FACTS, MYTHS, AND REFLECTIONS ON THE USE OF MAXIMUM TOLERATED DOSE INCHEMICAL CARCINOGENESIS (REVIEW)

The introduction and the subsequent use of maximum tolerated dose (MTD ) or, more correctly, the estimated maximum tolerated dose (EMTD) in c hemical carcinogenesis is reviewed. A historical perspective followed by the chronological development of the concept is described and comme nted on. The justifications and the criticisms of the EMTD are outline d and rebuttals of the criticisms are presented. The extrapolation of estimated risk from animal bioassay to humans is given and the notion of the ideal experiment is elaborated upon briefly. It is concluded th at the EMTD is a necessary, crucial method in determining the carcinog enic activity of chemical substances and natural products until a bett er replacement is found.