Standardizing benchmark dose calculations to improve science-based decisions in human health assessments. Academic Article uri icon

abstract

  • BACKGROUND: Benchmark dose (BMD) modeling computes the dose associated with a prespecified response level. While offering advantages over traditional points of departure (PODs), such as no-observed-adverse-effect-levels (NOAELs), BMD methods have lacked consistency and transparency in application, interpretation, and reporting in human health assessments of chemicals. OBJECTIVES: We aimed to apply a standardized process for conducting BMD modeling to reduce inconsistencies in model fitting and selection. METHODS: We evaluated 880 dose-response data sets for 352 environmental chemicals with existing human health assessments. We calculated benchmark doses and their lower limits [10% extra risk, or change in the mean equal to 1 SD (BMD/L10/1SD)] for each chemical in a standardized way with prespecified criteria for model fit acceptance. We identified study design features associated with acceptable model fits. RESULTS: We derived values for 255 (72%) of the chemicals. Batch-calculated BMD/L10/1SD values were significantly and highly correlated (R2 of 0.95 and 0.83, respectively, n = 42) with PODs previously used in human health assessments, with values similar to reported NOAELs. Specifically, the median ratio of BMDs10/1SD:NOAELs was 1.96, and the median ratio of BMDLs10/1SD:NOAELs was 0.89. We also observed a significant trend of increasing model viability with increasing number of dose groups. CONCLUSIONS: BMD/L10/1SD values can be calculated in a standardized way for use in health assessments on a large number of chemicals and critical effects. This facilitates the exploration of health effects across multiple studies of a given chemical or, when chemicals need to be compared, providing greater transparency and efficiency than current approaches.

published proceedings

  • Environ Health Perspect

author list (cited authors)

  • Wignall, J. A., Shapiro, A. J., Wright, F. A., Woodruff, T. J., Chiu, W. A., Guyton, K. Z., & Rusyn, I.

complete list of authors

  • Wignall, Jessica A||Shapiro, Andrew J||Wright, Fred A||Woodruff, Tracey J||Chiu, Weihsueh A||Guyton, Kathryn Z||Rusyn, Ivan