IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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Haufroid et al. (2001) examined possible influences of genetic polymorphisms in
metabolic enzymes on the metabolism of styrene (average concentration, 18.2 ppm
[77.5 mg/m 3 ]) in 30 workers from a glass fibre-reinforced plastics factory. The presence
of the rare CYP2E1*1B allele was associated with increased excretion of urinary
mandelic and phenylglyoxylic acids as well as mercapturic acid metabolites. Individuals
deficient in glutathione S-transferase (GST) M1 excreted less than one-half the amount
of mercapturic acids, a minor pathway in humans, compared with GSTM1– proficient
individuals.
De Palma et al. (2001) examined polymorphisms in GSTM1-1 and T1-1 and microsomal
epoxide hydrolase in 56 styrene-exposed workers (geometric mean exposure,
157 mg/m 3 , time-weighted average over 8 h). GSTM1-1 was identified as the primary
isozyme for conjugation of glutathione with styrene 7,8-oxide. Workers who were positive
for GSTM1-1 excreted 5–6 times more phenylhydroxyethylmercapturic acids than
did individuals who were GSTM1-1-deficient. No association was found between microsomal
epoxide hydrolase polymorphisms and excretion of the mercapturic acids.
(d ) Excretion
Only small amounts of styrene (0.7–4.4%) are exhaled unchanged (see IARC, 1994a
for details). This has been confirmed in more recent studies, in which 0.7–2.2% of the
amount of inhaled styrene was found unchanged in the exhaled breath of four subjects
exposed to 50 ppm [213 mg/m 3 ] styrene for 2 h (Johanson et al., 2000). Small amounts
of styrene are also excreted unmetabolized in the urine (Pezzagno et al., 1985; Gobba
et al. 1993). Ramsey et al. (1980) examined the pharmacokinetics of inhaled styrene
(80 ppm [341 mg/m 3 ]) in four human volunteers and calculated half-life values of 0.6 and
13.0 h for the two phases of elimination.
Brugnone et al. (1993) measured styrene concentrations in blood of 76 exposed
workers at the end of the work shift and the morning after, and reported a half-life of elimination
of 3.9 h.
4.1.2 Experimental systems
(a) Absorption
IARC MONOGRAPHS VOLUME 82
McDougal et al. (1990) compared the dermal absorption of vapours from several
organic chemicals in male Fischer 344 rats. The animals breathed fresh air through a
latex mask. For styrene (3000 ppm [12 800 mg/m 3 ] for 4 h), a maximal blood concentration
of about 10 μg/mL and a permeability constant of 1.753 cm/h were reported. In a
mixed exposure situation (inhalation and skin absorption), the skin uptake was estimated
to account for 9.4% of the total uptake in these rats. Morgan et al. (1991) examined the
dermal absorption of styrene in Fischer 344 rats. When administered neat (2 mL of
styrene in a sealed dermal cell), the peak blood level of styrene, reached after 1 h, was
5.3 μg/mL. Absorption decreased when the styrene was diluted with water.