CALCULATION OF BENCHMARK DOSES FROM TERATOLOGY DATA

The benchmark dose approach has several potential advantages over the no observed adverse effect level (NOAEL) as a basis for risk assessmen t of toxic chemicals, based upon animal toxicity data. The practical u se of the benchmark dose has been evaluated by applying dose-response models to an extensive historical database of teratology bioassays. Do ses corresponding to 1 and 5% increases in incidence of lesions are ca lculated and compared to NOAELs. The statistical accuracy of these est imates was determined by calculating confidence intervals. The lower c onfidence limit on the 5% benchmark dose (LED05) is found to be compar able to the NOAEL for most datasets, and slightly higher on average. B enchmark doses at the 1% level could not be estimated accurately (i.e. , they had wide confidence intervals) for a significant fraction of th e datasets. LED01 values were lower on average than the NOAEL. Based o n these results, it is concluded that benchmark doses for a 5% increas es in incidence can be calculated for most datasets, and could be used as a satisfactory basis for risk assessment, e.g., to set reference d oses or acceptable daily intakes. An exception occurs when the benchma rk dose exceeds the highest dose of the study. This is only likely to occur when the chemical causes a small, but significant, increase in a finding that is uncommon in untreated animals. (C) 1994 Academic Pres s, Inc.