CHARACTERIZING DOSE-RESPONSE I - CRITICAL-ASSESSMENT OF THE BENCHMARKDOSE CONCEPT

We present a critical assessment of the benchmark dose (BMD) method in troduced by Crump((1)) as an alternative method for setting a characte ristic dose level for toxicant risk assessment. The no-observed-advers e-effect-level (NOAEL) method has been criticized because it does not use all of the data and because the characteristic dose level obtained depends on the dose levels and the statistical precision (sample size s) of the study design. Defining the BMD in terms of a confidence boun d on a point estimate results in a characteristic dose that also varie s with the statistical precision and still depends on the study dose l evels.((2)), Indiscriminate choice of benchmark response level may res ult in a BMD that reflects little about the dose-response behavior ava ilable from using all of the data. Another concern is that the definit ion of the BMD for the quantal response case is different for the cont inuous response case. Specifically, defining the BMD for continuous da ta using a ratio of increased effect divided by the background respons e results in an arbitrary dependence on the natural background for the endpoint being studied, making comparison among endpoints less meanin gful and standards more arbitrary. We define a modified benchmark dose as a point estimate using the ratio of increased effect divided by th e full adverse response range which enables consistent placement of th e benchmark response level and provides a BMD with a more consistent r elationship to the dose-response curve shape.