ToxSci Advance Access published online on August 28, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm219
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Published by Oxford University Press 2007.
Effects of Altered Food Intake During Pubertal Development in Male and Female Wistar Rats
Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711
1 To whom correspondence should be addresses at MD-72, NHEERL, U.S. EPA, Alexander Drive, Research Triangle Park, NC 27711. Fax: 919 541-5138 Email: Laws.susan{at}epa.gov
Received May 14, 2007; revision received August 8, 2007; accepted August 14, 2007
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Abstract |
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The U.S.EPA is currently validating assays that will be used in a Tier I Screening Battery to detect endocrine disrupting chemicals. A primary concern with the Protocols for the Assessment of Pubertal Development and Thyroid Function in Juvenile Male and Female Rats is that a nonspecific reduction in body weight (BWT) during the exposure period may potentially confound the interpretation of effects on the endocrine endpoints. Wistar rats were underfed 10, 20, 30 or 40% less than the ad libitum food consumed by controls from postnatal days (PND) 22 -42 (females) or PND 23-53 (males). Terminal BWT of females and males were 2, 4, 12 ,19% and 2, 6, 9,19% lower than controls, respectively. In the females, neither the age of pubertal onset nor any of the thyroid hormone endpoints were affected by FR that led to a 12% decrease in BWT. Similarly, none of the male reproductive endpoints examined were altered by FR that led to a 9% BWT decrease. However, decreased T3 and T4 was observed in FR males with a 9% reduced BWT. While these data support the use of the maximum tolerated dose (MTD) for BWT (10%) for the female protocol, effects on the male thyroid endpoints indicate that a slightly lower limit (
6% BWT loss) may be appropriate for the male pubertal protocol, and in cases where the BWT loss approaches 9-10%, additional studies and/or a weight of evidence approach should be used when interpreting the data for the thyroid endpoints.
Key Words: Pubertal development; food restriction; endocrine disruptors.
* Authors contributed equally to this work
Disclaimer: This manuscript has been reviewed in accordance with the policy of the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendations for use.