title: Standardizing benchmark dose calculations to improve science-based decisions in human health assessments.
abstract: BACKGROUND
  Benchmark dose (BMD) modeling computes the dose associated with a prespecified response level. While offering advantages over traditional points of departure (PODs), such as no-observed-adverse-effect-levels (NOAELs), BMD methods have lacked consistency and transparency in application, interpretation, and reporting in human health assessments of chemicals.
  
  
  OBJECTIVE
  We aimed to apply a standardized process for conducting BMD modeling to reduce inconsistencies in model fitting and selection.
  
  
  METHODS
  We evaluated 880 dose-response data sets for 352 environmental chemicals with existing human health assessments. We calculated benchmark doses and their lower limits [10% extra risk, or change in the mean equal to 1 SD (BMD/L10/1SD)] for each chemical in a standardized way with prespecified criteria for model fit acceptance. We identified study design features associated with acceptable model fits.
  
  
  RESULTS
  We derived values for 255 (72%) of the chemicals. Batch-calculated BMD/L10/1SD values were significantly and highly correlated (R2 of 0.95 and 0.83, respectively, n = 42) with PODs previously used in human health assessments, with values similar to reported NOAELs. Specifically, the median ratio of BMDs10/1SD:NOAELs was 1.96, and the median ratio of BMDLs10/1SD:NOAELs was 0.89. We also observed a significant trend of increasing model viability with increasing number of dose groups.
  
  
  CONCLUSIONS
  BMD/L10/1SD values can be calculated in a standardized way for use in health assessments on a large number of chemicals and critical effects. This facilitates the exploration of health effects across multiple studies of a given chemical or, when chemicals need to be compared, providing greater transparency and efficiency than current approaches.
authors.affiliation: Department of Environmental Sciences and Engineering, and.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Wignall
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Shapiro
authors.forename: Fred A
authors.initials: FA
authors.lastname: Wright
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Woodruff
authors.forename: Weihsueh A
authors.initials: WA
authors.lastname: Chiu
authors.forename: Kathryn Z
authors.initials: KZ
authors.lastname: Guyton
authors.forename: Ivan
authors.initials: I
authors.lastname: Rusyn
mesh_terms: D019985:Benchmarking; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008962:Models, Theoretical; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment