Chemical-chemical interaction between cyanogenic toxicants and aldehydes: a mechanism-based QSAR approach to assess toxicological joint effects

Abstract

A QSAR approach was proposed to assess toxicological joint effects based on the mechanism of chemical-chemical interactions between cyanogenic toxicants and aldehydes. It has been observed that the chemical-chemical interaction between cyanogenic toxicants and aldehydes resulted in the formation of carbanion intermediates, and therefore this interaction led to different toxicological joint effects between cyanogenic toxicants and aldehydes. Analysis of this chemical-chemical interaction showed that the formation of carbanion intermediate highly depended on the charge of the carbon atom in the -CHO of aldehydes and this of the carbon atom (C*) in the carbochain of cyanogenic toxicant. By using the Hammett Constant (sgrp) to measure the charge of carbon atom in the -CHO of aldehydes, a mechanism-based QSAR approach (M=0.316-4.386sgrp with r2=0.933, SE=0.082, F=55.389, p=0.002, M=sum of toxic units) was proposed to assess the toxicological joint effects between -hydroxy-isobutyronitrile and individual aliphatic aldehydes. Another one (M=0.978-0.720sgrp with r2=0.852, SE=0.152, F=40.148, p=0.0001) was also proposed to assess the toxicological joint effects between -hydroxy-isobutyronitrile and individual aromatic aldehydes. Lastly, by using the charge of carbon atom (C*) in the carbochain of cyanogenic toxicant, a mechanism-based QSAR model (M=-0.161-7.721C* with r2=0.847, SE=0.227, F=27.657, p=0.003) was derived to assess toxicological joint effects between p-nitrobenzaldehyde and cyanogenic toxicants.