Neurochemical effects of chronic dietary and repeated high-level acute exposure to chlorpyrifos in rats

Stephanie Padilla, Renée S. Marshall, Deborah L. Hunter, Sharon Oxendine, Virginia C. Moser, Stanley B. Southerland, Richard B. Mailman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to those of higher, intermittent exposure. To that end, adult male rats were fed an anticholinesterase insecticide, chlorpyrifos (CPF), for 1 year at three levels of dietary exposure: 0, 1, or 5 mg/kg/day (0+oil, 1+oil, and 5+oil). In addition, half of each of these groups also received a bolus dosage of CPF in corn oil ("spiked" animals; 60 mg/kg initially and 45 mg/kg thereafter) every 2 months (0+CPF, 1+CPF, 5+CPF). Animals were analyzed after 6 or 12 months of dosing, and again 3 months after cessation of dosing (i.e., "recovery" animals - six experimental groups with n = 4-6/ group/time point). Cholinesterase (ChE) activity was measured in retina, whole blood, plasma, red blood cells, diaphragm, and brain [pons, striatum, and the rest of the brain (referred to simply as "brain")]. Muscarinic receptor density was assessed in retina, pons, and brain, whereas dopamine transporter density and the levels of dopamine and its metabolites were assessed in striatum. Cholinesterase activity at 6 and 12 months was not different in any of the tissues, indicating that a steady state had been reached prior to 6 months. The 1+oil group animals showed ChE inhibition only in the blood, whereas the 5+oil group exhibited ≥50% ChE inhibition in all tissues tested. One day after the bolus dose, all three groups (0+CPF, 1+CPF, 5+CPF) showed ≥70% ChE inhibition in all tissues. Muscarinic receptor density decreased only in the brain of the 5+oil and 5+CPF groups, whereas dopamine transporter density increased only at 6 months in all three spiked groups. Striatal dopamine or dopamine metabolite levels did not change at any time. Three months after CPF dosing ended, all end points had returned to control levels. These data indicate that, although chronic feeding with or without intermittent spiked dosages with CPF produces substantial biochemical changes in a dose- and tissue-related manner, there are no persistent biochemical changes.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalToxicological Sciences
Volume88
Issue number1
DOIs
StatePublished - Nov 1 2005

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Chlorpyrifos
Rats
Cholinesterases
Oils
Brain
Animals
Tissue
Dopamine
Dopamine Plasma Membrane Transport Proteins
Blood
Pons
Cholinesterase Inhibitors
Muscarinic Receptors
Insecticides
Metabolites
Retina
Corpus Striatum
Corn Oil
Level control
Diaphragms

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Padilla, S., Marshall, R. S., Hunter, D. L., Oxendine, S., Moser, V. C., Southerland, S. B., & Mailman, R. B. (2005). Neurochemical effects of chronic dietary and repeated high-level acute exposure to chlorpyrifos in rats. Toxicological Sciences, 88(1), 161-171. https://doi.org/10.1093/toxsci/kfi274
Padilla, Stephanie ; Marshall, Renée S. ; Hunter, Deborah L. ; Oxendine, Sharon ; Moser, Virginia C. ; Southerland, Stanley B. ; Mailman, Richard B. / Neurochemical effects of chronic dietary and repeated high-level acute exposure to chlorpyrifos in rats. In: Toxicological Sciences. 2005 ; Vol. 88, No. 1. pp. 161-171.
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Padilla, S, Marshall, RS, Hunter, DL, Oxendine, S, Moser, VC, Southerland, SB & Mailman, RB 2005, 'Neurochemical effects of chronic dietary and repeated high-level acute exposure to chlorpyrifos in rats', Toxicological Sciences, vol. 88, no. 1, pp. 161-171. https://doi.org/10.1093/toxsci/kfi274

Neurochemical effects of chronic dietary and repeated high-level acute exposure to chlorpyrifos in rats. / Padilla, Stephanie; Marshall, Renée S.; Hunter, Deborah L.; Oxendine, Sharon; Moser, Virginia C.; Southerland, Stanley B.; Mailman, Richard B.

In: Toxicological Sciences, Vol. 88, No. 1, 01.11.2005, p. 161-171.

Research output: Contribution to journalArticle

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AU - Padilla, Stephanie

AU - Marshall, Renée S.

