Integrated Approaches to Testing and Assessment
Integrated approaches to testing and assessment (IATAs) provide an means by which all relevant and reliable existing information about a chemical can be used to answer a defined hazard characterization question. Information considered can include toxicity data, exposure routes, use cases, and production volumes. This information is used to characterize outcomes that can inform regulatory decision-making.
The drawbacks of traditional toxicity testing approaches using laboratory animals may be overcome by the use of human cell-based, biochemical, and/or computational methods to predict chemical toxicity. But because of the complexity of toxicity mechanisms, data from several methods usually need to be considered in combination to adequately predict toxic effects. IATAs provide a means by which these data can be considered in combination. When necessary, IATAs can guide generation of new data, preferably using non-animal approaches, to inform regulatory decision-making.
A defined approach to testing and assessment can be used as part of an IATA or on its own to satisfy a need for hazard information. A defined approach consists of input data generated from identified methods and a data interpretation procedure, such as a machine-learning model, flowchart, or decision tree, through which the data are evaluated. Defined approaches are rule-based and do not utilize expert judgment.
Input data for defined approaches may be derived from in vitro test methods. They may also be obtained from computational approaches such as “read-across,” in which toxicity data from a known chemical are used to predict toxicity for another, similar chemical. The input data are run through the data interpretation procedure to generate a hazard prediction.
Examples of defined approaches:
- Sequential testing strategies use a fixed, stepwise approach to obtain and assess test data. They include interim decision points at which the user may either proceed to additional testing steps or stop testing and make a hazard prediction.
- Integrated testing strategies use an approach in which multiple sources of data or information are assessed at the same time to arrive at either a hazard prediction or a decision that more testing is needed.
More information about IATAs and defined approaches is available on the OECD website.
NICEATM is collaborating with the PETA International Science Consortium Ltd. (PISC), EPA, and member companies of the trade association CropLife America to develop an in vitro defined approach for classification of eye irritation potential of agrochemical formulations. This public-private partnership was established as a means to develop confidence in non-animal methods for identifying potential eye irritants and thus encourage adoption and use.
A three-phase prospective evaluation currently in progress will (1) assess the applicability of seven in vitro eye irritation/corrosion methods to agrochemical formulations and (2) develop a defined approach for agrochemical formulations testing for prediction of U.S. and international irritancy classifications.
In April 2018, 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.
NICEATM and collaborators have developed defined approaches to identify potential skin sensitizers (substances with the potential to cause allergic contact dermatitis).
- NICEATM and other NTP scientists collaborated with Procter & Gamble to develop an open-source version of a previously published proprietary integrated testing strategy.
- NICEATM and ICCVAM developed defined approaches that use data from three non-animal tests, read-across predictions of skin sensitization hazard, and physical properties such as partition coefficient to predict skin sensitization hazard and potency.
- NICEATM collaborated with Cosmetics Europe to evaluate multiple defined approaches for skin sensitization safety assessment that had been submitted to OECD.
NICEATM validated an defined approach developed by 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). Use of this defined approach has been accepted by the EPA as an alternative to three assays currently used in its Endocrine Disruptor Screening Program Tier I battery.
Similarly, NICEATM and EPA have developed a defined approach (Kleinstreuer et al. 2017) 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. EPA is currently considering whether this approach is potentially useful for replacement of existing tests currently required in the Endocrine Disruptor Screening Program. NICEATM, OECD, and EPA scientists recently 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.