Objective To assess the effects of non-occupational mixed exposure to cadmium， lead and perfluoroalkyl substances （PFASs） on thyroid hormones （TH） in healthy adult residents in Shanghai.

Methods In November 2018， adults in Shanghai Suburban Adult Cohort and Biobank study， who visited a community health service center for examination with no history of occupational exposure， thyroid diseases or chronic diseases， were recruited. A social-demographic information questionnaire survey was conducted and urine and blood samples were collected. Inductively coupled plasma mass spectrometry （ICP-MS） was used to measure their urinary cadmium （UCd）， blood cadmium （BCd） and blood lead （BPb） concentrations. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q/TOF MS） was used to measure 11 kinds of PFASs. Total and free triiodothyronine （TT3， FT3）， total and free thyroxine （TT4， FT4） and thyroid simulating hormones were measured by chemiluminescence enzyme-linked immunoassay. 436 participants were finally included and LASSO regression， multivariate regression and weighted quantile sum regression were used to evaluate the associations of these environmental pollutants with thyroid hormones.

Results Among the participants， 185 were male （42.5%） and the median age was 60 （P₂₅‒P₇₅： 50‒66）. The detection rates of urinary cadmium， blood cadmium and blood lead were all more than 95% and the detection rates of 7 PFASs （PFOS， PFOA， PFHxS， PFUnDA， PFNA， PFD， and PFBS） were more than 90%. The median exposure level of PFOA was the highest （49.6 µg‧L^-1） among PFASs， followed by PFHxS （22.8 µg‧L^-1） and PFOS （15.4 µg‧L^-1）， and the median exposure levels of urinary cadmium， blood cadmium and blood lead were 0.7 μg‧g^-1（Corrected for creatinine of urine）， 0.8 µg‧L^-1， and 15.4 µg‧L^-1， respectively. The results showed that UCd was negatively associated with TSH and BCd was positively associated with TT3， while PFASs mainly affected FT4， TT4， and TT3， with gender differences. In males， 7 PFASs had a significant negative mixture effect on TT3 and TT4， while the direction of effect of PFASs in females differed， with PFOS and PFUnDA having a significant positive correlation with FT4 and TT4 while PFDA having a significant negative correlation with FT4 and TT4.

Conclusion In a healthy population with no occupational exposure， co-exposure to cadmium， lead and PFASs affects different thyroid hormone indicators， and such effect could be gender-related， indicating that the effect of mixed exposure to metal and emerging compounds on thyroid functions warrants further attention.