National Academies Press: OpenBook

Infant Formula: Evaluating the Safety of New Ingredients (2004)

Chapter: C Redbook Table of Contents

« Previous: B Composition of Infant Formulas and Human Milk for Feeding Term Infants in the United States
Suggested Citation:"C Redbook Table of Contents." Institute of Medicine. 2004. Infant Formula: Evaluating the Safety of New Ingredients. Washington, DC: The National Academies Press. doi: 10.17226/10935.
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C
Redbook Table of Contents

Chapter I.

 

Introduction

 

 

   

A. Major Changes in the Revised Guidelines

 

 

   

1. Introduction

 

 

   

2. Changes in Determining Concern Levels and Recommended Toxicity Studies for Food Ingredients

 

 

   

3. Changes in Toxicity Testing Guidelines

 

 

   

4. Other Changes

 

 

   

B. Flexibility and Consistency in Guidelines for Toxicity Testing

 

 

   

C. Applicability of These Guidelines to the Safety Evaluation of all Food Ingredients

 

 

Chapter II.

 

Agency Review of Toxicology Information Submitted in Support of the Safety of Food Ingredients

 

 

   

A. Introduction

 

 

   

B. Expediting Review of Toxicology Information

 

 

   

C. Evaluating Toxicology Information

 

 

Chapter III.

 

Concern Levels and Recommended Toxicity Studies

 

 

   

A. Introduction

 

 

   

B. Concern Concentration Levels

 

 

   

C. Recommended Toxicity Tests

 

 

Chapter IV.

 

Guidelines for Preclinical Toxicity Studies

 

 

   

A. Introduction

 

 

   

B. General Recommendations for Toxicity Studies

 

 

   

1. General Guidelines for Designing and Conducting Toxicity Studies

 

 

   

2. Guidelines for Reporting Results of Toxicity Studies

 

 

   

3. Pathology Considerations in Toxicity Studies

 

 

Suggested Citation:"C Redbook Table of Contents." Institute of Medicine. 2004. Infant Formula: Evaluating the Safety of New Ingredients. Washington, DC: The National Academies Press. doi: 10.17226/10935.
×
   

4. Statistical Considerations in Toxicity Studies

 

 

   

5. Diets for Toxicity Studies

 

 

   

a. Types of Diets

 

 

   

i. Natural Ingredient Diets

 

 

   

ii. Purified Diets

 

 

   

b. Issues to Consider when Selecting Diets for Animals in Toxicity Studies

 

 

C.

 

Guidelines for Specific Toxicity Studies

 

 

   

1. Short-Term Tests for Genetic Toxicity

 

 

   

a. Bacterial Reverse Mutation Test

 

 

   

b. In Vitro Mammalian Chromosome Aberration Test

 

 

   

c. In Vitro Mouse Lymphoma TK+/– Gene Mutation Assay

 

 

   

d. In vivo Mammalian Erythrocyte Micronucleus Test

 

 

   

2. Acute Oral Toxicity Tests

 

 

   

3. Short-Term Toxicity Tests with Rodents and Non-Rodents

 

 

   

a. Short-Term Toxicity Studies with Rodents

 

 

   

b. Short-Term Toxicity Studies with Non-Rodents

 

 

   

4. Subchronic Toxicity Tests with Rodents and Non-Rodents

 

 

   

a. Subchronic Toxicity Studies with Rodents

 

 

   

b. Subchronic Toxicity Studies with Non-Rodents

 

 

   

5. One-Year Long-Term Toxicity Tests with Non-Rodents

 

 

   

6. Carcinogenicity Studies with Rodents

 

 

   

7. Combined Chronic Toxicity/Carcinogenicity Studies with Rodents

 

 

   

8. In Utero Exposure Phase for Addition to Carcinogenicity Studies with Rodents

 

 

   

9. Reproduction and Developmental Toxicity Studies

 

 

   

a. Guidelines for Reproduction Studies

 

 

   

b. Guidelines for Developmental Toxicity Studies

 

 

   

10. Neurotoxicity Studies

 

 

Chapter V.

 

Additional Recommended Studies

 

 

   

A. Introduction

 

 

   

B. Metabolism and Pharmacokinetic Studies

 

 

   

1. Recommended Metabolism and Pharmacokinetic Studies

 

 

   

2. Considerations in the Design of Pharmacokinetic Studies

 

 

   

a. Test Substance

 

 

   

b. Animals

 

 

   

c. Route of Administration

 

 

   

d. Dosage Regimen

 

 

   

e. Sampling

 

 

   

f. In Vitro Studies: Dose Response, Mechanism

 

 

   

g. Analysis of Data

 

 

   

h. Pregnancy/Lactation/Reproductive Studies

 

 

   

3. Analysis and Use of Data from Pharmacokinetic Studies

 

 

