Dahl A R
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185, USA.
Toxicology. 1996 Oct 28;113(1-3):273-7. doi: 10.1016/0300-483x(96)03456-7.
Available data suggest that: (1) the greater uptake of isoprene in mice relative to rats may not contribute to differences in sensitivity because the blood levels of total metabolites are similar in the two species; (2) in rats, saturation of blood levels of isoprene monoxide and the hydrocarbon could not be demonstrated at inhaled isoprene concentrations up to 8200 ppm, but saturation of blood levels of diols/diepoxide and of non-volatile metabolites occurred at approximately 1480 ppm (similar data are not reported for mice); (3) reaction of reactive isoprene metabolites with blood components in mice and rats is similar to reaction of butadiene metabolites in rats and much greater than that of butadiene metabolites in mice. This may contribute to the greater sensitivity of mice to butadiene carcinogenicity relative to isoprene carcinogenicity; (4) reported data do not conclusively show that differences in tissue concentrations of isoprene metabolites contribute to the differences in the relative potencies of isoprene and butadiene in mice or to the greater carcinogenic potency of isoprene in mice relative to that in rats.
(1)与大鼠相比,小鼠对异戊二烯的摄取量更高,但这可能并非导致敏感性差异的原因,因为两种物种中总代谢物的血液水平相似;(2)在大鼠中,吸入异戊二烯浓度高达8200 ppm时,一氧化异戊二烯和碳氢化合物的血液水平未出现饱和,但二醇/二环氧物和非挥发性代谢物的血液水平在约1480 ppm时出现饱和(未报告小鼠的类似数据);(3)小鼠和大鼠中活性异戊二烯代谢物与血液成分的反应类似于大鼠中丁二烯代谢物的反应,且远大于小鼠中丁二烯代谢物的反应。这可能是小鼠相对于异戊二烯致癌性对丁二烯致癌性更敏感的原因;(4)报告的数据并未确凿表明异戊二烯代谢物的组织浓度差异导致小鼠中异戊二烯和丁二烯相对效力的差异,或导致小鼠中异戊二烯相对于大鼠的致癌效力更高。