Interpretation and Extrapolation of Reproductive Data to Establish Human Safety Standards

I. Introduction.- II. Terminology and Definitions.- References.- III. Teratogenicity (Embryotoxicity) Studies: Design, Conduct, and Evaluation.- 3.1. Introduction.- 3.2. Protocol.- 3.3. Conduct of the Study.- 3.4. Evaluation of Animal Data.- References.- IV. Multigeneration Studies.- 4.1. Introduction.- 4.2. Test Protocols.- 4.3. Test Material.- 4.4. Test Species.- 4.5. Route of Administration.- 4.6. Method of Administration.- 4.7. Dose Levels.- 4.8. Performance of Multigeneration Studies.- 4.9. Evaluation of Animal Data.- References.- V. Behavioral-Functional Teratology.- 5.1. Introduction.- 5.2. Review Articles.- 5.3. Methods Currently in Use or Under Development.- 5.4. Current Status of Testing Procedures and Use.- 5.4.3.1. Food and Drug Administration.- 5.4.3.2. Environmental Protection Agency.- 5.5. Discussion.- References.- VI. In Vitro Developmental Toxicity Assays.- 6.1. Introduction.- 6.2. Assay Systems Using Submammalian Species.- 6.3. Assay Systems Using Mammalian Species.- 6.4. Role of In Vitro Assays for Teratogenicity.- References.- VII. Statistical Methods for Developmental Toxicity Studies.- 7.1. Introduction.- 7.2. Comparison Between Exposed and Unexposed Groups.- 7.3. Dose-Response Models.- 7 4 Summary and Conclusions.- References.- VIII. Epidemiology.- 8.1. Introduction.- 8.2. The Conduct of Epidemiologic Studies on Human Reproduction.- 8.3. Descriptive Studies.- 8.4. Etiologic Studies.- 8.5. Characteristics of an Acceptable Human Reproduction Study.- References.- IX. Extrapolation of Reproductive Risks from Animal and Human Data.- 9.1. Introduction.- 9.2. Classification of Chemicals for In Utero Effects.- 9.3. Methods of Risk Extrapolation.- References.- X. Guidelines for Reproductive Toxicity Tests in Different Countries With a Proposal for International Harmonization.- 10.1. Introduction.- 10.2. Current Guidelines for Reproductive Toxicity Testing.- 10.3. Harmonization of Guidelines.- 10.4. Steps Toward Harmonization.- 10.5. Conclusions.- References.