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Mutagenesis Advance Access originally published online on February 20, 2007
Mutagenesis 2007 22(3):209-215; doi:10.1093/mutage/gem005
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© The Author 2007. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Comparison of genotoxic potency of styrene 7,8-oxide with {gamma} radiation and human cancer risk estimation of styrene using the rad-equivalence approach

Lode Godderis1,2,*, P Aka3, M Kirsch-Volders3 and H Veulemans2

1Idewe, External Service for Prevention at Work, Interleuvenlaan 58, 3001 Heverlee, Belgium 2KULeuven, Occupational, Environmental and Insurance Medicine, Kapucijnenvoer 35/5, 3000 Leuven, Belgium 3VUB, Laboratorium voor Cellulaire Genetica, Pleinlaan 2, 1050 Brussel, Belgium

Styrene is suspected to cause lympho-hematopoietic malignancies through the formation of styrene 7,8-oxide. However, we are still unable to calculate the cancer risk for workers exposed to styrene using epidemiological data. The aims of this study were to determine the blood dose after styrene exposure and to compare the genotoxic potency of styrene 7,8-oxide and {gamma} radiation in order to calculate the cancer risk by means of the rad-equivalence approach. Leucocytes of 20 individuals were exposed to 0, 0.1, 0.2 or 0.3 mM styrene 7,8-oxide (1 h) or 1, 2 or 3 gray (=100, 200, 300 rad) {gamma} radiation. Genotoxicity was evaluated with the cytokinesis-block micronucleus assay. Comparison of the two slopes of the regression lines between micronuclei and dose revealed a genotoxic potency for styrene 7,8-oxide of 37 rad/mMh, corresponding with a median value derived from mutagenicity studies (1, 37, 208 rad/mMh). At exposure levels of 1 ppm styrene, a blood styrene 7,8-oxide concentration between 0.03 x 10–6 and 0.42 x 10–6 mM is to be expected using data of toxicokinetic models and human exposure studies. With the cancer risk per unit dose of {gamma} radiation as benchmark, we calculated a lifetime risk of acquiring a fatal lympho-hematopoietic cancer of 0.17 in 103 workers (between 0.037 x 10–3 and 5.0 x 10–3) exposed to 20 ppm styrene during 40 years.

* To whom correspondence should be addressed. Tel: +32 16 390411; Fax: +32 16 400236; Email: lode.godderis{at}idewe.be

Received on August 29, 2006; revised on January 11, 2007; accepted on January 15, 2007.


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