Dose additive maternal and offspring effects of oral maternal exposure to a mixture of three PFAS (HFPO-DA, NBP2, PFOS) during pregnancy in the Sprague-Dawley rat
Investigation of per- and polyfluoroalkyl substance (PFAS) health effects is critical due to issues associated with environmental persistence, widespread occurrence, biological half-life, toxicity, and nearly ubiquitous human and environmental exposure. We recently published data on a two PFAS mixture that included Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which produced dose additive maternal and neonatal effects. Here, we tested a more complex mixture of three PFAS that included PFOS and two more recently detected ether-linked PFAS relevant to the Cape Fear exposure area in North Carolina – Hexafluoropropylene oxide dimer acid (HFPO-DA or GenX) and Nafion byproduct 2 (NBP2). Further, in contrast to our prior PFAS mixture study, here we aged offspring animals to adulthood and leverage ORD/CPHEA expertise in cardiotoxicity and evaluated a subset of exposed animals using echocardiography techniques. We hypothesized that combined exposure to the 3 PFAS mixture would produce cumulative adverse effects in maternal and offspring rats.
To our knowledge, this is the second published study to rigorously demonstrate additive in vivo mammalian effects from combined exposure to PFAS. We previously reported numerous adverse maternal and pup effects for PFOS, HFPO-DA, and NBP2 individually and here the mixture of all three produced similar effects that were additive. Importantly, dose additive cumulative toxicity was clearly demonstrated by relative potency factor (RPF) analyses, which is a major component of the OW Draft mixtures framework for estimating human risk to multiple PFAS. Further, we identified significant thickening of the left ventricle anterior wall in offspring exposed in utero, indicating cardiotoxicity from developmental exposure PFAS.