Cancer bioassays maximum tolerated dose

Carr, C.J. Kolbye, A.C. A critique of the use of the maximum tolerated dose in bioassays to assess cancer risks from chemicals. Reg. Toxicol. Pharmacol. 1991,14, 78-87. 

The use in animal cancer bioassays of the estimated maximum tolerated dose, MTD, is perhaps the one issue that provokes the most heated scientific debates, as well as the greatest public skepticism about the meaning of animal data. First, what is the MTD Second, why is its use problematic ... 

There has been continuing controversy about the use of the maximum tolerated dose as the highest dose in chronic/cancer bioassays. Essentially, many consider that observation of cancer under conditions that are often unique to the experimental conditions provides little relevant information even in the context of hazard identification for hnmans, which are exposed to much lower doses (often six orders of magnitnde). 

Studies used to determine whether a chemical is carcinogenic, the so-called cancer bioassay, are conducted in separate life-long studies. Toxicology data collected in the above trials are used to determine the maximum tolerated dose (MTD) of a compound. This dose, and one-half the MTD, are then given... 

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