The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.
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TestSmart Endocrine Disruptors
February 25-26
Hyatt Fair Lakes Hotel
12777 Fair Lakes Circle
Fairfax, VA
Program Committee:
Richard A. Becker, American Chemistry Council
Alan M. Goldberg, Johns Hopkins University
Pamela J. Lein, Johns Hopkins University
Ellen K. Silbergeld, Johns Hopkins University
Gary Timm, US Environmental Protection Agency
James D. Yager, Johns Hopkins University
Proceedings for TestSmart -- Endocrine Disruptors
Endocrine Disruption — State of the Science
James D. Yager, Ph.D. and Pamela J. Lein, Ph.D.
Johns Hopkins University
Disruptors of What?
- Estrogens
- Androgens
- Thyroid Hormone
- Glucocortocoid Hormones
- Retinoids
US EPA - Endocrine Disruptor Methods Validation Subcommittee (EDMVS)
- Purpose: Provide advice to the EPA on scientific issues associated conduct of studies required for the validation of Tier 1 and Tier 2 assays for the EPA's EDSP
- Objectives: Provide independent advice and counsel on scientific and technical issues related to validation of EDSP Tier 1 & 2 assays including:
- Reduction of Animal Use
- Refining Procedures to make them less stressful
- Replacing Animals where Scientifically Appropriate
- After validation, to integrate data to optimize configuration of the Tier 1 screening battery
- EDMVS may examine new or innovative assays applicable for inclusion in a second phase of validation.
Endocrine Disruption — State of the Science
Two broad issues
- Discovery
- Basic Mechanisms
- Discovery of membrane ER
- Discovery of mitochondrial ER
- Role of estrogen metabolites as signaling molecules and genotoxins
- Epidemiology Studies
- Role of polymorphisms in phase I and phase II enzymes involved in estrogen metabolism as risk factors for cancer
- Basic Mechanisms
- Translation
- Screens
- Tests
- Contributors to interlaboratory variability (examples from paper by Ashby, J. APMIS 108, 805-813, 2000
Recent Discovery of Basic Mechanisms
Membrane Localization of ERa in MCF-& Cells
Song et al. Molec. Endocrinol. 16, 116-127, 2001
Immunolocalization via Confocal Microscopy
Chen, Yager, et al. unpublished observations
Immunolocalization via Immunogold Electron Microscopy
Chen, Yager, et al. unpublished observations
Hypothesis Regarding Cellular Effects of E2 and E2 Metabolites
Recent Discovery in Epidemiology
Synthesis & Oxidative Metabolism of E2/E1
Cavalieri et al., 2001
Translation of Discoveries to Screening and Testing
Ashby, J. APMIS 108, 805-813, 2000
Ashby, J. APMIS 108, 805-813, 2000
Ashby, J. APMIS 108, 805-813, 2000
Ashby, J. APMIS 108, 805-813, 2000
Ashby, J. APMIS 108, 805-813, 2000