US EPA

The benchmark dose (BMD) concept was applied to 246 conventional developmental toxicity datasets from government, industry and commercial laboratories. Five modeling approaches were used, two generic and three specific to developmental toxicity (DT models). BMDs for both quantal and continuous data were compared with statistically-derived NOAELs (NOSTASOTS) to determine similarities. Quantal (Q) endpoints included litter responses (e.g., one or more dead or malformed implants), and QBMDs were calculated using a quantal Weibull (OW) model. Two types of continuous (C) data were modeled, the proportion of implants affected per litter, and the change in fetal weight (both mean and distribution); continuous power (CP) and DT models were used to calculate CBMDS. CBMDs for a 5% change in response (QBMD05) were 6-fold lower, on average, than the corresponding NOAEL. CBMD05s on average were similar to the corresponding NOAELS, and CBMD05s from different models were similar to each other. Including litter size but not threshold improved the fit of the DT models. or fetal weight data, specific cutoff values were used to calculate BMDs that were similar on average to the corresponding NOAELS: (1) changes from the control mean , and (2) a 5 or 10% decrease in the proportion of fetuses below the 5th or 10th percentile, respectively, of the control distribution. These results support the use of BMDs as providing a more consistent basis for risk assessment than do NOAELs.

Kimmel, C. A., R. Kavlock, B. Allen, AND E. Faustman. APPLICATION OF BENCHMARK DOSE METHODOLOGY TO DATA FROM PRENATAL DEVELOPMENTAL TOXICITY STUDIES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/A-95/135 (NTIS PB96117536).

Proceedings of International Congress of Toxicology