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OECD Series on Adverse Outcome Pathways

An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a chemical and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude the regular update or new contributions to a given AOP in the AOP Wiki. While the AOP Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP. The number 1 in the OECD Series on Adverse Outcome Pathways is the Users’ Handbook, which is a supplement to the Guidance Document for developing and assessing AOPs. This handbook contains an updated template for AOP development and provides focused and practical instructions for both AOP developers and reviewers.

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Adverse Outcome Pathway on Aromatase Inhibition Leading to Reproductive Dysfunction (in Fish)

This adverse outcome pathway details the linkage between inhibition of gonadal aromatase activity in females and reproductive dysfunction, as measured through the adverse effect of reduced cumulative fecundity and spawning. Initial development of this AOP draws heavily on evidence collected using 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 aromatase, or in silico predictions of the ability to inhibit aromatase, as a means to identify chemicals with known potential to adversely affect fish populations and potentially other oviparous vertebrates.

English

Keywords: repeat-spawning fish species, Fish Short Term Reproduction Assay, reproductive toxicity, aromatase inhibition, reduced cumulative fecundity
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