Public Health Risks of PFAS-Related Immunotoxicity Are Real.

PURPOSE OF REVIEW: The discovery of per- and polyfluoroalkyl substances (PFAS) in the environment and humans worldwide has ignited scientific research, government inquiry, and public concern over numerous adverse health effects associated with PFAS exposure. In this review, we discuss the use of PFAS immunotoxicity data in regulatory and clinical decision-making contexts and question whether recent efforts adequately account for PFAS immunotoxicity in public health decision-making. RECENT FINDINGS: Government and academic reviews confirm the strongest human evidence for PFAS immunotoxicity is reduced antibody production in response to vaccinations, particularly for tetanus and diphtheria. However, recent events, such as the economic analysis supporting the proposed national primary drinking water regulations and clinical monitoring recommendations, indicate a failure to adequately incorporate these data into regulatory and clinical decisions. To be more protective of public health, we recommend using all relevant immunotoxicity data to inform current and future PFAS-related chemical risk assessment and regulation. Biological measures of immune system effects, such as reduced antibody levels in response to vaccination, should be used as valid and informative markers of health outcomes and risks associated with PFAS exposure. Routine toxicity testing should be expanded to include immunotoxicity evaluations in adult and developing organisms. In addition, clinical recommendations for PFAS-exposed individuals and communities should be revisited and strengthened to provide guidance on incorporating immune system monitoring and other actions that can be taken to protect against adverse health outcomes.

The effect of per and polyfluoroalkyl substance (PFAS) exposure on gestational diabetes mellitus and its subclinical risk factors: A systematic review and meta-analysis protocol.

BACKGROUND: Multiple lines of evidence suggest that exposure to per- and polyfluoroalkyl substances (PFAS) may alter glucose homeostasis, particularly during pregnancy, and may affect risk for developing gestational diabetes mellitus (GDM). While previous systematic reviews have been conducted on this topic, they did not assess internal validity of the included studies and their search strategies were narrowly focused. OBJECTIVE: The objective of this study is to assess the effect of higher PFAS exposure (defined by individual compounds or mixtures measured before or during pregnancy) on GDM and subclinical measures of impaired glucose homeostasis (measured during pregnancy) compared to lower PFAS exposure in pregnant. METHODS: We developed our systematic review protocol in accordance with the Navigation Guide. Peer-reviewed journal and grey literature searches were piloted in to identify relevant studies and refine our search terms and strategy. We also piloted the study screening criteria and data extraction form in DistillerSR, and refined our protocol accordingly. The risk of bias assessment protocol was adapted from Navigation Guide guidance and will be piloted and performed in DistillerSR. Pending the identification of comparable studies, quantitative meta-analyses will be performed where possible. Study results that cannot be quantitatively synthesized will be included in a narrative synthesis. The quality and strength of the body of evidence will be evaluated using Navigation Guide methodology, which is informed by guidance from the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation (GRADE). We also made refinements to the quality of evidence considerations based on guidance from the National Institute of Environmental Health Sciences (NIEHS) Office of Health Assessment and Translation (OHAT). FUNDING: This work was supported by the Systematizing Data on Per- and Polyfluoroalkyl Substances and Health Northeastern University TIER 1 Award.

Systems toxicogenomics of prenatal low-dose BPA exposure on liver metabolic pathways, gut microbiota, and metabolic health in mice.

Bisphenol A (BPA) is an industrial plasticizer widely found in consumer products, and exposure to BPA during early development has been associated with the prevalence of various cardiometabolic diseases including obesity, metabolic syndrome, type 2 diabetes, and cardiovascular diseases. To elucidate the molecular perturbations underlying the connection of low-dose prenatal BPA exposure to cardiometabolic diseases, we conducted a multi-dimensional systems biology study assessing the liver transcriptome, gut microbial community, and diverse metabolic phenotypes in both male and female mouse offspring exposed to 5 µg/kg/day BPA during gestation. Prenatal exposure to low-dose BPA not only significantly affected liver genes involved in oxidative phosphorylation, PPAR signaling and fatty acid metabolism, but also affected the gut microbial composition in an age- and sex-dependent manner. Bacteria such as those belonging to the S24-7 and Lachnospiraceae families were correlated with offspring phenotypes, differentially expressed liver metabolic genes such as Acadl and Dgat1, and key drivers identified in our gene network modeling such as Malat1 and Apoa2. This multiomics study provides insight into the relationship between gut bacteria and host liver genes that could contribute to cardiometabolic disease risks upon low-dose BPA exposure.

