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Redbook 2000
July 2007
III. Recommended Toxicity Studies
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.
This chapter provides a general description of how FDA determines which toxicological studies are recommended in order for FDA to evaluate the safety of food ingredients (i.e., direct food additives, color additives used in food, food contact substances, previously referred to as indirect food additives, etc.). A determination that a reasonable certainty of no harm will result from the proposed use(s) of food ingredients is required before manufacturers and distributors can market them in the United States (see sections 70.3 and 170.3 of Title 21 of Code of Federal Regulations). The determination of reasonable certainty of no harm is contingent upon the results of toxicological studies, exposure information, and other types of information submitted in petitions and notifications. Details related to the evaluation of toxicological information is provided in Chapter II of Redbook. Safety data submitted for evaluation of Generally Recognized As Safe (GRAS) substances and bioengineered foods may result from specialized tests which are not represented in Redbook. In certain cases, the classical toxicological studies presented in Redbook may be recommended and useful in the evaluation of these substances. The reader is directed to more specific guidance for each type of submission as follows:
Food and Color Additives Program
- Questions and Answers about the Petition Process
- Guidance for Industry: Summary Table of Recommended Toxicological Testing for Additives Used in Food
- Estimating Exposure to Direct Food Additives
- Concern Levels and Recommended Toxicity Tests for Direct Food Additives and Color Additives Used in Food ("draft" 1993 Redbook II)
Food Contact Substance Notification Program
- Guidance for Industry: Preparation of Food Contact Notifications for Food Contact Substances: Toxicology Recommendations
- Guidance for Industry: Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact Substances: Chemistry Recommendations
- Guidance for Industry: Preparation of Food Contact Notifications: Administrative
GRAS Notification Program and Biotechnology
- Frequently Asked Questions About GRAS
- How to Submit a GRAS Notice
- Biotechnology
- List of Completed Consultations on Bioengineered Foods
Generally speaking, the determination of the types of toxicological studies that should be submitted as part of a petition or notification for a food ingredient is based on information about the compound of interest as well as the exposure to the compound via its proposed use(s). Information about the compound includes the toxicological effects on various biological systems (i.e., nature of effect, target, magnitude of response per unit dose, etc.) which may be derived from toxicological studies which have been conducted with this compound. Toxicological information on a similar compound or knowledge about compounds with a similar chemical structure or substructure may be helpful in instances where toxicological information on the compound of interest is limited.
Detailed guidance for specific toxicity studies are not included in this chapter. Guidance for the conduct of short-term studies for genetic toxicity, short-term toxicity studies with rodents and non-rodents, subchronic toxicity studies with rodents and non-rodents, chronic toxicity studies with rodents and non-rodents, carcinogenicity studies with rodents, combined chronic toxicity/carcinogenicity studies or chronic toxicity studies with rodents, in-utero exposure phase for addition to carcinogenicity studies or chronic toxicity studies with rodents, neurotoxicity, and reproduction and developmental toxicity studies, can be found in Chapter IV. C. of Redbook 2000. Guidance to assist the petitioner and notifier in developing strategies for assessing the metabolism and pharmacokinetics and immunotoxicity can be found in Chapter V of the "draft" 1993 Redbook II.
It is important to note that as data from the recommended set of toxicity studies are obtained, the results may be used to refine or adjust the type, sensitivity, and rigor of subsequent studies needed to evaluate the potential toxicological effects of the compound.