ToxSci Advance Access first published online on February 3, 2009
This version published online on March 10, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp017
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DEVELOPMENTAL EXPOSURE TO CHLORPYRIFOS INDUCES ALTERATIONS IN THYROID AND THYROID HORMONE LEVELS WITHOUT OTHER TOXICITY SIGNS IN CD1 MICE
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* Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
Food and Veterinary Toxicology Unit, Department of Veterinary Public Health and Food Safety
Service for Biotechnology and Animal Welfare, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
Corresponding author: Dr. Alberto Mantovani, Food and Veterinary Toxicology Unit, Dept. Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome Italy, Tel +39 (0)6 4990 2658/2815, Fax +39 (0)6 4990 2658, e-mail: alberto.mantovani{at}iss.it
Received November 4, 2008; revision received December 19, 2008; accepted January 22, 2009
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Abstract |
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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 day 15-18. After delivery, pups were treated subcutaneously on post-natal day (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum 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 PND2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND150 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.Tthyroid may be a sensitive target to CPF developmental exposure possibly leading to long term effects on thyroid function. Since thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.
Key Words: thyroid; adrenals; Chlorpyrifos; endocrine disrupters; development; mice.
De Angelis and Tassinari contributed equally to the study. Email Address of all authors: simona.deangelis{at}iss.it; roberta.tassinari{at}iss.it; francesca.maranghi{at}iss.it; agostino.eusepi{at}iss.it; antonio.divirgilio{at}iss.it; flavia.chiarotti{at}iss.it; laura.ricceri{at}iss.it; aldina.venerosi{at}iss.it; enzo.gilardi{at}iss.it; gabriele.moracci{at}iss.it; gemma.calamandrei{at}iss.it; antonella.olivieri{at}iss.it; alberto.mantovani{at}iss.it.