The Benchmark Dose (BMD) approach is a scientifically more advanced method compared to the No Observed Adverse Effect Level (NOAEL) approach for deriving a Point of Departure for risk assessment. The BMD method pre-defines a specific effect, referred to as the Benchmark Response (BMR) and estimates the dose (BMD) associated with the specified effect. The BMD is estimated from the complete dose response dataset by fitting dose response models. Statistical uncertainties in the data are taken into account in the confidence interval around the BMD, the lower limit of which (denoted as BMDL) is the Point of Departure for deriving exposure limits.
PROAST is suitable for an in depth analysis of a single dataset, but also for a quick (automated) analysis of a whole series of endpoints (responses), which may be useful for analysing complete studies.
PROAST can be applied to:
• dose-response data from all sorts of in vivo studies (animal, human or eco-toxicological).
• concentration-response data from in vitro studies.
• high throughput data (e.g. gene expression as a function of dose).
• combined dose-response datasets for similar endpoint in a single analysis.
• non-linear regression in any other field of science.
An important feature of PROAST is that it allows for comparing dose-responses among various subgroups, e.g. among sexes, among study durations, or among replicate studies. Based on statistical analysis PROAST indicates if the various dose-response relationships differ among the subgroups, and if so, how (e.g. in background response, in sensitivity to the chemical, or in dose-response shape).
New in PROAST: Graphical User Interface
The present version (38.9) has the possibility to run PROAST in a user-friendly Graphical User Interface (GUI) for standard applications. The GUI was developed by (and in collaboration with) the Health and Safety Laboratory in Buxton, United Kingdom.
US-EPA developed the Benchmark Dose Software (BMDS). This package is equally suitable for dose-response analysis and deriving a BMDL from dose-response data. The Dutch National Institute of Public Health and the Environment and EPA collaborate to achieve consistency between the BMDS and PROAST software. Both PROAST and BMDS have their advantages and disadvantages. Example of the advantages of PROAST is the possibility of statistically comparing dose-responses among subgroups, and the larger flexibility in plotting.
To install the PROAST software (copyright RIVM) on your computer, download the zipped folder “PROAST38.9.zip” to your computer. Unzip the folder and you will see a number of files (including the zipped PROAST software – do NOT unzip it). Open the word document “PROAST quick start.doc”, and follow the instructions for downloading R from the internet and installing PROAST. The downloaded folder also contains a manual and a number of exercises.
If you are interested to be informed about updates of PROAST or other relevant information, send an e-mail to firstname.lastname@example.org.
A concise discussion of the BMD approach can be found in EFSA (2009). See Slob (2002; Toxicological Sciences 66, 298-312) for a discussion of covariates in comparing dose-response relationships among subgroups.