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Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood.

Publication ,  Journal Article
Slotkin, TA; Brown, KK; Seidler, FJ
Published in: Environ Health Perspect
October 2005

Developmental exposure to chlorpyrifos alters cell signaling both in the brain and in peripheral tissues, affecting the responses to a variety of neurotransmitters and hormones. We administered 1 mg/kg/day chlorpyrifos to rats on postnatal days 1-4, a regimen below the threshold for systemic toxicity. When tested in adulthood, chlorpyrifos-exposed animals displayed elevations in plasma cholesterol and triglycerides, without underlying alterations in nonesterified free fatty acids and glycerol. This effect was restricted to males. Similarly, in the postprandial state, male rats showed hyperinsulinemia in the face of normal circulating glucose levels but demonstrated appropriate reduction of circulating insulin concentrations after fasting. These outcomes and sex selectivity resemble earlier findings at the cellular level, which identified hepatic hyperresponsiveness to gluconeogenic inputs from beta-adrenoceptors or glucagon receptors. Our results thus indicate that apparently subtoxic neonatal chlorpyrifos exposure, devoid of effects on viability or growth but within the parameters of human fetal or neonatal exposures, produce a metabolic pattern for plasma lipids and insulin that resembles the major adult risk factors for atherosclerosis and type 2 diabetes mellitus.

Duke Scholars

Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

October 2005

Volume

113

Issue

10

Start / End Page

1291 / 1294

Location

United States

Related Subject Headings

  • Toxicology
  • Sex Factors
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Male
  • Insecticides
  • Hyperlipidemias
  • Hyperinsulinism
  • Growth
 

Citation

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Slotkin, T. A., Brown, K. K., & Seidler, F. J. (2005). Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood. Environ Health Perspect, 113(10), 1291–1294. https://doi.org/10.1289/ehp.8133
Slotkin, Theodore A., Kathleen K. Brown, and Frederic J. Seidler. “Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood.Environ Health Perspect 113, no. 10 (October 2005): 1291–94. https://doi.org/10.1289/ehp.8133.
Slotkin TA, Brown KK, Seidler FJ. Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood. Environ Health Perspect. 2005 Oct;113(10):1291–4.
Slotkin, Theodore A., et al. “Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood.Environ Health Perspect, vol. 113, no. 10, Oct. 2005, pp. 1291–94. Pubmed, doi:10.1289/ehp.8133.
Slotkin TA, Brown KK, Seidler FJ. Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood. Environ Health Perspect. 2005 Oct;113(10):1291–1294.

Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

October 2005

Volume

113

Issue

10

Start / End Page

1291 / 1294

Location

United States

Related Subject Headings

  • Toxicology
  • Sex Factors
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Male
  • Insecticides
  • Hyperlipidemias
  • Hyperinsulinism
  • Growth