IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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(iv) Protein adducts
Christakopoulos et al. (1993) compared 17 styrene-exposed reinforced-plastics
workers (years of exposure: 0.2–15; mean, 6.7) with 11 non-exposed controls and found
linear correlations between concentrations of haemoglobin adducts and free styrene
7,8-oxide in blood (r = 0.71), styrene glycol in blood (r = 0.94) and mandelic acid in
urine (r = 0.92). [The Working Group noted that no information was available on styrene
exposure concentrations for these workers.] Severi et al. (1994) looked for haemoglobin
adducts of styrene 7,8-oxide in 52 workers having an average styrene exposure of
31 mg/m 3 and found none (detection limit of 10 pmol/g).
Yeowell-O’Connell et al. (1996) measured adducts in 48 workers exposed to both
styrene (0.9–235 mg/m 3 ; mean, 64.3 mg/m 3 ) and styrene 7,8-oxide (13.4–525 μg/m 3 ;
mean, 159 μg/m 3 for 20 subjects) in a boat-building plant. They found no increase in the
amount of haemoglobin adducts, but levels of albumin adducts increased with exposures
to both styrene and styrene 7,8-oxide. Further analysis of these data (Rappaport et al.,
1996) indicated that the albumin adducts correlated better with airborne styrene
7,8-oxide than with styrene in those individuals for whom exposure to both chemicals
was measured. Fustinoni et al. (1998) compared 22 workers selected on the basis of high
levels of exposure to styrene (estimated to be about 100 mg/m 3 ) with 15 controls. The
mean levels of 2-phenylethanol and 1-phenylethanol — obtained by chemical cleavage
of styrene 7,8-oxide–cysteine adducts — were respectively 2.84 and 0.60 nmol/g
albumin and 5.44 and 0.43 nmol/g haemoglobin for the workers and 2.74 and
0.50 nmol/g albumin and 5.27 and 0.39 nmol/g haemoglobin for controls. Differences
between workers and controls were significant only when the data for the workers were
stratified for high exposure. Johanson et al. (2000) exposed four male volunteers to 50
ppm [213 mg/m 3 ] [ 13 C 8]styrene for 2 h. Maximal concentrations of styrene 7,8-oxide in
blood (average, 6.7 nM) were seen at 2 h. Hydroxyphenylethylvaline was estimated at
0.3 pmol/g globin. The major (> 95%) portion of the [ 13 C 8]styrene metabolites in urine
was derived from hydrolysis of styrene 7,8-oxide, with less than 5% coming from metabolism
via the phenylacetaldehyde pathway.
(b) Experimental systems (see Table 13 for references)
Results from studies published since the previous evaluation of styrene are summarized
in Table 13.
(i) DNA adducts
IARC MONOGRAPHS VOLUME 82
Both N7- and O 6 -deoxyguanosine adducts were formed in NMRI mouse liver, lung
and spleen evaluated 3 h after a single intraperitoneal injection of styrene at doses
ranging from 0.28 to 4.35 mmol/kg bw (Pauwels et al., 1996). A dose–response relationship
was reported for both adducts in all three tissues. The N7-alkyldeoxyguanosine was
more abundant than the O 6 -deoxyguanosine adduct and the levels of both adducts were
highest in lung tissue. Samples of liver and lung DNA, taken from CD-1 mice and
Sprague-Dawley rats 42 h after a 6-h exposure to 160 ppm [682 mg/m 3 ] [ 14 C]styrene,