Mast T J, Weigel R J, Westerberg R B, Schwetz B A, Morrissey R E
Battelle-Pacific Northwest Laboratory, Richland, Washington 99352.
Fundam Appl Toxicol. 1992 Feb;18(2):255-65. doi: 10.1016/0272-0590(92)90054-l.
Sprague-Dawley rats and Swiss (CD-1) mice were exposed to 0, 600, 1800, or 5000 ppm THF (a four-carbon cyclic ether, widely used as an industrial solvent) vapors, 6 hr/day, 7 days/week (6-19 days of gestation (DG) for rats; 6-17 DG for mice). Body weights of pregnant rats in the 5000 ppm group were reduced at euthanization. There were no effects on the percentage of live rat fetuses/litter or on the fetal sex ratio. Fetal body weight was significantly reduced for the 5000 ppm group, but the incidence of abnormalities was not increased. Mice in the 1800 and 5000 ppm groups were sedated during exposure; approximately 27% of the mice in the 5000 ppm group died. Mean body and uterine weights of mice were reduced for the 1800 and 5000 ppm groups at euthanization (18 DG), but adjusted maternal weight gain was not affected at 1800 ppm. There was a reduction in the percentage of live fetuses/litter for the mice in 1800 and 5000 ppm groups (95% resorptions in the 5000 ppm group). Fetal weight and sex ratio in mice were not affected. An increase in the incidence of reduced sternebral ossifications was correlated to THF concentration, although differences between groups were not statistically significant. There were no increases in the incidences of other malformations or variations. These results suggest that THF may be embryotoxic in mice, but if the conceptus survives, development as assessed by this experimental design continues in a normal fashion. The no-observable-adverse-effect level (NOAEL) for maternal toxicity was 1800 ppm in both rats and mice. The NOAEL for developmental toxicity was 1800 ppm in rats and 600 ppm in mice.
将斯普拉格-道利大鼠和瑞士（CD-1）小鼠暴露于浓度为0、600、1800或5000 ppm的四氢呋喃（一种四碳环醚，广泛用作工业溶剂）蒸气中，每天6小时，每周7天（大鼠为妊娠第6至19天；小鼠为妊娠第6至17天）。5000 ppm组的妊娠大鼠在安乐死时体重减轻。对活产大鼠胎儿/窝数百分比或胎儿性别比例没有影响。5000 ppm组的胎儿体重显著降低，但异常发生率没有增加。1800和5000 ppm组的小鼠在暴露期间出现镇静；5000 ppm组约27%的小鼠死亡。在安乐死时（妊娠第18天），1800和5000 ppm组的小鼠平均体重和子宫重量降低，但1800 ppm组的母体调整后体重增加不受影响。1800和5000 ppm组的小鼠活产胎儿/窝数百分比降低（5000 ppm组95%为吸收胎）。小鼠的胎儿体重和性别比例不受影响。胸骨骨化减少的发生率增加与四氢呋喃浓度相关，尽管各组之间的差异无统计学意义。其他畸形或变异的发生率没有增加。这些结果表明，四氢呋喃可能对小鼠具有胚胎毒性，但如果胚胎存活，按照本实验设计评估，发育将以正常方式继续。大鼠和小鼠母体毒性的未观察到有害作用水平（NOAEL）均为1800 ppm。大鼠发育毒性的NOAEL为1800 ppm，小鼠为600 ppm。
