Relationships between toxicity and structure of aliphatic nitriles

A retrospective structure-activity relationship (SAR) comparison was undertaken of several of the toxicological properties (acute and subchronic toxicity, teratogenicity, and biochemical mechanism studies) of a series of structurally similar aliphatic nitriles based on available published data. Members of this chemical class included several mononitriles (aceto-, propio-, butyro-, and acrylonitrile), dinitriles (succino- and adiponitrile), and cyanohydrin derivatives (lactonitrile and acetone cyanohydrin). Broadly defined, retrospective SAR analysis suggested that the toxicological profiles of this group of aliphatic nitriles were similar; however, unique differences were observed within each of the toxicity categories and nitrile subclasses as the toxicological focus narrowed. Additionally, the toxicological properties associated with acetonitrile, the first of this chemically similar series, were unique and quite different from others within the homologous series. Finally, knowledge regarding the mechanism of toxicological action provided valuable information in relating toxicological properties among the aliphatic nitriles.