The NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)
EPA finalizes guidance to waive toxicity tests on animal skin
On January 19, the U.S. Environmental Protection Agency (EPA) published final guidance that will allow researchers to forego testing chemicals on animal skin in certain circumstances. EPA is a member of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), which is supported by NICEATM.
The “Final Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Single-Active Ingredient and Supporting Retrospective Analysis” allows registrants to apply for waivers for studies on single-active ingredients used to develop end-use products. This guidance supports EPA’s efforts to identify opportunities for test waivers that can reduce animal use for testing required for pesticide registration. It also supports EPA’s broader goal to eliminate the use of mammals for chemical safety testing by 2035.
The January 19 announcement is available at https://content.govdelivery.com/accounts/USAEPAOPPT/bulletins/2ba0cd2/. A link to the guidance and more information about EPA waivers of animal tests are available at https://www.epa.gov/pesticide-registration/bridging-or-waiving-data-requirements.
New FDA report highlights progress in advancing alternatives
A new report by the U.S. Food and Drug Administration (FDA) provides updates on activities to advance the development of alternatives to animal use and their application to regulatory decision-making. The report, “Advancing New Alternative Methodologies at FDA,” is available at https://www.fda.gov/media/144891/download. FDA is an ICCVAM member agency.
The FDA Alternative Methods Working Group developed this report to highlight the agency’s progress in laying the groundwork for integrating alternatives to animal testing into FDA regulatory programs. The report describes activities within eight FDA offices and centers, as well as FDA working groups and interagency partnerships such as ICCVAM and Tox21. It also summarizes FDA’s engagement to advance alternatives to animal testing in international venues such as the International Cooperation on Cosmetic Regulation and the Organisation for Economic Co-operation and Development.
A link to the report and information about other activities of the FDA Alternative Methods Working Group is available at https://www.fda.gov/alternativemethods.
Minutes available from 2020 SACATM meeting
Minutes from the September 2020 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) are now available at https://ntp.niehs.nih.gov/events/past/index.html?type=SACATM. SACATM, a federally chartered advisory group, meets annually to advise ICCVAM, NICEATM, and the Director of the National Institute of Environmental Health Sciences (NIEHS) and NTP regarding the statutorily mandated duties of ICCVAM and NICEATM activities.
Recognizing the occasion of ICCVAM’s 20th anniversary, SACATM members and commenters praised ICCVAM’s work to advance alternatives to animal testing and identified opportunities for further progress. Specific areas mentioned included genotoxicity and carcinogenicity and replacement of animal use for antibody production. One day of the meeting was devoted to considering sources, management, and quality of data that are needed to evaluate new methods, as well as computational tools that can both support evaluation of new methods and predict toxicity. Presentations covered the variability in animal data, applications of machine learning, and in vitro human-based models that incorporate genetic diversity.
NICEATM and ICCVAM activities at SOT
A webpage summarizing NICEATM and ICCVAM activities at the March 12-26 virtual Society of Toxicology (SOT) annual meeting is now available at https://ntp.niehs.nih.gov/go/niceatm-sot21. Please refer to this page as you plan your SOT itinerary.
NICEATM and ICCVAM will have a strong presence at SOT. NICEATM is presenting ten posters and four platform presentations, and ICCVAM members are coauthors on seven posters and four talks. ICCVAM members Warren Casey (NIEHS) and Suzanne Fitzpatrick (FDA) will speak at the continuing education course “Establishing Confidence in Organ-on-a-chip Systems for Toxicity Testing: Lung-on-a-chip as an Example”. Agnes Karmaus (ILS, contractor supporting NICEATM) will speak at the continuing education course “Understanding Tox21/ToxCast High-throughput Screening Data and Applications to Modeling”.
A complete program overview can be found at https://www.toxicology.org/events/am/AM2021/program-overview.asp.
Report available for 2019 Acute Toxicity Workshop
The 2019 workshop “Mind the Gaps: Prioritizing Activities to Meet Regulatory Needs for Acute Systemic Lethality” reviewed developments in the prediction of acute oral lethality for chemicals and mixtures, as well as progress and needs in the understanding and modeling of mechanisms of acute lethality. A new report and other materials from the workshop are available at https://ntp.niehs.nih.gov/go/atwksp-2019. The workshop was co-organized by NICEATM and the Physicians Committee for Responsible Medicine.
Workshop participants concluded that a variety of approaches will be needed to fully replace the use of animals for acute systemic toxicity testing. In the near term, non-testing approaches could be used for some assessments. These approaches, which include waiving tests, applying computational models to evaluating toxicity of single chemicals, and calculating the acute lethality of mixtures based on the LD50 values of mixture components, may be particularly useful for chemicals in the very toxic or non-toxic classification ranges. Other needs identified in the workshop include development of agency policies that provide the contexts under which mathematical approaches for mixtures’ assessment are acceptable, improved understanding of the variability of in vivo reference data, and mechanistically based in vitro or in silico models developed to support non-testing approaches.
Sullivan et al. 2021. Mind the gaps: Prioritizing activities to meet regulatory needs for acute systemic lethality. ALTEX. https://doi.org/10.14573/altex.2012121
NICEATM research featured in special issue of Chemical Research in Toxicology
Two papers describing NICEATM research are now available online from Chemical Research in Toxicology. Both papers will be included in a special issue of the journal co-edited by Acting NICEATM Director Nicole Kleinstreuer.
- A cardiotoxicity profile was developed for the Tox21 chemical library focusing on high-throughput screening assays having targets related to cardiovascular failure modes. The profile was able to identify drugs with known cardiotoxic effects. This approach may enable development of new hypotheses around environmental chemicals of potential interest for adverse cardiovascular outcomes using Tox21/ToxCast data.
Krishna et al. 2020. High-throughput screening to identify chemical cardiotoxic potential. Chem Res Toxicol. https://doi.org/10.1021/acs.chemrestox.0c00382
- Saagar is a novel set of extensible chemistry-aware substructures that support interpretable predictive models and read-across protocols. Saagar features are interpretable and efficiently characterize diverse chemical collections, making them a better choice for building interpretable predictive in silico models and read-across protocols.
Sedykh et al. 2020. Saagar – a new, extensible set of molecular substructures for QSAR/QSPR and read-across predictions. Chem Res Toxicol. https://doi.org/10.1021/acs.chemrestox.0c00464