A mechanism-based cancer risk assessment for 1,4-dichlorobenzene

Butterworth, Byron E., Aylward, Lesa L. and Hays, Sean M. (2007) A mechanism-based cancer risk assessment for 1,4-dichlorobenzene. Regulatory Toxicology and Pharmacology, 49 2: 138-148. doi:10.1016/j.yrtph.2007.06.004

Author Butterworth, Byron E.
Aylward, Lesa L.
Hays, Sean M.
Title A mechanism-based cancer risk assessment for 1,4-dichlorobenzene
Journal name Regulatory Toxicology and Pharmacology   Check publisher's open access policy
ISSN 0273-2300
Publication date 2007-11-01
Year available 2007
Sub-type Article (original research)
DOI 10.1016/j.yrtph.2007.06.004
Open Access Status Not yet assessed
Volume 49
Issue 2
Start page 138
End page 148
Total pages 11
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Formatted abstract
1,4-Dichlorobenzene (DCB) induced liver cancer in male and female B6C3F1 mice in a gavage bioassay and in male and female BDF1 mice in an inhalation bioassay. The weight of the evidence convincingly indicates that the mouse liver tumors induced by 1,4-DCB were via a nongenotoxic-mitogenic/promotional mode of action by forcing the growth of spontaneous precancerous lesions. Doses insufficient to exhibit mitogenic or promotional activity would not be expected to increase the risk of cancer. Benchmark dose modeling of the tumor response was conduced for the combined inhalation and oral gavage bioassay data sets based on an absorbed dose basis to establish the dose or airborne concentration corresponding to 1% extra risk. Assuming that as a point of departure and dividing by an uncertainty factor of 300, yielded a value of 0.1 ppm, representing a rational estimate of an airborne concentration for the human population below which there is unlikely to be any increased risk of cancer during a lifetime. In contrast, the default model that assumes a genotoxic mode of action estimates a one in one-million increased lifetime risk of cancer at an airborne concentration of 0.00004 ppm, some 2500-fold lower than the mechanism-based model and 1,875,000-fold lower than the no observed effect concentration for induced cancer of 75 ppm in the inhalation bioassay.
Keyword 1,4-Dichlorobenzene
Cancer risk assessment
Nongenotoxic-mitogenic carcinogens
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
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