What Is Lost in the Weismann Barrier?

The Weismann barrier has long been regarded as a basic tenet of biology. However, upon close examination of its historical origins and August Weismann's own writings, questions arise as to whether such a status is warranted. As scientific research has advanced, the persistence of the concept of the barrier has left us with the same dichotomies Weismann contended with over 100 years ago: germ or soma, gene or environment, hard or soft inheritance. These dichotomies distract from the more important questions we need to address going forward. In this review, we will examine the theories that have shaped Weismann's thinking, how the concept of the Weismann barrier emerged, and the limitations that it carries. We will contrast the principles underlying the barrier with recent and less recent findings in developmental biology and transgenerational epigenetic inheritance that have profoundly eroded the oppositional view of germline vs. soma. Discarding the barrier allows us to examine the interactive processes and their response to environmental context that generate germ cells in the first place, determine the entirety of what is inherited through them, and set the trajectory for the health status of the progeny they bear.

Heritable hazards of smoking: Applying the "clean sheet" framework to further science and policy.

All the cells in our bodies are derived from the germ cells of our parents, just as our own germ cells become the bodies of our children. The integrity of the genetic information inherited from these germ cells is of paramount importance in establishing the health of each generation and perpetuating our species into the future. There is a large and growing body of evidence strongly suggesting the existence of substances that may threaten this integrity by acting as human germ cell mutagens. However, there generally are no absolute regulatory requirements to test agents for germ cell effects. In addition, the current regulatory testing paradigms do not evaluate the impacts of epigenetically mediated intergenerational effects, and there is no regulatory framework to apply new and emerging tests in regulatory decision making. At the 50th annual meeting of the Environmental Mutagenesis and Genomics Society held in Washington, DC, in September 2019, a workshop took place that examined the heritable effects of hazardous exposures to germ cells, using tobacco smoke as the example hazard. This synopsis provides a summary of areas of concern regarding heritable hazards from tobacco smoke exposures identified at the workshop and the value of the Clean Sheet framework in organizing information to address knowledge and testing gaps.

Aquatic pesticide exposure in the U.S. as a result of non-agricultural uses.

Non-agricultural uses of pesticides are common in the U.S. and may thus lead to exposure of non-target ecosystems such as urban waterways. However, surface water exposure resulting from agricultural pesticide uses has received substantially more attention during the last decades. Here we conducted a literature review and meta-analysis of peer-reviewed studies to identify measured environmental concentrations (MEC) of pesticides in perennial surface water bodies due to non-agricultural uses in the U.S. Acute and chronic Aquatic Life Benchmarks (ALBacute, ALBchronic) for water-phase concentrations and regulatory threshold levels (RTLSED) for sediment concentrations were used for risk evaluations. Based on 10,755 MECs retrieved from 70 scientific studies, results show that a multitude of pesticide compounds (approx. 150) have been detected at 609 urban surface water sites. Particularly herbicides and insecticides were among the most frequently detected compounds in the water phase, whereas insecticides dominated detections in sediments. While overall acute (5.64% ALBacute exceedances; n = 9034 MEC) and chronic (9.31% ALBchronic exceedances; n = 9036 MEC) risks were comparably low in the water phase, 35% of sediment concentrations (n = 1621 MEC) exceeded RTLSED. Insecticides and particularly pyrethroids were identified as the main drivers of benchmark exceedances in both the water phase and sediments. In addition to pesticide type, a linear model analysis identified further drivers important for risks such as sampling methods. Overall insecticide risks in non-agricultural surface waters were significantly (by a factor of 1.9) lower than those already known from agricultural surface waters in the U.S. However, substantially higher risks in sediments were identified for urban compared with agricultural waterbodies. The present study provides the first comprehensive assessment of pesticides in urban surface waters in the U.S. with overall results indicating common occurrence and non-negligible risks particularly due to urban insecticide uses.