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 s pecific concentration limits for carcinogens in relation to labelling of pr eparations (formulations). The T25 is defined as the chronic dose rate whic h will give 25% of the animals tumours at a specific tissue site, after cor rection for spontaneous incidence, within the standard life-time of that sp ecies. The T25 is converted to the corresponding human dose descriptor, HT2 5, 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 availa ble exposure data. The corresponding human life-time cancer risk is then ob tained by using linear extrapolation by dividing the exposure dose with the coefficient (HT25/0.25). The results with this new method, which can easil y be calculated without computer programmes, are in excellent agreement wit h results from computer-based extrapolation methods such as the linearised multistage model and the benchmark method using LED10, even though the pres ent method only takes into consideration one single dose-response point. To overcome possible shortcomings of the present method, the estimated life-t ime risks are proposed to be accompanied by a commentary statement giving a n 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 o r lower than the calculated life-time risk. By using the present guidance a nd a harmonized set of criteria and default values, the calculation of life -time cancer risk should be transparent and easy to comprehend.