Developmental toxicology of acetonitrile in the Syrian golden hamster.
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.
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000097:Acetonitriles / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D006224:Cricetinae; D003486:Cyanides / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008647:Mesocricetus; D011247:Pregnancy; D013723:Teratogens
D000097:Acetonitriles; D003486:Cyanides; D013723:Teratogens; C032159:acetonitrile