ICCVAM Workgroups

Fostering the evaluation, promotion, and harmonization of alternatives to animal use for acute systemic toxicity testing has long been one of ICCVAM’s priorities. The Acute Toxicity Workgroup evaluates the usefulness of various types of data, data analyses, and testing approaches for classifying and predicting acute oral, dermal, and inhalation systemic toxicity. The workgroup has members from seven ICCVAM agencies.

Recent and ongoing activities include:

• Publishing a scoping document (Strickland et al. 2018) that identifies U.S. agency information requirements, needs, and decision contexts for acute systemic toxicity testing.
• Organizing a global project to develop in silico models of acute oral systemic toxicity that predict five specific endpoints needed by regulatory agencies (Mansouri et al. 2021).
• Analyzing variability of in vivo data used as benchmarks for evaluating alternative methods (Karmaus et al. 2022).
• Evaluating the usefulness of additivity formulas for hazard classification of formulations and mixtures (Hamm et al. 2021).
• Assessing the usefulness of available in vitro and in silico models for acute inhalation toxicity.
• Organizing a global project to develop in silico models of acute inhalation toxicity.

This ICCVAM workgroup was established in 2021 to explore opportunities for encouraging those using animal-based models to not only consider but actively pursue NAMs that could support their research goals while replacing, reducing, or refining their use of animal models. The workgroup has members from nine ICCVAM agencies. With input from appropriate stakeholders, it will develop a white paper on approaches that could potentially be used to foster the consideration and use of NAMs to replace, reduce, or refine live animal use by organizations currently using animals for testing. It will also foster communication and appropriate collaborations to encourage greater consideration of NAMs, and explore approaches to increase awareness of grants available to support development of alternatives.

While the focus of ICCVAM activities has largely been on human health, ICCVAM also recognizes the need to implement non-animal approaches for ecotoxicity testing. The Ecotoxicology Workgroup was established to provide expertise in identifying and evaluating in vitro and in silico methods to identify ecological and environmental hazards. The workgroup has members from seven ICCVAM agencies.

The workgroup compiled a summary of agency needs for ecotoxicity testing, emerging technologies for evaluating ecotoxicity and environmental safety, and the potential applicability of those technologies for regulatory testing (Ceger et al. 2022). The workgroup is currently evaluating ecotoxicology methods involving animal testing and what alternatives exist to replace, reduce, or refine animal use in the acute fish toxicity assay.

Per- and polyfluoroalkyl substances (PFAS) are a class of organofluorine chemicals that have been manufactured and used for decades. They have been identified as highly persistent and bioaccumulative in the environment, biota, and humans. There is no consensus definition of PFAS, and depending on how they are defined, the number of compounds considered PFAS can differ widely. While there is broad national and international interest in understanding PFAS hazards, many challenges remain to effectively and efficiently doing so due to the same properties that make them so widespread in their use and application. ICCVAM established its PFAS workgroup in 2023 to provide expertise in identifying and evaluating new approach methodologies (NAMs) to predict PFAS toxicity. The workgroup has members from eight ICCVAM agencies.

The workgroup will initially develop a summary of agency needs for assessing PFAS and how those can be met using NAMs. This summary will be used to advance the development and evaluation of defined approaches for screening, testing and assessment of relevant endpoints. Additionally, the workgroup will address the development and implementation of alternative approaches to reduce and replace animal use for PFAS testing following four key steps: (1) reviewing current PFAS definition(s); (2) identifying testing efforts among regulatory and non-regulatory agencies and related challenges; (3) identifying data gaps and opportunities in application of alternative approaches; and (4) identifying and addressing both scientific and non-scientific (including regulatory) needs and challenges.

ICCVAM also establishes expert groups to facilitate communication among agencies on a specific area of interest. Expert groups can be established from workgroups that have completed their charge tasks, or by agency representatives that share interest in a topic for which no specific activity has been identified. ICCVAM currently has expert groups in the areas of developmental and reproductive toxicity, developmental immunotoxicity, FAIR data standards, in vitro to in vivo extrapolation, metrics, microphysiological systems, nanomaterials, ocular and dermal irritation, read-across, skin sensitization, and validation.