PFAS chemicals have garnered substantial attention in recent years as more toxicity information is published and as regulations for PFAS are developed. Research on these chemicals was the focus of the Symposium “Developmental Toxicity of Per- and Polyfluoroalkyl Substances (PFAS): Current In Vivo Approaches and Application to Human Health Risk Assessment,” which was chaired by Drs. Justin Conley and AtLee Watson and presented in early May as part of the 2020 SOT Virtual Meeting.
This session featured excellent in vivo research involving gestational and early-life exposure to PFAS. The studies investigated a wide range of toxicological outcomes, including effects on neurodevelopment and the immune system. Extending this research into policy and regulation, the second half of the session was dedicated to learning how these in vivo data are being used to determine PFAS health advisory levels.
Dr. Katie O’Shaughnessy opened the session with a talk on a specific PFAS chemical, perfluorohexanesulfonate (PFHxS). Dr. O’Shaughnessy discussed the interplay between PFHxS and thyroid hormones in a rat model of neurodevelopmental disorders. PFHxS exposure during gestation and lactation led to reduced thyroid hormone levels in neonatal serum. However, hormone concentrations in the neonatal brain were unaffected, and PFHxS was not observed to induce developmental neurotoxicity.
Dr. Justin Conley compared the observed effects and mechanisms of emerging and legacy PFAS. GenX and NBP2 are two emerging PFAS with little peer-reviewed toxicity literature. When comparing GenX and NBP2 exposure in rats during gestation, both compounds produced adverse maternal and neonatal effects, but in slightly different ways and at different doses. From these studies, dysregulation of fetal glucose supply emerged as a key event in PFAS toxicity, with the fetuses showing perturbations in many glucose metabolism genes.
Dr. Jamie DeWitt pivoted the discussion to the effects of PFAS on the immature immune system. The developing immune system may be disrupted by PFAS during critical windows of sensitivity, leading to deficits that may not be observable until adulthood. Developmental exposure to some PFAS has been found to reduce antibody responses and antibody production.
Drs. Helen Goeden and Thorhallur Halldorsson concluded the session with talks on the various regulatory approaches to PFAS. Dr. Goeden explained how the Minnesota Department of Health developed a toxicokinetic model to consider indirect PFAS exposure pathways, like breastfeeding and placental transfer. Breastfeeding was found to be an extremely important pathway for perfluorooctanoic acid (PFOA), and as a result, Minnesota’s guidance level was calculated to protect breastfed infants from PFOA. Giving an international perspective, Dr. Halldorsson discussed ongoing work by the European Food Safety Authority (EFSA) on risk assessment related to the presence of PFAS in food. This opinion includes revision of the provisional tolerable daily intake values set in the EFSA 2018 opinion on perfluorooctane sulfonate (PFOS) and PFOA. This new opinion with inclusion of new studies indicates that vaccination response may be more important than previously thought.
A common tie between some of the talks was the proposal of dose addition to address the issue of co-exposure to multiple PFAS—though there is still more work to be done for PFAS mixture approaches. PFAS-induced developmental immunotoxicity appears to be a notable effect that needs further characterization for risk assessment, as underscored in the talks from Drs. Dewitt and Haldorsson.
This session showcased some great work being conducted to understand PFAS toxicity, especially during the sensitive windows of exposure throughout development. As a PhD student in this field, I’m certainly interested to see how the exciting future and follow-up studies planned by the speakers expand our knowledge of this huge class of contaminants.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo or 2020 SOT Virtual Meeting. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.