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IMPACT OF BODY WEIGHT CHANGE ON THE EDSTAC TIER 1 MALE AND FEMALE PUBERTAL PROTOCOLS
Citation:
Cooper, R L., T E. Stoker, J M. Ferrell, K Bremser, AND S C. Laws. IMPACT OF BODY WEIGHT CHANGE ON THE EDSTAC TIER 1 MALE AND FEMALE PUBERTAL PROTOCOLS. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
IMPACT OF BODY WEIGHT CHANGE ON THE EDSTAC TIER I MALE AND FEMALE PUBERTAL PROTOCOLS. R.L. Cooper, T.E. Stoker, K. McElroy, J. Ferrell, K. Leffler, K. Bremser and S.C. Laws. Endocrinology Branch, Reproductive Toxicology Division, NHEERL, ORD, USEPA, RTP, NC. Sponsor: R.J. Kavlock
A primary concern with the Endocrine Disruptor Screening and Testing Committee?s (EDSTAC) Tier I male and female pubertal protocol is that a nonspecific reduction in body weight (bw) may potentially confound the interpretation of the effects on the endocrine enpoints of interest. To assess the relationship between growth rate and pubertal development, male and female Wistar rats were underfed to 90, 80, 70 and 60% of the ad libitum food consumption observed in controls. The females were underfed postnatal day (PND) 21-42. This regimen resulted in decreased terminal body weights (bw) of 1.8, 4.1, 12.1, and 18.8% of the ad libitum controls. Vaginal opening, uterine weight and thyroid hormone values were not altered in any of the underfed female groups. Although decreases in bw of 12.1 and 18.8% did significantly lower absolute ovarian weight, relative ovarian weight was not affected. Thus, there were no significant differences in any of the female reproductive endpoints measured in accordance with the female pubertal protocol. In the male, underfeeding from PND 23-53 resulted in terminal bw decreases of 2.0, 6.0, 9.0, and 19.5% of the ad libitum controls. Preputial separation, epididymal or testes weights were not different from control in any of the underfed males. Although a decrease in the absolute weight of the ventral prostate and seminal vesicle was noted in those males with a 19.5% decrease in bw, the relative weights of these tissues were not different than controls. A decrease in thyroid stimulating hormone levels was observed in males with the 19.5% reduction in bw, while both T3 and T4 were significantly reduced in the males with a 9 and 19.5% reduction in bw. Importantly, there were no significant alterations of the male reproductive endpoints at less than 9.0% decreased bw. These data demonstrate that reduced bw over a range of 2-9% do not confound the reproductive endpoints in either pubertal protocols and that keeping the dose range below the MTD (defined as a 10% reduction in bw) will provide valid data concerning a compound?s potential effect on these endocrine dependent events. (This abstract does not necessarily reflect EPA policy)