Evaluation of multigenerational effects of 2-ethylhexyl 4-hydroxybenzoate in Japanese medaka.

The Japanese medaka (Oryzias latipes) extended one-generation reproduction test (MEOGRT) (Test Guideline 890.2200) is a Tier 2 test within the Endocrine Disruptor Screening Program of the US Environmental Protection Agency (US EPA). A modified MEOGRT was used to evaluate multigenerational effects of 2-ethylhexyl 4-hydroxybenzoate (2-EHHB) under flow-through conditions starting with adults (parent generation, F0) through a 3-week reproductive phase of the second generation (F2). Fish were exposed to one of five 2-EHHB test concentrations or a dechlorinated tap water control. Fecundity was affected at the lowest exposure (5.32 µg/L) and greater sensitivity occurred in the F1 and F2 generations. Percent fertility was also diminished from no effect level observed in the F0 generation to 101 and 48.8 µg/L in the F1 and F2 generations, respectively. Growth indices were decreased for F0 adult females and F1 subadults and adults at 48.8 µg/L 2-EHHB. Histopathologic examination of gonads, liver, kidney, and thyroid yielded possible delayed reproductive tract development in F1 subadult males, masculinization of the renal phenotype in F1 adult females (renal tubular eosinophilia) and reduced hepatic energy storage (liver glycogen vacuoles) in F1 (11.3 and 48.8 µg/L) and F2 (48.8 and 101 µg/L) males and females, respectively. Endocrine-related findings included a decrease in anal fin papillae in F2 adult males at 101 µg/L. Results of this study demonstrate effects on growth, development, and reproduction that may be mediated by endocrine (weak estrogenic) and nonendocrine mechanisms. Duration of the MEOGRT should not be routinely extended beyond the OCSPP 890 guideline study design.

Trends in the Regulation of Per- and Polyfluoroalkyl Substances (PFAS): A Scoping Review.

Products containing per- and polyfluoroalkyl substances (PFAS) have been used for decades in industrial and consumer products. These compounds are persistent in the environment, bioaccumulative, and some are toxic to humans and other animals. Since the early 2000s, laws, policies, and regulations have been implemented to reduce the prevalence of PFAS in the environment and exposures to PFAS. We conducted a scoping literature review to identify how PFAS are regulated internationally, at the U.S. national level, and at the U.S. state level, as well as drivers of and challenges to implementing PFAS regulations in the U.S. This review captured peer-reviewed scientific literature (e.g., PubMed), grey literature databases (e.g., SciTech Premium Collection), Google searches, and targeted websites (e.g., state health department websites). We identified 454 relevant documents, of which 61 discussed the non-U.S. PFAS policy, 214 discussed the U.S. national-level PFAS policy, and 181 discussed the U.S. state-level PFAS policy. The drivers of and challenges to PFAS regulation were identified through qualitative analysis. The drivers of PFAS policy identified were political support for regulation, social awareness of PFAS, economic resource availability, and compelling scientific evidence. The challenges to implementing PFAS regulations were political limitations, economic challenges, unclear scientific evidence, and practical challenges. The implications for PFAS policy makers and other stakeholders are discussed.

Perfluoroalkyl substances exposure and immunity, allergic response, infection, and asthma in children: review of epidemiologic studies.

BACKGROUND: Increased exposure to perfluoroalkyl substances (PFAS) potentially affects infant and childhood health through immunosuppression. Given rapidly evolving research on PFAS, it is important to comprehensively examine the impact of PFAS exposure among the pediatric population as new research becomes available due to potential fragility of the developing immune system. OBJECTIVES: This review assessed the effects of PFAS fetal, infant and childhood exposures upon the development of immune function during early life stages. METHODS: Researchers completed a literature review, searching PubMed for human studies published since 2010 for PFAS and health outcomes among infants and children. Included articles incorporated key search terms in the title or abstract; non-research reports and non-English papers were excluded. The search identified 518 studies for possible inclusion. Following hands-on review, 34 were determined relevant. Subsequent analyses found 8 additional relevant articles, totaling 42 studies. RESULTS: Major immune-related sequelae from PFAS exposures on infant and child health outcomes documented in recent literature include:• Strong indication of immunosuppression, with diminished childhood antibody response to vaccination, particularly with PFOA, PFOS and PFHxS exposures.• Some indication of increased risks of childhood infectious diseases/infections, particularly from PFOS exposures.• Limited indication of an effect of PFAS exposure on allergic reactions/allergen specific IgE antibodies.• Limited indication of an effect of PFAS exposure on atopic dermatitis (AD).• Limited indication of an effect of PFAS exposure on asthma and lung function. CONCLUSION: This review summarizes recent findings of PFAS effects on infant and childhood immune health. Evidence of immunosuppression, diminished vaccine efficacy, and increased risk of infections, allergies, asthma and AD were described following in utero, infant, and early childhood PFAS exposures. Further investigation is warranted to characterize PFAS exposure pathways and potential modes of action in relation to PFAS effects on the developing immune system. Incontrovertible proof of PFAS immunotoxic effects could optimally be obtained by a large prospective study cohort of mothers and children from infancy through school-age. Regular assessments of circulating antibodies and response to infant and childhood vaccines during growth years could prove invaluable.