The metabolism of 14C-dichloroethyne was studied in rats by inhalation in a dynamic nose-only exposure system. 14C-Dichloroethyne was generated in 95-99% yield from 14C-trichloroethene by alkaline dehydrochlorination. 2. After inhalation of 20 ppm and 40 ppm dichloroethyne for 1 h, the retention rates were 17.6% and 15.6% of the radioactivity introduced into the exposure system, respectively. During the period of observation (96 h), almost quantitative elimination of the dose was observed. Elimination with urine accounted for 60.0% (40 ppm) and 67.8% (20 ppm) of absorbed radioactivity and elimination with faeces for 27% (40 ppm) and 27.7% (20 ppm), 3.4-3.5% remained in the carcasses. 3. Metabolites of dichloroethyne identified are: N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, dichloroethanol, dichloroacetic acid, oxalic acid and chloroacetic acid in urine; N-acetyl-S-(1,2-dichlorovinyl-L-cysteine in faeces. 4. In bile of rats exposed to 40 ppm of dichloroethyne, S-(1,2-dichlorovinyl)glutathione was the only metabolite identified. Biliary cannulation did not influence the renal excretion of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, indicating that glutathione conjugate formation occurs in the kidney. 5. The results suggest that two metabolic pathways are operative in dichloroethyne metabolism in vivo. Cytochrome P450-dependent oxidation represents a minor pathway accounting for the formation of 1,1-dichloro compounds after chlorine migration. The major pathway is the biosynthesis of toxic glutathione conjugates. Organ-specific toxicity and carcinogenicity of dichloroethyne is due most likely to the topographical distribution of gamma-glutamyl transpeptidase which is concentrated mainly in the kidney in rats.
摘要
在动态单鼻暴露系统中，通过吸入法对大鼠体内14C - 二氯乙炔的代谢进行了研究。14C - 二氯乙炔由14C - 三氯乙烯经碱性脱氯化氢反应生成，产率为95 - 99%。2. 吸入20 ppm和40 ppm二氯乙炔1小时后，放射性保留率分别为引入暴露系统放射性的17.6%和15.6%。在观察期（96小时）内，几乎观察到剂量的定量消除。经尿液排出的放射性占吸收放射性的60.0%（40 ppm）和67.8%（20 ppm），经粪便排出的占27%（40 ppm）和27.7%（20 ppm），3.4 - 3.5%保留在 carcasses中。3. 鉴定出的二氯乙炔代谢产物有：尿液中的N - 乙酰 - S -（1,2 - 二氯乙烯基）- L - 半胱氨酸、二氯乙醇、二氯乙酸、草酸和氯乙酸；粪便中的N - 乙酰 - S -（1,2 - 二氯乙烯基）- L - 半胱氨酸。4. 在暴露于40 ppm二氯乙炔的大鼠胆汁中，鉴定出的唯一代谢产物是S -（1,2 - 二氯乙烯基）谷胱甘肽。胆管插管不影响N - 乙酰 - S -（1,2 - 二氯乙烯基）- L - 半胱氨酸的肾脏排泄，表明谷胱甘肽共轭物的形成发生在肾脏中。5. 结果表明，体内二氯乙炔代谢存在两条代谢途径。细胞色素P450依赖性氧化是次要途径，负责氯迁移后1,1 - 二氯化合物的形成。主要途径是有毒谷胱甘肽共轭物的生物合成。二氯乙炔的器官特异性毒性和致癌性很可能归因于γ - 谷氨酰转肽酶的拓扑分布，该酶主要集中在大鼠的肾脏中。
