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HERO ID
3223705
Reference Type
Journal Article
Title
Consideration of non-linear, non-threshold and threshold approaches for assessing the carcinogenicity of oral exposure to hexavalent chromium
Author(s)
Haney, J
Year
2015
Is Peer Reviewed?
1
Journal
Regulatory Toxicology and Pharmacology
ISSN:
0273-2300
EISSN:
1096-0295
Volume
73
Issue
3
Page Numbers
834-852
Language
English
PMID
26493004
DOI
10.1016/j.yrtph.2015.10.011
Web of Science Id
WOS:000367279400020
Abstract
A non-linear approach, consistent with available mode of action (MOA) data, is most scientifically defensible for assessing the carcinogenicity of oral exposure to hexavalent chromium (CrVI). Accordingly, the current paper builds upon previous studies (Haney, 2015a, 2015b) to first develop a non-linear, non-threshold approach as well as a non-linear threshold approach for assessing the oral carcinogenicity of CrVI, and then utilizes available MOA analyses and information for selection of the most scientifically-supported approach. More specifically, a non-linear, non-threshold dose-response function was developed that adequately describes the non-linearity predicted for potential human excess risk versus oral dose due to the sub-linear relationship between oral dose and internal dose (added mg Cr/kg target tissue) across environmentally-relevant doses of regulatory interest. Additionally, benchmark dose modeling was used to derive a reference dose (RfD of 0.003 mg/kg-day) with cytotoxicity-induced regenerative hyperplasia as a key precursor event to carcinogenesis in the mouse small intestine. This RfD value shows remarkable agreement with that published previously (0.006 mg/kg-day) based on a more scientifically-sophisticated, physiologically-based pharmacokinetic modeling approach (Thompson et al., 2013b). The RfD approach is the most scientifically-defensible approach based on the weight-of-evidence of available MOA information and analyses conducted for the most scientifically-supported MOA.
Keywords
Chromium; Hexavalent; Carcinogenicity; Regulatory; Cancer; Toxicity; Oral exposure
Tags
IRIS
•
Chromium VI
Considered
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January 2015 - April 2016
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