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.


Adverse Outcome Pathway on Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)

This AOP details the linkage between binding and activation of androgen receptor (AR) in

females and reductions in cumulative fecundity and spawning. AR-mediated activities are

among the major concerns in endocrine disruptor screening programs. Cumulative

fecundity is the apical endpoint considered in the OECD 229 Fish Short Term Reproduction

Assay. It is also one of several variables with demographic significance in forecasting fish

population trends. Therefore, this AOP supports the use of measures of AR activation as a

means to identify chemicals with potential to adversely affect fish populations. At present,

this AOP is largely supported by evidence from small laboratory model fish species. While

many aspects of the biology underlying this AOP are largely conserved across oviparous

vertebrates, its relevance to vertebrate classes other than fish, or to fish species employing

different reproductive strategies has not been established. Thus, the applicability domain

should be carefully considered when evaluating fit-for-purpose.


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