Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6–9 Years of age : a cross-sectional analysis within the C8 health project

Background: Exposure to some perfluoroalkyl substances (PFAS), such as perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA), may alter levels of sex hormones and insulin-like growth factor-1 (IGF-1) in animals. Human studies on this topic are scarce and none have been conducted in young children. Objectives: To investigate the relationship between levels of PFAS and estradiol, total testosterone and IGF-1 in 2,292 children (aged 6-9 years) from the C8 Health Project living near a chemical plant in the Mid-Ohio Valley (USA) with local contamination from PFOA. Methods: Serum samples were collected in 2005-2006 and analyzed for PFAS, sex hormones and IGF-1. Results from regression models were expressed as the adjusted percentage difference (95% CI) per sex-specific interquartile range (IQR) increment of each PFAS serum concentration. Analyses by PFAS quartiles were also conducted. Results: Median concentrations of PFHxS, PFOA, PFOS, and PFNA were 8, 35, 22, and 1.7 ng/mL in boys and 7, 30, 21, and 1.7 ng/mL in girls. In boys, PFOA concentrations were significantly associated with testosterone levels (-4.9% [-8.7, -0.8%]); PFOS with estradiol (-4.0% [-7.7, -0.1%]), testosterone (-5.8% [-9.4, -2.0%]), and IGF-1 (-5.9% [-8.3, -3.3%]); and PFNA with IGF-1 (-3.5% [-6.0, -1.0%]). In girls, significant associations were found between PFOS and testosterone (-6.6% [-10.1, -2.8%]) and IGF-1 (-5.6% [-8.2, -2.9%]); and PFNA and IGF-1 (-3.8% [-6.4, -1.2%]). In both sexes, the magnitudes of the associations decreased monotonically across quartiles for testosterone and PFOS, and for IGF-1 and both PFOS and PFNA. Conclusions: To our knowledge, this is the first study suggesting that PFAS are associated with lowe