Uterine Changes in Female Mice Following Lifetime Inhalation of Wholly Vaporized Unleaded Gasoline: A Possible Relationship to Observed Liver Tumors?

Abstract

An increased incidence of primary hepatocellular tumors was reported in female B6C3F1 mice following lifetime exposure to high levels (2056 ppm) of wholly vaporized unleaded gasoline. This effect was not observed in male mice, nor in females exposed to either 67 or 292 ppm gasoline. No explanation for the sex and dose-specific effect was discussed in the initial report or has been subsequently published. At necropsy, a decreased incidence of enlarged/cystic uteri was also noted among high dose females; however, no correlating histopathologic changes were reported. Because the liver neoplastic response was limited to the females, and because spontaneous liver tumors are known to be influenced by the hormonal environment, we reexamined the uterine tissues microscopically. We observed a dramatic difference among treatment groups in the severity of cystic endometrial hyperplasia. The incidence of moderate cystic endometrial hyperplasia at the terminal sacrifice was 76% in the control animals whereas none of the animals at the highest exposure level had lesions that were graded moderate or severe. In addition, uterine atrophy was present in 35% of mice examined at the high exposure level and was absent in other groups. The changes noted are consistent with an altered hormonal influence on the uterus. The finding of a decrease in cystic endometrial hyperplasia and an increase in uterine atrophy in the same dose group in which liver tumors were found suggests that these effects may be interrelated.