Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street Rm. 510, Box G-E5, Providence, Rhode Island, 02912, United States.
Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street Rm. 510, Box G-E5, Providence, Rhode Island, 02912, United States.
Environ Toxicol Pharmacol. 2019 May;68:1-3. doi: 10.1016/j.etap.2019.02.003. Epub 2019 Feb 16.
Trichloroethylene (TCE) is a persistent environmental contaminant that causes male reproductive toxicity. We investigated whether transient increases in TCE exposure modulated male reproductive toxicity by exposing rats via daily oral to repeated gavage exposures (1000 mg/kg/day) and through drinking water (0.6% TCE) for 14 weeks. The gavage route resulted in reversible reduction of epididymis weight, and reduced body weight that persisted for up to 12-weeks after cessation of exposure. Physiologically-based pharmacokinetic modeling predicted that the gavage route results in higher C and AUC exposure of TCE compared to drinking water exposure, explaining the observed differences in toxicity between dosing regimens.
三氯乙烯（TCE）是一种持久性环境污染物，会导致男性生殖毒性。我们通过每日口服重复灌胃暴露（1000mg/kg/天）和通过饮用水（0.6%TCE）暴露 14 周来研究 TCE 暴露的短暂增加是否会调节男性生殖毒性。灌胃途径导致附睾重量可逆性降低，体重减轻，在停止暴露后持续长达 12 周。基于生理的药代动力学模型预测，与饮水暴露相比，灌胃途径会导致 TCE 的 C 和 AUC 暴露更高，这解释了两种给药方案之间毒性差异的原因。
