Cummings A M, Ebron-McCoy M T, Rogers J M, Barbee B D, Harris S T
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Fundam Appl Toxicol. 1992 Feb;18(2):288-93. doi: 10.1016/0272-0590(92)90057-o.
Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC following exposure during early pregnancy, the current experiments were designed to evaluate the effect of exposure to MBC during early pregnancy on developmental parameters of offspring. Rats were administered MBC at 0, 100, 200, 400, or 600 mg/kg/day during Days 1-8 of pregnancy and killed on Day 11 or Day 20 of gestation. On Day 11, embryos were assessed for survival rate, growth parameters, and anomalies. On Day 20, standard developmental toxicity evaluations were performed. Doses of 200 to 600 mg/kg/day MBC reduced embryonic survival by Day 11; exposure to MBC at 100 to 600 mg/kg/day reduced the number of fetuses surviving on Day 20. Evidence of developmental delay was apparent on Day 11 at all doses, and fetal weight was reduced by Day 20. MBC produced a dose-dependent increase in developmental defects seen on Day 11 and in several malformations observed on Day 20. MBC exposure during the first week of pregnancy was shown to be embryotoxic, resulting in embryonic death, growth retardation, and developmental abnormalities when evaluated on Days 11 or 20 of gestation.
2-苯并咪唑氨基甲酸甲酯(MBC)及其母体化合物苯菌灵用作农业杀菌剂。这两种化学物质在器官形成期给药时均具有胚胎毒性,且苯菌灵具有致畸性。基于先前一项研究表明孕期早期接触MBC后不存在母体效应,当前实验旨在评估孕期早期接触MBC对后代发育参数的影响。在妊娠第1至8天,给大鼠分别按0、100、200、400或600毫克/千克/天的剂量给予MBC,并在妊娠第11天或第20天处死。在第11天,评估胚胎的存活率、生长参数和异常情况。在第20天,进行标准的发育毒性评估。到第11天,200至600毫克/千克/天剂量的MBC降低了胚胎存活率;100至600毫克/千克/天剂量接触MBC降低了第20天存活胎儿的数量。在第11天,所有剂量下均明显出现发育迟缓迹象,到第20天胎儿体重减轻。MBC导致第11天出现的发育缺陷以及第20天观察到的几种畸形呈剂量依赖性增加。在妊娠第一周接触MBC被证明具有胚胎毒性,在妊娠第11天或第20天评估时会导致胚胎死亡、生长迟缓以及发育异常。