The committee considered several options relative to the use of the MTD as the highest dose for use in carcinogenicity screening studies. These options were initially proposed by the participants in the MTD workshop organized by the committee in consultation with the federal liaison group. The first option would retain the status quo, with the possible addition of lower doses in addition to the MTD. The second option would use a high dose that is an arbitrary fraction of the EMTD. The third option would redefine the MTD, basing it on studies of the dose dependence of physiologic effects expected to alter carcinogenic response. The fourth option would use MTD testing as part of an overall testing strategy that separates carcinogens from noncarcinogens and provides information useful for determining human relevance; this could take one of two forms—a two-track system that comprises full testing and limited testing and a system of sequential studies. These options are presented below and are followed by discussions of their advantages and disadvantages.
Continue carcinogenicity screening studies with the MTD as the highest dose according to current practice (with the inclusion of lower doses as well).