Emerging Contaminants Summit
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Emerging Contaminants Summit
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Linda Hall Linda Hall
Senior Associate Toxicologist
GSI Environmental

Dr. Hall is a Senior Associate Toxicologist with GSI Environmental, with expertise in environmental toxicology and human health. She has actively followed the emerging science of PFAS toxicology. She is a task co-lead for the ITRC PFAS team; co-authored the Fact Sheet PFAS Regulations, Guidance, and Advisories, and contributed to and coordinated sections of the technical document on human health, ecological toxicology, regulations, and risk assessment. She has worked as a toxicology expert on PFAS projects involving AFFF in drinking water, manufacturing releases, and health effects of PFAS from food chain transfer from crops grown on soils amended with biosolids.



PLATFORM PRESENTATION

Is Regulation of PFAS as a Class Supported by the Science?

The prevalence, structural diversity, and lack of toxicity data for the thousands of individual per- and polyfluoroalkyl substances (PFAS) in commerce have increasingly led to calls to regulate these chemicals as a class as a means of increasing oversight of this largely-unregulated group of chemicals. Regulation of PFAS as a class implies that their adverse effects are mediated by similar toxicologic modes of action (MOA) for the non-cancer endpoints of interest; the dose-response relationships are linear, and individual PFAS have toxic potencies that remain proportional to one another throughout the dose range of interest. Currently-available evidence indicates that these criteria are not met for the majority of PFAS in commercial use whose toxicity remains uncharacterized. But for the relatively well-studied perfluoroalkyl acids (PFAAs), there are sufficient similarities in certain adverse effects to suggest that additivity and thus dose-response linearity may exist. Indeed, several states and countries effectively regulate PFAAs as a class based on the assumption that their adverse effects are additive. For the PFAAs, toxicity is mediated by binding to nuclear receptors (NRs). These NRs are ligand-activated transcription factors that regulate the expression of genes by binding to DNA. Dose additivity has been shown to be relevant for chemicals that bind NRs, although the evidence is limited to a single NR and a single biological pathway. Activation of one NR – peroxisome proliferator activated receptor alpha (PPAR?) is undoubtedly a common response to those PFAAs studied to date. However, there are multiple critical effects that have been identified for PFAAs, and some of these are known to be PPAR?-independent. For certain critical effects, significant uncertainty remains regarding the underlying toxicologic MOA. We considered the evidence for additivity of PFAS, focusing on the MOA(s) for the PFAAs PFOA, PFOS, PFHxS, and PFNA. We considered developmental and immune system impacts, liver toxicity, and changes in body weight, and evaluated the evidence that an adverse effect was mediated by PPAR? or another NR. We concluded that certain critical effects appear to have a shared MOA and support the concept of additivity for these endpoints. However, the existence of multiple MOAs and endpoint-specific MOAs suggest additivity across PFAAs is not supported by currently-available data – even for this small and relatively well-defined sub-class of PFAAs.


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