Guidance for Industry and Other Stakeholders

Toxicological Principles for the Safety
Assessment of Food Ingredients
Redbook 2000

Additional copies are available from:
Office of Food Additive Safety, HFS-200
Center for Food Safety and Applied Nutrition
Food and Drug Administration
5100 Paint Branch Parkway
College Park, MD 20740
(Tel)301-436-1200
http://www.cfsan.fda.gov/guidance.html

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Food Safety and Applied Nutrition
July 2000; Updated July 2007

Guidance for Industry and Other Stakeholders¹

Toxicological Principles for the Safety
Assessment of Food Ingredients
Redbook 2000

Note to reader: Individual chapters/sections of this internet version of "Redbook" are available as linked documents via the Table of Contents. The date of revision for each chapter and /or chapter section is provided in the Table of Contents and the individual documents. These revisions supersede previous versions of Redbook^2,3.

I. Introduction (July 2007 )

II. Agency Review of Toxicology Information Submitted in Support of the Safety Assessment of Food Ingredients (available in 1993 Draft "Redbook II")

III. Recommended Toxicity Studies (July 2007 )

IV. Guidelines for Toxicity Studies

Introduction (November 2003)
General Recommendations for Toxicity Studies
1. General Guidelines for Designing and Conducting Toxicity Studies (November 2003)
2. Guidelines for Reporting Results of Toxicity Studies (November 2003)
3. Pathology Considerations in Toxicity Studies (July 2000)
4. Statistical Considerations in Toxicity Studies (July 2000)
5. Diets for Toxicity Studies (available in 1993 Draft "Redbook II")
Guidelines for Specific Toxicity Studies
1. Short-Term Tests for Genetic Toxicity (July 2000)
  1. Bacterial Reverse Mutation Test (July 2000)
  2. In vitro Mammalian Chromosomal Aberration Test (November 2003)
  3. In vitro Mouse Lymphoma TK ^+/- Gene Mutation Assay (April 2006)
  4. In vivo Mammalian Erythrocyte Micronucleus Test (July 2000)
2. Acute Oral Toxicity Tests (available in 1993 Draft "Redbook II")
3. Short Term Toxicity Studies
  1. Short-Term Toxicity Studies with Rodents (November 2003)
  2. Short-Term Toxicity Studies with Non-Rodents (November 2003)
4. Subchronic Toxicity Studies
  1. Subchronic Toxicity Studies with Rodents (November 2003)
  2. Subchronic Toxicity Studies with Non-Rodents (November 2003)
5. Chronic Toxicity Studies
  1. Chronic Toxicity Studies with Rodents (July 2007)
  2. One-Year Toxicity Studies with Non-Rodents (November 2003)
6. Carcinogenicity Studies with Rodents (January 2006)
7. Combined Chronic Toxicity/Carcinogenicity Studies with Rodents (July 2007 )
8. In Utero Exposure Phase for Addition to Carcinogenicity Studies with Rodents (July 2007 )
9. Reproduction and Developmental Toxicity Studies
  1. Guidelines for Reproduction Studies (July 2000)
  2. Guidelines for Developmental Toxicity Studies (July 2000)
10. Neurotoxicity Studies (July 2000)

V. Additional Studies (available in 1993 Draft "Redbook II")

Introduction
Metabolism and Pharmacokinetic Studies
Immunotoxicity Studies

VI. Human Studies

Clinical Evaluation of Food Ingredients (available in 1993 Draft "Redbook II")
Epidemiology Studies (October 2001)

VII. Glossary: Acronyms and Definitions (April 2004)

¹This guidance has been prepared by the Office of Food Additive Safety in the Center for Food Safety and Applied Nutrition at the U.S. Food and Drug Administration.

²Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food (also known as Redbook I), U.S. Food and Drug Administration, Bureau of Foods (now CFSAN), 1982. May be purchased from: National Technical Information Services (NTIS), 5285 Port Royal Road, Springfield, VA 22161, Telephone (703) 605-6000, NTIS Order Number PB83-170696.

³Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food 1993 Draft "Redbook II" Table of Contents

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Hypertext updated by dms/dav/cjm/msl/emw July 3, 2007