Association between Combined Sewer Overflow Events and Gastrointestinal Illness in Massachusetts Municipalities with and without River-Sourced Drinking Water, 2014-2019.

BACKGROUND: Combined sewer overflow (CSO) events release untreated wastewater into surface waterbodies during heavy precipitation and snowmelt. Combined sewer systems serve ∼40 million people in the United States, primarily in urban and suburban municipalities in the Midwest and Northeast. Predicted increases in heavy precipitation events driven by climate change underscore the importance of quantifying potential health risks associated with CSO events. OBJECTIVES: The aims of this study were to a) estimate the association between CSO events (2014-2019) and emergency department (ED) visits for acute gastrointestinal illness (AGI) among Massachusetts municipalities that border a CSO-impacted river, and b) determine whether associations differ by municipal drinking water source. METHODS: A case time-series design was used to estimate the association between daily cumulative upstream CSO discharge and ED visits for AGI over lag periods of 4, 7, and 14 days, adjusting for temporal trends, temperature, and precipitation. Associations between CSO events and AGI were also compared by municipal drinking water source (CSO-impacted river vs. other sources). RESULTS: Extreme upstream CSO discharge events (>95th percentile by cumulative volume) were associated with a cumulative risk ratio (CRR) of AGI of 1.22 [95% confidence interval (CI): 1.05, 1.42] over the next 4 days for all municipalities, and the association was robust after adjusting for precipitation [1.17 (95% CI: 0.98, 1.39)], although the CI includes the null. In municipalities with CSO-impacted drinking water sources, the adjusted association was somewhat less pronounced following 95th percentile CSO events [CRR= 1.05 (95% CI: 0.82, 1.33)]. The adjusted CRR of AGI was 1.62 in all municipalities following 99th percentile CSO events (95% CI: 1.04, 2.51) and not statistically different when stratified by drinking water source. DISCUSSION: In municipalities bordering a CSO-impacted river in Massachusetts, extreme CSO events are associated with higher risk of AGI within 4 days. The largest CSO events are associated with increased risk of AGI regardless of drinking water source. https://doi.org/10.1289/EHP14213.

Manganese in residential drinking water from a community-initiated case study in Massachusetts.

BACKGROUND: Manganese (Mn) is a metal commonly found in drinking water, but the level that is safe for consumption is unknown. In the United States (U.S.), Mn is not regulated in drinking water and data on water Mn concentrations are temporally and spatially sparse. OBJECTIVE: Examine temporal and spatial variability of Mn concentrations in repeated tap water samples in a case study of Holliston, Massachusetts (MA), U.S., where drinking water is pumped from shallow aquifers that are vulnerable to Mn contamination. METHODS: We collected 79 residential tap water samples from 21 households between September 2018 and December 2019. Mn concentrations were measured using inductively coupled plasma mass spectrometry. We calculated descriptive statistics and percent of samples exceeding aesthetic (secondary maximum containment level; SMCL) and lifetime health advisory (LHA) guidelines of 50 µg/L and 300 µg/L, respectively. We compared these concentrations to concurrent and historic water Mn concentrations from publicly available data across MA. RESULTS: The median Mn concentration in Holliston residential tap water was 2.3 µg/L and levels were highly variable (range: 0.03-5,301.8 µg/L). Mn concentrations exceeded the SMCL and LHA in 14% and 12% of samples, respectively. Based on publicly available data across MA from 1994-2022, median Mn concentration was 17.0 µg/L (N = 37,210; range: 1-159,000 µg/L). On average 40% of samples each year exceeded the SMCL and 9% exceeded the LHA. Samples from publicly available data were not evenly distributed between MA towns or across sampling years. IMPACT STATEMENT: This study is one of the first to examine Mn concentrations in drinking water both spatially and temporally in the U.S. Findings suggest that concentrations of Mn in drinking water frequently exceed current guidelines and occur at concentrations shown to be associated with adverse health outcomes, especially for vulnerable and susceptible subpopulations like children. Future studies that comprehensively examine exposure to Mn in drinking water and its associations with children's health are needed to protect public health.

Potential Policy and Community Implications of Equitable Organic Waste, Compost, and Urban Agricultural Systems in the United States.

