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

 

 



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