Benchmark Dose Analysis of the Developmental Toxicity of Boric Acid in Rats. Bruce C. Allen, ICF Kaiser International, P. 0. Box 14348, Research Triangle Park, NC 27709; and Philip L. Strong, U.S. Borax Inc., 26877 Tourney Rd., Valencia, CA 91355
The benchmark dose (BMD) approach has been proposed as a superior alternative to NOAEL-based approaches for noncancer risk assessment. Recent investigations have shown that the BMD approach is applicable to and useful for analysis of developmental toxicity data collected in standard Segment II experiments. The present investigation extends those results with a case study of developmental toxicity observed following in utero exposure to boric acid and the BMD approach applied to malformation/variation endpoints and fetal weight changes (the most sensitive observation with respect to BMD estimation) from two rat studies. The BMD analysis of the boric acid results addresses several issues that can arise in the course of reference dose calculation. The first of the two rat studies failed to identify a NOAEL; the present analysis demonstrates the advantage of the BMD approach in such cases. Approaches for considering different severities of related effects, in this case malformations and variations associated with the 13th and 14th ribs, are presented; among other approaches, weighted proportions are defined for determining BMDs for overall rib effects. The second rat study examined responses at lower doses in order to identify a NOAEL; the existence of the second study provides an opportunity to consider how to combine data from two or more studies in order to improve the accuracy and precision of estimates related to BMD calculations. Accuracy improved as a result of increased information about the dose-response relationship in the region near the effect level of interest. Precision improved because of increased numbers of dose groups and observations within groups, reducing the width of the confidence intervals that are the basis for BMD estimation and thus increasing the BMDs themselves.