Perfluoroalkyl substances, sex hormones, andinsulin-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. Humanstudies 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 andIGF-1 in 2,292 children (aged 6-9 years) from the C8 Health Project living near a chemical plant in theMid-Ohio Valley (USA) with local contamination from PFOA.Methods: Serum samples were collected in 2005-2006 and analyzed for PFAS, sex hormones andIGF-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 byPFAS quartiles were also conducted.Results: Median concentrations of PFHxS, PFOA, PFOS, and PFNA were 8, 35, 22, and 1.7 ng/mL inboys and 7, 30, 21, and 1.7 ng/mL in girls. In boys, PFOA concentrations were significantly associatedwith 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%]). Ingirls, significant associations were found between PFOS and testosterone (-6.6% [-10.1, -2.8%]) andIGF-1 (-5.6% [-8.2, -2.9%]); and PFNA and IGF-1 (-3.8% [-6.4, -1.2%]). In both sexes, the magnitudesof the associations decreased monotonically across quartiles for testosterone and PFOS, and for IGF-1and both PFOS and PFNA.Conclusions: To our knowledge, this is the first study suggesting that PFAS are associated with lowe