Benchmark Dose Software (BMDS) Development, Maintenance, and User Support

Objective/Intended Use

The primary purpose of the BMDS project is to develop software to support Agency risk assessors in their analysis of the kinds of dose-response data that are used by EPA to assess the health risks of pollutants. BMDS has been used within several EPA program offices to estimate benchmarks such as cancer slope factors, reference doses (RfDs) and reference concentrations (RfCs), which are used along with other scientific information to prioritize Agency efforts, set standards and establish regulations. BMDS can also be used for other purposes, as reflected by its customer base expanding to over 2,000 registered non-EPA users in over 80 countries.

Abstract

Until recently, EPA dose-response assessments relied on the determination of no-observed-adverse-effect levels (NOAELs), which represent the highest experimental dose for which no adverse health effects have been documented. Using the NOAEL in determining RfDs and RfCs has long been recognized as having limitations in that it 1) is limited to one of the doses in the study and is dependent on study design; 2) does not account for variability in the estimate of the dose-response; 3) does not account for the slope of the dose-response curve; and 4) cannot be applied when there is no NOAEL, except through the application of an uncertainty factor (Crump, 1984; Kimmel and Gaylor, 1988). BMDS assists risk assessors in defining a starting point of departure (POD) for computation of a reference value (RfD or RfC) or slope factor not as dependent upon study design. Use of BMD methods involves fitting mathematical models to dose-response data and using the different results to select a POD associated with a predetermined benchmark response (BMR). BMDS facilitates this by providing simple data-management tools and an easy-to-use interface to run multiple models on the same dose-response data set.

Project Status

Version 1.4 of BMDS (publically released in May, 2004) consists of 16 models used by EPA risk assessors for the evaluation of dichotomous, continuous and nested toxicological dose-response data. At this time, BMDS offers models that are appropriate for the analysis of dichotomous (quantal) data (Gamma, Logistic, Log-Logistic, Multistage, Probit, Log-Probit, Quantal-Linear, Quantal-Quadratic, Weibull), continuous data (Linear, Polynomial, Power, Hill) and nested developmental toxicology data (NLogistic, NCTR, Rai & Van Ryzin). Results from all models include a reiteration of the model formula and model run options chosen by the user, goodness-of-fit information, the BMD, and the estimate of the lower-bound confidence limit on the BMD (BMDL). Model results are presented in textual and graphical output files which can be printed or saved and incorporated into other documents.

EPA plans to continually improve and expand the BMDS system. Additions under consideration for future versions of BMDS include models for the assessment of time-to-effect (e.g., tumors or neurotoxicity), additional dichotomous models (e.g., Hill model), supplements to the continuous models (e.g., with Hybrid model capability), categorical regression models, additional statistics for evaluating fit at low doses and comparing models, and additional tools/models for the analysis of human data.

Project Start Date

04/01/2000

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