Renal toxicity of middle distillates of shale oil and petroleum in mice.

Abstract The tumorigenic potential of middle distillates (JP5, JP8, and diesel fuel marine) of shale oil and petroleum was studied by chronic dermal application on mice. These materials were applied to the backs of young C 3 Hf Bd mice three times weekly for 60 weeks. Cyclohexane was used as the vehicle. After 30 weeks of treatment, increased water consumption was observed in all test groups, and increased urine production was seen in many of these groups. Two mice that died in the last week of treatment had severe renal lesions. At the end of the experiment an additional 42 of 336 mice had similar renal lesions. Macroscopically, the characteristic renal lesion consisted of pale, irregular, depressed foci that appeared cuneiform when the kidney was bisected. These lesions appeared to be old infarcts, but microscopically they lacked the usual features of infarction, such as necrosis, hemorrhage, inflammation, and fibrosis. Instead, atrophied and degenerating nephrons supported by an intact reticulum were found. In addition, microscopic examination revealed a high incidence of papillary necrosis. The nature of the lesions suggests that the renal toxicity of these materials is mediated through some type of vascular phenomenon resulting in chronic ischemia. There appeared to be little difference between shale and petroleum-derived distillates (20 vs 24 affected mice, respectively). However, mice treated with shale-derived DFM were most severely affected, and female mice were affected preferentially.