Standardizing Benchmark Dose Calculations to Improve Science-Based Decisions in Human Health Assessments.

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, i...

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Publicado en:Environmental Health Perspectives Vol. 122; no. 5; pp. 499 - 506
Autores principales: Wignall, Jessica A., Shapiro, Andrew J., Wright, Fred A., Woodruff, Tracey J., Chiu, Weihsueh A., Guyton, Kathryn Z., Rusyn, Ivan
Formato: research tables/charts Journal Article
Publicado: National Institute of Environmental Health Sciences May2014
Acceso en línea:Ver este registro en EBSCOhost
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      dt: May2014
      vid: 122
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      pub: National Institute of Environmental Health Sciences
      place: Research Triangle Park, North Carolina
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        atl: Standardizing Benchmark Dose Calculations to Improve Science-Based Decisions in Human Health Assessments.
      aug:
        au:
          Wignall, Jessica A.
          Shapiro, Andrew J.
          Wright, Fred A.
          Woodruff, Tracey J.
          Chiu, Weihsueh A.
          Guyton, Kathryn Z.
          Rusyn, Ivan
        affil: Department of Environmental Sciences and Engineering, and Gillings School of Global Public Health, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA
      sug:
        subj:
          Benchmarking Methods
          Dose-Response Relationship Standards
          Data Analysis, Statistical
          Pearson's Correlation Coefficient
          Spearman's Rank Correlation Coefficient
          Two-Tailed Test
          Unpaired T-Tests
      ab: 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. Objectives: 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.
      pubtype: Academic Journal
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        tables/charts
        Journal Article
      ougenre: Article
    language: English
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