Benchmark Dose

The benchmark dose (BMD) approach is a statistical method for deriving a toxicological reference point from dose-response data. Unlike the NOAEL, which relies on the specific dose levels tested, the BMD approach models the full dose-response relationship and identifies the dose corresponding to a pre-defined change in response (the benchmark response, typically 5% or 10% above background).

EFSA has published guidance recommending the BMD approach as the preferred method for deriving reference points from toxicological studies. The approach offers several advantages over the NOAEL: it uses all available data rather than relying on a single dose group, it is less sensitive to study design choices, and it provides a measure of uncertainty through the confidence interval around the estimated BMD.

In practice, EFSA uses the lower confidence limit of the BMD (the BMDL) as the point of departure for risk assessment, analogous to how the NOAEL is used. The BMDL is then divided by appropriate safety factors to derive a health-based guidance value or compared to estimated human exposure to calculate a margin of exposure.

EFSA's BMD guidance and the associated software (PROAST) are publicly available. Applicants can strengthen their toxicological assessment by providing BMD analysis alongside the traditional NOAEL determination.