Jackson N M, Conolly R B
Toxicol Lett. 1985 Dec;29(2-3):191-9. doi: 10.1016/0378-4274(85)90041-4.
A renal toxicity of 4 h inhalation exposure to 1,1-dichloroethylene (vinylidene chloride; VDC) was studied in male Sprague-Dawley rats. Kidney wt./body wt. ratios, serum urea nitrogen and creatinine levels were significantly increased 24 h after exposure to 250 ppm or more of VDC. Histopathologic examination by light microscopy of hematoxylin and eosin (H&E)-stained sections revealed severe tubular necrosis with calcium deposits at the higher exposure concentrations. Specific staining for calcium oxalate was negative, indicating that biotransformation of VDC to oxalate is probably not responsible for its nephrotoxicity. Pretreatment with polychlorinated biphenyl (PCB) induced the level of renal cytochrome P-450. Phenobarbital (PBT) pretreatment did not alter the renal P-450 level, but both PCB and PBT pretreatments antagonized VDC nephrotoxicity. These pretreatments have also been reported to antagonize VDC-induced hepatotoxicity. In summary, inhalation of VDC is nephrotoxic in the rat; the mechanism of nephrotoxicity does not involve calcium oxalate formation, and the magnitude of nephrotoxicity does not correlate directly with the total amount of renal cytochrome P-450.
在雄性斯普拉格-道利大鼠中研究了吸入1,1-二氯乙烯（偏二氯乙烯；VDC）4小时的肾脏毒性。暴露于250 ppm或更高浓度的VDC后24小时，肾脏重量/体重比、血清尿素氮和肌酐水平显著升高。苏木精和伊红（H&E）染色切片的光镜组织病理学检查显示，在较高暴露浓度下出现严重的肾小管坏死并伴有钙沉积。草酸钙特异性染色为阴性，表明VDC向草酸盐的生物转化可能与其肾毒性无关。用多氯联苯（PCB）预处理可诱导肾脏细胞色素P-450水平升高。苯巴比妥（PBT）预处理不会改变肾脏P-450水平，但PCB和PBT预处理均能拮抗VDC的肾毒性。据报道，这些预处理也能拮抗VDC诱导的肝毒性。总之，吸入VDC对大鼠具有肾毒性；肾毒性机制不涉及草酸钙形成，且肾毒性程度与肾脏细胞色素P-450总量无直接相关性。
