Cancer bioassays interpretation

It seems likely that a high proportion of all chemicals, whether synthetic or natural, would be carcinogens if administered in the standard rodent bioassay at the MTD, primarily because of the effects of high doses on cell death and division and DNA damage and repair.6 Without additional data about how a chemical causes cancer, the interpretation of a positive result in a rodent bioassay is highly uncertain. The induction of cancer could be the result of the high doses tested and have no predictive value about what might occur at lower doses. 

Application of this 1/100 safety factor to the NOAEL (1 ng/kg/day or 1000 pg/kg/day) defined in the lifetime rat study (30) that is considered most definitive by essentially all of the regulatory agencies was the basis for the Ontario MOE expert panel to recommend a Maximum Daily Intake for 2,3,7,8-TCDD (or its toxic equivalent of other chlorinated dioxins and furans) of 10 pg/kg B.W./day for humans (38). This more recent approach used by these four non-U.S. groups demonstrate the manner in which carcinogenicits based lifetime exposure control limit recommendations for humans can be realistically derived from the data available from the animal cancer bioassays when interpreted in concert with the data available regarding the likely mechanism of action by which the carcinogenic response occurred in the animal bioassays. 

Gart JJ, Chu KC, Tarone RE (1979) Statistical issues in interpretation of chronic bioassay tests for carcinogenicity. J Natl Cancer Inst 62 957-974... 

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