Developmental exposure to chlorpyrifos induces alterations in thyroid and thyroid hormone levels without other toxicity signs in CD-1 mice

Toxicol Sci. 2009 Apr;108(2):311-9. doi: 10.1093/toxsci/kfp017. Epub 2009 Feb 3.


Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against household pests; these compounds receive an increasing consideration as potential endocrine disrupters. The aim of the present study was to examine the potential short- and long-term effects of CPF on thyroid and adrenal glands in CD1 mice following exposure at dose levels not inducing brain acetyl cholinesterase (AchE) inhibition, during gestational and/or postnatal vulnerable phases. Pregnant dams were treated with 0, 3, 6 mg/kg bw/day of CPF on gestational days 15-18. After delivery, pups were treated subcutaneously on postnatal days (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum thyroxin (T4), thyroid and adrenals histology and histomorphometry were evaluated in dams and in F1 mice. In dams at 6 mg/kg, decreased T4 levels and increased cell height in thyroid were observed, and adrenal histology showed a slightly increased vacuolization in the X-zone. In the F1, short-term morphological modifications (reduced follicular size at PND 2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND 150 with an apparent higher vulnerability of males. For the first time these results indicate that CPF exposure at dose levels not inducing brain AchE inhibition causes thyroid alterations in dams and in F1 CD1 mice. Thyroid may be a sensitive target to CPF developmental exposure possibly leading to long-term effects on thyroid function. Because thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Diseases / chemically induced
  • Adrenal Gland Diseases / pathology
  • Adrenal Glands / growth & development
  • Adrenal Glands / pathology
  • Animals
  • Animals, Newborn
  • Brain / drug effects
  • Brain / enzymology
  • Chlorpyrifos / toxicity*
  • Cholinesterase Inhibitors / toxicity*
  • Endocrine Disruptors / toxicity*
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Female
  • Insecticides / toxicity*
  • Male
  • Mice
  • Pregnancy
  • Thyroid Gland / growth & development*
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Hormones / biosynthesis*
  • Thyroxine / blood
  • Triiodothyronine / blood


  • Cholinesterase Inhibitors
  • Endocrine Disruptors
  • Insecticides
  • Thyroid Hormones
  • Triiodothyronine
  • Chlorpyrifos
  • Thyroxine