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Reproductive Toxicology Division
Reproductive Toxicology Division
Support to the EPA’s Endocrine Disruptor Screening Program (EDSP)
Team
- Ralph Cooper, Supervisory Research Biologist Biosketch
- Jerome Goldman, Research Biologist Biosketch
- Earl Gray, Research Biologist Biosketch Biosketch
- Susan Laws, Research Biologist Biosketch
- Tammy Stoker, Research Biologist Biosketch
- Vickie Wilson, Research Biologist Biosketch
Overview
In response to concerns that environmental chemicals may adversely affect human health by altering endocrine function, Congress mandated that the EPA develop an endocrine disruptor screening program (EDSP). To address the mandates, the Endocrine Disruptor Screening and Testing team has the task of developing a battery of novel and updated, in vivo and in vitro, screening and testing assays which could be validated as alternatives to current methods. The team and their work support EPA’s Office of Science, Coordination and Policy (OSCP), the Agency’s Endocrine Disruptor Methods Validation Subcommittee (EDMVS), and the international Organization for Economic Cooperation and Development (OECD).
The team’s research is focused on the following Long-Term Goals (LTG) in EPA’s Multi-Year Plans (MYP):
- MYP: Endocrine Disruptors
- LTG 3: Support of EPA’s Screening and Testing Programs
EDSP Projects
In Vitro Assays for Androgen and Estrogen Receptor Binding and Transcriptional Activation Assays
Contact: Vickie Wilson
The object of this research is to develop, standardize, and validate relatively sensitive, robust, and simple methods for pre-screening and screening chemicals that affect androgen and estrogen receptor function. The assays in this project include estrogen receptor (ER) binding, ER-mediated transcriptional activation assays, androgen receptor (AR) binding assays, and AR-mediated transcriptional activation assays. The Office of Science Coordination and Policy (OSCP) is currently coordinating efforts to standardize and validate these assays for potential use in EPA’s Endocrine Disruptor Screening Program (EDSP).
Development, Standardization and Prevalidation of the Endocrine Disruptor Screening Program Tier 1 Assay for Steroidogenesis
Contact: Jerome Goldman
This project focuses on the establishment of screening protocols for evaluating effects of chemicals on mammalian steroid production. Interlaboratory testing through the validation stage determines the suitability of the protocols. When completed and validated for use, the screening protocols are expected to be implemented as a component of a comprehensive test battery designed to permit decisions about endocrine disruption based upon “weight-of-evidence” considerations.
Development, Standardization, and Prevalidation of the EDSP Mammalian Assays
Contact: Tammy Stoker
This project addresses whether the Endocrine Disruptor Screening Program (EDSP) Tier I Mammalian Assays reliably detect endocrine disruptors that act through various mechanisms of action. Team members work to standardize and validate assays, such as (1) the pubertal protocols to detect various toxicants including those affecting the thyroid; (2) the Hershberger Assay for detection of androgenic and antiandrogenic activity: and (3) the revised multigenerational protocols in order to better characterize the range of adverse outcomes resulting from exposure to chemicals during gestation, lactation, and adulthood.
Recent Publications
Laws SC, Stoker TE, Ferrell JM, Hotchkiss MG, Cooper RL. 2007. Effects of altered food intake during pubertal development in male and female Wistar rats. Toxicol. Sci. 100:194-202. Abstract
Hartig PC, Cardon MC, Lambright CS, Bobseine KL, Wilson VS, Gray LE. 2007. Substitution of synthetic chimpanzee androgen receptor for human androgen receptor in competitive binding and transcriptional activation assays for EDC screening. Toxicol Lett. 174:89-97. Abstract
Cummings AM, Stoker TE, Kavlock RJ. 2007. Gender based differences in endocrine and reproductive toxicity. Environ Res. 104:96-107. Abstract
Owens W, Gray LE, Zeiger E, Walker M, Yamasaki K, Ashby J, Jacob E. 2007. The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo androgen and antiandrogen responses: Phase 2 dose-response studies. Environ Health Perspect. 115:671-8. Abstract
Owens W, Zeiger E, Walker M, Ashby J, Onyon L, Gray LE. 2006. The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo androgen and antiandrogen responses. Phase 1: Use of a potent agonist and a potent antagonist to test the standardized protocol. Environ Health Perspect. 114:1259-65. Abstract
Laws SC, Stoker TE, Goldman JM, Wilson VS, Gray LE, Cooper RL. (2006). The U.S. EPA's Endocrine Disruptor Screening Program: In vitro and in vivo mammalian Tier I screening assays. In: Developmental and Reproductive Toxicology, A Practical Approach. Ed.: R. Hood, CRC Press, Boca Raton, FL. pp. 489-523.
Stoker TE, Ferrell JM, Laws SC, Cooper RL, Buckalew AR. 2006. Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects of thyroid endpoints. Toxicology. 228:58-65. Abstract
Cooper RL, Lamb JC, Barlow SM, Bentley K, Brady AM, Doerrer NG, Eisenbrandt DL, Fenner-Crisp PA, Hines RN, Irvine LF and others. 2006. A tiered approach to life stages testing for agricultural chemical safety assessment. Crit Rev Toxicol. 36:69-98. Abstract
Carmichael NG, Barton HA, Boobis AR, Cooper RL, Dellarco V, Doerrer NG, Fenner-Crisp PA, Doe JE, Lamb IV JC, Pastoor, TB. 2006. Agricultural chemical safety assessment: a multisector approach to the modernization of human safety requirements. Crit Rev Toxicol. 36:1-7. Abstract
Laws SC, Yavanhxay S, Cooper RL, Eldridge J. 2006. Nature of the binding interaction of selected chemicals with rat estrogen receptors. Toxicol Sci. 94:46-56. Abstract
Gray LE, Wilson VS, Noriega NC, Lambright CS, Furr JR, Stoker TE, Laws SC, Goldman JM, Cooper RL, Foster P. 2004. Use of the laboratory rat as a model in endocrine disruptor screening and testing. 42:425-37. Abstract
Gray LE, Wilson VS, Stoker TE, Lambright CS, Furr JR, Noriega NC, Hartig PC, Cardon MC, Rosen MB, Ankley GT, Hotchkiss AK, Orlando EF, Guilette LJ, Kelce W. 2004. Environmental androgens and antiandrogens: An expanding chemical universe. In: R.Naz, editors. Endocrine Disruptors. 2nd Edition. Boca Raton, (FL): CRC Press LLC. p 313-345. Abstract
Stoker TE, Laws SC, Crofton KM, Hedge JM, Ferrell JM, Cooper RL. 2004. Assessment of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture, in the EDSP male and female pubertal protocols. Toxicol Sci. 78:144-155. Abstract