AU - Hunter, Deborah L.

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AU - Southerland, Stanley B.

AU - Mailman, Richard B.

PY - 2005/11/1

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N2 - Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to those of higher, intermittent exposure. To that end, adult male rats were fed an anticholinesterase insecticide, chlorpyrifos (CPF), for 1 year at three levels of dietary exposure: 0, 1, or 5 mg/kg/day (0+oil, 1+oil, and 5+oil). In addition, half of each of these groups also received a bolus dosage of CPF in corn oil ("spiked" animals; 60 mg/kg initially and 45 mg/kg thereafter) every 2 months (0+CPF, 1+CPF, 5+CPF). Animals were analyzed after 6 or 12 months of dosing, and again 3 months after cessation of dosing (i.e., "recovery" animals - six experimental groups with n = 4-6/ group/time point). Cholinesterase (ChE) activity was measured in retina, whole blood, plasma, red blood cells, diaphragm, and brain [pons, striatum, and the rest of the brain (referred to simply as "brain")]. Muscarinic receptor density was assessed in retina, pons, and brain, whereas dopamine transporter density and the levels of dopamine and its metabolites were assessed in striatum. Cholinesterase activity at 6 and 12 months was not different in any of the tissues, indicating that a steady state had been reached prior to 6 months. The 1+oil group animals showed ChE inhibition only in the blood, whereas the 5+oil group exhibited ≥50% ChE inhibition in all tissues tested. One day after the bolus dose, all three groups (0+CPF, 1+CPF, 5+CPF) showed ≥70% ChE inhibition in all tissues. Muscarinic receptor density decreased only in the brain of the 5+oil and 5+CPF groups, whereas dopamine transporter density increased only at 6 months in all three spiked groups. Striatal dopamine or dopamine metabolite levels did not change at any time. Three months after CPF dosing ended, all end points had returned to control levels. These data indicate that, although chronic feeding with or without intermittent spiked dosages with CPF produces substantial biochemical changes in a dose- and tissue-related manner, there are no persistent biochemical changes.

AB - Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to those of higher, intermittent exposure. To that end, adult male rats were fed an anticholinesterase insecticide, chlorpyrifos (CPF), for 1 year at three levels of dietary exposure: 0, 1, or 5 mg/kg/day (0+oil, 1+oil, and 5+oil). In addition, half of each of these groups also received a bolus dosage of CPF in corn oil ("spiked" animals; 60 mg/kg initially and 45 mg/kg thereafter) every 2 months (0+CPF, 1+CPF, 5+CPF). Animals were analyzed after 6 or 12 months of dosing, and again 3 months after cessation of dosing (i.e., "recovery" animals - six experimental groups with n = 4-6/ group/time point). Cholinesterase (ChE) activity was measured in retina, whole blood, plasma, red blood cells, diaphragm, and brain [pons, striatum, and the rest of the brain (referred to simply as "brain")]. Muscarinic receptor density was assessed in retina, pons, and brain, whereas dopamine transporter density and the levels of dopamine and its metabolites were assessed in striatum. Cholinesterase activity at 6 and 12 months was not different in any of the tissues, indicating that a steady state had been reached prior to 6 months. The 1+oil group animals showed ChE inhibition only in the blood, whereas the 5+oil group exhibited ≥50% ChE inhibition in all tissues tested. One day after the bolus dose, all three groups (0+CPF, 1+CPF, 5+CPF) showed ≥70% ChE inhibition in all tissues. Muscarinic receptor density decreased only in the brain of the 5+oil and 5+CPF groups, whereas dopamine transporter density increased only at 6 months in all three spiked groups. Striatal dopamine or dopamine metabolite levels did not change at any time. Three months after CPF dosing ended, all end points had returned to control levels. These data indicate that, although chronic feeding with or without intermittent spiked dosages with CPF produces substantial biochemical changes in a dose- and tissue-related manner, there are no persistent biochemical changes.

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Padilla S, Marshall RS, Hunter DL, Oxendine S, Moser VC, Southerland SB et al. Neurochemical effects of chronic dietary and repeated high-level acute exposure to chlorpyrifos in rats. Toxicological Sciences. 2005 Nov 1;88(1):161-171. https://doi.org/10.1093/toxsci/kfi274