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Interactive toxicity of chlorpyrifos and parathion in neonatal rats: role of esterases in exposure sequence-dependent toxicity.
Toxicol Appl Pharmacol. 2006 Jan 01; 210(1-2):142-9.TA

Abstract

We previously reported that sequence of exposure to chlorpyrifos and parathion in adult rats can markedly influence toxic outcome. In the present study, we evaluated the interactive toxicity of chlorpyrifos (8 mg/kg, po) and parathion (0.5 mg/kg, po) in neonatal (7 days old) rats. Rats were exposed to the insecticides either concurrently or sequentially (separated by 4 h) and sacrificed at 4, 8, and 24 h after the first exposure for biochemical measurements (cholinesterase activity in brain, plasma, and diaphragm and carboxylesterase activity in plasma and liver). The concurrently-exposed group showed more cumulative lethality (15/24) than either of the sequential dosing groups. With sequential dosing, rats treated initially with chlorpyrifos prior to parathion (C/P) exhibited higher lethality (7/23) compared to those treated with parathion before chlorpyrifos (P/C; 1/24). At 8 h after initial dosing, brain cholinesterase inhibition was significantly greater in the C/P group (59%) compared to the P/C group (28%). Diaphragm and plasma cholinesterase activity also followed a relatively similar pattern of inhibition. Carboxylesterase inhibition in plasma and liver was relatively similar among the treatment groups across time-points. Similar sequence-dependent differences in brain cholinesterase inhibition were also noted with lower binary exposures to chlorpyrifos (2 mg/kg) and parathion (0.35 mg/kg). In vitro and ex vivo studies compared relative oxon detoxification of carboxylesterases (calcium-insensitive) and A-esterases (calcium-sensitive) in liver homogenates from untreated and insecticide pretreated rats. Using tissues from untreated rats, carboxylesterases detoxified both chlorpyrifos oxon and paraoxon, while A-esterases only detoxified chlorpyrifos oxon. With parathion pretreatment, A-esterases still detoxified chlorpyrifos oxon while liver from chlorpyrifos pretreated rats had little apparent effect on paraoxon. We conclude that while neonatal rats are less capable than adults at detoxifying many organophosphorus insecticides including chlorpyrifos and parathion, toxicant-selective differences in detoxification play a role in sequence-dependent toxicity in both neonatal and adult rats with these two insecticides.

Authors+Show Affiliations

Department of Physiological Sciences, 264 McElroy Hall, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16260018

Citation

Kacham, R, et al. "Interactive Toxicity of Chlorpyrifos and Parathion in Neonatal Rats: Role of Esterases in Exposure Sequence-dependent Toxicity." Toxicology and Applied Pharmacology, vol. 210, no. 1-2, 2006, pp. 142-9.
Kacham R, Karanth S, Baireddy P, et al. Interactive toxicity of chlorpyrifos and parathion in neonatal rats: role of esterases in exposure sequence-dependent toxicity. Toxicol Appl Pharmacol. 2006;210(1-2):142-9.
Kacham, R., Karanth, S., Baireddy, P., Liu, J., & Pope, C. (2006). Interactive toxicity of chlorpyrifos and parathion in neonatal rats: role of esterases in exposure sequence-dependent toxicity. Toxicology and Applied Pharmacology, 210(1-2), 142-9.
Kacham R, et al. Interactive Toxicity of Chlorpyrifos and Parathion in Neonatal Rats: Role of Esterases in Exposure Sequence-dependent Toxicity. Toxicol Appl Pharmacol. 2006 Jan 1;210(1-2):142-9. PubMed PMID: 16260018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactive toxicity of chlorpyrifos and parathion in neonatal rats: role of esterases in exposure sequence-dependent toxicity. AU - Kacham,R, AU - Karanth,S, AU - Baireddy,P, AU - Liu,J, AU - Pope,C, Y1 - 2005/11/02/ PY - 2005/05/25/received PY - 2005/09/02/revised PY - 2005/09/29/accepted PY - 2005/11/2/pubmed PY - 2006/2/9/medline PY - 2005/11/2/entrez SP - 142 EP - 9 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 210 IS - 1-2 N2 - We previously reported that sequence of exposure to chlorpyrifos and parathion in adult rats can markedly influence toxic outcome. In the present study, we evaluated the interactive toxicity of chlorpyrifos (8 mg/kg, po) and parathion (0.5 mg/kg, po) in neonatal (7 days old) rats. Rats were exposed to the insecticides either concurrently or sequentially (separated by 4 h) and sacrificed at 4, 8, and 24 h after the first exposure for biochemical measurements (cholinesterase activity in brain, plasma, and diaphragm and carboxylesterase activity in plasma and liver). The concurrently-exposed group showed more cumulative lethality (15/24) than either of the sequential dosing groups. With sequential dosing, rats treated initially with chlorpyrifos prior to parathion (C/P) exhibited higher lethality (7/23) compared to those treated with parathion before chlorpyrifos (P/C; 1/24). At 8 h after initial dosing, brain cholinesterase inhibition was significantly greater in the C/P group (59%) compared to the P/C group (28%). Diaphragm and plasma cholinesterase activity also followed a relatively similar pattern of inhibition. Carboxylesterase inhibition in plasma and liver was relatively similar among the treatment groups across time-points. Similar sequence-dependent differences in brain cholinesterase inhibition were also noted with lower binary exposures to chlorpyrifos (2 mg/kg) and parathion (0.35 mg/kg). In vitro and ex vivo studies compared relative oxon detoxification of carboxylesterases (calcium-insensitive) and A-esterases (calcium-sensitive) in liver homogenates from untreated and insecticide pretreated rats. Using tissues from untreated rats, carboxylesterases detoxified both chlorpyrifos oxon and paraoxon, while A-esterases only detoxified chlorpyrifos oxon. With parathion pretreatment, A-esterases still detoxified chlorpyrifos oxon while liver from chlorpyrifos pretreated rats had little apparent effect on paraoxon. We conclude that while neonatal rats are less capable than adults at detoxifying many organophosphorus insecticides including chlorpyrifos and parathion, toxicant-selective differences in detoxification play a role in sequence-dependent toxicity in both neonatal and adult rats with these two insecticides. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/16260018/Interactive_toxicity_of_chlorpyrifos_and_parathion_in_neonatal_rats:_role_of_esterases_in_exposure_sequence_dependent_toxicity_ DB - PRIME DP - Unbound Medicine ER -