Do 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline data support the conclusion of threshold carcinogenic effects? |
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| Authors: | Chao Chen Kate Z Guyton |
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| Institution: | (1) National Center for Environmental Assessment, Office or Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, Mail code 8623-D, Washington, DC 20460, USA |
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| Abstract: | The objectives of this paper are to (1) reexamine the data that were used to support the conclusion of a threshold effect
for 2-amino-3,8-dimethylimidazo4,5-f] quinoxaline (MeIQx)-induced initiation and carcinogenicity at low doses in the rat
liver, and (2) discuss issues and uncertainties about assessing cancer risk at low doses. Our analysis is part of an effort
to understand proper interpretation and modeling of data related to cancer mechanisms and is not an effort to develop a risk
assessment for this compound. The data reanalysis presented herein shows that the low-dose initiation activity of MeIQx, which
can be found in cooked meat, cannot be dismissed. It is argued that the threshold effect for carcinogenic agents cannot be
determined by statistical non-significance alone; more relevant biological information is required. A biologically motivated
procedure is proposed for data analyses. The concept and procedure that are appropriate for analyzing MeIQx data are equally
applicable to other compounds with comparable data.
The ideas and approaches in this presentation are those of the authors and do not necessarily represent the positions or policies
of the USEPA. |
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| Keywords: | Risk assessment Low dose extrapolation Threshold |
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