ABSTRACT
INTRODUCTION Puberty in mammalian species is a period of rapid interactive endocrine and morphological changes. It is therefore not surprising that exposure to a variety of pharmaceutical and environmental compounds has been shown to dramatically alter pubertal development. This concern was recognized following the Food Quality Protection Act and Safe Drinking Water Amendments congressional mandate to the U.S. EPA to develop a screening program to evaluate endocrine disrupting chemicals (EDCs) in the environment. The agency chartered the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), which acknowledged the need for the development and standardization of protocols for the assessment of the impact of EDCs (1). It proposed a two-tiered approach to testing, with a Tier 1 set of in vivo and in vitro procedures to detect various modes of action on a “weight-of-evidence” consideration and a Tier 2 set of in vivo procedures to examine the dose-response relationships, confirm the mechanism of action, and determine adverse effects in multiple species. For these reasons, the EPA considered two protocols that were designed to detect alterations of pubertal development and thyroid function. In these two protocols, intact weanling female and male rats are exposed to the test substance for 21 or 31 days, respectively, during which pubertal indices are measured [vaginal opening (VO) in the female and preputial separation (PPS) in the male as markers of pubertal onset]. Upon necropsy, reproductive and thyroid tissues are weighed and evaluated histologically and serum taken for hormone analysis [see the Endocrine Disruptor Screening Program (EDSP) Web site for fully optimized protocols (2)].
