Search

Tri-o-cresyl phosphate (TOCP) and O-ethyl O-(4-cyanophenyl) phenylphosphonothioate (cyanofenphos, Surecide) were found to be delayed neurotoxicants. They were administered to chickens by gavage at 100 and 30 mgjkg•d for 15 d, respectively. In CD-1 mice neither TOCP nor cyanophenphos induced any of the usually recognized clinical symptoms of neuropathy when administered daily by gavage at 262 or 31.25 mg/kg-d for 30 d, respectively. In the chickens, TOCP and cyanofenphos produced about 98 and 90% in vivo inhibition of brain neurotoxic esterase (NTE) activity. In the mice, 24 h after the last daily dose, TOCP and cyanofenphos produced only about 50 and 40% in vivo inhibition of the brain NTE activity. Parathion [O,O-diethyl O-(4-nitrophenyl) phosphorothioate], at 2 or 6.75 mg/kg'd for 15 or 30 d, did not induce neuropathy in either chicken or mice and produced no significant in vivo inhibition of brain NTE activity at the end of the dosing regimen. The specific activity of NTE in control chicken brain crude homogenate was much higher than that in mouse brain homogenate. These results suggest that the differences between chickens and mice in susceptibility to neurotoxic organophosphates may be attributed to (1) inhibitor specificity of NTE forms in the brain in these two different animal species and/or (2) inability of the active metabolites of these neurotoxic compounds to reach the site of action.

Endrin, a chlorinated hydrocarbon insecticide, produces hyperexcitability of the human central nervous system. Acute endrin poisoning from bread made with contaminated flour resulted in sudden convulsions in three people. Recoveries were spontaneous, and symptoms were minimal. The endrin content was determined for the contaminated bread, the contaminated flour, and the specimens from four persons who had eaten the bread.

A direct method of assaying neurotoxic esterase (NTE) activity, using 4-nitrophenyl valerate, has been described. The technique was used to determine the bimolecular rate (ki), phosphorylation (k2), and affinity (Kd) constants for the reaction of hen brain microsomal NTE with mipafox. Results indicate that the new technique for assaying NTE makes detailed kinetic studies of NTE inhibition possible. The affinity and phosphorylation constants, Kd and k2, for the reaction of hen brain microsomal NTE with mipafox, were found to be 6.72 × 10−5M and 3.23 min−1, respectively. The bimolecular rate constant (ki) for this reaction was obtained by interpreting the results according to two different linear equations. The obtained values for ki by these interpretations were 4.8 × 104 and 4.0 × 104M−1 min−1, respectively.

A metabolite of DDT, 2,2-bis(p-chlorophenyl)ethanol, is a substrate of crystalline liver alcohol dehydrogenase. The oxidation of the substrate was detected spectrophotometrically. The p-nitrophenylhydrazone derivative of the product, 2,2-bis(p-chlorophenyl)acetaldehyde, was identified by comparing its mass spectrum and thin-layer chromatographic behavior with that of an authentic sample.