Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1.

Area of Science:

• Toxicology
• Risk Assessment
• Environmental Health

Background:

• The No-Observed-Adverse-Effect-Level (NOAEL) is a traditional method for deriving points of departure (POD) in risk assessments.
• NOAEL has significant limitations, including dependence on dose selection, spacing, sample size, and ignoring dose-response curve shape.

Purpose of the Study:

• To discuss the Benchmark Dose (BMD) methods and software developed by the U.S. Environmental Protection Agency (U.S. EPA).
• To compare U.S. EPA's BMD approach with recent European Food Safety Authority (EFSA) guidance.
• To highlight BMD as a preferred alternative to NOAEL in human health risk assessments.

Main Methods:

• Utilizes statistical modeling to analyze dose-response data.
• Employs the Benchmark Dose Software (BMDS) developed by the U.S. EPA.
• Considers the shape of the dose-response curve and study quality (e.g., sample size) via BMDL estimation.

Main Results:

• The BMD method is less dependent on study design parameters like dose selection and spacing compared to NOAEL.
• BMD, particularly the BMDL, provides a more robust POD by incorporating dose-response curve information and study quality.
• User-friendly software like BMDS has facilitated the widespread adoption of BMD methods globally.

Conclusions:

• The BMD approach overcomes key limitations of the NOAEL method for deriving PODs.
• BMD methods, supported by tools like BMDS, represent the current standard in toxicological risk assessment.
• The paper provides insights into U.S. EPA's BMD methodology and its comparison with EFSA guidance.