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MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES
Citation:
Gray Jr., L. E., J. R. Furr, M. G. Price, C J. Wolf, AND J S. Ostby. MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES. Presented at Society of Toxicology, Philadelphia, PA, March 19 - 23, 2001.
Description:
MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL
ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES.
Authors: L E Gray 1 , J Furr 1 , M G Price 2 , C J Wolf 3 and J S Ostby 1
Institutions: 1. Endocrinology Branch, Reproductive Toxicology Division, NHEERL, ORD, USEPA, Research Triangle Park, NC, USA 2. Zoology, North Carolina State University/EPA Cooperative Research, Raleigh, NC, USA. 3. EB/Toxicology Dept, USEPA/NCSU, Research Triangle Park, NC, USA
Within the last few years the scientific community has become concerned about the effects of endocrine disrupting chemicals (EDCs) on vertebrate reproduction. Clear cut examples of adverse effects of EDCs in fish and wildlife have led to speculation that EDCs also are affecting human reproduction and development. In this regard, 1996 legislation mandated that the U.S. EPA develop a validated Screening and Testing Program (STP) for estrogens and other endocrine active compounds, as deemed appropriate by the Administrator. A STP is needed to fill data gaps in the current testing paradigm. Current developmental toxicity and older multigenerational tests are not sensitive enough to detect the reproductive malformations induced by some EDCs. Even the current multigenerational reproduction test is unable to detect reproductive malformations that occur at a low incidence. Furthermore, many chemicals are not tested for developmental or reproductive toxicity at all. In response to the 1996 legislation, the USEPA formed an advisory committee known as EDSTAC. The EDSTAC Final Report (1998) recommended a Screening Battery (SB) to detect (anti)estrogen, (anti)androgens and (anti)thyroid activity (EAT) that arose from interaction with the nuclear receptors, altered hormone synthesis or hypothalamic_pituitary function. The initial focus on EAT resulted from an awareness that many anthropogenic chemicals act via these mechanisms and altering these hormones can induce adverse effects on reproduction and development in many species. The SB should detect EDCs that act across a broad range of metabolic activities and species including lower vertebrates. Only high priority chemicals would be screened and only those which were consistently positive in the SB would be tested, thus minimizing animal use. The proposed SB included five in vivo assays, three of which used mammals (about 100 or fewer rats/chemical). The three mammalian assays in the EDSTAC SB are 1) a uterotropic assay for estrogens and antiestrogens, 2) an assay to detect androgens and antiandrogens and 3) a "Female Pubertal Assay" to detect antithyroid, (anti)estrogen, steroid synthesis inhibitors and altered hypothalamic_ pituitary_ gonadal maturation. Alternative assays also were considered as potential replacements for assays in the SB. The process of developing a screening and testing program is ongoing within the USEPA and EU/OECD.
This abstract does not necessarily reflect USEPA policy.