Exposure Routes Shape Per- and Polyfluoroalkyl Substances' Toxicokinetics and Sex-Specific Bioaccumulation in Thai Tiger Frogs (Hoplobatrachus rugulosus).

This study investigated the sex-specific toxicokinetics of per- and polyfluoroalkyl substances (PFASs) in Thai tiger frogs via dermal and dietary exposure. The lower depuration rate constant (kd) of PFASs in the dermal group than in the dietary group results in a higher assimilation efficiency (11% vs 3.7% for males and 21% vs 4.4% for females) in the former. Female frogs exhibited higher kd than male frogs (0.19 vs 0.057 per day for perfluorocarboxylic acid (PFCA) and 0.20 vs 0.062 per day for perfluorosulfonic acid (PFSA), especially for long-chain PFCA and PFSA, but these differences were attenuated in the dermal group (0.048 vs 0.035 per day and 0.041 vs 0.041 per day). Generally, dietary exposure resulted in higher serum PFAS burdens in the exposure phase, whereas dermal exposure led to direct diffusion into multiple tissues with higher hepatic burdens. During depuration, hibernation-induced translocation of PFASs from eggs to the liver was more pronounced in the dietary group than in the dermal group. We hypothesize that bypassing hepatic and intestinal first-pass effects provides a plausible mechanistic explanation. This may potentially decrease PFAS binding to intestinal and hepatic transport proteins, possibly leading to slower transport-related activities, especially for female frogs. These findings demonstrated that exposure routes significantly shape PFAS toxicokinetics and the sex-specific accumulation in frogs. However, the precise molecular mechanisms merit further in-depth studies.