6:2 Chlorinated Polyfluoroalkyl Ether Sulfonates Exert Stronger Thyroid Homeostasis Disruptive Effects in Newborns than Perfluorooctanesulfonate: Evidence Based on Bayesian Benchmark Dose Values from a Population Study

Growing toxicologic evidence suggests that emerging perfluoroalkylsubstances (PFASs), like chlorinated polyfluoroalkyl ether sulfonate(Cl-PFESA), may be as toxic or more toxic than perfluorooctanesulfonate(PFOS) and perfluorooctanoic acid (PFOA). However, further investigationsare needed in terms of the human health risk assessment. This studyexamined the effects of emerging and legacy PFAS exposure on newbornthyroid homeostasis and compared the thyroid disruption caused by6:2 Cl-PFESA and PFOS using a benchmark dose approach. The healtheffects of mixture and individual exposure were estimated using thepartial least-squares (PLS) model and linear regression, respectively.A Bayesian benchmark dose (BMD) analysis determined the BMD valuefor adverse effect comparison between 6:2 Cl-PFESA and PFOS. The median(interquartile range) concentrations of 6:2 Cl-PFESA (0.573 [0.351-0.872]ng/mL), PFOS (0.674 [0.462-1.007] ng/mL), and PFOA (1.457 [1.034,2.405] ng/mL) were found to be similar. The PLS model ranked the PFASvariables' importance in projection (VIP) scores as follows:6:2 Cl-PFESA > PFOS > PFOA. Linear regression showed that 6:2Cl-PFESAhad a positive association with free triiodothyronine (FT3, P = 0.006) and triiodothyronine (T3, P =0.014), while PFOS had a marginally significant positive associationwith FT3 alone (P = 0.042). The BMD analysis indicatedthat the estimated BMD10 for 6:2 Cl-PFESA (1.01 ng/mL)was lower than that for PFOS (1.66 ng/mL) in relation to a 10% increasein FT3. These findings suggest that 6:2 Cl-PFESA, an alternative toPFOS, has a more pronounced impact on newborns' thyroid homeostasiscompared to PFOS and other legacy PFASs. Thyroid disruption comparison between emerging and legacyPFASs under human health risk assessment.