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National Toxicology Program

National Toxicology Program

UPDATE NewsletterUPDATE NewsletterJune 2020

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

By Catherine Sprankle

Leadership a key theme in ICCVAM public forum

At the May 21 public forum hosted by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), representatives of ICCVAM member agencies described work both to advance new approaches to safety testing of chemicals and medical products and to reduce the amount of testing required. Commenters at the forum commended the agencies’ progress and noted the importance of federal agencies taking leadership roles in reducing animal testing.

The annual public forum, usually an in-person event, was presented this year as a webinar that was attended by over 400 viewers. The event was organized by NICEATM, which provides support for ICCVAM.

In addition to government agencies, viewers represented pharmaceutical and chemical companies, animal welfare organizations, and test method developers. Presentations at the meeting included:

  • A presentation by DNTP scientist Mamta Behl focusing on organophosphorus flame retardants as a case study of how new approach methodologies could be used in hazard characterization and prioritization of developmental neurotoxins.
  • Presentations by representatives of three offices of the U.S. Environmental Protection Agency (EPA) describing research initiatives to develop new methods and regulatory initiatives to reduce requirements for animal testing. These activities address a directive issued last year by their administrator setting goals for reduction of animal testing.
  • A presentation by Suzanne Fitzpatrick, principal ICCVAM representative from the U.S. Food and Drug Administration (FDA), which stressed the involvement of high-level staff in efforts to connect with stakeholders and drive alternative methods development.
  • Updates from other agencies, including the U.S. Deparment of Agriculture, U.S. Department of Defense, Occupational Safety and Health Administration, National Center for Advancing Translational Sciences, and National Institute of Standards and Technology.

Presentations and a video recording of the public forum will be available later this month on the NTP website.

EPA requests public comment on draft risk assessment for antimicrobial chemicals

In a May 14 Federal Register notice, EPA requested comment on draft human health and ecological risk assessments for registration review of a group of antimicrobial chemicals known as isothiazolinones. EPA specifically requested comment on the use of an in vitro and artificial neural network-based defined approach to determine points of departure used in the isothiazolinone draft risk assessments instead of using laboratory animal data to evaluate risks for dermal sensitization. Comments are due by July 13; the Federal Register notice includes instructions on how to submit comments.

The draft risk assessments rely heavily on work done by NTP, NICEATM, and ICCVAM. The in vitro testing was conducted by the NTP Toxicology Branch. NICEATM analyzed the in vitro data and ran the artificial neural network-based defined approach to provide quantitative potency predictions used to determine points of departure. The ICCVAM Skin Sensitization Expert Group reviewed the NTP testing report and the NICEATM analyses before data were provided to EPA for development of the risk assessments. The use of in vitro and in chemico assays and neural network-based defined approaches is the first use of such information in regulatory risk assessment.

EURL ECVAM recommends use of nonanimal-derived antibodies

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) has recommended that end-users and other stakeholders recognize the scientific validity of nonanimal-derived antibodies and stop using animals for antibody development and production. The recommendation is based on the opinion of EURL ECVAM’s scientific advisory committee. It states that animals should no longer be used for the development and production of antibodies for research, regulatory, diagnostic and therapeutic applications. It also challenges misconceptions about nonanimal-derived antibodies and highlights the scientific and economic benefits of their use. The report containing the recommendation is available on the European Joint Research Centre website; a news release summarizing the report’s recommendations is also available on the website.

Use of nonanimal-derived antibodies was the topic of the 2020 ICCVAM Communities of Practice webinar, presented in January. One of the webinar presenters, Rebecca Clewell, served on the scientific advisory committee on whose opinion the EURL ECVAM recommendation was based. EURL ECVAM and ICCVAM are both members of the International Cooperation on Alternative Test Methods.

Recent publications

  • A paper coauthored by Paul Brown, ICCVAM representative from the FDA Center for Drug Evaluation and Research, discusses the center’s view on the opportunities and challenges of using new approach methodologies in drug development, especially for regulatory purposes.

Avila et al. 2020. An FDA/CDER perspective on nonclinical testing strategies: Classical toxicology approaches and new approach methodologies (NAMs). Regulatory Toxicology and Pharmacology. https://doi.org/10.1016/j.yrtph.2020.104662.

  • NICEATM Acting Director Nicole Kleinstreuer, ICCVAM FDA Principal Representative Suzanne Fitzpatrick, and ICCVAM Read Across Workgroup Chair Grace Patlewicz co-authored a report from a workshop that considered read-across as a new approach methodology for regulatory toxicology. The report concludes that read-across is potentially a major tool for risk assessment.

Rovida et al. Internationalization of read-across as a validation new approach method (NAM) for regulatory toxicology. ALTEX. https://doi.org/10.14573/altex.1912181.

  • A paper in the journal Nucleic Acids Research describes InterPred, an online tool that combines 17 quantitative structure activity relationship models to allow users to predict the probability that a new chemical will interfere with different combinations of cellular and technology conditions used in high-throughput screening applications. The paper was coauthored by Kleinstreuer and computational chemist Kamel Mansouri (ILS, contractor supporting NICEATM).

Borrel et al. 2020. InterPred: a webtool to predict chemical autofluorescence and luminescence interference. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa378.

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The Update Newsletter is produced by NTP Office of Liaison, Policy, and Review. 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 Liaison, Policy, and Review and Editor-in-Chief: Mary Wolfe | Managing Editor: Anna Lee Mosley