BACKGROUND: Urban organic waste diverted from landfills for use as compost feedstock may help mitigate and adapt to the effects of our changing climate. Yet, compost produced from urban food and yard waste is often a source of contaminants harmful to human and environmental health. Efforts by multiple municipalities are increasing residential and commercial food and yard waste collection; however, finished, tested compost is typically unavailable to those contributing the waste and whose gardens would benefit. OBJECTIVES: This commentary evaluates the relative equity and safety of U.S. organic waste cycles in relation to urban and peri-urban agriculture (UA) and waste stewardship. We a) explore historical structures that have led to siloed food and waste systems and b) provide recommendations to promote safer compost production from urban organic waste inputs. The engagement of intersectional partners in the creation of equitable policies and contracts that integrate food and waste justice is crucial to this work. METHODS: A 15-y relationship between community, academic, and government partners in Boston, Massachusetts, has increased access to health-promoting community gardens. Historical concerns raised by gardeners resulted in improvement to the quality of compost sourced from municipal organic waste and motivated a case study of Boston and three other cities (Seattle, Washington; San Francisco, California; New York, New York). This case study provides the approaches used to source, collect, process, test, and deliver urban organic waste as compost for UA. It informed recommendations to improve the safety and equity of organic waste-to-compost cycles. DISCUSSION: Strict feedstock regulation and required compost safety testing are essential to produce safe, city-sourced compost. Balancing the needs of landfill diversion with equitable distribution to all contributors, particularly low-income and food-insecure people, will help concentrate UA benefits within marginalized communities. Adoption of a public health lens may help ensure the safety of nutrient-rich compost available for urban growers through legislation at state and local levels, along with explicit industry contracts. https://doi.org/10.1289/EHP12921.

Unknown Organofluorine Mixtures in U.S. Adult Serum:Contribution from Pharmaceuticals?

Organofluorines occur in human serum as complex mixtures of known and unidentified compounds. Human biomonitoring traditionally uses targeted analysis to measure the presence of known and quantifiable per- and polyfluoroalkyl substances (PFAS) in serum, yet characterization of exposure to and quantification of PFAS are limited by the availability of methods and analytical standards. Studies comparing extractable organofluorine (EOF) in serum to measured PFAS using organofluorine mass balance show that measurable PFAS only explain a fraction of EOF in human serum and that other sources of organofluorine may exist. The gap in fluorine mass balance has important implications for human biomonitoring because the total body burden of PFAS cannot be characterized and the chemical species that make up unidentified EOF are unknown. Many highly prescribed pharmaceuticals contain organofluorine (e.g., Lipitor, Prozac) and are prescribed with dosing regimens designed to maintain a therapeutic range of concentrations in serum. Therefore, we hypothesize organofluorine pharmaceuticals contribute to EOF in serum. We use combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assess differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compare them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) shows the fraction of EOF not explained by Σ44 PFAS ranged from 15% to 86%. Self-reported use of organofluorine pharmaceuticals is associated with a 0.36 ng F/mL (95% CL: -1.26 to 1.97) increase in UOF, on average, compared to those who report not taking organofluorine pharmaceuticals. Our study is the first to assess sources of UOF in U.S. serum and examine whether organofluorine pharmaceuticals contribute to EOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by differences in analytical measurements. Future analyses using EOF should consider multiple extraction methods to include cations and zwitterions. Whether organofluorine pharmaceuticals are classified as PFAS depends on the definition of PFAS.

Application of probabilistic methods to address variability and uncertainty in estimating risks for non-cancer health effects.

Human health risk assessment currently uses the reference dose or reference concentration (RfD, RfC) approach to describe the level of exposure to chemical hazards without appreciable risk for non-cancer health effects in people. However, this "bright line" approach assumes that there is minimal risk below the RfD/RfC with some undefined level of increased risk at exposures above the RfD/RfC and has limited utility for decision-making. Rather than this dichotomous approach, non-cancer risk assessment can benefit from incorporating probabilistic methods to estimate the amount of risk across a wide range of exposures and define a risk-specific dose. We identify and review existing approaches for conducting probabilistic non-cancer risk assessments. Using perchloroethylene (PCE), a priority chemical for the U.S. Environmental Protection Agency under the Toxic Substances Control Act, we calculate risk-specific doses for the effects on cognitive deficits using probabilistic risk assessment approaches. Our probabilistic risk assessment shows that chronic exposure to 0.004 ppm PCE is associated with approximately 1-in-1,000 risk for a 5% reduced performance on the Wechsler Memory Scale Visual Reproduction subtest with 95% confidence. This exposure level associated with a 1-in-1000 risk for non-cancer neurocognitive deficits is lower than the current RfC for PCE of 0.0059 ppm, which is based on standard point of departure and uncertainty factor approaches for the same neurotoxic effects in occupationally exposed adults. We found that the population-level risk of cognitive deficit (indicating central nervous system dysfunction) is estimated to be greater than the cancer risk level of 1-in-100,000 at a similar chronic exposure level. The extension of toxicological endpoints to more clinically relevant endpoints, along with consideration of magnitude and severity of effect, will help in the selection of acceptable risk targets for non-cancer effects. We find that probabilistic approaches can 1) provide greater context to existing RfDs and RfCs by describing the probability of effect across a range of exposure levels including the RfD/RfC in a diverse population for a given magnitude of effect and confidence level, 2) relate effects of chemical exposures to clinical disease risk so that the resulting risk assessments can better inform decision-makers and benefit-cost analysis, and 3) better reflect the underlying biology and uncertainties of population risks.

