Interpretation and Extrapolation of Reproductive Data to Establish Human Safety Standards

ISBN-13: 9780387969626 / Angielski / Miękka / 1998 / 133 str.

K. Ed Khera; K. S. Khera; H. C. Grice

Opis

The International Life Sciences Institute ( LSI) is a scientific foundation that addresses critical health and safety issues of national and international con cern. ILSI promotes international cooperation by providing the mechanism for scientists from government, industry, and universities to work together on cooperative programs to generate and disseminate scientific data. The mem bers and trustees of the institute believe that questions regarding health and safety are best resolved when scientists can examine and discuss issues as an independent body separate from the political pressures of individual countries and the economic concerns of individual companies. Frequently, meaningful assessment of the risk of a test substance is hindered by the inherent inconsistencies in the system. The development and refine ment of methods and systems to evaluate the safety of chemicals have evolved in a rapid and largely unplanned fashion. Attempts to improve the system have mainly been directed toward broad general concerns, with little attention being given to specific problems or issues. A failure to resolve these problems has frequently resulted in increased testing costs and complications in the assessment and extrapolation of the results to humans. Publicity surrounding toxicologic issues makes it difficult for governments to deal effectively with these problems. In response to these difficulties, ILSI has assembled highly qualified and renowned scientists from research institutes, universities, government, and industry with relevant scientific knowledge and expertise regarding the issues that complicate risk assessment procedures."

Spis treści

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.- 3.4.1. Statistical Analysis.- 3.4.2. Maternal Toxicity.- 3.4.3. Embryo-Fetal Toxicity.- 3.4.3.1. Aberrations and Malformations.- 3.4.3.2. Mortality and Weight Reduction.- 3.4.3.3. Prioritization of Chemicals for Testing.- 3.4.3.4. Concurrent and Historical Controls.- 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.- 5.3.1. CNS Effects.- 5.3.2. Functional Testing Procedures.- 5.3.2.1. Postnatal Alteration of Gastrointestinal, Reproductive, Renal, Hematologic, and Hepatic Function.- 5.3.2.2. Alteration of Biochemical Endpoints.- 5.3.2.3. Alteration of Renal Functions.- 5.3.2.4. Alteration of Cardiac Functions.- 5.3.2.5. Alteration in Pulmonary Functions.- 5.3.2.6. Reproductive Functional Alteration.- 5.3.2.7. Immunocompetence Alteration.- 5.4. Current Status of Testing Procedures and Use.- 5.4.1. Great Britain.- 5.4.2. Japan.- 5.4.3. United States.- 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.- 6.2.1. Invertebrate Models.- 6.2.2. Nonmammalian Vertebrate Models.- 6.3. Assay Systems Using Mammalian Species.- 6.3.1. Embryo Culture Models.- 6.3.2. Embryo Limb-Bud Organ and Cell Culture Models.- 6.3.3. Embryonic Palatal Cell Models.- 6.3.4. Cultured-Cell Attachment Models.- 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.- 9.2.1. Category A.- 9.2.2. Category B.- 9.2.3. Category C.- 9.2.4. Category D.- 9.2.5. Chemicals of Ill-Defined Category.- 9.3. Methods of Risk Extrapolation.- 9.3.1. No-Effect Level Model and the Safety Factor.- 9.3.2. Mathematical Models.- 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.