Disease relevance of LEPTOPHOS

• The results indicated that leptophos induced severe ataxia and paralysis in sheep following about 4 months of treatment [1].
• Separation and toxicity of enantiomers of organophosphorus insecticide leptophos [2].
• Recent investigation into a possible association between exposure to Leptophos and neurological symptoms in insecticide factory workers makes study of the neurological effects of Leptophos in the experimental situation particularly important [3].
• The neurodegenerative properties of the organophosphate ester leptophos (LEP) and the carbamate ester carbaryl (CB), both of which can cause neuropathic effects in animals, were investigated in differentiating mouse N2a neuroblastoma cells [4].
• Delayed neurotoxicity induced by leptophos, an organophosphorus insecticide, was intensified in hens when phenylmethylsulfonyl fluoride (PMSF) at dose of 30, 60, and 120 mg/kg body weight was administered at different time intervals (24 hr, 3 days, and 5 days) for each dose of PMSF after the hens were exposed to 30 mg/kg (i.v.) of leptophos [5].

High impact information on LEPTOPHOS

• A comparison of the bimolecular rate constants (ki) for inhibition of electric eel acetylcholinesterase (AChE) by the oxono (i.e., P=O) and thiono (i.e., P=S) analogues of parathion, methylparathion, leptophos, fonofos, sarin, and soman revealed that the oxono/thiono ratios of ki values varied from 14 for soman to 1240 for parathion [6].
• TOCP (10 to 100 mg/kg), leptophos (25 to 150 mg/kg), and DBDCV (1.0 to 4.0 mg/kg) inhibited both brain and lymphocyte NTE activity in a dose-related manner with good correlation of inhibition between tissues taken 24 hr after exposure (r2 = 0.53 to 0.67; p less than 0.020 to 0.001) [7].
• In the case of leptophos-treated sheep, numerous prominent degenerative lesions of axons were observed in spinal cords and brains [1].
• Metabolism and pharmacokinetics of a single oral dose of O-4-bromo-2,5-dichlorophenyl O-methyl phenylphosphonothioate (Leptophos) in hens [8].
• Residues of phosvel in plasma and in adipose tissue of hens after single oral administration [9].

Chemical compound and disease context of LEPTOPHOS

• On the other hand, Leptophos and EPN when administered orally at sublethal or lethal levels clearly produced a delayed neurotoxic ataxia in treated mice [10].
• 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 [10].
• Ascorbic acid caused hypoglycemia with sublethal doses of leptophos, chlorpyrifos, and diazinon [11].

Biological context of LEPTOPHOS

• Immunological surveillance and toxicity in mice exposed to the organophosphate pesticide, leptophos [12].
• Chemistry and toxicology of pesticide chemicals. II. Stability of leptophos [13].
• Inhibition of mitochondrial electron transport systems by phosvel and some environmental conversion products [14].
• A comparative study between five organophosphorus insecticides: Leptophos, EPN, Cyanofenphos, Chlorpyrifos and Diazinon, was carried out for acute oral toxicity to white rats and for their in vivo interaction at 1/10th of LD50 doses with the activity of six serum enzymes after 4 wks from oral administration [11].

Anatomical context of LEPTOPHOS

• Radioactive carbaryl, carbofuran, parathion, leptophos, and DDT were added to cigarettes and the mainstream smoke was directed to the lungs of rats via the trachea [15].
• No difference was observed in the sensitivity of flyhead and thorax acetylcholinesterase to leptophos-oxon in vitro, and tolerance to leptophos by the resistant strain is explained in terms of decreased rates or penetration and minor differences in metabolism [16].
• Assuming that Leptophos resembles TOCP in this regard, peripheral nerve damage would be the expected earliest change, especially in the low-dose situation in the human [3].
• On the contrary, the evident accumulation of leptophos was observed in only sciatic nerve with RIVInj [17].
• Leptophos in laid egg yolk was detected every day for 10 days, and the highest concentration of leptophos in egg yolk was observed on the 6th day after administration to hens [18].

Associations of LEPTOPHOS with other chemical compounds

• Diethyl 4-nitrophenyl phosphate (paraoxon), tri-2-cresyl phosphate (TOCP), methyl 2,5-dichloro-4-bromophenyl phenylphosphonothionate (leptophos), and di-n-butyl-2,2-dichlorovinyl phosphate (di-n-butyl dichlorvos, DBDCV) were used to examine the relationship between lymphocyte and brain NTE inhibition in hens [7].
• In vitro neurotoxic esterase assay using leptophos oxon analogs as inhibitors [19].
• Enantiomers of leptophos were separated by high-performance liquid chromatography with a Whelk-O1 column using 3% dichloromethane in n-hexane as mobile phase [2].
• Inhibitory effect of leptophos on carboxylesterase (isocarboxazid amidase) in rat liver [20].
• At this dose Leptophos produces degeneration of the spinal cord in a pattern similar to that seen with tri-o-cresyl phosphate (TOCP) [3].

Gene context of LEPTOPHOS

• Inhibition of neurite outgrowth in N2a cells by leptophos and carbaryl: effects on neurofilament heavy chain, GAP-43 and HSP-70 [4].
• In comparing neurotoxic esterase (NTE) inhibition properties of a series of phenylphosphonates, it was discovered that certain compounds including leptophos inhibited mipafox-insensitive phenylvalerate hydrolases [19].
• Leptophos is a potent acetylcholinesterase inhibitor which causes delayed central-peripheral neuropathy [21].
• For EPN and leptophos, bromine activation resulted in greater inhibition of NTE than RLM [22].
• Enzyme assays of CNP revealed a decrease in brain CNP activity at the time of maximal locomotor impairment after a single, oral dose of leptophos [23].

Analytical, diagnostic and therapeutic context of LEPTOPHOS

• Delayed neurotoxicity from continous low-dose oral administration of leptophos to hens [24].
• Delayed neurotoxicity from long-term low-level topical administration of leptophos to the comb of hens [25].
• The activity of ISOCase decreased to 29 and 0% of control 24 h after treatment with leptophos at doses of 2.5 and 5.0 mg/kg, respectively [20].
• Eight groups received intravenous injection of 30 mg/kg of leptophos or 40 mg/kg of TOCP (four groups in each) [26].

References