Interpretation And Extrapolation Of Reproductive Data To Establish Human Safety Standards (current Issues In Toxicology)

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. This monograph focuses on extrapolating data from animal reproduction studies to assess exposure levels acceptable for human reproduction which are consistent with the maintenance of public health. The interpretation and extrapolation of animal data for predicting human health effects from reproductive toxicants is a complex process with many uncertainties. This document attempts to outline some of the factors involved in the process, taking into account biological responses relevant to the test compound in experimental animals and humans. The guidelines for reproductive toxicity tests in different countries are summarized and a proposal for international harmonization is presented. The strengths and limitations of the test systems employed are also discussed. The monograph is intended for individuals interested or involved in safety assessment of chemicals. Front Matter....Pages i-xii Introduction....Pages 1-4 Terminology and Definitions....Pages 5-7 Teratogenicity (Embryotoxicity) Studies: Design, Conduct, and Evaluation....Pages 9-20 Multigeneration Studies....Pages 21-40 Behavioral-Functional Teratology....Pages 41-58 In Vitro Developmental Toxicity Assays....Pages 59-68 Statistical Methods for Developmental Toxicity Studies....Pages 69-80 Epidemiology....Pages 81-90 Extrapolation of Reproductive Risks From Animal and Human Data....Pages 91-113 Guidelines for Reproductive Toxicity Tests in Different Countries With a Proposal for International Harmonization....Pages 115-133