Benchmarks derived from quantitative endpoints - an approach accounting for litter effects

The use of quantitative variables for risk assessment suffers from the lack of a clear-cut definition of risk. The proposals of Chen and Gaylor (1992) and of Kodell and West (1993) showed a way out of this dilemma. Additional risk is defined as the increase in probability of being in an abnormal state for an exposed individual. In this paper we show how this approach can be generalized to situations where an additional source of variability, often called litter effect, is present. This occurs often in studies on teratogenicity. The coverage of confidence bounds on the additional risk is shown to be sufficient using a small simulation study.