ICCVAM Biennial Report 2018-2019

The mission of the Tri-Services Toxicology Consortium is to communicate, coordinate, and optimize toxicology needs throughout DoD by providing a central point of contact to DoD toxicology resources. The Consortium currently includes over 200 individuals from 11 organizations within DoD, seven of which have laboratories.

The Consortium convened three meetings during 2018 and 2019. These meetings supported ongoing efforts in improving in silico predictions of molecular targets, understanding of toxicant/microbiome interactions, and development and use of NAMs in phased approaches to toxicity data collection and hazard assessment. Significant recent accomplishments include:

• A DoD instruction that established the Consortium as a technical organization authorized and directed by the Deputy Assistant Secretary of Defense for Environment to participate in technical reviews and evaluation of techniques and methods for toxicology assessments.
• Substance-specific technical reviews concerning chromium, antimony trioxide, di(2-ethylhexyl) phthalate and hexamethylenetramine, trichloroethylene, and PFAS.
• Establishment of DoD technical representation on relevant government and scientific committees.
• Development of a draft DoD Strategic Roadmap to Promote the Use of New Approach Methodologies in Rapid Chemical Hazard Assessment.

In February 2019, FDA announced policies aimed at modernizing the oversight and regulation of dietary supplements. Among the steps FDA is taking to implement these policies include collaboration with industry to support the development of new products, ingredients, and delivery systems while protecting public health and safety. To support this collaboration, FDA, NIEHS, and the non-profit Health and Environmental Sciences Institute signed a memorandum of understanding establishing the Botanical Safety Consortium. The consortium includes over 20 participants from industry, academia, and government to promote scientific advances in evaluating the safety of botanical ingredients and mixtures in dietary supplements. This group will look at novel ways to use cutting-edge toxicology tools, including alternatives to animal testing, to promote the goals of safety and effectiveness.

Under the Office of the Chief Scientist in the Office of the Commissioner, FDA has chartered an Alternative Methods Working Group with representatives from all of FDA. The goals of this work group are to strengthen FDA’s long commitment to promoting the development and use of new technologies and to reduce animal testing, to discuss new alternative in vitro/in silico/in vivo methods across FDA and to interact with federal government partners and other global stakeholders to facilitate discussion and development of draft performance criteria for such assays.

Rodent cancer bioassays are currently required by regulatory authorities for the carcinogenicity assessment of industrial chemicals, agrochemicals, food additives, pharmaceuticals, and environmental pollutants. These studies are expensive and time-consuming and use large numbers of animals. The relevance of these studies to human biology has also been questioned. For this reason, there is increased interest in mechanistic approaches for carcinogenicity assessment that reduce testing on animals and provide information more relevant to protecting human health.

EPA is partnering with agrochemical industry stakeholders, the University of South Florida, and the PETA International Science Consortium Ltd. in the Rethinking Carcinogenicity Assessment for Agrochemicals Project. This project is exploring how requirements for rodent cancer bioassays might be replaced with a weight-of-evidence approach that would consider criteria based on potential triggers and indicators of carcinogenesis. In this project, case studies will be reviewed to determine whether the cancer risk indicated in bioassay results could have been predicted by weight-of-evidence criteria. The goal of the project is to produce a guidance document that will describe a weight-of-evidence framework for carcinogenicity assessment. The project will be described in a Society of Toxicology webinar to be presented in early 2020 and in two abstracts (Papieni; Hilton et al.) accepted for presentation at the Society of Toxicology 2020 annual meeting.

EPA has formed strategic partnerships with organizations in multiple sectors to encourage the use of alternative toxicity testing methods in decision making. These activities will lead to more timely chemical evaluations that may better inform protection of human health and the environment.

• EPA is collaborating with NICEATM and international partners on an analysis of dermal absorption data to assess the feasibility of using data from in vitro studies alone to estimate dermal absorption.
• EPA is collaborating with NICEATM, the PETA International Science Consortium Ltd., and CropLife America member companies to develop an in vitro defined approach for hazard classification of eye irritation potential of agrochemical formulations.
• EPA collaborated with Syngenta to support development of a 3D in vitro inhalation toxicity model to derive a point of departure for inhalation toxicity for the fungicide chlorothalonil.
• EPA is working with Unilever to advance chemical safety for consumer products through case studies focused on five chemicals. The goal of the collaboration is to develop new, more efficient approaches for chemical hazard assessment, including high-throughput transcriptomics. The case studies are using new chemical data, such as data from ToxCast, to evaluate chemicals.
• EPA and Proctor & Gamble are collaborating to advance the use of a new technology developed by EPA researchers that incorporates metabolic competency into HTS assays.
• EPA is collaborating with the Minnesota Department of Health to use alternative approaches to evaluate chemicals in drinking water.
• A retrospective study conducted by EPA and People for the Ethical Treatment of Animals explored the quantitative and qualitative contributions of risk assessment methods using single oral dose and subacute dietary toxicity endpoints to the overall conclusions of acute avian risk.

Details of these and other projects can be found on EPA’s Collaborative Agreements for Computational Toxicology Research webpage.