Nabila S. Ahmed

Neurotoxicity of organophosphorus insecticides leptophos and EPN

Phosfolan, chlorpyrifos, and stirophos when applied to white mice at sublethal doses did not induce any delayed neurotoxic effect. On the other hand, Leptophos and EPN when administered orally at sublethal or lethal levels clearly produced a delayed neurotoxic ataxia in treated mice. The five tested organophosphorus insecticides were compared for their ability to inhibit cholinesterase, neurotoxic esterases and monoamine oxidase. I50 values were estimated for each case. The results revealed that all five compounds were inhibitors of cholinesterase, but only Leptophos and EPN were shown to be potent inhibitors for both neurotoxic esterase and monoamine oxidase in the mouse brain. Additional particular properties of both Leptophos and EPN were found in their ability to cause delayed neurotoxic ataxia in chickens and sheep fed once on sublethal doses of these compounds. It is believed that the phosphonate ester configuration of EPN and Leptophos has a specific mode of toxic action which is mainly located at the central nervous system. It is also postulated that these delayed neurotoxic agents might inhibit postganglionic sympathetic neurons, thus resulting in chronic paralytic effects.

Assessment of lead toxicity in traffic controllers of Alexandria, Egypt, road intersections

Blood lead level (BPbL) was determined in forty-five traffic controllers working on Alexandria road intersections. Central nervous system dysfunction in the subjects studied was investigated by means of performance tests. Biochemical indicators related to lead exposure such as delta-aminolevulinic acid dehydratase and hemoglobin in their blood were also determined. Results indicated that most of the subjects studied have a comparably high BPbL. They also showed significantly poorer performance scores than that obtained in a previous study with a group of textile workers of the same age and educational levels. The mean of the BPbL in the traffic controllers was found to be 68.28 +/- 13.22 micrograms/dl. This is a very high level compared to an acceptable level of 30.00 micrograms/dl. All neurobehavioral symptoms demonstrated in the traffic controllers could be attributed to a high level of lead exposure.

Delayed neuropathy in sheep by the phosphonothioate insecticide cyanofenphos

Cyanofenphos (surecide)(R), 25% E.C., O-ethyl O-(4-cyanophenyl) phenylphosphonothioate, was orally administered to one year old lambs at sublethal doses of 1 mg, 2 mg and 4 mg active ingredient kg-1 day-1 for time intervals 60, 45 and 30 days respectively. Irreversible paralytic ataxia symptoms of delayed neuropathy appeared at about 80, 50 and 30 days respectively. In weekly blood samples, AChE (acetylcholine-sterase) and MAO (monoamine oxidase) activities were inhibited depending upon level of dosing and time interval. However no significant correlation was found between the extent of plasma AChE and MAO inhibition and the onset of ataxia symptoms. In brain samples from ataxiated animals, AChE, MAO and NTE (neurotoxic esterase) activities were assayed simultaneously with untreated animal. Direct correlation was shown between in vivo NTE inhibition and the occurrence of delayed neuropathy. Cyanofenphos is the third compound of the phenyl phosphonothioate type on the market showing delayed neuropathy together with Leptophos and EPN.

Subcellular distribution op neurotoxic esterase activity in lamb and mouse brain

Brain tissue samples of mice (7.6 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 might 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

Five organophosphorous insecticides: Leptophos, EPN, Cyanofenphos, 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.

Effect of pre‐exposure on acute toxicity of organophosphorus insecticides to white mice

LD50 and in vitro ChE I50 values of Chlorpyrifos, Leptophos, Phosfolan, and Stirophos against white mice showed that the formulated insecticides were higher in their mammalian toxicity than the corresponding technical materials. Pretreatment of mice with a sublethal dose of Phosfolan potentiated the toxicity of post-treatment with formulated Stirophos, Phosfolan, or Chlorpyrifos, but antagonized the toxicity of post-treatment with Leptophos. On the other hand, pretreatment with sublethal doses of Leptophos resulted in potentiation of Stirophos or Phosfolan, but decreased the toxicity of Chlorpyrifos or Leptophos. Pretreatment of mice by sublethal dose of Phosfolan synergized the in vivo inhibitory power of post-treatment by Phosfolan, Chlorpyrifos or Leptophos against brain and Plasma ChE. On the other hand pretreatment with sublethal doses of Leptophos antagonized the inhibitory power of post-treatment with either Chlorpyrifos, Leptophos or Stirophos against mice brain-ChE.

Distribution and metabolism of O-ethyl O-4-nitrophenyl phenylphosphonothioate after a single oral dose in one-week old chicks.

The toxicokinetics and metabolism of a single 1 mg (2.7 μCi/kg) oral dose of uniformly phenyl-labeled [14C]EPN (O-ethyl O-4-nitrophenyl [14C]phenylphosphonothioate) have been studied in 1-week old chicks. One control and three treated chicks were killed at each of the following time intervals: 0.5, 2, 4, 8, and 12 days. Radioactivity was rapidly absorbed from the gastrointestinal tract and distributed in all tissues. 14C in tissues reached a peak of 16.9% of the dose after 0.5 day and decreased to 0.6% at 4 days. The tissues of the gastrointestinal tract had the highest concentration of radioactivity, followed by bile and liver. Among nervous tissues, concentration of 14C was highest in the peripheral nerves. The spinal cord had the next highest concentration, while the brain had the least. After 4 days 91.3% of the 14C had been eliminated in the combined urinary-fecal excreta. By the end of the 12-day experiment this percentage reached 93.1%. No 14C was detected in the expired CO2. Following the oral administration of [14C]EPN, a monophasic body level curve was observed. The half-life for the elimination of 14C from chick body was 16 h, corresponding to a rate constant of 0.04 h−1. Most of the excreted 14C materials were identified as O-ethyl phenylphosphonic acid, phenylphosphonic acid, and O-ethyl phenylphosphonothioic acid.

Efficacy of dried seed powder of some plant species as soil amendment against Meloidogyne incognita (Tylenchida: Meloidogynidae) on tomato

The nematicidal activity of dried ground seeds of Ammi majus, Matricaria chamomilla, Ricinus communis, Brassica alba, B. oleracea, Peganum harmala, Solanum nigrum, Raphanus sativus and Eucalyptus sp. was assessed against the root-knot nematode, Meloidogyne incognita, infecting tomato in a glasshouse. The powdered seeds of the tested plants were incorporated into the soil at the rate of 5 g/kg and their nematicidal activity was compared with that of the synthetic nematicide carbofuran at the rate of 0.01 g a.i./kg. The effects of the treatments on the growth of tomato were also examined. The populations of M. incognita in the soil and root galling of tomato were significantly suppressed by the powdered seeds of all the plant species tested, with the greatest reduction occurring in soil amended with M. chamomilla, followed by soil treated with powdered seeds of A. majus, S. nigrum, R. communis and Eucalyptus sp. The efficacy of B. oleracea, B. alba, M. chamomilla and R. communis in reducing the number of J2 in the soil was similar to that of carbofuran. All amendments, except powdered seeds of M. chamomilla and A. majus significantly increased shoot length compared to the untreated inoculated plants. Shoot weight was significantly increased in soil amended with powdered seeds of B. oleracea, B. alba, R. communis, P. harmala and S. nigrum, but not in soil amended with the other seed powders when compared with untreated inoculated soil. Significant increases in root length occurred in pots amended with seed powder of B. alba, R. communis and Eucalyptus and in root weight for P. harmala. None of the tested dried seeds was phytotoxic to tomato plants at the applied rate.

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

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 organophosphorus compounds for such effect.