohort study. Although the Nigerian government has provided emergency drinking water, other UNEP recommendations have not been implemented. We aimed to (i) follow up on UNEP recommendations by investigating health symptoms associated with exposure to contaminated water; and (ii) assess the adequacy and utilization of the government-supplied emergency drinking water. Methods We recruited 200 participants from Ogale and a reference community, Eteo, and administered questionnaires to investigate water use, perceived water safety, and self-reported health symptoms. Results Our multivariate regression analyses show statistically significant associations between exposure to Ogale drinking water and self-reported health symptoms consistent with petroleum exposure. Participants in Ogale more frequently reported health symptoms related to neurological effects (OR = 2.8), hematological effects (OR = 3.3), and irritation (OR = 2.7). Conclusions Our results are the first from a community relying on drinking water with such extremely high concentrations of benzene and other hydrocarbons. The ongoing exposure and these pilot study results highlight the need for more refined investigation as recommended by UNEP.

We conducted a sensitivity analysis of the commonly employed pressure-based direct integrity test (DIT), the most sensitive test for defects in low-pressure hollow fiber (LPHF) microfiltration and ultrafiltration systems used in drinking water treatment. Incorporating uncertainty to assess the practice of DIT, we find the resolution in some tests may be insufficient to verify the presence of a barrier to oocysts of Cryptosporidium. Applying distributions and boundaries derived from literature and practice, we solved for the defect size resolution (DSR) using Monte Carlo and Probability Bounds Analysis for five commercial membrane designs. Surface tension was modeled using annual temperature profiles from three rivers. Contact angle measurement error and variability were derived from literature, respectively, as a standard deviation of 5.7 degrees and +/- 9.6 degrees median change due to natural organic matter (NOM) fouling. These measures of contact angle uncertainty and variability were combined in a normal distribution with the discrete values currently applied. Additionally we considered model uncertainty, applying the maximum bubble pressure method, an established method of surface tension measurement in liquids in which the maximum air pressure in a submerged capillary is developed after the contact angle becomes zero prior to bubble formation. Where the DSR exceeds 3 microm the test design is not compliant with applicable drinking water regulations. Implications include uncertain and variable log-removal values (LRV) as determined by DIT due to the possible emergence of defects large enough to allow oocysts to pass without detection by the DIT. Specifically, we found the DSR may exceed 3 microm and may be as large as 8 microm. With the variable contact angle model, all lower bound possibilities are compliant, whereas the upper bound is over 80% noncompliant for three of five commercial designs. Using the Maximum Bubble Pressure Method, the lower bounds in three designs start to exceed 3 microm for between 50 and 100% of the produced water, whereas the upper bounds of the DSR completely exceed 3 microm for four of five commercial designs examined.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a flame retardant widely used in furniture containing polyurethane foam. It is a carcinogen, endocrine disruptor, and potentially neurotoxic. Our objectives were to characterize exposure of adult office workers (n = 29) to TDCPP by measuring its primary metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), in their urine; measuring TDCPP in dust from their homes; offices and vehicles; and assessing possible predictors of exposure. We identified TDCPP in 99% of dust (GM = 4.43 μg/g) and BDCPP in 100% of urine samples (GM = 408 pg/mL). Concentrations of TDCPP were significantly higher in dust from vehicles (GM = 12.5 μg/g) and offices (GM = 6.06 μg/g) than in dust from the main living area (GM = 4.21 μg/g) or bedrooms (GM = 1.40 μg/g) of worker homes. Urinary BDCPP concentrations among participants who worked in a new office building were 26% of those who worked in older buildings (p = 0.01). We found some evidence of a positive trend between urinary BDCPP and TDCPP in office dust that was not observed in the other microenvironments and may be related to the timing of urine sample collection during the afternoon of a workday. Overall our findings suggest that exposure to TDCPP in the work environment is one of the contributors to the personal exposure for office workers. Further research is needed to confirm specific exposure sources (e.g., polyurethane foam), determine the importance of exposure in other microenvironments such as homes and vehicles, and address the inhalation and dermal exposure pathways. Keywords: BDCPP, Chlorinated tris, Dust, Human exposure, Organophosphate flame retardant, TDCPP

The United States Environmental Protection Agency (USEPA) is finalizing its vapor intrusion guidelines. One of the important issues related to vapor intrusion is background concentrations of volatile organic chemicals (VOCs) in indoor air, typically attributed to consumer products and building materials. Background concentrations can exist even in the absence of vapor intrusion and are an important consideration when conducting site assessments. In addition, the development of accurate conceptual models that depict pathways for vapor entry into buildings is important during vapor intrusion site assessments. Sewer gas, either as a contributor to background concentrations or as part of the site conceptual model, is not routinely evaluated during vapor intrusion site assessments. The research described herein identifies an instance where vapors emanating directly from a sanitary sewer pipe within a residence were determined to be a source of tetrachloroethylene (PCE) detected in indoor air. Concentrations of PCE in the bathroom range from 2.1 to 190 ug/m3 and exceed typical indoor air concentrations by orders of magnitude resulting in human health risk classified as an "Imminent Hazard" condition. The results suggest that infiltration of sewer gas resulted in PCE concentrations in indoor air that were nearly two-orders of magnitude higher as compared to when infiltration of sewer gas was not known to be occurring. This previously understudied pathway whereby sewers serve as sources of PCE (and potentially other VOC) vapors is highlighted. Implications for vapor intrusion investigations are also discussed.

