Metabolism of Cyanox in the rat. I. Absorption, disposition, excretion and biotransformation

Abstract

1. To examine the metabolic fate of Cyanox [O-4-cyanophenyl O, O-dimethyl phosphorothioate, cyanophos, CYAP], rats of both sexes were administered [phenyl-¹⁴C]Cyanox as a single oral dose at levels of 0.5mg/kg (low-dose group) or 25mg/kg (high-dose group), or as multiple doses at 50 mg/kg/day once daily for 7 days (repeat-dose group).

2. The radiocarbon was almost completely eliminated from rats within 7 days after administration in both low- and high-dose groups. ¹⁴C-recoveries (expressed as % relative to the dosed ¹⁴C) in faeces and urine were 2–3 and 95–96% respectively for the low-dose and 13–14 and 86% respectively for the high-dose.

3. ¹⁴C-tissue residues on the seventh day after a single administration were generally low. Peak ¹⁴C-concentrations in blood and kidney occurred at 0.5 h (high-dose) and decreased rapidly thereafter.

4. Sex-related differences in the amounts of metabolites were observed in both groups. With the low-dose, the major metabolite was 4-cyanophenylsulphate in both sexes. However, in the high-dose, the major metabolites were 4-cyanophenyl sulphate and desmethylcyanoxon in males, but 4-cyanophenyl sulphate and desmethylcyanox in females. These findings indicate that the amounts or the types of enzymes responsible for oxidative desulphuration or oxidative dearylation in males are different from those in females. In the male rat given repeat doses significant differences in the amounts of metabolites in excreta were observed between early and final dosing.

5. The greater formation of desmethylcyanoxon in the male rat in the high-dose case is consistent with the higher incidence of toxicity in this sex.