Response Relationships in Carcinogenesis and Mechanisms of Carcinogenic Action

Dose—Response Relationships in Carcinogenesis and Mechanisms of Carcinogenic Action 

Risk assessment frequently involves estimating safe exposure concentrations for exposure durations that were not tested experimentally. Generally applicable biologically based models have to be applied. Before developing such a model, extensive data are needed to build its form as well as to estimate how well it conforms to the observed data to support confidence in results. 

The first benchmark study of dose-response relationships in chemical carcinogenesis was reported by Druckrey (1943) with 4-dimethylaminoazobenzene (4-DAB), also known as butter yellow, in BDIII rats. Within the range of daily dosages from 3 to 30 mg per rat, the time up to the appearance of liver cancer (T) was found to be inversely proportional to the daily dose d). The product of the 

Daily Dose, d (mg/rat) Median Tumor Induction Time, t (days) Total Dose, D (mg/rat) 

Assuming a linear relationship between the daily dosage (d) and the 4-DAB concentration (c) at the site of carcinogenic action, Eq. (3.1) would read as 

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