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Interactive toxicity of the organophosphorus insecticides chlorpyrifos and methyl parathion in adult rats.
Toxicol Appl Pharmacol. 2004 Apr 15; 196(2):183-90.TA

Abstract

The acute interactive toxicity following exposure to two common organophosphorus (OP) insecticides, chlorpyrifos (CPF) and methyl parathion (MPS), was investigated in adult male rats. Oral LD1 values were estimated by dose-response studies (CPF = 80 mg/kg; MPS = 4 mg/kg, in peanut oil, 1 ml/kg). Rats were treated with both toxicants (0.5 or 1 x LD1) either concurrently or sequentially, with 4-h intervals between dosing. Functional signs of toxicity (1-96 h) and cumulative lethality (96 h) were recorded. Rats treated with CPF (1 x LD1) did not show any signs of toxicity although MPS (1 x LD1) elicited slight to moderate signs (involuntary movements) within 1-2 h. Concurrent exposure (LD1 dosages of both CPF and MPS) caused slight signs of toxicity only apparent between 24 and 48 h after dosing. When rats were treated sequentially with MPS first followed by CPF 4 h later, slight signs of toxicity were noted between 6 and 24 h, whereas reversing the sequence resulted in 100% lethality within 1 h of the second dosage. Following exposure to lower dosages (0.5 x LD1), the CPF first group showed higher signs of cholinergic toxicity compared with MPS first or concurrent groups. Cholinesterase inhibition in plasma, diaphragm, and frontal cortex was generally higher in rats treated sequentially with CPF first than in those treated initially with MPS from 4 to 24 h after dosing. Plasma and liver carboxylesterase inhibition at 4 h was also significantly higher in the CPF first (62-90%) compared with MPS first (22-43%) group, while at 8 and 24 h, there was no significant difference between any of the treatment groups. ChE inhibition assays to evaluate in vitro hepatic detoxification of oxons indicated that carboxylesterase (CE)- and A-esterase-mediated pathways are markedly less important for methyl paraoxon (MPO) than chlorpyrifos oxon (CPO) detoxification. CPF pretreatment blocked hepatic detoxification of methyl paraoxon while MPS pretreatment had minimal effect on hepatic CPO detoxification ex vivo. These findings suggest that the sequence of exposure to two insecticides that elicit toxicity through a common mechanism can markedly influence the cumulative action at the target site (acetylcholinesterase, AChE) and consequent functional toxicity.

Authors+Show Affiliations

Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

15081265

Citation

Karanth, Subramanya, et al. "Interactive Toxicity of the Organophosphorus Insecticides Chlorpyrifos and Methyl Parathion in Adult Rats." Toxicology and Applied Pharmacology, vol. 196, no. 2, 2004, pp. 183-90.
Karanth S, Liu J, Olivier K, et al. Interactive toxicity of the organophosphorus insecticides chlorpyrifos and methyl parathion in adult rats. Toxicol Appl Pharmacol. 2004;196(2):183-90.
Karanth, S., Liu, J., Olivier, K., & Pope, C. (2004). Interactive toxicity of the organophosphorus insecticides chlorpyrifos and methyl parathion in adult rats. Toxicology and Applied Pharmacology, 196(2), 183-90.
Karanth S, et al. Interactive Toxicity of the Organophosphorus Insecticides Chlorpyrifos and Methyl Parathion in Adult Rats. Toxicol Appl Pharmacol. 2004 Apr 15;196(2):183-90. PubMed PMID: 15081265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactive toxicity of the organophosphorus insecticides chlorpyrifos and methyl parathion in adult rats. AU - Karanth,Subramanya, AU - Liu,Jing, AU - Olivier,Kenneth,Jr AU - Pope,Carey, PY - 2003/09/29/received PY - 2003/12/10/accepted PY - 2004/4/15/pubmed PY - 2004/5/20/medline PY - 2004/4/15/entrez SP - 183 EP - 90 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 196 IS - 2 N2 - The acute interactive toxicity following exposure to two common organophosphorus (OP) insecticides, chlorpyrifos (CPF) and methyl parathion (MPS), was investigated in adult male rats. Oral LD1 values were estimated by dose-response studies (CPF = 80 mg/kg; MPS = 4 mg/kg, in peanut oil, 1 ml/kg). Rats were treated with both toxicants (0.5 or 1 x LD1) either concurrently or sequentially, with 4-h intervals between dosing. Functional signs of toxicity (1-96 h) and cumulative lethality (96 h) were recorded. Rats treated with CPF (1 x LD1) did not show any signs of toxicity although MPS (1 x LD1) elicited slight to moderate signs (involuntary movements) within 1-2 h. Concurrent exposure (LD1 dosages of both CPF and MPS) caused slight signs of toxicity only apparent between 24 and 48 h after dosing. When rats were treated sequentially with MPS first followed by CPF 4 h later, slight signs of toxicity were noted between 6 and 24 h, whereas reversing the sequence resulted in 100% lethality within 1 h of the second dosage. Following exposure to lower dosages (0.5 x LD1), the CPF first group showed higher signs of cholinergic toxicity compared with MPS first or concurrent groups. Cholinesterase inhibition in plasma, diaphragm, and frontal cortex was generally higher in rats treated sequentially with CPF first than in those treated initially with MPS from 4 to 24 h after dosing. Plasma and liver carboxylesterase inhibition at 4 h was also significantly higher in the CPF first (62-90%) compared with MPS first (22-43%) group, while at 8 and 24 h, there was no significant difference between any of the treatment groups. ChE inhibition assays to evaluate in vitro hepatic detoxification of oxons indicated that carboxylesterase (CE)- and A-esterase-mediated pathways are markedly less important for methyl paraoxon (MPO) than chlorpyrifos oxon (CPO) detoxification. CPF pretreatment blocked hepatic detoxification of methyl paraoxon while MPS pretreatment had minimal effect on hepatic CPO detoxification ex vivo. These findings suggest that the sequence of exposure to two insecticides that elicit toxicity through a common mechanism can markedly influence the cumulative action at the target site (acetylcholinesterase, AChE) and consequent functional toxicity. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/15081265/Interactive_toxicity_of_the_organophosphorus_insecticides_chlorpyrifos_and_methyl_parathion_in_adult_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041008X04000092 DB - PRIME DP - Unbound Medicine ER -