Developmental exposures to per and polyfluoroalkyl substances
Globally, biomonitoring data demonstrate virtually all humans carry residues of multiple per- and polyfluoroalkyl substances (PFAS). Despite pervasive co-exposure and known adverse effects of some PFAS, limited mixtures-based in vivo PFAS toxicity research has been conducted and even fewer studies have examined maternal and offspring effects when PFAS or combinations of PFAS are orally administered during pregnancy and lactation. The goal of these studies was to evaluate the effects of sodium tridecafluoro-2,4,6,8,10-pentaoxadodecan-12-oate (PFO5DoA), heptadecafluorooctanesulfonic acid potassium salt (PFOS), Nafion byproduct 2 (NBP2), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), sodium 2,2-difluoro-2-(trifluoromethoxy)acetate (PFMOAA), perfluorohexanesulfonic acid (PFHxS), and a combination of GenX, NBP2, and PFOS. We orally exposed pregnant Sprague-Dawley rats during gestation (with some studies extending to the postnatal period) to PFO5DoA (0.1 - 10 mg/kg-day), PFOS (0.1 - 30 mg/kg-day), NBP2 (0.3 - 30 mg/kg-day), PFHxS (3 - 125 mg/kg-day), PFMOAA (0.01 - 500 mg/kg-day), GenX (1 - 500 mg/kg-day), or combination of GenX, NBP2, PFOS (1.1 GenX; 0.1 NBP2; 0.03 PFOS - 110 GenX; 10 NBP2; 3 PFOS in mg/kg-day) and vehicle control (0.5% Tween-80 for PFO5DoA and water everything else). Targeted RNA-seq (BioSpyder Technologies whole transcriptome rat) was performed on dam and pup livers with some additional fetal and maternal tissues for comparison to apical response.