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National Toxicology Program

National Toxicology Program

UPDATE NewsletterUPDATE NewsletterMay 2022

NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)

By Catherline Sprankle

ICCVAM public forum May 26-27

A virtual public forum will be held Thursday, May 26, and Friday, May 27, from 10:00 a.m. until about 4:00 p.m. EDT both days. This event is held annually by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to share information and facilitate direct communication of ideas and suggestions from stakeholders. ICCVAM receives support from NICEATM. At the public forum, NICEATM, ICCVAM, and ICCVAM agencies will describe activities both to advance new approaches to safety testing of chemicals and medical products and to reduce the amount of testing required.

Information and links to register to attend and to present oral public statements are available on the NTP website. Registration is required to view the public forum and will be open through the end of the meeting on May 27. Interested persons may also register to present oral public statements with associated slides on topics relevant to ICCVAM's mission. Requests to present oral statements during the meeting will be accepted on a first-come, first-served basis as time permits. The deadline for registering to present oral public statements is Friday, May 20.

NICEATM scientist discusses computational pipeline for cardiotoxicity in May 12 webinar

NICEATM scientist Shagun Krishna will discuss “Computational Cardiotoxicity: Building an AI-assisted Pipeline” at a webinar on Thursday, May 12 at 10:00-11:00 a.m. EDT. The webinar is the last in a series presented by the Health and Environmental Sciences Institute featuring early-career scientists who have conducted compelling research related to cardiovascular safety and risk assessment.

Krishna’s research involves development of a pipeline for cardiovascular risk assessment of pharmaceutical and environmental chemicals. She has led a project to interpret Tox21/ToxCast high-throughput screening assay data, map the assay targets to biological pathways that represent key failure modes in cardiovascular disease, and use the observed patterns of bioactivity to screen and rank chemicals for potential cardiotoxicity. Her research applies cheminformatics, artificial intelligence, and machine learning in a variety of ways, including building structure–activity relationship models and developing evidence maps of the literature supporting environmental contributions to cardiovascular effects.

Proceedings available from workshop on NAMs for human health risk assessment; Next workshop May 12

A December 9, 2021, workshop considered the potential utility and expectations for the future use of new approach methodologies (NAMs) in risk assessment and to reflect on the challenges to their implementation. Proceedings of the workshop are now available.

During the workshop, experts from academia, industry, government, and other organizations discussed current scientific knowledge with regard to traditional toxicity studies and NAMs. The workshop addressed three critical questions:

  • How are traditional toxicity studies used in informing chemical safety decisions?
  • What do we know about the variability and concordance of traditional mammalian toxicity studies?
  • What are the needs and expectations of different stakeholders?

The workshop was convened by an ad hoc committee of the National Academies of Sciences, Engineering, and Medicine exploring the topic of “Variability and Relevance of Current Laboratory Mammalian Toxicity Tests and Expectations for New Approach Methods for use in Human Health Risk Assessment.” The panel’s goal is to set data-driven and science-based expectations for NAMs based on the variability and relevance of the traditional toxicity testing models. Acting NICEATM Director Nicole Kleinstreuer and ICCVAM Member Elijah Petersen (National Institute of Standards and Technology) are serving on the committee.

The panel’s next public workshop will be held on Thursday, May 12.

EURL ECVAM issues status report on alternatives

The European Union Joint Research Centre for Alternatives to Animal Testing (EURL ECVAM) has issued its 2021 “Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches.” An April 7 news article announced availability of the report. EURL ECVAM is a partner organization in the International Cooperation on Alternative Test Methods along with ICCVAM and other international validation organizations.

The report describes research, development, and validation activities, as well as initiatives that promote the regulatory and international adoption and use of alternative approaches and their dissemination. Activities described in the report include:

  • Development of NAMs to identify chemicals with potential endocrine activity.
  • Exploration of approaches to replace, reduce, or refine animal use for batch testing of vaccines.
  • Evaluation of methods to identify potential genotoxins and sensitizers.

EURL ECVAM, which is part of the European Commission's Joint Research Centre, coordinates research and validation studies on alternatives to animal testing within the European Union. EURL ECVAM also shares knowledge about and promotes use of alternative methods.

Videos available from ICE training sessions

Videos are now available from a recent training session on the Integrated Chemical Environment (ICE). The training was organized by the Physicians Committee for Responsible Medicine, and the videos are available on their website.

Attendees at this two-day event learned directly from NICEATM developers how to use ICE tools for data and assay exploration. ICE is a free online suite that houses curated toxicity and physicochemical property data and a variety of tools to analyze and visualize chemical data. These tools provide access to data adhering to FAIR principles-—Findable, Accessible, Interoperable, and Reusable—for analyses including in vitro to in vivo extrapolation and physiologically based pharmacokinetic modeling.

Recent publications

  • A paper in Frontiers in Toxicology describes a collaborative exercise to evaluate how application of standardized phenotype terminology improves data consistency. The exercise suggested that utilizing a common data standard not only reduces the heterogeneity of reported terms but increases agreement and repeatability among different laboratories. The project was part of the NTP Systematic Evaluation of the Application of Zebrafish in Toxicology program; NICEATM scientist Jon Hamm (Inotiv, contractor supporting NICEATM) is senior author.
    Thessen et al. 2022. Implementation of zebrafish ontologies for toxicology screening. Front Toxicol. https://doi.org/10.3389/ftox.2022.817999.
  • A paper coauthored by Acting NICEATM Director Nicole Kleinstreuer examines how parameterization of in vitro to in vivo extrapolation models affects the outputs of those models for predicting thyroid bioactivity. The paper also proposes a range of potentially thyroid-relevant doses that incorporate uncertainty in modeling choices and in vitro assay data.
    Carlson et al. 2022. Impact of high-throughput model parameterization and data uncertainty on thyroid-based toxicological estimates for pesticide chemicals. Environ Sci Tehcnol. https://doi.org/10.1021/acs.est.1c07143.
  • A paper in Frontiers in Pharmacology describes applications of tools provided in ICE for pharmacokinetic modeling and in vitro to in vivo extrapolation. The paper highlights recent improvements to these tools and discusses their potential to facilitate broader application and acceptance of these techniques.
    Hines et al. 2022. Application of an accessible interface for pharmacokinetic modeling and in vitro to in vivo extrapolation. Front Pharmacol. https://doi.org/10.3389/fphar.2022.864742.

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The Update Newsletter is produced by NTP Office of Policy, Review, and Outreach. The text is not copyrighted and can be reprinted without permission. If you use parts of the Update Newsletter in your publication, we ask that you provide us with a copy for our records. We welcome your comments and suggestions.

Director of Office of Policy, Review, and Outreach and Editor-in-Chief: Mary Wolfe | Managing Editor: Anna Lee Mosley