Tags

Type your tag names separated by a space and hit enter

In vivo interaction between chlorpyrifos and parathion in adult rats: sequence of administration can markedly influence toxic outcome.
Toxicol Appl Pharmacol. 2001 Dec 15; 177(3):247-55.TA

Abstract

Organophosphorus insecticides (OPs) generally act through a common mechanism of toxicity initiated by inhibition of acetylcholinesterase (AChE). We studied the in vivo interactive toxicity of two common OPs, chlorpyrifos (CPF) and parathion (PS), in adult male rats. Dose-response studies estimated the acute oral LD1 values for the two OPs (CPF = 80 mg/kg po; PS = 4 mg/kg po) and these dosages or relative proportions were used to evaluate interactive toxicity. Three treatment strategies were evaluated: CPF followed by PS 4 h later (CPF-1st), PS followed by CPF 4 h later (PS-1st), and simultaneous (concurrent) exposures. Using LD1 dosages, rats in the CPF-1st and concurrent groups exhibited more cholinergic toxicity (i.e., salivation, lacrimation, urination, and diarrhea signs and involuntary movements) and higher lethality (7/8 and 6/8, respectively, beginning 1 h after PS) than those in the PS-1st group (2/8 lethality, beginning 3 days after CPF). Sequential exposures to lower dosages (CPF vs PS: 60 vs 3 mg/kg; 40 vs 2 mg/kg) led to more extensive neurotoxicity in the CPF-1st group compared to the other groups. Following lower dosages (40 vs 2 mg/kg), brain ChE inhibition was more extensive in the CPF-1st group at all time points (64-85%) and the concurrent group at 4 and 24 h after exposure (46-83%) compared to rats receiving PS first (7-48%). No differences were noted however, in plasma (71-93% inhibition) or liver (72-81%) cholinesterase activities nor were there group-related differences in plasma (50-60% inhibition) or liver (>85% inhibition) carboxylesterase activities. Incubation of liver samples with oxons in the presence or absence of calcium (i.e., 2 mM CaCl(2) or EGTA) prior to addition of ChE (striatal sample) substantially blocked ChE inhibition by CPO (IC50: without liver = 4 nM; liver + calcium = 279 nM; liver + EGTA = 48 nM) but had lesser effects on PO-mediated inhibition (IC50: without liver = 17 nM; liver + EGTA = 56 nM; liver + calcium = 57 nM). Liver homogenate from animals preexposed to PS substantially decreased ChE inhibition by CPO when calcium was included (IC50: +EGTA = 8 nM; +calcium = 225 nM), but liver homogenate from animals preexposed to CPF was ineffective at blocking PO-induced inhibition (IC50: +EGTA = 16 nM; +calcium = 16 nM). We conclude that prior inhibition of carboxylesterase activity impacts toxicity of subsequent exposure to PS more than CPF because of more active detoxification of CPO by A-esterase. Together, these findings indicate that interactive toxicity from combined exposures to two OP insecticides can be markedly influenced by the sequence of administration.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11749124

Citation

Karanth, S, et al. "In Vivo Interaction Between Chlorpyrifos and Parathion in Adult Rats: Sequence of Administration Can Markedly Influence Toxic Outcome." Toxicology and Applied Pharmacology, vol. 177, no. 3, 2001, pp. 247-55.
Karanth S, Olivier K, Liu J, et al. In vivo interaction between chlorpyrifos and parathion in adult rats: sequence of administration can markedly influence toxic outcome. Toxicol Appl Pharmacol. 2001;177(3):247-55.
Karanth, S., Olivier, K., Liu, J., & Pope, C. (2001). In vivo interaction between chlorpyrifos and parathion in adult rats: sequence of administration can markedly influence toxic outcome. Toxicology and Applied Pharmacology, 177(3), 247-55.
Karanth S, et al. In Vivo Interaction Between Chlorpyrifos and Parathion in Adult Rats: Sequence of Administration Can Markedly Influence Toxic Outcome. Toxicol Appl Pharmacol. 2001 Dec 15;177(3):247-55. PubMed PMID: 11749124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo interaction between chlorpyrifos and parathion in adult rats: sequence of administration can markedly influence toxic outcome. AU - Karanth,S, AU - Olivier,K,Jr AU - Liu,J, AU - Pope,C, PY - 2001/12/26/pubmed PY - 2002/1/26/medline PY - 2001/12/26/entrez SP - 247 EP - 55 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 177 IS - 3 N2 - Organophosphorus insecticides (OPs) generally act through a common mechanism of toxicity initiated by inhibition of acetylcholinesterase (AChE). We studied the in vivo interactive toxicity of two common OPs, chlorpyrifos (CPF) and parathion (PS), in adult male rats. Dose-response studies estimated the acute oral LD1 values for the two OPs (CPF = 80 mg/kg po; PS = 4 mg/kg po) and these dosages or relative proportions were used to evaluate interactive toxicity. Three treatment strategies were evaluated: CPF followed by PS 4 h later (CPF-1st), PS followed by CPF 4 h later (PS-1st), and simultaneous (concurrent) exposures. Using LD1 dosages, rats in the CPF-1st and concurrent groups exhibited more cholinergic toxicity (i.e., salivation, lacrimation, urination, and diarrhea signs and involuntary movements) and higher lethality (7/8 and 6/8, respectively, beginning 1 h after PS) than those in the PS-1st group (2/8 lethality, beginning 3 days after CPF). Sequential exposures to lower dosages (CPF vs PS: 60 vs 3 mg/kg; 40 vs 2 mg/kg) led to more extensive neurotoxicity in the CPF-1st group compared to the other groups. Following lower dosages (40 vs 2 mg/kg), brain ChE inhibition was more extensive in the CPF-1st group at all time points (64-85%) and the concurrent group at 4 and 24 h after exposure (46-83%) compared to rats receiving PS first (7-48%). No differences were noted however, in plasma (71-93% inhibition) or liver (72-81%) cholinesterase activities nor were there group-related differences in plasma (50-60% inhibition) or liver (>85% inhibition) carboxylesterase activities. Incubation of liver samples with oxons in the presence or absence of calcium (i.e., 2 mM CaCl(2) or EGTA) prior to addition of ChE (striatal sample) substantially blocked ChE inhibition by CPO (IC50: without liver = 4 nM; liver + calcium = 279 nM; liver + EGTA = 48 nM) but had lesser effects on PO-mediated inhibition (IC50: without liver = 17 nM; liver + EGTA = 56 nM; liver + calcium = 57 nM). Liver homogenate from animals preexposed to PS substantially decreased ChE inhibition by CPO when calcium was included (IC50: +EGTA = 8 nM; +calcium = 225 nM), but liver homogenate from animals preexposed to CPF was ineffective at blocking PO-induced inhibition (IC50: +EGTA = 16 nM; +calcium = 16 nM). We conclude that prior inhibition of carboxylesterase activity impacts toxicity of subsequent exposure to PS more than CPF because of more active detoxification of CPO by A-esterase. Together, these findings indicate that interactive toxicity from combined exposures to two OP insecticides can be markedly influenced by the sequence of administration. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/11749124/In_vivo_interaction_between_chlorpyrifos_and_parathion_in_adult_rats:_sequence_of_administration_can_markedly_influence_toxic_outcome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(01)99312-3 DB - PRIME DP - Unbound Medicine ER -