EFSA | Pathways relevant for the identification of substances having endocrine disruptors properties

Hormone-related cancers, like breast, endometrium, ovary, prostate, testis and thyroid, share commonalities in the mechanism of carcinogenesis. Endogenous and exogenous hormones drive cell proliferation, increasing the opportunity for the accumulation of random genetic errors. Progression to a malignant phenotype depends on a series of somatic mutations that occur during cell division. Therefore, endocrine disrupter chemicals (EDCs) can act as exogenous substances promoting target tissue cell proliferation leading to neoplasms.

One relatively common example is the uterine adenocarcinoma, a common human malignancy that can be induced experimentally in laboratory animals following treatment with EDCs. However, a direct link on the occurrence of rodent uterine adenocarcinoma and an endocrine mode of action relevant to human is not immediate, mostly because the hazard can only be characterized at the end of the carcinogenicity study. To investigate the link between an endocrine mode action and the uterine adenocarcinoma, and therefore identify EDCs, the Adverse Outcome Pathway (AOP) conceptual framework is considered a scientifically sound and regulatory acceptable method to be applied in order to investigate early Key Events (KEs) or Molecular Initiating Events (MIEs) that can be investigated in-vitro or in in-vivo short studies.