Perfluoroalkyl substances (PFASs) are a group of man-made fluorinated organic compounds that are widely used in industrial and consumer products due to the thermal stability, and hydrophobic and oleophobic properties (Lindstrom et al., 2011). Nevertheless, perfluorooctane-sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), the two most widely used PFASs, have been listed as persistent organic pollutants since they were found to be highly toxic, bioaccumulative, long-distance migratory and environmentally persistent (Liu et al., 2022a). Humans are widely exposed to PFASs through contaminated food, drinking water, dust, and consumer products (Haug et al., 2011; Banzhaf et al., 2017; Akhbarizadeh et al., 2020), which results in a high detection rate of PFASs in biological samples.

Accumulating evidence has suggested that exposure to PFASs is associated with a range of adverse health conditions, and that the liver and thyroid are the target organs for PFASs (Coperchini et al., 2017; Costello et al., 2022). Rodent studies showed consistent evidence for PFASs hepatotoxicity, including increased liver weight and histopathological alterations (Costello et al., 2022). On the other hand, laboratory data suggested that PFASs may be thyroid toxicants that cause hypothalamic-pituitary-thyroid axis disorders by regulating the biosynthesis and transport of thyroid hormones and by interfering with thyroid receptors (Weiss et al., 2009; Ren et al., 2016; Coperchini et al., 2017). There are, of course, numerous epidemiological studies that have attempted to explore the effects of PFASs exposure on human liver and thyroid function, but the results are controversial (Olsen et al., 2003; Khalil et al., 2018; Mora et al., 2018; Salihovic et al., 2018; Nian et al., 2019; Xiao et al., 2020; Li et al., 2021; Derakhshan et al., 2022; Jensen et al., 2022; Li et al., 2022; Liu et al., 2022a). In addition to differences in study design, population characteristics and sample size, potential interactions between PFASs (additive or antagonistic) may account for the inconsistent results. As the study on mixtures in the field of environmental epidemiology continues to evolve, researchers are committed to quantify the risk of disease caused by environmental chemical mixtures, which may be helpful to identify modifiable exposures that are amenable for public health interventions (Braun et al., 2016).

To our knowledge, three studies reported the combined effects of mixed PFASs on liver enzymes with a positive association in general population of Chinese and Canadian adults (Borghese et al., 2022; Liu et al., 2022a) and a nonsignificant association in the European birth cohort (Stratakis et al., 2020). Furthermore, five population-based studies evaluated the overall association between PFASs exposure and thyroid hormones, including one study in the general adult population in China (Li et al., 2022) and four studies in pregnant women or newborns in China, Boston, and the United States (Aimuzi et al., 2020; Lebeaux et al., 2020; Preston et al., 2020; Guo et al., 2021). Thus, the epidemiological evidence for joint effects of PFASs mixtures on liver and thyroid function remains insufficient, especially for adults.

Sex differences in the rate of elimination of PFASs have been reported. Breastfeeding and menstruation were one of the pathways of PFASs excretion (Thomsen et al., 2010; Mondal et al., 2014; Wong et al., 2014), which may lead to rapid elimination of PFASs in young women (Attanasio, 2019). Moreover, the liver was considered a sexually dimorphic organ, since it could express sex hormone receptors (Attanasio, 2019). Thyroid-related disorders showed a sex-specific prevalence, with a 5-20-fold higher susceptibility in women than in men (Tunbridge et al., 1977; Vanderpump et al., 1995; Gietka-Czernel, 2017), for which the sex steroid environment may be a key determinant (Baksi and Pradhan, 2021). Therefore, the sex-specific effects of PFASs exposure on liver and thyroid function deserve profound consideration.

The purpose of this study was to assess single and overall associations of PFASs with biomarkers of liver and thyroid function and to explore potential modified effect of sex in a Chinese adult population.