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.

ABSTRACT

Growing toxicologic evidence suggests that emerging perfluoroalkyl substances (PFASs), like chlorinated polyfluoroalkyl ether sulfonate (Cl-PFESA), may be as toxic or more toxic than perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA). However, further investigations are needed in terms of the human health risk assessment. This study examined the effects of emerging and legacy PFAS exposure on newborn thyroid homeostasis and compared the thyroid disruption caused by 62 Cl-PFESA and PFOS using a benchmark dose approach. The health effects of mixture and individual exposure were estimated using the partial least-squares (PLS) model and linear regression, respectively. A Bayesian benchmark dose (BMD) analysis determined the BMD value for adverse effect comparison between 62 Cl-PFESA and PFOS. The median (interquartile range) concentrations of 62 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 PFAS variables' importance in projection (VIP) scores as follows 62 Cl-PFESA > PFOS > PFOA. Linear regression showed that 62 Cl-PFESA had a positive association with free triiodothyronine (FT3, P = 0.006) and triiodothyronine (T3, P = 0.014), while PFOS had a marginally significant positive association with FT3 alone (P = 0.042). The BMD analysis indicated that the estimated BMD10 for 62 Cl-PFESA (1.01 ng/mL) was lower than that for PFOS (1.66 ng/mL) in relation to a 10% increase in FT3. These findings suggest that 62 Cl-PFESA, an alternative to PFOS, has a more pronounced impact on newborns' thyroid homeostasis compared to PFOS and other legacy PFASs.