A science-based agenda for health-protective chemical assessments and decisions: overview and consensus statement.

The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a "safe" or "no-risk" level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

Impact of High-Throughput Model Parameterization and Data Uncertainty on Thyroid-Based Toxicological Estimates for Pesticide Chemicals.

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 (n = 45). Depending on the model structure used for IVIVE analysis, up to 35 chemicals produced EAD values lower than the POD. A total of 10 chemicals produced EAD values higher than the POD regardless of the model structure. The relationship between IVIVE-derived EAD values and the in vivo-derived POD values is highly dependent on model parameterization. Here, we derive a range of potentially thyroid-relevant doses that incorporate uncertainty in modeling choices and in vitro assay data.

Implications of PFAS definitions using fluorinated pharmaceuticals.

There are 9,000+ per- and polyfluoroalkyl substances (PFAS) in existence, which makes studying and regulating PFAS individually, or even as small mixtures, infeasible. Multiple PFAS definitions based on structure have been proposed, yet these definitions do not consider the implications for the full suite of organofluorine chemicals. For example, organofluorine pharmaceuticals, whose use may be essential and are found in human serum and wastewater, are not uniformly identified across all definitions. Using nine definitions prepared by various stakeholders, we screened the 360 organofluorine pharmaceuticals approved and used globally between 1954 and 2021. Definitions ranged in their inclusion of organofluorine pharmaceuticals (1%-100%). The most inclusive definitions include several top prescribed pharmaceuticals, e.g., Prozac and Lipitor. This analysis provides a framework against which organizations can make decisions about how best to proceed when defining PFAS.

Multiple metals in children's deciduous teeth: results from a community-initiated pilot study.

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.

Predicting the effects of per- and polyfluoroalkyl substance mixtures on peroxisome proliferator-activated receptor alpha activity in vitro.

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 h 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.

Comparison of Recreational Fish Consumption Advisories Across the USA.

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. 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.

The association of cadmium and lead exposures with red cell distribution width.

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.

Balancing incomplete COVID-19 evidence and local priorities: risk communication and stakeholder engagement strategies for school re-opening.

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.

PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding.

We synthesize current understanding of the magnitudes and methods for assessing human and wildlife exposures to poly- and perfluoroalkyl substances (PFAS). Most human exposure assessments have focused on 2 to 5 legacy PFAS, and wildlife assessments are typically limited to targeted PFAS (up to ~30 substances). However, shifts in chemical production are occurring rapidly, and targeted methods for detecting PFAS have not kept pace with these changes. Total fluorine measurements complemented by suspect screening using high-resolution mass spectrometry are thus emerging as essential tools for PFAS exposure assessment. Such methods enable researchers to better understand contributions from precursor compounds that degrade into terminal perfluoroalkyl acids. Available data suggest that diet is the major human exposure pathway for some PFAS, but there is large variability across populations and PFAS compounds. Additional data on total fluorine in exposure media and the fraction of unidentified organofluorine are needed. Drinking water has been established as the major exposure source in contaminated communities. As water supplies are remediated, for the general population, exposures from dust, personal care products, indoor environments, and other sources may be more important. A major challenge for exposure assessments is the lack of statistically representative population surveys. For wildlife, bioaccumulation processes differ substantially between PFAS and neutral lipophilic organic compounds, prompting a reevaluation of traditional bioaccumulation metrics. There is evidence that both phospholipids and proteins are important for the tissue partitioning and accumulation of PFAS. New mechanistic models for PFAS bioaccumulation are being developed that will assist in wildlife risk evaluations. Environ Toxicol Chem 2021;40:631-657. © 2020 SETAC.

Predicting the Activation of the Androgen Receptor by Mixtures of Ligands Using Generalized Concentration Addition.

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.

Human health risks due to airborne polychlorinated biphenyls are highest in New Bedford Harbor communities living closest to the harbor.

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.

Altered lipid homeostasis in a PCB-resistant Atlantic killifish (Fundulus heteroclitus) population from New Bedford Harbor, MA, U.S.A.

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.

Lead exposure to children from consumption of backyard chicken eggs.

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.