You are here:
DOSE RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY: II. COMPARISON OF GENERIC BENCHMARK DOSE ESTIMATES WITH NO OBSERVED ADVERSE EFFECT LEVELS
Citation:
Allen, B., R. Kavlock, C. Kimmel, AND E. Faustman. DOSE RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY: II. COMPARISON OF GENERIC BENCHMARK DOSE ESTIMATES WITH NO OBSERVED ADVERSE EFFECT LEVELS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/111.
Description:
The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large data base of 246 developmental toxicity experiments compiled for use in comparing alternative approaches to developmental toxicity risk assessment. BMD estimates derived were compared to corresponding statistically derived NOAELs. Comparisons have been based on proportion of affected litters (a quantal response variable) and on the proportion of affected offspring within each litter (a continuous response variable). A quantal Weibull model was used to calculate generic BMDs for the quantal response variable (QBMDs) and a continuous power model was used to calculate generic BMDs for the continuous response variable (CBMDs) at three levels of additional risk (10%, 5%, and 1%). CBMD05s (continuous benchmark doses for 5% risk) and CNOAELs (statistically derived NOAELs based on the continuous response variable) were similar, with over 98% of the data subsets having CBMD05 and CNOAEL values that differed by less than an order of magnitude. In contrast, QNAOELs tended to be greater than corresponding QBMD10s. The observed conservatism of the QBMD values was attributed to two factors, lower maximum likelihood estimates for the quantal model and wider confidence intervals around the maximum likelihood estimates. Comparisons of different quantitative dose response assessments for developmental toxicity experiments should help us to identify appropriate risk assessment approaches for developmental toxicity risk assessment.