This issue of the BELLE Newsletter invited six experts to independently address three critical questions of public health and regulatory importance. The questions posed are:

1. Does the understanding of the mechanisms of toxicity affect how agencies such as the U.S. EPA assess risks from exposure to toxic substances?

2. Does an understanding of the mechanisms by which the body adapts (e.g., detoxifies, repairs, etc.) to the effects of exposures to toxic substances affect how agencies such as the U.S. EPA assess risks from exposures to toxic substances?

3. If low doses of toxic agents induce apparently beneficial responses (e.g., enhanced longevity, lower incidence of disease), how does and/or could agencies such as U.S. EPA address this?

These initial questions were posed at an earlier BELLE Conference to representatives of six U.S. federal agencies (EPA, ATSDR, FDA, NRC, DOE, CPCS) having responsibilities with toxic substances. Their responses were published as part of a monograph from that conference (Environmental Health Perspectives, 106(Suppl.1):273-394, 1998. Numerous comments were received indicating that it would be of considerable interest to invite a broader range of scientists, especially those outside of the federal government, to render their views on the same three questions. Consequently, the six experts contributing to this issue are drawn from academia, industry, consulting, and state government. After the responses were received Professor James E. Klaunig of the Indiana University School of Medicine, provided a summary of the invited expert commentaries. His summary is provided at the end of the invited commentaries.