Carney E W, Thorsrud B A, Dugard P H, Zablotny C L
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674, USA.
Birth Defects Res B Dev Reprod Toxicol. 2006 Oct;77(5):405-12. doi: 10.1002/bdrb.20091.
The potential for trichloroethylene (TCE) and perchloroethylene (PERC) to induce developmental toxicity was investigated in Crl:CD (SD) rats whole-body exposed to target concentrations of 0, 50, 150 or 600 ppm TCE or 0, 75, 250 or 600 ppm PERC for six hours/day, seven days/week on gestation day (GD) 6-20 and 6-19, respectively. Actual chamber concentrations were essentially identical to target with the exception of the low PERC exposure level, which was 65 ppm. The highest exposure levels exceeded the limit concentration (2 mg/L) specified in the applicable test guidelines. Maternal necropsies were performed the day following the last exposure. Dams exposed to 600 ppm TCE exhibited maternal toxicity, as evidenced by decreased body weight gain (22% less than control) during GD 6-9. There were no maternal effects at 50 or 150 ppm TCE and no indications of developmental toxicity (including heart defects or other terata) at any exposure level tested. Therefore, the TCE NOEC for maternal toxicity was 150 ppm, whereas the embryo/fetal NOEC was 600 ppm. Maternal responses to PERC were limited to slight, but statistically significant reductions in body weight gain and feed consumption during the first 3 days of exposure to 600 ppm, resulting in a maternal NOEC of 250 ppm. Developmental effects at 600 ppm consisted of reduced gravid uterus, placental and fetal body weights, and decreased ossification of thoracic vertebral centra. Developmental effects at 250 ppm were of minimal toxicological significance, being limited to minor decreases in fetal and placental weight. There were no developmental effects at 65 ppm.
在妊娠第6至20天和第6至19天，分别对Crl:CD(SD)大鼠进行全身暴露，使其每天6小时、每周7天接触目标浓度为0、50、150或600 ppm的三氯乙烯(TCE)或0、75、250或600 ppm的全氯乙烯(PERC)，研究TCE和PERC诱导发育毒性的可能性。除低PERC暴露水平为65 ppm外，实际舱内浓度与目标浓度基本相同。最高暴露水平超过了适用测试指南中规定的极限浓度(2 mg/L)。在最后一次暴露后的第二天进行母鼠尸检。暴露于600 ppm TCE的母鼠表现出母性毒性，妊娠第6至9天体重增加减少(比对照组少22%)即为证据。50或150 ppm TCE时未出现母性影响，在任何测试暴露水平下均未出现发育毒性迹象(包括心脏缺陷或其他畸形)。因此，TCE对母性毒性的无观察效应浓度(NOEC)为150 ppm，而胚胎/胎儿的NOEC为600 ppm。母鼠对PERC的反应仅限于在暴露于600 ppm的前3天体重增加和采食量略有但具有统计学意义的减少，导致母性NOEC为250 ppm。600 ppm时的发育影响包括妊娠子宫、胎盘和胎儿体重减轻，以及胸椎椎体骨化减少。250 ppm时的发育影响具有最小的毒理学意义，仅限于胎儿和胎盘重量略有下降。65 ppm时未出现发育影响。
