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Jeffery A. Foran and the ILSI Risk Science Working Group on Dose Selection

ILSI Risk Science Institute, Washington, D.C. 20036 USA

Abstract

Dose selection in chronic rodent bioassays has been one of the most debated issues in risk assessment. The Committee on Risk Assessment Methods of the National Research Council attempted, but failed, in 1993 to reach consensus on how to select doses for chronic rodent bioassays. However, a more recent effort conducted by the ILSI Risk Science Institute has resulted in a consensus set of principles for dose selection, including selection of the highest dose for chronic rodent bioassays. The principles encourage a move away from sole reliance on a maximum tolerated dose (MTD) , as it has been traditionally defined (primarily by body weight and histopathology) , and toward the use of sound scientific and toxicologic principles for the selection of all doses in the chronic bioassay. Specifically, the principles recommend that dose selection for chronic studies must be based on sound toxicologic principles ; dose selection should consider human exposure ; dose selection should be based on a variety of endpoints and effects derived from prechronic studies ; and dose selection should consider physicochemical and other factors. Implementation of the principles internationally will have two important benefits: improvement in the quality and consistency of the rodent bioassay and international harmonization of dose selection procedures. Key words: chronic rodent bioassays, dose selection, principles. Environ Health Perspect 105:18-20 (1997)

Address correspondence to J.A. Foran, ILSI Risk Science Institute, 1126 16th. St., NW, Washington, D.C. 20036 USA.

The principles for dose selection are a distillation of 3 years of work by many people, most prominently the members of the ILSI Risk Science Institute working group on dose selection. We thank A. Gasper for providing secretarial support throughout the project, S. Carter and D. Dalisera for administrative support, and G. Scarano for technical support. This project was conducted under a cooperative agreement with the U.S. Environmental Protection Agency, Office of Pesticide Programs. The financial support of the EPA and the American Crop Protection Association is gratefully acknowledged. While the principles represent the consensus of the working group members, they do not necessarily represent the policies, positions, or opinions of their respective agencies and organizations.

Received 9 September 1996 ; accepted 30 October 1996.