High organofluorine concentrations in municipal wastewater affect downstream drinking water supplies for millions of Americans.

Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024.

An oat fiber intervention for reducing PFAS body burden: A pilot study in male C57Bl/6 J mice.

Perfluoroalkyl substances (PFAS) are a major public health concern, in part because several PFAS have elimination half-lives on the order of years and are associated with adverse health outcomes. While PFAS can be transported into bile, their efficient reuptake by intestinal transporter proteins results in minimal fecal elimination. Here, we tested the hypothesis that consumption of oat β-glucan, a dietary supplement known to disrupt the enterohepatic recirculation of bile acids, will reduce PFAS body burdens.

Chemical mixtures of mercury, PCBs, PFAS, and pesticides in freshwater fish in the US and the risks they pose for fish consumption.

Background: Freshwater fish are important food sources that also pose risks to human and wildlife health because of the bioaccumulation of environmental chemicals in their tissues. Although most studies, fish consumption advisories, and regulations focus on individual contaminants, fish consumers are exposed to mixtures of chemicals, including legacy contaminants and contaminants of emerging concern, that can have combined effects. Chemicals of emerging concern represent one source of hazard, but legacy contaminants can still pose threats to fish consumers due to their persistence in the environment.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Perfluorooctanoic acid induces liver and serum dyslipidemia in humanized PPARα mice fed an American diet.

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.

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.

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.

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.

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.

Perfluorooctanoic acid activates multiple nuclear receptor pathways and skews expression of genes regulating cholesterol homeostasis in liver of humanized PPARα mice fed an American diet.

Humans are exposed to per- and polyfluoroalkyl substances (PFAS) in their drinking water, food, air, dust, 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.

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.

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.

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.