Willhite C C
Teratology. 1983 Jun;27(3):313-25. doi: 10.1002/tera.1420270305.
Pregnant hamsters were exposed to acetonitrile by inhalation, ingestion, or ip injection during the early primitive streak stage of embryogenesis. Inhalation of 1,800 or 3,800 ppm acetonitrile for 60 min failed to induce malformations in the near-term offspring whereas inhalation of 5,000 or 8,000 ppm acetonitrile was associated with production of severe axial skeletal (dysraphic) disorders. One fetus afflicted with extrathoracic ectopia cordis was recovered from a dam exposed to 8,000 ppm acetonitrile. An oral or ip dose of 100-400 mg/kg acetonitrile in hamsters of equivalent gestational age also caused malformations identical to those noted following inhalation exposure. Some dams exposed to the highest concentrations or doses of acetonitrile displayed overt signs of poisoning. Multiple injections of sodium thiosulfate antagonized the mortality and signs of intoxication associated with acetonitrile treatment. Offspring of thiosulfate-treated hamsters exposed to acetonitrile failed to exhibit the marked teratogenic response that was associated with exposure to equivalent concentrations or doses of acetonitrile alone. Elevated concentrations of cyanide and thiocyanate were detected in all tissues studied at 2.5 hr after an oral or ip dose of acetonitrile. Cyanide was liberated when acetonitrile was incubated in vitro with hamster liver slices or NADPH-fortified hepatic microsomal preparations. The results suggested that in vivo liberation of cyanide from acetonitrile was responsible for the production of terata.
在胚胎发育的早期原条阶段，将怀孕的仓鼠通过吸入、摄入或腹腔注射的方式暴露于乙腈中。在近期后代中，吸入1800或3800 ppm乙腈60分钟未能诱导畸形，而吸入5000或8000 ppm乙腈则与严重的轴向骨骼（脊柱裂）疾病的产生有关。从暴露于8000 ppm乙腈的母鼠中回收了一只患有胸外心脏异位的胎儿。给相同胎龄的仓鼠口服或腹腔注射100 - 400 mg/kg乙腈也会导致与吸入暴露后观察到的相同畸形。一些暴露于最高浓度或剂量乙腈的母鼠表现出明显的中毒迹象。多次注射硫代硫酸钠可对抗与乙腈治疗相关的死亡率和中毒迹象。硫代硫酸钠处理过的仓鼠暴露于乙腈后的后代未表现出与单独暴露于同等浓度或剂量乙腈相关的明显致畸反应。口服或腹腔注射乙腈2.5小时后，在所有研究的组织中均检测到氰化物和硫氰酸盐浓度升高。当乙腈在体外与仓鼠肝切片或NADPH强化的肝微粒体制剂一起孵育时会释放出氰化物。结果表明，乙腈在体内释放氰化物是产生畸形的原因。
