Biles R W, Schroeder R E, Holdsworth C E
Exxon Biomedical Sciences, Inc., Exxon Research & Engineering Co., East Millstone, NJ 08873.
Toxicol Ind Health. 1987 Dec;3(4):519-34. doi: 10.1177/074823378700300406.
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 gestation and from days 5-21 lactation of the litters (F1a) (no exposures days 0-4 lactation). A second litter (F1b) 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 comparison of treated animals with air sham controls. The mating indices and fertility indices in exposed animals for both mating intervals (F1a and F1b) were not significantly different from controls. Pregnancy rates were comparable between treated and control females for the first litter interval (F1a) but were slightly lower (not statistically significant) than control on the second litter interval (F1b). Treated animal mean gestation length and the mean number of pups at birth were not statistically different from controls. The pup viability indices at birth were comparable for control and treated groups for the F1a generation, but the mid- and high-dose groups displayed a slight statistically significant decrease in the F1b generation; the decrease was not considered to be biologically 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.
将雄性大鼠暴露于浓度分别为300、1300和3400 ppm的甲基叔丁基醚（MtBE）中，每天暴露6小时，每周暴露5天，持续12周，然后将其与暴露于相同浓度3周的雌性大鼠交配。暴露持续至交配期，雌性大鼠在妊娠期以及幼崽（F1a）出生后第5至21天的哺乳期继续暴露（出生后第0至4天不暴露）。在相同的交配和交配后暴露方案下产生了第二窝幼崽（F1b）。在整个实验的实际操作阶段，未观察到成年动物（F0）出现治疗的不良影响。唯一显著的发现是低剂量和高剂量雌性（F0）大鼠肾盂扩张的发生率增加。将处理过的动物与空气假对照组进行比较时，所有性腺重量、雄性附属生殖器官重量、器官与体重之比以及生殖器官组织病理学均无异常。在两个交配间隔期（F1a和F1b），暴露动物的交配指数和生育指数与对照组无显著差异。在第一窝幼崽间隔期（F1a），处理过的雌性大鼠和对照雌性大鼠的怀孕率相当，但在第二窝幼崽间隔期（F1b），处理组的怀孕率略低于对照组（无统计学意义）。处理过的动物平均妊娠期长度和出生时幼崽的平均数量与对照组无统计学差异。F1a代对照组和处理组幼崽出生时的活力指数相当，但在F1b代中，中剂量和高剂量组显示出轻微的统计学显著下降；这种下降不被认为具有生物学意义，可能也与处理无关。在两个窝次间隔期，对照组和处理组的窝仔存活指数相当。中剂量和高剂量雌性大鼠的幼崽在哺乳期第14天和第21天的平均体重略低（无统计学意义），但这被认为与处理无关。在哺乳期第21天处死的幼崽中，最常见的尸检观察结果是肾盂扩张。这似乎与处理无关。结论是，在大鼠两代一窝繁殖试验中，吸入MtBE对大鼠生殖毒性影响较小。
