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Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities.

Publication ,  Journal Article
Moser, VC; Chanda, SM; Mortensen, SR; Padilla, S
Published in: Toxicological sciences : an official journal of the Society of Toxicology
December 1998

Young rats are more sensitive than adults to a single oral dose of chlorpyrifos, an organophosphorus pesticide. A direct comparison of chlorpyrifos effects in young (postnatal day 17; PND17), adolescent (PND27), and adult (70 days) Long-Evans rats was conducted to determine quantitative and possibly qualitative differences in sensitivity in terms of behavioral changes and cholinesterase (ChE; total cholinesterase activity) inhibition at these three ages. Male and female rats were administered chlorpyrifos orally at one of two doses (PND17, 5 or 20 mg/kg; PND27, 20 or 50 mg/kg; adult, 20 or 80 mg/kg) and tested at either 3.5 or 6.5 h after dosing. Behavioral testing included observational evaluations and measurements of motor activity and was followed immediately by tissue collection for ChE determination in brain and blood. For both behavioral changes and ChE inhibition, peak effects occurred at 3.5 h in adult male and PND27 rats (both sexes) and at 6.5 h in adult female and PND17 rats (both sexes). Comparisons of the 20 mg/kg dose across ages showed generally less ChE inhibition and fewer behavioral effects with increasing age, except that the adult females were similar to the PND27 rats. The high dose used for each age group produced similar brain ChE inhibition (80-90%) and generally similar behavioral effects. Interestingly, a few end-points in the young rats were less affected than in adults at this level of ChE inhibition. The degree of ChE inhibition in the brain more closely paralleled the blood inhibition in the younger rats, compared to the adults. Carboxylesterase (CaE) and A-esterase are known to play an important role in the detoxification of organophosphates and may be partially responsible for these sensitivity differences. Liver and plasma CaE and A-esterase activities were measured in untreated male rats on PND1, 4, 7, 12, 17, and 21 and in adults of both sexes (82-92 days old). Preweanling rats had considerably less activity of both enzymes, and adult females had less liver CaE activity than males. These differences in detoxifying enzymes correlate with the age-related differences in behavioral and biochemical effects, as well as the gender differences seen in adult rats, and thus may be a major influence on the differential sensitivity to chlorpyrifos.

Duke Scholars

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

December 1998

Volume

46

Issue

2

Start / End Page

211 / 222

Related Subject Headings

  • Toxicology
  • Time Factors
  • Sex Factors
  • Rats, Long-Evans
  • Rats
  • Motor Activity
  • Male
  • Liver
  • Female
  • Esterases
 

Citation

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ICMJE
MLA
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Moser, V. C., Chanda, S. M., Mortensen, S. R., & Padilla, S. (1998). Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities. Toxicological Sciences : An Official Journal of the Society of Toxicology, 46(2), 211–222. https://doi.org/10.1006/toxs.1998.2526
Moser, V. C., S. M. Chanda, S. R. Mortensen, and S. Padilla. “Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities.Toxicological Sciences : An Official Journal of the Society of Toxicology 46, no. 2 (December 1998): 211–22. https://doi.org/10.1006/toxs.1998.2526.
Moser VC, Chanda SM, Mortensen SR, Padilla S. Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities. Toxicological sciences : an official journal of the Society of Toxicology. 1998 Dec;46(2):211–22.
Moser, V. C., et al. “Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities.Toxicological Sciences : An Official Journal of the Society of Toxicology, vol. 46, no. 2, Dec. 1998, pp. 211–22. Epmc, doi:10.1006/toxs.1998.2526.
Moser VC, Chanda SM, Mortensen SR, Padilla S. Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities. Toxicological sciences : an official journal of the Society of Toxicology. 1998 Dec;46(2):211–222.
Journal cover image

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

December 1998

Volume

46

Issue

2

Start / End Page

211 / 222

Related Subject Headings

  • Toxicology
  • Time Factors
  • Sex Factors
  • Rats, Long-Evans
  • Rats
  • Motor Activity
  • Male
  • Liver
  • Female
  • Esterases