Use of mode of action data to inform a dose–response assessment for bladder cancer following exposure to inorganic arsenic

In the recent National Research Council report on conducting a dose–response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose–r...

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Bibliographic Details
Published in:Toxicology in vitro 2014-10, Vol.28 (7), p.1196-1205
Main Authors: Gentry, P.R., Yager, J.W., Clewell, R.A., Clewell, H.J.
Format: Article
Language:English
Subjects:
Animals
Arsenic
Arsenic - pharmacokinetics
Arsenic - standards
Arsenic - toxicity
Bladder
Carcinogens - pharmacokinetics
Carcinogens - standards
Carcinogens - toxicity
Dose-Response Relationship, Drug
Gene Expression Regulation
Genomics
Humans
In vitro
Mice
Mode of action
Risk Assessment
Urinary Bladder Neoplasms - chemically induced
Urinary Bladder Neoplasms - epidemiology
Urinary Bladder Neoplasms - metabolism
Water Pollutants, Chemical - pharmacokinetics
Water Pollutants, Chemical - standards
Water Pollutants, Chemical - toxicity
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Summary:In the recent National Research Council report on conducting a dose–response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose–response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose–response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose–response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7–43ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations
ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2014.05.011