The Selection of Doses in Chronic Toxicity/Carcinogenicity Studies Age-Associated (Geriatric) Pathology: Its Impact on Long-Term Toxicity Studies

The International Life Sciences Institute (ILSI) is a scientific foundation which addresses critical health and safety issues of national and international concern. ILSI promotes international cooperation by providing the mechanism for sci­ entists from government, industry and universities to work together on co­ operative programs to generate and disseminate scientific data. The members and trustees of the Institute believe that questions regarding health and safety are best resolved when scientists can examine and discuss issues, as an in­ dependent 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 refinement of methods and systems to evalute the safety of chemicals have evolved in a rapid and largely unplanned fashion. Attempts to improve the system have largely 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. In response to these difficulties, ILSI has assembled highly qualified and renowned scientists from research institutes, universities, government and in­ dustry, with relevant scientific knowledge and expertise regarding the issues that complicate risk assessment procedures.

The Selection of Doses in Chronic Toxicity/Carcinogenicity Studies.- I. Introduction.- II. Factors Relating to the Dose Selection.- III. Principles for Dose Selection.- IV. Evaluation and Interpretation of Experimental Findings.- V. Recommendations for Future Research on Dose Selection.- VI. Summary.- VII. Glossary of Terms — As They Pertain to Toxicology.- VIII. References.- Age-Associated (Geriatric) Pathology: Its Impact on Long-Term Toxicity Studies.- I. Introduction.- II. Types of Long-Term Tests.- III. Factors Related to the Aging Process that Influence the Design and Conduct of Long-Term Rodent Studies.- IV. Age-Associated Diseases: How They Complicate Long-Term Toxicity Studies.- V. Effect of Aging on Drug Metabolism.- VI. Duration of Long-Term Studies.- VII. Cost of Conducting Toxicity Studies with Durations of 18, 24, or 30 Months.- VIII. Conclusions.- IX. Areas in Need of Future Research.- X. Summary.- XI. References.