Leveraging the African clawed frog (Xenopus laevis) for Understanding Stage- and Sex-Specific Toxicokinetics and Effects of PFAS

Per- and polyfluoroalkyl substances (PFAS) are a group of emerging global contaminants used in a variety of industrial processes and consumer products, such as personal care products and fast-food wrappers. However, due to their carbon-fluorine bonds, these chemicals resist degradation and persist in the environment. PFAS toxicity is driven by a compound’s functional group and chain length with perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide dimer acid (GenX) being of focal concern due to their toxicity to wildlife and presence in the environment. Despite growing concern regarding these contaminants, inadequate attention has been given to evaluating what organismal characteristics influence uptake and depuration of these chemicals, such as life stage and sex. Xenopus laevis tadpoles are a useful model to assess the influence of sex on PFAS kinetics since they have a life history that includes a gill to lung transition. Previous studies have shown that air-breathing organisms depurate PFAS more slowly than water-breathing organisms, but this relationship has never been directly tested. Sex has been shown to be an important factor in the depuration of PFOA for rats, with female rats depurating PFOA in four hours while males depurate in four days. The early portion of bioaccumulation curves are also understudied even though tadpoles accumulate PFAS rapidly, reaching steady state within 48 hours of exposure. Xenopus laevis are used to study multiple endpoints for endocrine disrupting chemicals including PFAS. Despite this, toxicity reference values (TRVs) have not been described for the uptake and elimination of PFAS using X. laevis. To address these gaps in knowledge, I first developed TRVs for X. laevis tadpoles exposed to PFOA throughout metamorphosis and evaluated the influence of sex on phenotypic endpoints. Results showed a no observed effect concentration (NOEC) of 11.1 ppm for body mass at day 14 and no effect of sex on apical endpoints. Next, I described the early bioaccumulation of four PFAS with differing structure (chain lengths and functional groups). PFOS was the only chemical to bioaccumulate with a log bioconcentration factor (BCF) at 10 and 1,000 ppm of 1.33 and 1.18, respectively. PFHxS, PFOA, and GenX had BCFs less than 0. Finally, I examined the impact of life-stage and sex on X. laevis tadpole and juvenile depuration rates. Larval tadpoles depurated four times faster than juveniles, indicating a significant effect of life stage on elimination rates. Sex had no influence on elimination rates. These are the first studies conducted evaluating the significance of life stage and sex in toxicokinetics of PFAS in amphibians.