Chronic effects of the PFAS precursor 6:2 FTS on <i>Xenopus laevis</i> tadpole growth and development

The per and polyfluoroalkyl substance (PFAS) precursor alternative, 6:2 fluorotelomer sulfonate (6:2 FTS), has been detected globally. The central aim of this work was to evaluate the chronic toxicity of 6:2 FTS for this understudied PFAS. Using the amphibian African clawed frog Xenopus laevis, we tested the main hypothesis that, regardless of sex, the sensitivity of this model to 6:2 FTS would be comparable with that of North American amphibians. Larvae were exposed to 6:2 FTS (1.2-1,200 ppb) from Niewkoop and Faber (NF) stages 51 to 65, which took a range of 24 to 42 days. We found significant growth stimulation at 120 ppb (26% mass increase, 6% snout-vent-length increase) without traditional dose-dependency. This growth stimulation coincided with a nonsignificant developmental delay at 120 ppb (38.0 ± 2.9 vs. 35.5 ± 1.8 days to NF 65). The nonmonotonic response yielded dual no observed effect concentration/lowest observed effect concentration (NOEC/LOEC) interpretations: (1) growth stimulation with a NOEC = 12 ppb and a LOEC = 120 ppb; and (2) adverse effects with a NOEC = 1,200 ppb. Xenopus laevis sensitivity to 6:2 FTS appears comparable with North American native amphibians (reported NOECs: 800-1,800 ppb), although the stimulation response and lack of a dose response complicates their application for assessing ecological risks. Although genetic sexing enabled sex-specific analysis in this species, no differences in sensitivity or accumulation rates were detected. These findings highlight the critical importance of endpoint selection in PFAS risk evaluation and supports previous findings with other amphibians showing that exposure to environmentally relevant 6:2 FTS concentrations should not adversely affect growth and development.