Klimisch H J, Hellwig J, Hofmann A
BASF Aktiengesellschaft, Department of Toxicology, Ludwigshafen, FRG.
Arch Toxicol. 1992;66(6):373-81. doi: 10.1007/BF02035125.
Prenatal toxicity of toluene was determined in two separate studies by inhalation exposure of Himalayan rabbits. In the first study 15 artificially inseminated females per group were exposed to 30, 100, or 300 ppm and in the second study 20 artificially inseminated females per group inhaled 100 or 500 ppm. In each case the rabbits were exposed for 6 hours per day from day 6 post-insemination (p.i.) to day 18 p.i. The respective controls inhaled conditioned clean air under the same exposure conditions. No signs of maternal toxicity were observed. All data obtained on gestational parameters were found to be within the variation range reported for this rabbit strain. The fetal external, soft tissue and skeletal findings were seen in toluene exposed fetuses in a frequency similar to the corresponding and/or historical controls. Differences observed between the groups were not concentration dependent and were considered incidental rather than compound related. Therefore, toluene was not embryotoxic, fetotoxic, or teratogenic for rabbits exposed during the period of organogenesis. The highest concentration tested under these conditions (500 ppm) was found to be a no-observable-adverse-effect level (NOAEL) for both the adult and the fetal Himalayan rabbit. Based on these and previous results of animal studies of prenatal toxicity, a safety or uncertainty factor approach is considered for setting limits of exposure for women at workplaces. A pregnancy guidance value of 20 ppm is proposed.
通过让喜马拉雅兔吸入甲苯，在两项独立研究中测定了甲苯的产前毒性。在第一项研究中，每组15只人工授精的雌性兔子分别暴露于30、100或300 ppm的甲苯环境中；在第二项研究中，每组20只人工授精的雌性兔子吸入100或500 ppm的甲苯。在每种情况下，兔子从授精后第6天（p.i.）至第18天每天暴露6小时。相应的对照组在相同暴露条件下吸入经调节的清洁空气。未观察到母体毒性迹象。所有关于妊娠参数的数据均在该兔种报告的变异范围内。在暴露于甲苯的胎儿中观察到的胎儿外部、软组织和骨骼方面的情况，其出现频率与相应的和/或历史对照组相似。各实验组之间观察到的差异与浓度无关，被认为是偶然的而非与化合物相关。因此，在器官形成期暴露于甲苯的兔子，甲苯对其不具有胚胎毒性、胎儿毒性或致畸性。在这些条件下测试的最高浓度（500 ppm）被确定为成年和胎儿喜马拉雅兔的无可见不良作用水平（NOAEL）。基于这些以及之前关于产前毒性的动物研究结果，考虑采用安全或不确定系数法来设定工作场所女性的接触限值。建议的妊娠指导值为20 ppm。