   

a. Data Reporting and Parameter Estimation

 

 

   

b. Pharmacokinetic Models: Data Interpretation and Predicting Effects

 

 

   

4. Use of Pharmacokinetic Results for Study Design and Risk Assessment

 

 

   

a. Design of Toxicity Studies

 

 

   

b. Setting Dose Levels

 

 

   

c. Determining Mechanisms of Toxicity

 

 

Suggested Citation:"C Redbook Table of Contents." Institute of Medicine. 2004. Infant Formula: Evaluating the Safety of New Ingredients. Washington, DC: The National Academies Press. doi: 10.17226/10935.
×
   

d. Improving the Risk Assessment Process/Safety Assessment

 

 

   

5. References

 

 

   

C. Immunotoxicity Studies

 

 

   

1. Immunity: A Brief Review

 

 

   

2. Key Concepts in Immunotoxicity Testing

 

 

   

3. Indicators of Possible Immune Toxicity

 

 

   

4. Expanded Type 1 Immunotoxicity Tests

 

 

   

5. Type 2 Immunotoxicity Tests

 

 

   

6. Relevance of Primary Indicators of Immune Toxicity to Health

 

 

   

7. Adequacy and Reliability of Primary Indicators of Immune Toxicity

 

 

   

8. Recommendations for Further Immunotoxicity Testing when Primary Indicators are Positive

 

 

   

9. Animal Models for Immunotoxicity Tests

 

 

   

10. Recommended Strategy for Assessing the Immunotoxic Potential of Food Ingredients

 

 

   

11. Conclusion

 

 

Chapter VI.

 

Human Studies

 

 

   

A. Clinical Evaluation of Food Ingredients

 

 

   

1. General Considerations for Clinical Studies of Food Ingredients

 

 

   

2. Specific Considerations for Clinical Studies of Food Ingredients

 

 

   

3. Sequence of Clinical Studies for Food Ingredients

 

 

   

4. Submitting Reports of Clinical Studies on Food Ingredients

 

 

   

5. Appendix A—Principles of Institutional Review and Informed Consent

 

 

   

B. Epidemiology Studies

 

 

Chapter VII.

 

Emerging Issues

 

 

   

A. Introduction

 

 

   

B. Macro-Additives

 

 

   

C. Safety of Food Ingredients Developed by Biotechnology

 

 

   

D. Enzymes

 

 

   

E. Microbially Derived Food Ingredients

 

 

   

F. Advances in the Development of Alternatives to Toxicity Testing

 

 

   

G. Heritable and Somatic Genetic Toxicity

 

 

Chapter VIII.

 

Glossary: Acronyms and Definitions

 

 

NOTE: Food ingredients include: direct food additives, color additives used in food, Generally Recognized as Safe substances, food contact substances, and constituents or impurities of any of the above. Bolded text denotes a section that has been finalized and is found only online in the Redbook 2000 (OFAS, 2003); the other information is found only in Redbook II-Draft (OFAS, 2001).

REFERENCES

OFAS (Office of Food Additive Safety). 2001. Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food. Redbook II-Draft. Washington, DC: OFAS, Center for Food Safety and Applied Nutrition, Food and Drug Administration.

OFAS. 2003. Redbook 2000. Toxicological Principles for the Safety of Food Ingredients. Online. Center for Food Safety and Applied Nutrition, Food and Drug Administration. Available at http://www.cfsan.fda.gov/~redbook/red-toca.html. Accessed November 19, 2003.

Suggested Citation:"C Redbook Table of Contents." Institute of Medicine. 2004. Infant Formula: Evaluating the Safety of New Ingredients. Washington, DC: The National Academies Press. doi: 10.17226/10935.
×
Page 183
Suggested Citation:"C Redbook Table of Contents." Institute of Medicine. 2004. Infant Formula: Evaluating the Safety of New Ingredients. Washington, DC: The National Academies Press. doi: 10.17226/10935.
×
Page 184
Suggested Citation:"C Redbook Table of Contents." Institute of Medicine. 2004. Infant Formula: Evaluating the Safety of New Ingredients. Washington, DC: The National Academies Press. doi: 10.17226/10935.
×
Page 185
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Infant formulas are unique because they are the only source of nutrition for many infants during the first 4 to 6 months of life. They are critical to infant health since they must safely support growth and development during a period when the consequences on inadequate nutrition are most severe. Existing guidelines and regulations for evaluating the safety of conventional food ingredients (e.g., vitamins and minerals) added to infant formulas have worked well in the past; however they are not sufficient to address the diversity of potential new ingredients proposed by manufacturers to develop formulas that mimic the perceived and potential benefits of human milk. This book, prepared at the request of the Food and Drug Administration (FDA) and Health Canada, addresses the regulatory and research issues that are critical in assessing the safety of the addition of new ingredients to infants.

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