Title
Oral-to-inhalation route extrapolation in occupational health risk assessment: A critical assessment
Author
Rennen, M.A.J.
Bouwman, T.
Wilschut, A.
Bessems, J.G.M.
de Heer, C.
TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO
Publication year
2004
Abstract
Due to a lack of route-specific toxicity data, the health risks resulting from occupational exposure are frequently assessed by route-to-route (RtR) extrapolation based on oral toxicity data. Insight into the conditions for and the uncertainties connected with the application of RtR extrapolation has not been clearly described in a systematic manner. In our opinion, for a reliable occupational health risk assessment, it is necessary to have insight into the accuracy of the routinely applied RtR extrapolation and, if possible, to give a (semi-)quantitative estimate of the possible error introduced. Therefore, experimentally established no-observed-adverse-effect-levels for inhalation studies were compared to no-adverse-effect-levels predicted from oral toxicity studies by RtR extrapolation. From our database analysis it can be concluded that the widely used RtR extrapolation methodology based on correction for differences in (estimates of) absorption is not generally reliable and certainly not valid for substances inducing local effects. More experimental data are required (from unpublished data or new experiments) to get insight into the reliability of RtR extrapolation and the possibility to derive an assessment factor to account for the uncertainties. Moreover, validated screening methods to predict/exclude the occurrence of local effects after repeated exposure are warranted. Especially, in cases where chemical exposure by inhalation or skin contact cannot be excluded route-specific toxicity studies should be considered to prevent from inadequate estimates of human health risks. © 2003 Elsevier Inc. All rights reserved.
Subject
Health Chemistry
Food and Chemical Risk Analysis
Inhalation
Local effects
Oral
Respiratory
Risk assessment
Route extrapolation
Accuracy
Analytical error
Data base
Inhalation
Intermethod comparison
Occupational exposure
Occupational hazard
Priority journal
Quantitative analysis
Reliability
Risk assessment
Screening test
Administration, Inhalation
Administration, Oral
Animals
Dose-Response Relationship, Drug
Humans
Models, Biological
No-Observed-Adverse-Effect Level
Occupational Exposure
Pesticides
Predictive Value of Tests
Research Design
Risk Assessment
Species Specificity
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DOI
https://doi.org/10.1016/j.yrtph.2003.09.003
TNO identifier
237605
ISSN
0273-2300
Source
Regulatory Toxicology and Pharmacology, 39 (1), 5-11
Document type
article