Assessing placental transfer and in utero reproductive effects in rats of a short-chained paraffin with in vitro endocrine disrupting properties

Abstract

Chlorinated paraffins (CPs) are industrial chemicals detected widely in the environment and human tissues, raising concerns due to their persistence, bioaccumulation, and potential health risks. CPs with lower chlorination or shorter carbon chain lengths can cross the placenta and have been detected in breast milk, indicating fetal and early postnatal exposure. Both in vitro and in vivo studies suggest that CPs exhibit endocrine-disrupting properties, particularly affecting reproductive development. This study investigates the developmental effects and placental transfer of 1,2,9,10-tetrachlorodecane (T₄C₁₀), a short-chained CP congener, by exposing pregnant rats from gestation days 7 to 21. T₄C₁₀ concentrations were measured in fetal and maternal blood, fetal steroid hormone levels were measured, and targeted gene expression was analyzed in the fetal genital tubercle. Despite prior in vitro evidence of endocrine-disrupting activity, in vivo exposure to T₄C₁₀ did not significantly affect reproductive parameters, including the anogenital distance (AGD), fetal steroid hormone profiles, or expression of androgen- and estrogen-regulated genes in the developing genital tubercle. The low systemic T₄C₁₀ levels in maternal and fetal blood suggest rapid metabolism or sequestration in adipose tissue, supported by increased liver weight in the exposed dams. These findings suggest that while T₄C₁₀ can cross the placenta, its bioavailability in vivo may be insufficient to elicit measurable endocrine-disrupting effects on reproductive development. This study underscores the importance of accounting for toxicokinetics when extrapolating in vitro findings to in vivo endpoints.