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showed increased levels of N7-deoxyguanosine adducts for both species (Boogaard
et al., 2000b). The adduct level in rat lung fractions enriched in type II cells was approximately
three times higher than that in total lung, whereas the adduct level in mouse lung
fractions enriched in Clara cells was similar to that of total lung. In these studies, the
covalent binding indices (CBI) were all below 0.5.
Otteneder et al. (2002) did not detect O 6 -deoxyguanosine adducts in DNA from lung
tissue of CD-1 mice or CD rats exposed to 160 ppm or 500 ppm [682 or 2130 mg/m 3 ]
styrene, respectively for two weeks (6 h per day, five days per week). The limit of
detection in the 32 P-postlabelling method used in this study was one adduct per 10 7
nucleotides. However, both α and β isomers of O 6 -dG-styrene 7,8-oxide adducts were
detected in DNA from CD rats that were exposed by inhalation to 1000 ppm
[4260 mg/m 3 ] styrene for two years (6 h per day, five days per week). The authors noted
that DNA adduct formation in tissue homogenates did not reflect either the species difference
in carcinogenicity nor the target organ specificity of styrene.
(ii) Mutation and allied effects
Positive and negative results have previously been reported for styrene-induced
mutations in Salmonella typhimurium (IARC, 1994a). Positive results were reported in
studies using strains TA1530 or TA1535 with the addition of an exogenous metabolic
activation system. No new data on mutations in S. typhimurium have been reported.
Results from one study of somatic mutations in Drosophila melanogaster were negative.
This study used both insecticide-susceptible (IS) and -resistant (IR) strains, which
differ in their activities of drug-metabolizing enzymes, to evaluate mutations in the w/w+
mosaic assay. Females were exposed to styrene at a concentration of 1040 μg/mL in the
feed medium. Although negative results were reported for the IS strain, positive results
were seen in the IR strain at this dose. Two studies of the induction of sister chromatid
exchange in human lymphocytes exposed to styrene in vitro also gave positive results.
These observations are consistent with those from earlier studies.
DNA strand breaks were induced in liver, kidney, bone marrow and lymphocytes of
C57BL/6 mice given a single intraperitoneal injection of styrene. On the other hand,
neither chromosomal aberrations nor sister chromatid exchange were seen in
lymphocytes of Fischer 344 rats exposed to styrene by inhalation at a concentration of
1000 ppm [4260 mg/m 3 ] for 6 h per day on five days per week for four weeks.
4.4.2 Styrene 7,8-oxide
(a) Humans
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No data on effects of exposure of humans to styrene 7,8-oxide alone were available
to the Working Group.