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Review of DOD's Approach to Deriving an Occupational Exposure Level for Trichloroethylene (2019) / Chapter Skim
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5 Quantitative Dose-Response Assessment and Derivation of Occupational Exposure Levels
Pages 40-49

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From page 40...
... Additional considerations for advancing studies might include weighing human versus animal data, choice of animal species, exposure route and duration, accuracy of exposure data, the relevance of exposure timing, reliable outcome measurement, and the precision of results. DOD's draft report states that "After scoring all studies, points of departure (PODs)
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From page 41...
... NOTE: HEC/HED, health effect concentration/health effect dose; OEL, occupational exposure level; POD, point of departure; UF, uncertainty factor. SOURCE: Adapted from NRC 2014.
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From page 42...
... There are clearly uncertainties when using other routes of exposure for setting an inhalational OEL, but they can be lessened with the application of PBPK modeling and Bayesian uncertainty adjustment approaches for studies determined to be of otherwise sufficient quality for dose-response assessments. Another approach DOD could consider is performing dose-response metaanalyses to derive a composite POD for each end point.
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From page 43...
... The committee offers a few suggestions that could provide additional support and ultimately improve confidence in several of the potential internal dosemetrics and HEC derivations. Specifically, the PBPK model does not have a component designed for pregnant or lactating animals, which is a potential limitation for internal dose metric determinations for pregnant or nursing mothers exposed to TCE in the workplace.
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From page 44...
... physiology and realistic durations from actual job profiles into PBPK simulations for selected end points most likely to drive the OEL. This will allow DOD to take advantage of the PBPK capabilities rather than using estimations that assume all processes involved in estimating internal dose metrics for each POD and HEC are linearly related.
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From page 45...
... , is to include all health end points within a unified framework for dose-response assessment, with an emphasis on distinguishing risk assessment models by mode of action rather than cancer versus noncancer. DOD estimated risks for kidney cancer, and for kidney cancer and nonHodgkin's lymphoma (NHL)
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From page 46...
... Furthermore, it would be prudent to balance the discussion by considering the possibility that the cancer risk was underestimated. For example, DOD estimated the 1 in 1,000 excess risks for kidney cancer at the proposed OEL using background cancer rates from 20052006, similar to the time frame of the Charbotel et al.
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From page 47...
... , in addition to the current presentation of occupational exposure levels associated with various benchmark cancer risks. Following this, an explicit discussion of the acceptability of estimated cancer risk levels at the proposed OEL is warranted.
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From page 48...
... Without the same level of evaluation, DOD's use of human studies to either support decisions on PODs or assess cancer risks appear arbitrary, lack transparency, and reduce confidence in the assessment; Because DOD has a PBPK model, it should consider including both oral and inhalation studies for all end points considered in the dose-response assessment. This can strengthen DOD's choices of internal dose metrics for cross-species comparisons and improve confidence in the overall approach to deriving HECs; Quantitative scores should not be used to rate studies (also see Chapter 4)
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From page 49...
... 1990. Physiologically based pharmacokinetic modeling of the lactating rat and nursing pup: A multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid.
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Key Terms

  • occupational exposure
  • cancer risk
  • pbpk model
  • internal dose
  • cancer risks

  • draft report
  • dod draft
  • proposed oel
  • based pharmacokinetic
  • exposure level

  • dose metrics
  • inhalation exposures
  • estimated cancer
  • excess risk
  • exposure data

  • benchmark dose
  • pbpk modeling
  • oel determinations
  • improve confidence
  • nhl combined

  • cancer slope
  • dod report
  • workplace exposure
  • exposure levels
  • dod estimated

  • dose metric
  • health protective
  • risk information
  • dose comparisons
  • inhalation studies


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