O,S,S-Trimethyl phosphorodithioate and O,O,S-triethyl phosphorothioate: Pharmacokinetics in rats and effect of pretreatment with compounds affecting the drug processing systems

O,S,S-Trimethyl phosphorodithioate and O,O,S-triethyl phosphorothioate cause lung damage in rats. After oral or intravenous injection they are distributed rapidly with the body water and concentrations in plasma and tissues are equal. The rate of disposal of both compounds has been determined in control, and phenobarbitone- and piperonyl butoxide-pretreated rats. After pretreatment with phenobarbitone, rates of disposal are increased and the toxicity of both compounds is reduced in proportion. After piperonyl butoxide, this relationship between rates of disposal and toxicity is changed. The relevance of these findings to the mechanism whereby these trialkyl phosphorothioates cause lung damage is discussed.