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

• Published in: Toxicology and applied pharmacology Vol. 254; no. 2; pp. 181 - 191
• Main Authors: Davis, J. Allen, Gift, Jeffrey S., Zhao, Q. Jay
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 15.07.2011; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMALS; Benchmark dose; Benchmark dose software; Benchmarking - methods; Benchmarking - trends; BENCHMARKS; Biological and medical sciences; Carcinogens, Environmental - administration & dosage; Carcinogens, Environmental - pharmacokinetics; Carcinogens, Environmental - toxicity; COMPARATIVE EVALUATIONS; COMPUTER CODES; computer software; Continuous data; Dichotomous data; Dose-Response Relationship, Drug; DOSES; Dose–response; EVALUATION; food safety; human health; Humans; Medical sciences; NATIONAL ORGANIZATIONS; Nested data; No-Observed-Adverse-Effect Level; NOAEL; peroxidase; Point of departure; POLLUTION CONTROL AGENCIES; PUBLIC HEALTH; RISK ASSESSMENT; SAFETY; Sample Size; Software - trends; spatial distribution; Toxicology; United States; United States Environmental Protection Agency; United States Environmental Protection Agency - trends; US EPA; US ORGANIZATIONS; United States; USA; Dichotomous data; Dose–response; Risk assessment; NOAEL; Point of departure; Nested data; Benchmark dose software; Continuous data; Benchmark dose; Evaluation; Continuous; Method; Dose activity relation; Risk factor; Dose-response; Software
• DOI: 10.1016/j.taap.2010.10.016
• ISSN: 0041-008X; 1096-0333

Traditionally, the No-Observed-Adverse-Effect-Level (NOAEL) approach has been used to determine the point of departure (POD) from animal toxicology data for use in human health risk assessments. However, this approach is subject to substantial limitations that have been well defined, such as strict dependence on the dose selection, dose spacing, and sample size of the study from which the critical effect has been identified. Also, the NOAEL approach fails to take into consideration the shape of the dose–response curve and other related information. The benchmark dose (BMD) method, originally proposed as an alternative to the NOAEL methodology in the 1980s, addresses many of the limitations of the NOAEL method. It is less dependent on dose selection and spacing, and it takes into account the shape of the dose–response curve. In addition, the estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality (i.e., sample size). With the recent advent of user-friendly BMD software programs, including the U.S. Environmental Protection Agency's (U.S. EPA) Benchmark Dose Software (BMDS), BMD has become the method of choice for many health organizations world-wide. This paper discusses the BMD methods and corresponding software (i.e., BMDS version 2.1.1) that have been developed by the U.S. EPA, and includes a comparison with recently released European Food Safety Authority (EFSA) BMD guidance.