Wilmer J W, Spencer P J, Ball N, Bus J S
Wilmer Tox Consulting, Langnau am Albis, Switzerland.
Mutagenesis. 2014 May;29(3):209-14. doi: 10.1093/mutage/geu006. Epub 2014 Mar 11.
The in vivo genotoxic potential of trichloroethylene (TCE) was evaluated by examining the incidence of micronucleated polychromatic erythrocytes (MN-PCEs) in the bone marrow. Groups of male CD rats were exposed by inhalation to targeted concentrations of 0 (negative control), 50, 500, 2500 or 5000 ppm for 6 consecutive hours on a single day. The exposure concentrations were selected to overlap those employed by a published study that reported a 2- to 3-fold increase in the frequency of micronuclei in male rats following a single inhalation exposure to 5, 500 and 5000 ppm TCE for 6h but not following repeated exposure to similar concentrations. In addition, any treatment-related findings were assessed in the context of potential TCE-induced hypothermia. Clinical signs consistent with marked TCE-induced sedation were observed in rats exposed to 5000 ppm and subsequently three rats died prior to the end of the 6h exposure period. No remarkable changes in body temperature were observed in surviving animals monitored with transponders before and after exposures. There were no statistically significant increases in the frequencies of MN-PCEs in groups treated with the test material as compared to the negative controls. The positive control animals showed a significant increase in the frequency of MN-PCEs and a decrease in the relative proportion of PCEs among erythrocytes as compared to the negative control animals. There were no statistically significant differences in the per cent PCEs in groups treated with the test material. As no increase in the incidence of micronuclei was observed in any of the TCE exposure groups, kinetochore analyses were not performed. Under the experimental conditions used, TCE was considered to be negative in the rat bone marrow micronucleus test.
通过检测骨髓中微核多染红细胞(MN-PCEs)的发生率,评估了三氯乙烯(TCE)的体内遗传毒性潜力。将雄性CD大鼠分组,在一天内连续6小时吸入目标浓度为0(阴性对照)、50、500、2500或5000 ppm的TCE。选择这些暴露浓度是为了与一项已发表研究中使用的浓度重叠,该研究报告称,雄性大鼠单次吸入5、500和5000 ppm TCE 6小时后,微核频率增加了2至3倍,但重复暴露于类似浓度后未出现这种情况。此外,在潜在的TCE诱导的体温过低的背景下评估了任何与治疗相关的发现。在暴露于5000 ppm的大鼠中观察到与明显的TCE诱导的镇静一致的临床体征,随后三只大鼠在6小时暴露期结束前死亡。在用应答器监测的存活动物中,暴露前后均未观察到体温有明显变化。与阴性对照相比,用测试材料处理的组中MN-PCEs的频率没有统计学上的显著增加。与阴性对照动物相比,阳性对照动物的MN-PCEs频率显著增加,红细胞中PCEs的相对比例降低。用测试材料处理的组中PCEs的百分比没有统计学上的显著差异。由于在任何TCE暴露组中均未观察到微核发生率增加,因此未进行动粒分析。在所使用的实验条件下,TCE在大鼠骨髓微核试验中被认为是阴性的。