About Benchmark Dose Software (BMDS)
What is Benchmark Dose Software
The EPA developed the Benchmark Dose Software (BMDS) application as a tool to help Agency risk assessors facilitate applying benchmark dose (BMD) methods to EPA's hazardous pollutant risk assessments.
EPA risk assessors use the models in BMDS to estimate reference doses (RfDs), reference concentrations (RfCs), and slope factors, which are used along with other scientific information, to set standards that protect human health from the effects of chemical exposures.
A specific focus of BMDS is the estimation of a statistical benchmark dose (BMD), including bounds (e.g., 95% confidence intervals) on such estimates. The BMD is a chemical dose or concentration that produces a predetermined change in the response rate (i.e., the "benchmark") of an adverse effect, such as weight loss or tumor incidence.
The BMDS Glossary defines "BMD" as follows:
An 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.
The BMD is a range, rather than a fixed number. For example, the benchmark dose (lower confidence limit) (BMDL) can be regarded as a dose where the observable physical effect is less than the predetermined benchmark response (BMR).
BMDS provides easy access to numerous dose-response models that the user may select from and/or compare, to make predictions about the quantitative relationship between the dose or exposure of a chemical or chemical mixture associated with a given response level. An assessor can run multiple models on the same dose-response dataset.
BMDS is consistent with the EPA Risk Assessment Forum's Benchmark Dose Technical Guidance Document (U.S. EPA, 2012) and the technical guidance for choosing the appropriate stage of a Multistage model for cancer modeling.
BMDS Models & Results
The BMDS suite of models are appropriate for analyzing dichotomous (quantal) data, continuous data, nested developmental toxicology data, and multiple tumors.
Results from all models include the model formula, the 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 using tables and graphs, and the results can be exported to a Microsoft Word-based report that can be printed, saved, and used as the basis for an appendix.
History
In 1995, EPA's Risk Assessment Forum published guidance on the BMD approach in the assessment of noncancer health risk (U.S. EPA, 1995). The guidance listed several advantages of the BMD approach over the use of No Observed Adverse Effect Levels (NOAELs) and Lowest Observed Adverse Effect Levels (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.
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Date |
Milestone |
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1995 |
EPA's Risk Assessment Forum (RAF) published the initial guidelines on the use of the benchmark dose approach for assessing noncancer health risk. EPA's National Center for Environmental Assessment (NCEA) Division in RTP, NC began development of the EPA's benchmark dose software (BMDS) application. |
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2000-10 |
BMDS 1.2.1 released. Contained new versions of the continuous Polynomial and Hill models. |
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2001-02 |
Released the source code for BMDS version 1.2.1 models . |
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2001-03 |
BMDS 1.3 released. Contained new continuous polynomial, power, and Hill Models; new dichotomous multistage, Weibull, and gamma models; improved user interface. |
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2002-01 |
BMDS 1.3.1 released, with a revised help manual and user interface. |
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2003-05 |
BMDS 1.3.2 released, containing revised polynomial and nested logistic models compatible with Windows 2000 |
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2007-02 |
BMDS 1.4.1 released, adding a multistage cancer model and removing the Quantal-Quadratic dichotomous model. |
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2007-08 |
BMDS 1.4.1b released, with an updated help file. |
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2007-11 |
BMDS 1.4.1c released, updating dichotomous models that were included on BMDS version 1.4.1b. |
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2008-07 |
BMDS 2.0 released, with a revised user interface and risk assessment modeling framework, and a new set of quantal models with alternative background (i.e., background additive to dose) and asymptote (i.e., Hill model) parameters, as well as a Beta Exponential set of models. |
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2009-07 |
BMDS 2.1 released, with numerous enhancements to the models and the user interface. |
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2009-11 |
BMDS 2.1.1 (Build 55) released, with flexible reporting features, and sample session and model option files to assist with running batch operations. |
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2009-12 |
EPA released a Time-To-Tumor Multistage Weibull Model ("MSW"). The model is run from a Windows command prompt window, data is submitted in a text file, and output is sent to a text file. |
