Science Inventory

Application of Benchmark Dose Methodology to a Variety of Endpoints and Exposures

Citation:

Application of Benchmark Dose Methodology to a Variety of Endpoints and Exposures. U.S. Environmental Protection Agency, Office of Research and Development, National Center For Environmental Assessment, Research Triangle Park Office, Research Triangle Park, NC, 1999.

Description:

This latest beta version (1.1b) of the U.S. Environmental Protection Agency (EPA) Benchmark Dose Software (BMDS) is being distributed for public comment. The BMDS system is being developed as a tool to facilitate the application of benchmark dose (BMD) methods to EPA hazardous pollutant risk assessments.

Within this risk assessment process, EPA calculates reference doses (RfDs) and reference concentrations (RfCs), which are used along with other scientific information to set standards for noncancer human health effects. Until recently, RfDs and RfCs have been determined from 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 many limitations, including its somewhat subjective reliance on experimental dose spacing and its inability to adequately account for variability in the dose-response slopes. The BMD approach (Crump, 1984; Kimmel and Gaylor, 1988) has been developed to address these limitations. The EPA Risk Assessment Forum has written guidelines for the use of the BMD approach in the assessment of noncancer health risk (U.S. EPA, 1995) and the EPA Benchmark Dose Workgroup is in the process of drafting technical guidance for the application of the BMD approach in cancer and noncancer dose-response assessments.

Use of BMD methods involve fitting mathematical models to dose-response data and using the different results to select a BMD that is associated with a predetermined benchmark response (BMR), such as a 10% increase in the incidence of a particular lesion or a 10% decrease in body weight gain. BMDS facilitates these operations by providing simple data-management tools and an easy-to-use interface to run multiple models on the same dose-response data set. At this time, BMDS offers sixteen (16) different models that are appropriate for the analysis of dichotomous (quantal) data (9 models; Gamma, Logistic, Log-Logisitic, Multistage, Probit, Log-Probit, Quantal-Linear, Quantal-Quadratic, Weibull), continuous data (4 models; Linear, Polynomial, Power, Hybrid) and nested developmental toxicology data (3 models; NLogistic, NCTR, Rai & Van Ryzin). Results from these models include goodness-of-fit information, the BMD, and the estimate of the lower-bound confidence limit on the BMD (the BMDL). Model results are presented in textual and graphical output files which can be printed or saved and incorporated into other documents. Running the models on a data set consists of four basic steps.

Step 1: Create a data set using the BMDS spreadsheet facility, or import a data set from a text, Excel or Lotus spreadsheet file.
Step 2: Select the appropriate model based on the type of data set being evaluated.
Step 3: Specify the parameters associated with the model that was selected.
Step 4: Run the Model and view the textual and graphical results.

More complete documentation for use of BMDS is provided within the program in the form of detailed help windows, which are designed to guide you through each of these steps. Hard copy documentation of the software functionality is not being offered or maintained at this time due to difficulties presented by the rapid rate of change that the BMDS is undergoing. Those seeking general guidance on the use of the BMD approach in health risk assessments should consult the EPA Risk Assessment Forum publication (U.S. EPA, 1995).

EPA plans to continually improve and expand the BMDS system. A prior beta test version of the BMDS (version 1.0b) was reviewed in May-June, 1997 by risk assessors and statisticians from within EPA and from outside organizations. The EPA is requesting that all public comments on this version (version 1.1b) of BMDS be submitted to bmds.ncea@epa.gov by March 31, 1999.