Delayed neurotoxicity in the wild mallard duckling caused by the organophosphorus insecticides cyanofenphos and leptophos

Abstract

The susceptibility of wild mallard ducklings to the delayed neurotoxic effect of the neurotoxic organophosphorus insecticides cyanofenphos and leptophos was evaluated following a daily dosing regimen. Ducklings were treated daily with either cyanofenphos or with leptophos at different dose levels for 90 days, or until they died, or became paralyzed. A control group of ducklings given corn oil at 1 ml/kg daily for 90 days was used for comparison. All treated birds were observed daily for any clinical signs of neurotoxicity during the course of this study. All of the surviving ducklings that were treated with cyanofenphos at 4 mg/kg/day or leptophos at 10 mg/kg/day developed clinical signs of delayed neurotoxicity after 7 to 11 weeks of intoxication. Symptoms included leg weakness, ataxia, severe ataxia and paralysis. The observed clinical signs were confirmed by histological changes found in the spinal cords of the treated birds. These changes were of the type associated with organophosphorus‐induced delayed neuropathy (OPIDN). These results demonstrate that wild mallard ducklings are susceptible to OPIDN and this avian species can be used in screening organophos‐phorus compounds for such effect.     

Subcellular distribution op neurotoxic esterase activity in lamb and mouse brain

Abstract

Brain tissue samples of nice (7.5 g from 25 mouse brains and lamb (25 g) were homogenized and subcellular fractions prepared in order to assay the distribution of neurotoxic esterase (NTE) activity. The specific inhibitor, N,N‐diisopropylphosphorodiamidic fluoride (mipafox) was synthesized and purified. Maximum specific activity of NTE was reached in the microsomal fraction (110,000 g) while the enzyme activity in the soluble fraction (110,000 g) was extremely low. This subcellular distribution of NTE activity in mammal brains is an original contribution. Brain microsomal fraction is suggested to be a more reliable source for the highest activity of NTE. The specific activity of NTE of lamb brain was much higher than that of mouse brain. This night help interpretation of the characteristic species variation in susceptibility to NTE inhibitors which are known to be potent delayed neurotoxic agents.     

Biochemical interaction of six op delayed neurotoxicants with several neurotargets

Abstract

Five organophosphorous insecticides: Leptophos, EPN, Cyano‐fenphos, trichloronate and salithion proved to cause irreversible ataxia not only to chicken but also to mice and sheep. TOCP was included as a reference. Cyanofenphos blocked the catecholamine B‐receptor binding activity with ³H‐norepinephrine at a level similar to that of the specific inhibitor propranolol in the mouse heart preparation. In the lamb heart preparation, the B‐receptor was more sensitive to Leptophos, salithion and TOCP than to propranolol. The six compounds and their oxons were screened for their in‐vitro inhibition to monamine oxidase (MAO), acetyl cholinesterase (AChE) and neurotoxic esterase (NTE) in the brain of either mouse, lamb or chicken. It is believed that their AChE inhibition stands for their acute toxicity, while NTE inhibition is responsible for their paralytic ataxia.