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Integrated Testing Strategies

An integrated testing strategy is a part of an integrated approach to testing and assessment that relies on:

  • Input data generated from identified methods
  • A data interpretation procedure, such as a machine-learning model, flowchart, or decision tree, through which the data are evaluated

NICEATM, in collaborations with other scientists, has developed integrated testing strategies for skin sensitization and endocrine disruption.

Integrated Testing Strategies for Skin Sensitization

On April 10, the U.S. Environmental Protection Agency (EPA) released a draft Science Policy to reduce animal use by using defined approaches to identify potential skin sensitizers. The draft policy is the result of national and international collaboration among ICCVAM, NICEATM, Cosmetics Europe, the European Union Reference Laboratory for Alternatives to Animal Testing, and Health Canada’s Pest Management Regulatory Agency, including projects described below. Comments on the draft skin sensitization policy can be submitted to docket EPA-HQ-OPP-2016-0093 at www.regulations.gov through June 9.
Project Description Publication
Open source tools for implementation of defined approaches to skin sensitization testing and assessment NICEATM and industry scientists from Cosmetics Europe are writing open-source code to reproduce defined approaches submitted to the OECD for skin sensitization testing and assessment. Data on 128 chemicals to evaluate these defined approaches are also being developed as part of this project.
Integrated testing strategy using non-animal data to predict skin sensitization hazard NICEATM and ICCVAM developed an integrated testing strategy that uses non-animal data to predict the skin sensitization hazard of chemicals using three approaches: prediction of murine local lymph node assay outcomes, prediction of human skin sensitization hazard, and prediction of human or animal skin sensitization potency. The latter strategy enables classification of skin sensitizers as “weak” or “strong” without animal tests.
  • Prediction of murine local lymph node assay outcomes: Strickland et al. 2016. Integrated decision strategies for skin sensitization hazard. J Appl Toxicol 36(9):1150-62
  • Prediction of human skin sensitization hazard: Strickland et al. 2017. Multivariate models for prediction of skin sensitization hazard. J Appl Toxicol 37(3):347-360
  • Prediction of human or animal skin sensitization potency: Zang et al. 2017. Prediction of skin sensitization potency using machine learning approaches. J Appl Toxicol 37(7):792-805
Open-source software for implementation of an integrated testing strategy based on a Bayesian network NICEATM and collaborators with Procter & Gamble developed open-source software for implementation of an integrated testing strategy for skin sensitization potency based on a Bayesian network. Pirone et al. 2014. Open source software implementation of an integrated testing strategy for skin sensitization potency based on a Bayesian network. ALTEX 31:336-340

Integrated Testing Strategies for Endocrine Disruption

Project Description Publication
Identification of chemicals with the potential to interact with the androgen receptor NICEATM and EPA have developed an integrated testing strategy that combines data from 11 high throughput screening assays with a computational model to identify chemicals with the potential to interact with the androgen receptor. Kleinstreuer et al. 2016. Development and validation of a computational model for androgen receptor activity. Chem Res Toxicol 30(4):946-964
Identification of chemicals with the potential to interact with the estrogen receptor NICEATM validated an integrated testing strategy developed by the EPA that combines data from 18 high throughput screening assays with a computational model to identify chemicals with the potential to interact with the estrogen receptor. Browne et al. 2015. Screening chemicals for estrogen receptor bioactivity using a computational model. Environ Sci Technol 49:8804-8814