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An Approach to Risk Assessment for TiO2

An Approach to Risk Assessment for TiO2 Titanium dioxide (TiO2) is a poorly soluble, low-toxicity (PSLT) particle. Fine TiO2 (<2.5 μm) has been shown to produce lung tumors in rats exposed to 250 mg/m3, and ultrafine TiO2 (< 0.1 μm diameter) has been shown to produce lung tumors in rats at 10 mg/m3. We have evaluated the rat dose-response data and conducted a quantitative risk assessment for TiO2. Preliminary conclusions are: (1) Fine and ultrafine TiO2 and other PSLT particles show a consistent dose-response relationship when dose is expressed as particle surface area; (2) the mechanism of TiO2 tumor induction in rats appears to be a secondary genotoxic mechanism associated with persistent inflammation; and (3) the inflammatory response shows evidence of a nonzero threshold. Risk estimates for TiO2 depend on both the dosimetric approach and the statistical model that is used. Using 7 different dose-response models in the U.S. Environmental Protection Agency (EPA) benchmark dose software, the maximum likelihood estimate (MLE) rat lung dose associated with a 1 per 1000 excess risk ranges from 0.0076 to 0.28 m2/g-lung of particle surface area, with 95% lower confidence limits (LCL) of 0.0059 and 0.042, respectively. Using the ICRP particle deposition and clearance model, estimated human occupational exposures yielding equivalent lung burdens range from approximately 1 to 40 mg/m3 (MLE) for fine TiO2, with 95% LCL approximately 0.7–6 mg/m3. Estimates using an interstitial sequestration lung model are about one-half as large. Bayesian model averaging techniques are now being explored as a method for combining the various estimates into a single estimate, with a confidence interval expressing model uncertainty. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Inhalation Toxicology Taylor & Francis

An Approach to Risk Assessment for TiO2

Dankovic, David; Kuempel, Eileen; Wheeler, Matthew
Inhalation Toxicology , Volume 19 (sup1): 8 – Jan 1, 2007
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References (47)

Publisher
Taylor & Francis
Copyright
© 2007 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted
ISSN
1091-7691
eISSN
0895-8378
DOI
10.1080/08958370701497754
Publisher site
See Article on Publisher Site

Abstract

Titanium dioxide (TiO2) is a poorly soluble, low-toxicity (PSLT) particle. Fine TiO2 (<2.5 μm) has been shown to produce lung tumors in rats exposed to 250 mg/m3, and ultrafine TiO2 (< 0.1 μm diameter) has been shown to produce lung tumors in rats at 10 mg/m3. We have evaluated the rat dose-response data and conducted a quantitative risk assessment for TiO2. Preliminary conclusions are: (1) Fine and ultrafine TiO2 and other PSLT particles show a consistent dose-response relationship when dose is expressed as particle surface area; (2) the mechanism of TiO2 tumor induction in rats appears to be a secondary genotoxic mechanism associated with persistent inflammation; and (3) the inflammatory response shows evidence of a nonzero threshold. Risk estimates for TiO2 depend on both the dosimetric approach and the statistical model that is used. Using 7 different dose-response models in the U.S. Environmental Protection Agency (EPA) benchmark dose software, the maximum likelihood estimate (MLE) rat lung dose associated with a 1 per 1000 excess risk ranges from 0.0076 to 0.28 m2/g-lung of particle surface area, with 95% lower confidence limits (LCL) of 0.0059 and 0.042, respectively. Using the ICRP particle deposition and clearance model, estimated human occupational exposures yielding equivalent lung burdens range from approximately 1 to 40 mg/m3 (MLE) for fine TiO2, with 95% LCL approximately 0.7–6 mg/m3. Estimates using an interstitial sequestration lung model are about one-half as large. Bayesian model averaging techniques are now being explored as a method for combining the various estimates into a single estimate, with a confidence interval expressing model uncertainty.

Journal

Inhalation Toxicology – Taylor & Francis

Published: Jan 1, 2007

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