A simple method for quantitative risk assessment of non-threshold carcinogens based on the dose descriptor T25

This report provides guidance for using the dose-descriptor T25 from animal studies as a basis for quantitative risk characterisation of non-threshold carcinogens. T25 is presently used within the European Union for setting specific concentration limits for carcinogens in relation to labelling of preparations (formulations). The T25 is defined as the chronic dose rate which will give 25% of the animals tumours at a specific tissue site, after correction for spontaneous incidence, within the standard life-time of that species. The T25 is converted to the corresponding human dose descriptor, HT25, by dividing it with the appropriate scaling factor for interspecies dose scaling based on comparative metabolic rates. Subsequently, the human dose (expressed in mg per kg body-weight per day) is calculated from the available exposure data. The corresponding human life-time cancer risk is then obtained by using linear extrapolation by dividing the exposure dose with the coefficient (HT25/0.25). The results with this new method, which can easily be calculated without computer programmes, are in excellent agreement with results from computer-based extrapolation methods such as the linearised multistage model and the benchmark method using LED10, even though the present method only takes into consideration one single dose-response point. To overcome possible shortcomings of the present method, the estimated life-time risks are proposed to be accompanied by a commentary statement giving an overall evaluation of data that may have bearing on the carcinogenic risk and that may indicate whether the real human risk is likely to be higher or lower than the calculated life-time risk. By using the present guidance and a harmonized set of criteria and default values, the calculation of life-time cancer risk should be transparent and easy to comprehend.