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Pure Appl. Chem., 2003, Vol. 75, No. 11-12, pp. 2081-2098

Experience with new testing guidelines with endocrine-sensitive end-points

R. W. Tyl

Center for Life Sciences and Toxicology, RTI International, 3040 Cornwallis Road, P.O.Box 12194, Research Triangle Park, NC 27709-2194, USA

Abstract: Concerns about the effects of endocrine disruptors on humans and wildlife have resulted in revised governmental testing guidelines (e.g., U.S. Environmental Protection Agency, Organization for Economic Cooperation and Development, U.S. Food and Drug Administration), adding endpoints to enhance their capability to detect endocrine active compounds. Based on experience with these testing guidelines, I present my opinions and data on study design, performance, results, endpoints, interpretation, and recommendations for improvement. New regulatory endpoints must be reproducible, robust, sensitive, relevant, and consistent. These new endpoints are appropriate: anogenital distance, examination of culled pups on postnatal day 4, examination for retained nipples/areolae in preweanling males, weanling necropsy, acquisition of puberty in offspring, prebreed estrous cyclicity, reproductive organ weights and histopathology, and andrology. Endpoints considered not appropriate are ovarian primordial follicle counts, stage of estrous for parental females at demise, and single blood sample at necropsy to measure circulating levels of relevant hormones. In conclusion: (1) regulatory guidelines represent only the minimum requirements and should/will change as science improves and scientific and societal concerns arise; (2) scientists must interact to identify and refine new methods, endpoints, and mechanisms; (3) the objective of these studies is to provide good science and useful information for risk assessment. Regulatory agencies should convene workshops with stakeholders to discuss issues such as new fundamental/applied information, mechanisms, and current and new endpoints. Interactions will lead to enhanced science, periodic revisions of testing guidelines, and improved risk assessment.