Identification of the associations between co-exposure to organophosphate flame retardants and thyroid dysfunction and exposure risk factors in residents of Shanghai, China.

Toxicological studies indicate that organophosphate flame retardants (OPFRs) may cause thyroid dysfunction. However, population epidemiologic evidence is still limited and little is known about the effects of mixed exposures to OPFRs. This study included 436 community residents from Shanghai, China. We measured the levels of 9 OPFRs in 3 categories and 5 commonly used thyroid function indicators (TFIs) in serum samples from all participants. Multiple linear regression and restricted cubic spline model were used to examine the association between exposure to individual OPFRs and TFIs. Weighted quantile sum regression and Bayesian kernel-machine regression models were used to elucidate the joint impact of mixed OPFRs on thyroid function and the dose-response relationship. Machine learning combined with the SHapley Additive exPlanations algorithm identified important risk factors for exposure to OPFRs in the population. The results indicated that the residents were generally exposed to OPFRs. Exposure to either single or mixed OPFRs was significantly associated with TFI levels, particularly free thyroxine (FT4) and free triiodothyronine (FT3). Tri-n-butyl-phosphate (TBP), Tris-2-butoxy ethyl-phosphate (TBEP), and Tris-2-chloroethyl-phosphate (TCEP) were major contributors to the co-exposure effect. The dose-response relationship further revealed the trend in the impact of OPFRs on thyroid function. Education, occupation, age, body mass index, personal annual income, indoor time, and mollusk intake are noteworthy risk characteristics for population exposure to OPFRs. These findings suggest that OPFRs are environmental drivers of thyroid dysfunction in humans and provide clues for further risk management.