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AOP description: Androgen receptor agonism leading to reproductive dysfunction (in fish)
Villeneuve, D. AOP description: Androgen receptor agonism leading to reproductive dysfunction (in fish). U.S. Environmental Protection Agency, Washington, DC, 2013.
This adverse outcome pathway details the linkage between binding and activation of androgen receptor as a nuclear transcription factor in females and the adverse effect of reduced cumulative fecundity in repeat-spawning fish species. Cumulative fecundity is the most apical endpoint considered in the OECD 229 Fish Short Term Reproduction Assay. The OECD 229 assay serves as screening assay for endocrine disruption and associated reproductive impairment (OECD 2012). Cumulative fecundity is one of several variables known to be of demographic significance in forecasting fish population trends. Therefore, this AOP has utility in supporting the application of measures of androgen receptor binding and activation as a nuclear transcription factor as a means to identify chemicals with known potential to adversely affect fish populations.
The proposed paradigm for toxicity testing in the 21st century, seeks to make greater and more effective use of mechanistic toxicology data, which focus on measures of the initiation or progression of potentially adverse outcomes, rather than direct observation of the apical adverse outcome themselves. The adverse outcome pathway (AOP) framework is very useful for understanding and communicating predictive linkages/relationships among endpoints across biological levels of organization, particularly linking early events measured at low levels of organization to apical adverse outcomes relevant to risk assessment. In order for AOPs to be useful in a regulatory context, it is critical that AOP knowledge be provided in an accessible and searchable format and that a defensible scientific foundation for the predictive relationships depicted in the AOPs are described. This AOP description document linking the molecular initiating event of androgen receptor agonism with reproductive dysfunction in fish was developed as an example for other AOP developers to follow as they develop AOP knowledge and submit AOP information to the AOP knowledge-base or to OECD’s AOP development program for review and endorsement (see http://www.oecd.org/env/ehs/testing/molecularscreeningandtoxicogenomics.htm). Overall, it is expected that as other AOPs, following the examples developed here, are deposited to the AOP knowledge-base, the information will be readily accessible to risk assessors from OCSPP and OW with an interest in utilizing mechanistic data in their assessments and decision-making. The OECD AOP KB, with support from both the U.S. EPA and the European Commission, is to become the single authoritative source of AOP information internationally (i.e., among OECD member countries).
Record Details:Record Type: DOCUMENT (PUBLISHED REPORT/REPORT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
MID-CONTINENT ECOLOGY DIVISION