Defined Approaches for Endocrine Disruption

Defined approaches to testing and assessment combine data from multiple sources to support hazard evaluations. Defined approaches rely on:

• Input data generated from specific sources.
• A data interpretation procedure such as a machine-learning model, flowchart, or decision tree, through which the input data is run.
• A simultaneous assessment of the input data to arrive at either a hazard prediction or a decision that more testing is needed.

Defined approaches are a type of integrated approach to testing and assessment. These approaches answer a defined hazard characterization question within a specific regulatory context.

NICEATM and EPA scientists developed a defined approach (Browne et al. 2015) that combines data from 18 HTS assays to identify chemicals with the potential to interact with the estrogen receptor pathway. Use of this integrated testing strategy has been accepted by the EPA as an alternative to three assays currently used by the Tier 1 battery of the EPA Endocrine Disruptor Screening Program (EDSP).

Similarly, NICEATM and EPA scientists developed a defined approach (Kleinstreuer et al. 2017) that combines data from 11 HTS assays with a mathematical model to identify chemicals with the potential to interact with the androgen receptor pathway. The EPA is currently considering whether this approach is potentially useful for replacement of existing tests currently required in the EDSP. NICEATM, OECD, and EPA scientists have published companion papers establishing a reference database (Browne et al. 2018) and using it to evaluate the performance (Kleinstreuer et al. 2018) of the androgen receptor model.