Abstract

Tri-o-cresyl phosphate (TOCP) and triphenyl phosphite (TPP) are known to be neurotoxic in several species. In a previous study, we found that the subcutaneous administration of the compounds may result in toxicological effects which are prolonged in comparison to administration by other routes. In order to test the hypothesis that slow absorption from the injection site could account for our results, we monitored the disappearance of either compound from the injection site using in vivo 31P nuclear magnetic resonance (NMR). In addition, the test samples and some potential metabolites were examined in vitro with NMR. The disappearance of equimolar doses of subcutaneously injected TOCP (1187 mg/kg) and TPP (1000 mg/kg) from the injection site, with time, showed a biphasic pattern. The first phase took place within a few hours, while the second phase was very slow, with a half-life of about 2 weeks for both compounds. These results may account for the prolonged neuropathy target enzyme inhibition and explain the delayed neurotoxicity produced by subcutaneous injection of TOCP and TPP. Two animals given TPP exhibited an atypical pattern, in that the TPP apparently converted to diphenyl phosphonic acid within several hours of injection. In these hens, this phenomenon was accompanied by acute lethality. The conversion to diphenyl phosphonic acid also took place when the TPP was placed in an aqueous solution in vitro. Diphenyl phosphonic acid may play a role in the unique toxicity of TPP.