US EPA

With the availability of BMDS 2.0 on the BMDS web site, EPA is providing (a) results of the external review (charge to reviewers and reviewer comments), (b) EPA responses to the review comments, and (c) a report describing development and testing of the models in BMDS 2.0 with new background parameters.

The new quantal dose-response models having alternative background parameters were externally reviewed by experts in June, 2007. Reviews were generally positive and confimed that the functioning of the computer code has been rigorously tested.

The new models are modifications of the current quantal models in BMDS. They were developed by modifying existing source codes, changing the code only as necessary. Addition of these new models to the suite of models in BMDS expands the range of alternatives available for fitting dose-response curves using generally accepted types of models.

Five new models implement an alternative form of background term, one that is additive to the dose. These are the multistage, cancer, log-probit, gamma, and Weibull models. The current versions of these models have a background term that is directly additive to the response probability. Models with background terms additive to dose were proposed and analysed in peer-reviewed papers by leading experts over 20 years ago, so they are not new to risk analysis. One type of model, log-logistic, will not be provided in a version with background additive to dose, because of technical difficulties causing unreliable convergence on solutions. Two quantal models, probit and logistic, that currently have no explicit background response parameter will become available in that form.

Thus, with the exception of the log-logistic, all the BMDS quantal models will be available in BMDS 2 in two versions, differing in the background term. Current versions of quantal models keep the names used in BMDS 1.4.1b. New versions with an alternative background parameter are distinctively named to identify them clearly, e.g., Weibull-BgDose, or Probit-BgResp.

EPA announces the availability of documents associated with the external review of new quantal dose-response models having alternative background parameters (e.g., background additive to dose). These models are made available within the new graphical user interface for BMDS, BMDS Version 2.0 (beta test version)

These documents are final.

U.S. EPA. BMDS 2.0 Beta With New Quantal Model Development External Review Reports and Supporting Documents.