Epidemiological studies increasingly indicate that polychlorinated biphenyls (PCBs) contribute to the risk of non-Hodgkin’s lymphoma (NHL). In rodent bioassays, PCBs have long been demonstrated to be liver carcinogens, and excess tumors in the thyroid, lung, and other organs have been observed in more recent studies. Leukemias and lymphomas now classified as NHL were observed in one bioassay in which a concurrent infection was also reported. Clinical and epidemiological studies show immunosuppression and inflammation are strong risk factors for NHL, and both epidemiology and toxicology studies show that PCBs are immunosuppressive and cause inflammation. We reviewed published carcinogenesis bioassays conducted using commercial PCB products, individual congeners, and congener mixtures, with a focus on bioassay protocols and immune-related observations. Based on a mode-of-action framework for PCBs, we suggest that an immune challenge in conjunction with PCB exposure may be necessary for the observation of NHL. We conclude that the lack of concordance between human epidemiology and animal bioassays with respect to NHL may simply be the result of the bioassay methodology used, and not a difference in underlying biology. The lack of concordance should not be construed as evidence that PCBs do not contribute to the risk of NHL.

Trichlorfon is a widely used broad-spectrum agricultural insecticide. Few studies have evaluated the effects of trichlorfon on developing fetuses, especially at early stages of development after low-level maternal exposures. In this study, we evaluated the direct effects of trichlorfon on preimplantation mouse embryos after 30days of maternal exposure (2, 10 and 50mg/kg/day) via drinking water. On gestation day 3 (dg3), blastocysts were collected and evaluated for changes in gross morphology; cell number; the presence of interphase, metaphase, micronuclei (MN) cells and fragmented and pycnotic nuclei. Embryos in the 50mg/kg/day group had a significantly reduced mean cell number per embryo. Furthermore, there was a significant increase in the frequency of pycnotic nuclei and an absence of metaphase cells in the 50mg/kg/day treated group. None of the developmental endpoints evaluated were observed in the 2 and 10mg/kg/day trichlorfon-treated groups. A simultaneous decrease in the cell number and an increase in the frequencies of absent metaphases and pycnotic nuclei indicate that embryonic developmental deficits observed in the 50mg/kg/day exposure group were associated with cytotoxicity.

Mapping of cis-diamminedichloroplatinum(II) (cis-DDP, cisplatin) DNA adducts over >3000 nucleotides was carried out using a replication blockage assay. The sites of inhibition of modified T4 DNA polymerase, also referred to as stop sites, were analyzed to determine the effects of local sequence context on the distribution of intrastrand cisplatin cross-links. In a 3120 base fragment from replicative form M13mp18 DNA containing 24.6% guanine, 25.5% thymine, 26.9% adenine and 23.0% cytosine, 166 individual stop sites were observed at a bound platinum/nucleotide ratio of 1-2 per thousand. The majority of stop sites (90%) occurred at G(n>2) sequences and the remainder were located at sites containing an AG dinucleotide. For all of the GG sites present in the mapped sequences, including those with Gn(>)2, 89% blocked replication, whereas for the AG sites only 17% blocked replication. These blockage sites were independent of flanking nucleotides in a sequence of N(1)G*G*N(2) where N(1), N(2) = A, C, G, T and G*G* indicates a 1,2-intrastrand platinum cross-link. The absence of long-range sequence dependence was confirmed by monitoring the reaction of cisplatin with a plasmid containing an 800 bp insert of the human telomere repeat sequence (TTAGGG)(n). Platination reactions monitored at several formal platinum/nucleotide ratios or as a function of time reveal that the telomere insert was not preferentially damaged by cisplatin. Both replication blockage and telomere-insert plasmid platination experiments indicate that cisplatin 1,2-intrastrand adducts do not form preferentially at G-rich sequences in vitro.

Evaluating the potential environmental consequences associated with dredging and dredged material disposal is a challenging task. Scientific advancements have made possible the collection of large amounts of complex technical information. The dredged material manager must often weigh and balance multiple and sometimes conflicting lines of evidence to reach a decision; and each decision involves a certain level of uncertainty. The application of Environmental Risk Assessment methods will increase a manager's ability to make objective management decisions when data collected in Tiers 1-111 of the dredged material evaluation framework are insufficient for decision making.

An SV40-based in vitro replication system has been used to examine the effects of platinum compounds on eukaryotic DNA replication. Plasmid templates containing the SV40 origin of replication were modified with the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP, cisplatin) or the inactive analogues (Pt(dien)Cl){sup +} and trans-DDP. The platinated plasmids were used as templates for DNA synthesis by the DNA polymerases present in cytosolic extracts prepared from human cell lines HeLa and 293. Bifunctional adducts formed by cis- and trans-DDP inhibited DNA replication by 95% at a bound drug to nucleotide ratio ((D/N){sub b}) of