What is Benchmark Dose Software (BMDS)?
The EPA developed the Benchmark DoseBenchmark DoseAn exposure due to a dose of a substance associated with a specified low incidence of risk, generally in the range of 1% to 10%, of a health effect; or the dose associated with a specified measure or change of a biological effect. Software (BMDS) as a tool to help Agency risk assessors facilitate applying benchmark dose (BMDBMDAn exposure due to a dose of a substance associated with a specified low incidence of risk, generally in the range of 1% to 10%, of a health effect; or the dose associated with a specified measure or change of a biological effect.) methods to EPA's hazardous pollutant risk assessments. BMDS is consistent with the EPA Risk Assessment Forum's Benchmark Dose Technical Guidance Document (U.S. EPA, 2012).
EPA uses BMD methods to estimate reference dosereference doseAn estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious effects during a lifetime.s (RfDs) and reference concentrationreference concentrationAn estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.s (RfCs), which are used along with other scientific information to set standards for noncancer human health effects.
Prior to the 1990's, RfDs and RfCs had been determined from no-observed-adverse-effect levels (NOAELNOAELAn exposure level at which there are no statistically or biologically significant increases in the frequency or severity of adverse effects between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered as adverse or precursors to adverse effects. In an experiment with several NOAELs, the regulatory focus is primarily on the highest one, leading to the common usage of the term NOAEL as the highest exposure without adverse effect. See also: LOAEL.s), which represent the highest experimental dose for which no statistically significant adverse health effects were reported or, in the absence of a NOAEL, the lowest-observed-adverse-effect levels (LOAELLOAELThe lowest dose or exposure level of a chemical in a study at which there is a statistically or biologically significant increase in the frequency or severity of an adverse effect in the exposed population as compared with an appropriate, unexposed control group. See also: NOAEL.).
- It is limited to one of the doses in the study and is dependent on study design
- It does not account for variability in the estimate of the dose-response
- It does not account for the slope of the dose-response curve
- It cannot be applied when there is no NOAEL, except through the application of an uncertainty factor (Crump, 1984; Kimmel and Gaylor, 1988).
A goal of the BMD approach is to define a starting point of departurepoint of departureThe point on a dose-response curve established from experimental data, e.g., the benchmark dose, generally corresponding to an estimated low effect level (e.g., 1% to 10% incidence of an effect). Depending on the mode of action and available data, some form of extrapolation below the POD may be employed for low-dose risk assessment or the POD may be divided by a series of uncertainty factors to arrive at a reference dose. (POD) for the computation of a reference value (RfD or RfC) or slope factorslope factorAn upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime exposure to an agent. This estimate, usually expressed in units of proportion (of a population) affected per mg/kg-day, is generally reserved for use in the low-dose region of the dose-response relationship, that is, for exposures corresponding to risks less than 1 in 100. that is more independent of study design. Using BMD methods involves 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.
In 1995, EPA's Risk Assessment Forum published guidance on the BMD approach in the assessment of noncancer health risk (U.S. EPA, 1995) which listed several advantages of the BMD approach over use of NOAELs and LOAELs. In 1995, EPA's National Center for Environmental Assessment (NCEA) initiated a project to develop benchmark dose software to assist Agency risk assessors in deriving benchmark dose values for use in Agency risk assessments.
BMDS facilitates Agency risk assessment operations by providing simple data-management tools and an easy-to-use interface to run multiple models on the same dose-response dataset. 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 (BMDLBMDLA lower one-sided confidence limit on the BMD.). Model results are presented in textual and graphical output files that can be printed or saved and incorporated into other documents.
BMDS has been continually improved and enhanced since its initial release in 1999. BMDS now contains thirty (30) different models that are appropriate for the analysis of dichotomous (quantal) data, continuous data, nested developmental toxicology data, multiple tumor analysis, and concentration-time data.
The BMDS Timeline describes more details of BMDS development history and brief details of BMDS releases.