Transcriptomic dose response assessment of PFAS chemicals 3:3 fluorotelomer carboxylic acid, 7:3 fluorotelomer alcohol, and perfluorohexanesulfonamide

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of anthropogenic chemicals, and their widespread use in manufacturing and commerce has led to introduction of these chemicals into the environment. Owing to the lack of traditional toxicology data on the majority of PFAS, novel testing methods that provide supporting information to inform human health impacts in a relatively short time frame will be increasingly important. The US Environmental Protection Agency’s (EPA) Transcriptomic Assessment Process (ETAP) was recently implemented by the Agency as an efficient and cost-effective method to begin assessing potential human health impacts of chemicals that lack traditional toxicity testing data. The method involves short-term oral dosing in male and female adult rats over a five-day interval, followed by transcriptomic dose-response assessment in twelve tissues to determine a point of departure. The ETAP point of departure identifies the dose at which there are no coordinated transcriptional changes that would indicate a potential toxicity of concern. However, this approach does not explore any specific association with hazard or mechanism. Reported here are ETAP results for three PFAS chemicals: 3:3 fluorotelomer carboxylic acid (3:3 FTCA), 7:3 fluorotelomer alcohol (7:3 FTOH), and perfluorohexanesulfonamide (PFHxSA). The transcriptomic points of departure associated with the tested chemicals, as assessed via ETAP and allometrically scaled to human equivalent doses, were 0.00235 (3:3 FTCA), 0.0152 (7:3 FTOH), and 0.00358 (PFHxSA) mg/kg-day.