Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace – Part I adjustments to the adult systemic model.

California's Division of Occupational Safety and Health has initiated a process to update its standards for exposure to lead in workplaces. In support of this effort, the state's Office of Environmental Health Hazard Assessment evaluated the age-specific, bio-kinetic model of lead metabolism in huma...

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Published in:Journal of Occupational & Environmental Hygiene Vol. 17; no. 6; pp. 283 - 301
Main Authors: Vork, Kathleen L., Carlisle, James C.
Format: equations & formulas research tables/charts Journal Article
Published: Taylor & Francis Ltd Jun2020
Online Access:View this record in EBSCOhost
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      jtl: Journal of Occupational & Environmental Hygiene
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      dt: Jun2020
      vid: 17
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      pub: Taylor & Francis Ltd
      place: Philadelphia, Pennsylvania
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        10.1080/15459624.2020.1743845
        144304601
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        atl: Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace – Part I adjustments to the adult systemic model.
      aug:
        au:
          Vork, Kathleen L.
          Carlisle, James C.
        affil: Air and Site Assessment and Climate Indicators Branch, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California
      sug:
        subj:
          Work Environment
          Lead Pharmacokinetics
          Occupational Exposure
          Models, Theoretical
          Human
          Blue Collar Workers
          Lead Urine
          Lead Blood
          Cortical Bone
          Regression
          Retirement
          Occupational Exposure Standards
      ab: California's Division of Occupational Safety and Health has initiated a process to update its standards for exposure to lead in workplaces. In support of this effort, the state's Office of Environmental Health Hazard Assessment evaluated the age-specific, bio-kinetic model of lead metabolism in humans, originally published by R.W. Leggett in 1993. This model was ultimately chosen for its physiologic realism and practicality in characterizing the relationship between air lead concentrations and blood lead levels in chronically exposed worker and its practicality in making necessary adjustments. Leggett's original model systematically under-predicts bone and blood levels in workers such that several adjustments to the parameters are needed to improve predictions for occupational exposure scenarios. The aim of this work is to incorporate new information about the bio-kinetics of lead in workers and to adjust the Leggett model to improve its predictions. The Leggett model was evaluated by comparing its predictions with information on lead concentrations in bone, blood, and urine from workers and other chronically exposed adults. Key model parameters were identified based upon a review of the relevant exposure assessment and modeling literature. Adjustments to the model parameters were made based on empirical evidence. They included reducing the level of lead in blood (BLL) where the rate of decrease in red blood cell binding begins and ends, lead accumulation rate in cortical bone, the rate of lead elimination in trabecular bone, and rate of lead transferred from diffusible plasma to urine. Regression methods and visual inspection of plotted data were used to assess the effect of adjustments on model predictions. When compared with the original, the adjusted Leggett model more accurately predicted lead concentrations observed in active and retired workers. Also, the adjusted Leggett model required less lead uptake to reach the same BLLs for BLLs less than 25 µg/dL and more time for BLLs to decline than the original Leggett model. These findings are important for defining an adequately protective occupational standard for lead exposure.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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