Acute Lethal Toxicity Quantitative Structure-Activity Relationships for Electrophiles and Pro-Electrophiles: Mechanistic and Toxicokinetic Principles

TL;DRAbstract

Published data on acute lethal toxicity of aniline and nitrobenzene derivatives to fish can be correlated with an electrophilic reactivity descriptor based on substituent constants (proposed to relate to electrophilicity of the corresponding C-nitroso compounds, the aniline and nitrobenzene derivatives being regarded as pro-electrophiles). Likewise, published data on acute lethal toxicity of reactive halogen compounds can be correlated with an electrophilic reactivity parameter based on measured rate constants for reaction with a reference nucleophile, 4-nitrobenzylpyridine. In both cases, incorporation of a lipophilicity descriptor does not improve the quantitative structure-activity relationship (QSAR). A toxicokinetic model is proposed, whereby the electrophilic reaction leading to the toxic effect is assumed to take place in an aqueous biological medium separated from the external aqueous environment by a lipid barrier. Based on consideration of whether environment-lipid partition,

Chat with Paper

AI Agents for this Paper