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2010-06 |
BMDS 2.1.2 (Build 60) released, with numerous model and user interface enhancements. |
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2011-09 |
BMDS 2.2 (Build 66) released, with multiple tumor analysis capability, trend test for dichotomous data, changes to variable name handling in option files, and default column headers for new datasets. |
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2011-12 |
BMDS 2.2 (Build 67) released, with minor modifications to the user interface. |
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2012-02 |
Released source code files and executable files for BMDS 2.2 models. |
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2012-09 |
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2013-04 |
BMDS 2.4 released, addressing issues related to data entry and running the MS_Combo and ten Berge models. |
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2013-08 |
BMDS 2.4 redistributed with an updated version of the Excel-based BMDS Wizard. |
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2014-05 |
BMDS 2.5 released, with updated BMDS Wizard, and enhancements and fixes for plotting and some models. |
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2014-07 |
Distributed a new version of the BMDS continuous polynomial model to fix issue with incorrect parameter estimates. |
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2015-02 |
BMDS 2.6 released with improvements to nested models, parameter standard error reporting, parameter initialization for continuous models, file and path name handling, and regional settings for the decimal separator. Also included was an updating BMDS Wizard and a feature for BMDS to detect and install software updates. |
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2017-08 |
BMDS 2.7 released, with several enhancements and fixes, along with an updated BMDS Wizard. |
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2018-09 |
BMDS 3.0 released as a Microsoft Excel-based product. |
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2019-02 |
BMDS 3.1 released, compatible with all 32- and 64-bit versions of Excel released since 2007. Also included multiple UI enhancements, and minor programmatic fixes and improvements. |
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2019-07 |
BMDS 3.1.1 released. Included Cumulative Distributive Function (CDF) table to BMDS results, ability to import .dax datasets from BMDS 2.x and 3.x, several MS_Combo (Multitumor) modifications, and a change in the “Test Threshold” default value to be consistent with the BMDS Technical Guidance on Choosing Appropriate Stage of a Multistage Model for Cancer Modeling. |
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2019-11 |
BMDS 3.1.2 released with multiple minor fixes, changes, and enhancements. |
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2020-08 |
BMDS 3.2 included numerous fixes/enhancements to existing continuous models, improved error messages to aid bug reporting, UI enhancements, and bug fixes. |
| 2022-03 | BMDS 3.2.0.1 removed the preview versions of Bayesian continuous models. No other changes or enhancements were made. |
| 2022-10 |
BMDS 3.3 and BMDS Online released to the public on the same day. BMDS 3.3 contained significant “under-the-hood” improvements to the BMDS model code library to provide better overall performance, consistent results with previous BMDS releases, and better error management. The BMDS model code library is used also by BMDS Online, which enabled researchers to perform dose-analysis research using BMDS models from a web browser. |
| 2023-03-08 | BMDS 3.3.1 and BMDS Online (release 2023.03) were updated with bug fixes to dichotomous scaled residual calculations and to reduced model deviance. |
| 2023-03-21 | BMDS 3.3.2 and BMDS Online (release 2023.03.1) were updated with a bug fix to dichotomous scaled residual calculations that occurred when estimated probability equals one. |
| 2024-11 | BMDS Online (release 24.1) was updated to include Multistage/Multitumor and Nested Dichotomous models. The deployment also included the rollout of BMDS Desktop and pybmds for offline use. With this release, BMDS Online is the Agency's primary dose-response modeling platform, replacing BMDS 3.3.2. |
External and Peer Reviews
Because BMDS is the Agency's tool for estimating risk assessments, the validity and reliability of its statistical models are of paramount importance. The following peer reviews and expert summaries were issued of the BMDS applications and its models as they were developed and eventually released.
- 2000 Peer Review Workshop on the Draft Benchmark Dose Technical Guidance
- 2000 External Review of BMDS Version 1.1b and EPA Responses
- 2007 External Review of the Exponential Model
- 2007 External Review of Dichotomous (Quantal) Models
- 2007 External Review of the Multistage Weibull Time-to-Tumor Model
- 2008 External Review of the Concentration x Time (ten Berge) Model
- 2011 External Peer Review of EPA’s MS_COMBO Multi-tumor Model and Test Report
- 2018 External Review of Bayesian Models and Model Averaging Software