FDA Releases its Expanded Decision Tree, a New Tool for Toxicity Screening of Chemicals in Food

This release follows hard on the heels of the FDA’s June 18 publication for public comment of a general description of its “Post Market Assessment Prioritization Tool” that we discussed in a previous alert. The EDT modernizes and expands upon the earlier Cramer Decision Tree, first published in 1978.[1] It offers a more refined, systematic, and structure-based approach to classifying chemicals according to their estimated chronic oral toxicity. Prior to its current release, the tool was first evaluated and refined through an external peer-review process. The FDA plans to further refine it over time, based partly on public input. The tool is intended to support both pre-market and post-market safety assessments of food ingredients, food contact substances, and contaminants.

Key Features and Functionality

• Structure-Based Screening: The EDT uses a highly refined set of detailed, structure-based questions to classify chemicals into toxicity categories with greater specificity than the Cramer Decision Tree.

• Data Integration: The tool leverages a comprehensive database that includes toxicological, metabolic, and chemical data from a wide range of sources, including regulatory agencies and scientific literature.

• Predictive Capability: The EDT is designed to predict both the chronic oral toxicity potential of structurally defined organic chemicals, many of which may have limited or no available safety data, and a safe exposure level known as the Threshold of Toxicological Concern (TTC).

• Automation and Efficiency: While currently a manual process requiring expert input, the FDA is developing an automated version to enable rapid, reproducible screening and to reduce the burden on agency staff.

Regulatory and Industry Implications

• Pre-Market Review: The EDT will assist the FDA in evaluating new food additives and food-contact substances by providing a preliminary estimate of toxicity, helping to identify data gaps and assessing the need for further testing or information.

• Post-Market Surveillance: The tool will be used to prioritize chemicals for post-market review, especially those with limited or outdated safety data, and to inform decisions on whether additional research or regulatory action is warranted.

• Transparency and Consistency: The EDT supports a more transparent and consistent approach to chemical safety evaluation, aligning with international best practices and regulatory expectations.

• Reduction in Animal Testing: By leveraging existing data and predictive modeling, the EDT aims to reduce reliance on animal testing in chemical safety assessments.

• Stakeholder Engagement: The FDA has already engaged a broad spectrum of stakeholders in developing the EDT, and will continue to seek input from industry, scientific experts, and the public to refine the tool and ensure its broad applicability and acceptance.

Limitations and Scope

• The EDT is currently validated only for chronic oral exposure and does not apply to certain substances such as toxic metallic and non-metallic elements, non-hydrolyzable polymers, proteins and large peptides, and nanomaterials.

• The tool does not replace statutory review and approval processes but serves as a supplemental resource to support regulatory decision-making.

Conclusion

The FDA believes that its release of the EDT represents a significant advance in the agency’s ability to efficiently and systematically assess the safety of chemicals in the food supply. For the food industry, the EDT is intended to offer a transparent, science-based framework that can streamline regulatory submissions, support risk management, and enhance consumer safety. The FDA’s ongoing development and planned automation of the EDT, along with opportunities for stakeholder engagement, signal its move towards a more modern, data-driven form of regulatory oversight of food chemical safety.

Our team will continue to monitor developments and provide updates as they become available. Please reach out to your ArentFox Schiff attorney contact or one of the authors with questions.