Methyl Tertiary Butyl Ether Inhalation in Rats: a Single Generation Reproduction Study

Abstract

Male rats exposed to target concentrations of methyl tertiary butyl ether (MtBE) at 300, 1300 and 3400 ppm for 6 hours/day, 5 days/ week for 12 weeks were mated to female rats exposed to the same concentrations for a 3-week period. Exposures continued through the mating period and the females continued exposures during ges tation and from days 5-21 lactation of the litters (F _1a) (no expo sures days 0-4 lactation). A second litter (F _1b) was produced under the same mating and post mating exposure regimen. No adverse effect of treatment was observed with the adult animals (Fo) throughout the in-life portion of the study. The only remarkable finding was an increased incidence of dilated renal pelves in the low- and high-dose females (Fo). All gonad weights, male accessory reproductive organ weights, organ-to-body weight ratios and reproductive organ histopathology were unremarkable upon com parison of treated animals with air sham controls. The mating indi ces and fertility indices in exposed animals for both mating intervals (F _1a and F _1b) were not significantly different from con trols. Pregnancy rates were comparable between treated and con trol females for the first litter interval (F _1a) but were slightly lower (not statistically significant) than control on the second litter inter val (F _1b ). Treated animal mean gestation length and the mean number of pups at birth were not statistically different from con trols. The pup viability indices at birth were comparable for control and treated groups for the F _1a generation, but the mid- and high- dose groups displayed a slight statistically significant decrease in the F _1b generation; the decrease was not considered to be biologi cally significant and perhaps not treatment-related. Litter survival indices were comparable between control and treated groups for both litter intervals. Pups of mid- and high-dose females had slightly lower (not statistically significant) mean weights at days 14 and 21 of lactation but this was not considered treatment-related. The most frequent post-mortem observation for pups sacrificed at day 21 of lactation was dilated renal pelves. This did not appear to be related to treatment. It is concluded that MtBE inhalation in rats results in little adverse reproductive toxicity as shown in a two litter, one generation reproduction assay in rats.