In vivo and in vitro release of cyanide from neurotoxic aminonitriles

Abstract

Cyanide release from neurotoxic aminonitriles was measured following in vitro incubation with both microsomes and liver slices. Investigation of cyanide released as urinary thiocyanate following ip aminonitrile administration to rats was also measured. The yield of cyanide in the in vivo study, as measured by the mole percent of administered dose, was greatest from dimethylaminonitrile (DMAA), followed by trimethylaminopropionitrile (TMAPN), dimethylaminopropionitrile (DMAPN), 3,3'‐iminodipropionitrile (IDPN), dimethylaminobutyronitrile (DMABN), and monomethylaminopropionitrile (MMAPN). Urinary excretion of thiocyanate accounted for 48.9% of the administered DMAA, 11.6% of TMAPN, 8.0% of DMAPN, 6.8% of IDPN, 3.1% of DMABN, and 1.8% of MMAPN. Incubation of aminonitriles and related compounds with microsomes or liver slices from rats yielded measurable quantities of cyanide from all the compounds tested except for DMABN, TMABN, and succiononitrile. Quantitative evaluation of the yield of formaldehyde by demethylation following microsomal incubation was also determined. The signs of acute toxicity in rats after ip administration of KCN were similar only to those in rats administered DMAA.