IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

472
IARC MONOGRAPHS VOLUME 82
more than the number expected (SMR, 1.1; 95% CI, 0.88–1.3). There were 48 observed
deaths from leukaemia in the overall cohort (SMR, 1.3; 95% CI, 0.97–1.7). There was a
statistically significant excess of leukaemia among workers in polymerization (15 deaths;
SMR, 2.5; 95% CI, 1.4–4.1), maintenance labour (13 deaths; SMR, 2.7; 95% CI, 1.4–4.5)
and laboratories (10 deaths; SMR, 4.3; 95% CI, 2.1–7.9), which were three areas with
potential for relatively high exposure to 1,3-butadiene or styrene monomers. Among the
‘ever hourly-paid’ workers with 10 or more years of employment and 20 or more years
since hire, there was a significant excess of leukaemia deaths (28 deaths; SMR, 2.2;
95% CI, 1.5–3.2).
Delzell et al. (2001) and Sielken & Valdez-Flores (2001) re-analysed the University
of Alabama results on leukaemia deaths within the US and Canadian cohorts. In these
studies, the exposure assessments for 1,3-butadiene and styrene were revised, as compared
with the earlier report (Macaluso et al., 1996) and exposure estimates were developed
for dimethyldithiocarbamate (DMDTC). [The Working Group noted that, unlike in
the earlier report, assessment of exposure was performed after knowing the jobs and
departments of the leukaemia cases.] Workers from two facilities had exposure records
of insufficient quality and were dropped from the original study, leaving 13 130 men
from six of the plants, and 59 deaths from leukaemia (medical records were obtained for
48 cases and one case was an acute unspecified leukaemia) during 1943–91 (in 234 416
person–years). Vital status was known for over 99% of the subjects, and death certificates
were available for 98% of the decedents. In the within-cohort comparisons (Poisson
regression), unlike in the cohort (SMR) study, all leukaemia deaths (leukaemia being
either an underlying or a contributing cause of death) were used; 49 of the leukaemia
deaths were confirmed from medical records. About 79% of the cohort subjects were
exposed to 1,3-butadiene, the median cumulative exposure being 71 ppm–years
[301 mg/m 3 –years], and 85% to styrene, with a median cumulative exposure of 17 ppm–
years [72 mg/m 3 –years], and 62% to DMDTC with a median cumulative exposure 1 of
373.9 mg–years/cm. Poisson regression analyses with the individual exposures indicated
a positive and monotonically increasing association between grouped cumulative exposure
to styrene (relative risks of 1.0, 1.2, 2.3 and 3.2, for exposures of 0, > 0–< 20.6,
20.6–< 60.4 and ≥ 60.4 ppm–years) and leukaemia, and between exposure to 1,3-butadiene
and leukaemia. For both of the exposures, a statistically significant relative risk
was obtained for the highest cumulative exposure category (for styrene: relative risk, 3.2;
95% CI, 1.2–8.8; 18 deaths; for 1,3-butadiene: relative risk, 3.8; 95% CI, 1.6–9.1; 17
deaths). The exposure–response relationship for DMDTC and leukaemia did not increase
monotonically, but a significantly increased relative risk was observed for each of the
exposed groups. In models that included all three exposures, the exposure–response
1 The DMDTC exposure estimation procedure yielded: (1) an estimate of the concentration of DMDTC in
the solution wetting the skin of the exposed worker (in mg/cm 3 ); (2) an estimate of the skin surface exposed
(in cm 2 ); and (3) an estimate of the frequency and duration of exposure. The exposure intensity unit was
(mg/cm 3 ) × (cm 2 ) = mg/cm.