Acute Toxicity Of Chlorpyrifos Research Articles

Preventive Effect of the Extract of Du-Zhong (Tochu) Leaf and Ginseng Root on Acute Toxicity of Chlorpyrifos.

The preventive effects of the extract (DP-extract) prepared from leaves of Eucommia ulmoides OLIVER, Eucommiaceae (Du-Zhong leaf) and roots of Panax ginseng C.A. MEYER (Ginseng), which are widely used as healthful teas, on acute toxicity of chlorpyrifos, a common organophosphorus insecticide, were investigated in mice. A 50% lethal dose of chlorpyrifos was 16.9% higher in the group pretreated with DP-extract for 3 weeks (6.66 g of dried leaves and root/kg/d, p.o.) than in the chlorpyrifos alone group. Cholinesterase (ChE) activities in serum were higher and the residual chlorpyrifos in liver was lower in mice pretreated with DP-extract than in the chlorpyrifos-alone group. Hepatic cytochrome P450 content, activities of NADPH-cytochrome c reductase and carboxylesterase (EC3.1.1.1) in livers of DP-extract pretreated mice were significantly higher than those of untreated control immediately after chlorpyrifos injection. The activities of those enzymes were also significantly higher in the DP-extract pretreated mice than the controls. Northern blot analysis of microsomes from livers of DP-extract pretreated mice revealed the increased transcription of NADPH-cytochrome c reductase and carboxylesterase. These results suggest that DP-extract increased the activities of cytochrome P450 and carboxylesterase and accelerated detoxification of chlorpyrifos to prevent the acute toxicity of the organophosphorus insecticide.

Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae.

The acute toxicity of chlorpyrifos, methylchlorpyrifos, parathion and methylparathion to three age classes of Artemia salina was determined. In general, A. salina 24-h old was less sensitive to these organophosphorous insecticides (OPI) than A. salina 48-h old and A. salina 48-h old was significantly more tolerant than A. salina 72-h old, in contrast, chlorpyrifos was equally toxic to A. salina 48- and 72-h old. There were some differences among the three age classes of A. salina in the relative order of toxicity of OPI tested. The rank order of toxicity to A. salina 48-h old was methylparathion < parathion < methyl-chlorpyrifos < chlorpyrifos, while to A. salina 24- and 72-h old it was methylparathion = parathion < methyl-chlorpyrifos < chlorpyrifos. The protective effect of the cholinergic antagonists atropine, hexamethonium, pirenzepine and 11-(2-((diethyl-amino)methyl)-1-piperidinylacetyl)-5, 11-dihydro-6H-pyrido(2,3-b)-(1,4)-benzodiazepine-6-one (AF-DX 116) and a cholinesterase-reactivating oxime 2-pyridine aldoxime methochloride (2-PAM) on the mortality due to four selected OPI in Artemia salina 24-h old was investigated. The lethal action of OPI tested was completely prevented by pretreatment of Artemia salina 24-h old with 2-PAM (10(-5) M) and atropine (10(-4 )M). However no concentration of hexamethonium, pirenzepine or AF-DX 116 protected 100% of the animals poisoned by LC84 of the OPI selected, maximum protection obtained was 71 to 88%. In contrast, the maximum inhibition of mortality obtained with AF-DX 116 pretreatment was about 55% because this compound was used at concentrations which were non toxic to control Artemia salina. Atropine, hexamethonium, pirenzepine, AF-DX 116 and 2-PAM afforded 50 % protection (IC50) of Artemia salina against mortality by LC84 of the OPI selected at concentrations in the range of 6.62x10(-7)-1.6x10(-6) M, 2. 38x10(-4)-2.05x10(-3)M, 8.91x10(-7)-1.24x10(-6) M, 9.66x10(-8)-1. 34x10(-7 )M, and 1.95x10(-8)-2.73x10(-8 )M, respectively. Pretreatment of atropine plus 2-PAM to determine whether this combination afforded greater inhibition of the lethality induced by four OPI tested than pretreatment with either atropine or 2-PAM alone was investigated. Atropine (10(-5) M) in combination with 2-PAM (10(-7 )M) inhibited completely the acute toxicity of all OPI tested, while the pretreatment with atropine (10(-6) M) plus 2-PAM at the same concentration gave a inhibition of mortality (about 62%) significantly greater than each antagonist alone (about 14 and 46%, respectively).

Factors involved in the differential acute toxicity of the insecticides chlorpyrifos and methyl chlopyrifos in mice

The ip LD 50s of the insecticides chlorpyrifos [ O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate] and methyl chlorpyrifos [ O,O-dimethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate] were determined to be 192 and 2325 mg/kg, respectively, in male mice. In an attempt to explain this 12-fold difference in toxicity, the extent of glutathione (GSH)-dependent detoxification of chlorpyrifos, methyl chlorpyrifos, and their oxygen analogs was examined. Incubation of 1000 nmol of insecticides with GSH-fortified mouse liver cytosol resulted in the disappearance of 458 and 819 nmol of chlorpyrifos oxon and methyl chlorpyrifos, respectively. However, chlorpyrifos and methyl chlorpyrifos oxon were not substrates for GSH-dependent biotransformation in vitro. Pretreatment of mice with diethyl maleate resulted in a 2.0- and 8.5-fold increase in the acute toxicities of chlorpyrifos and methyl chlorpyrifos, respectively. Administration of methyl chlorpyrifos (1000 mg/kg) to mice produced a marked, prolonged depletion of hepatic GSH, while administration of chlorpyrifos (70 mg/kg) resulted in a moderate, transient decrease in hepatic GSH content. Both doses inhibited brain and plasma cholinesterase, and brain and liver nonspecific esterase activities to a similar degree. HPLC analyses of brain concentrations of methyl chlorpyrifos and chlorpyrifos revealed that brain levels of methyl chlorpyrifos 46 times greater than those of chlorpyrifos were required to achieve the same degree of brain cholinesterase inhibition. Furthermore, the concentration of methyl chlorpyrifos oxon needed to produce 50% inhibition of bovine red blood cell or mouse brain cholinesterase was 480 times greater than that required for chlorpyrifos oxon. These data suggest that differences in the extent of GSH-mediated detoxification can account for only a portion of the observed differences in acute toxicity between chlorpyrifos and methyl chlorpyrifos.