Teratogenic effects of aliphatic nitriles

Area of Science:

• Toxicology
• Developmental Biology
• Teratology

Background:

• Aliphatic nitriles, including acrylonitrile and propionitrile, are known industrial chemicals.
• Previous studies indicate these nitriles can be metabolized to cyanide in vivo.
• Cyanide is a potent toxicant, and its role in nitrile-induced developmental toxicity requires further investigation.

Purpose of the Study:

• To investigate the teratogenic potential of acrylonitrile and propionitrile in hamsters.
• To determine the protective effects of sodium thiosulfate against nitrile-induced developmental toxicity and maternal toxicity.
• To explore the hypothesis that cyanide release mediates the teratogenic effects of these nitriles.

Main Methods:

• Pregnant hamsters were administered intraperitoneal injections of acrylonitrile or propionitrile on Day 8 of gestation.
• Sodium thiosulfate was administered to assess its protective effects against maternal and embryonic toxicity.
• Offspring were examined for teratogenic malformations, including exencephaly, encephalocoeles, and rib anomalies.

Main Results:

• Acrylonitrile and propionitrile induced significant teratogenic effects, such as exencephaly and rib malformations, in offspring.
• These nitriles also caused substantial maternal toxicity at the tested doses.
• Sodium thiosulfate administration effectively protected both dams and embryos from the toxic and teratogenic effects of the nitriles.
• Teratogenic effects were observed even when maternal toxicity was masked by sodium thiosulfate treatment.

Conclusions:

• The teratogenic effects of acrylonitrile and propionitrile in hamsters are likely mediated by the metabolic release of cyanide.
• Sodium thiosulfate acts as an effective antagonist against both the maternal toxicity and teratogenicity induced by these aliphatic nitriles.
• These findings support the role of cyanide as a key toxic metabolite in nitrile-induced developmental abnormalities.