Melchiors Mikala, Rosenmai Anna Kjerstine, Cariou Ronan, Pedersen Mikael, Christiansen Sofie, Svingen Terje
National Food Institute, Technical University of Denmark, Kgs. Lyngby DK-2800, Denmark.
Oniris, INRAE, LABERCA, 44300 Nantes, France.
Curr Res Toxicol. 2025 May 9;8:100237. doi: 10.1016/j.crtox.2025.100237. eCollection 2025.
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 and 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 (TC), a short-chained CP congener, by exposing pregnant rats from gestation days 7 to 21. TC 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 evidence of endocrine-disrupting activity exposure to TC 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 TC 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 TC can cross the placenta, its bioavailability may be insufficient to elicit measurable endocrine-disrupting effects on reproductive development. This study underscores the importance of accounting for toxicokinetics when extrapolating findings to endpoints.
氯化石蜡（CPs）是在环境和人体组织中广泛检测到的工业化学品，因其持久性、生物累积性和潜在健康风险而引发关注。氯化程度较低或碳链长度较短的CPs能够穿过胎盘，并且已在母乳中被检测到，这表明胎儿和出生后早期会接触到它们。体外和体内研究均表明，CPs具有内分泌干扰特性，尤其会影响生殖发育。本研究通过在妊娠第7天至21天对怀孕大鼠进行暴露，来探究短链CP同系物1,2,9,10 - 四氯癸烷（TC）的发育影响和胎盘转运情况。测量了胎儿和母体血液中的TC浓度，测定了胎儿类固醇激素水平，并分析了胎儿生殖结节中的靶向基因表达。尽管此前有证据表明TC具有内分泌干扰活性，但暴露于TC并未显著影响生殖参数，包括肛门与生殖器距离（AGD）、胎儿类固醇激素谱或发育中的生殖结节中雄激素和雌激素调节基因的表达。母体和胎儿血液中较低的全身TC水平表明其在脂肪组织中快速代谢或被隔离，暴露母鼠肝脏重量增加支持了这一点。这些发现表明，虽然TC可以穿过胎盘，但其生物利用度可能不足以对生殖发育产生可测量的内分泌干扰效应。本研究强调了在将研究结果外推至相关终点时考虑毒代动力学的重要性。
