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C. Hgucdt. C. Reu~cmrll.editors
133
LEUKEMIA AND APLASTIC AiiiiZ!CA I N A SiiOEWORKEFi COH@tlT EXPOSED TO BENZENE
.E.PAC1 1, E. BUIATTI 1. A.R. SENIOR1 COSTANTINI 1, L. M I L I G i 1.
14. QUI" 1, J. KALDOR 2 , L. SIMONATO 2 , R WINCKELMANN 2
-1 Center for Study and Prevention of Cancer
2 KARC Lyon
INTRODUCTlOr~
A retrospective cohort study of shoe workers w a s carried ou: in the largest shoe manufacturing plant i n Florence (1). B e x c ne w a s used as a s o l v e n t i n g l u e s d u r i n g the 1950s and 1960s i n shoe production and c a s e s of leukemia and a p l a s t i c anaemia occurred i n t h i s plant. A national regulatjon Illsited the use of benzene i n 1963 and s i n c e 1965 benzene h a s no; been used i . : t h i s i n d u s t r y i n q u a n t i t i e s g r e a t e r than 2% by w e i x t .
I hATERIALS AND METHODS t-lembers of the conor'c s t u d y are workP.-lj r e c o t ~ s di n --.? 317.n.; :?*1nt;-y cs h a v i a 2 been e,aalo.f?*ion o r s f t e r 01.01.1950. The .analysis ? r e s e n t e d ilere is r e s t r i c t e d 'ia che s u b j e c t s a t W Q ~ K %tween 1953-1964; the p e r i o d in wich oenzene w a s used. Y.\e follow- up ended on 31.12.1984 and n a t i o n a l i t a l i a n populat i o n m o r t a l i t y rates o b t a i n e d by t h e WHO were used f o r scandard i z a t i o n by age, s e x and c a l e n d a r period. Additional evidence of t h e cause of death w a s c o l l e c t e d for the cases of leukemia and a p l a s t i c anaemia using several sources of information ( c l i n i c a l recoras, legal proceedings, documentation, published reports 1. The data a n a l y s i s w a s c a r r i e d o u t using the Person Year Program
(2).
THE EXPOSURE ASSESSMENT
A preliminary assessment of the average concentration of ben-
zene i n the g e n e r a l room a i r of the p l a n t w a s made over the t i -
me period when benzene w a s used.
-.
Plant records, testimonies submitted for legal proceedings, in-
terviews w i t h p l a n t managers and older workers, and site v i s i t s
were used t o make the benzene exposure estlmates.
The q u a n t i t y of benzene t h a t w a s used w a s estimated u s i n g infof
mation i n c l u d i n g the annual production of shoes. the amount of
glue used for each p a i r of shoes, the percentage of benzene c o ~
tained i n the glues and the d i s t r i b u t i o n of glue use throughout
the plant.
Blue p r i n t s and engineerifig records were used t o e s t i m a t e the
air changes p e r
hour on each floor from n a t u r a l and mechanA
cal ventilation. A range of concentrations of benzene w a s than
estimated usirig a dynamic model considering continuos v e n t i l a -
-
134
Fig.1 a ) Cases and work p e r i o d b ) Ag evenrear E crooonmc eanit rra c i o n o f benzene 5n
.-
11 10
9
aC 8
es 7 s6
-
5 4
3 2
1
7940
4
A
50 ' '60
'70
J
leukaemia
A aplastic
anaemia dwhomas
-wpeorrikod
'80 years
p'
tion rates w i t The benzene a i t e h a v e r a g e s i3
.when windows h
dows
RESULTS
I n the whole neoplasm and 1 kemias, 1 "otr. p l a s t i c anaemi the aplastic a ( 95% CI:146-6-
Figure 1 shows the cohort ove benzene a i r cc
Table 1 and 2 in the subconc duration of ex (1953 i f they
DISCUSSION
The p a t t e r r . s t i c anaemia c in the cohort tionship betwe A relevant fir, after the e l i x nalysis did nc duration of ex there w a s misc popul a t1on. We are c o n d u c t 1 t e an index of the exposure 7 lne exposure 5 benzene concer athifig zone a i that involved
I
1940 50 '60 '70 '80 years
I 135
t i o n r a t e s w i t h t h e windows open and closed. I The benzene air c o n c e n t r a t i o n s p r e s e n t e d i n Figure 1 a r e weigh-
ted averages of t h i s range assuming a '3.5 month cool p e r i o d when windows would be s h u t and a 8.5 month period of open Windows.
RESULTS
I n the whole cohort 1 c a s e of lymphatic:. and hem a t o p o i e t i c neoplasm and 1 a p l a s t i c anaemia o c c u r r e d among females: s i x leg kemias, 1 " other lympatic and hematopoietic neoplasm" and 6 aplastic anaemias among males. The SMRs f o r males were 1566 for the a p l a s t i c anaemia (95% CI: 547-3264) and 400 f o r leukemia (95% CI:146-870).
F i g u r e 1 shows the p a t t e r n of occurrence of the case s e r i e s i n the cohort over time compared w i t h the annual e s t i m a t e s of t h e benzene air concentration the plant.
Table 1 and 2 show the leukemia and a p l a s t i c anemia m o r t a l i t y i n t h e subcohort exposed t o benzene i n the period 1953-1964 by duration of exposure and r i s k i n t e r v a l since first exposure (1953 i f they were a t work b e f o r e t h i s date).
DISCUSSION
The p a t t e r n of the occurrence o f cases of leukemia and apla-
- s t i c anaemia over t i m e is c o n s i s t e n t w i t h the r e s u l t s o b t a i n e d
i n the cohort mortality study showing a strong temporal relationship between benzene exposure and deaths. A r e l e v a n t f i n d i n g is t h a t no cases occurred i n people a t work
* a f t e r the e l i m i n a t i o n of t h e benzene exposure. However, the a-
1 n a l y s i s d i d not show an i n c r e a s i n g r i s k w i t h e i t h e r l a t e n c y or d u r a t i o n of exposure. A p o s s i b l e e x p l a n a t i o n for t h i s is t h a t there w a s m i s c l a s s i f i c a t i o n of the exposure within the s t u d y population. We -conducting a more precise exposure assessment t o c a l c u l a te an index of exposure f o r i n d i v i d u a l s i n the cohort based on the exposure t o benzene i n each job over time. "ne exposure f o r each j o b w i l l i n c l u d e an e s t i m a t e of the a i r - benzene concentration i n work areas and an estimate of the brea t h i n g zone a i r c o n c e n t r a t i o n and s k i n exposure for the j o b s that involved the direct a p p l i c a t i o n of benzene-based glues.
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136
TABLE 1 LEUKEMIA MORTALITY I N COHORT STUDY POPULATION
.-
Observed (0).expected (E), and Standardised Mortality Ratios
(SMR) f o r leukemia by d u r a t i o n exposure and r i s k i n t e r v a l s i n c e first exposure i n the exposed sub-cohort (Males).
Risk i n t e r v a l since first exposure (years)
Duration of employ. i n the period 1953-1964 ( y e a r s )
0-4 5-9 10-19
i1 0.13 753 4 1
1 0.13 719
i1 0.16 611 1-5 2 0.36 555
3 0.44 679 25
3 0.72 416
TABLE 2
APLASTIC ANAEMIA MORTALITY I N COHORT STUDY POPULATION
Observed (01,expected (E) and Standardized Mortality Ratios
( SMR )
by duration of exposure and r i s k i n t e r -
V a l s i n c e first exposure i.n t h e exposed sub- cohort (Males).
Duration of employ. (years-)
--y-e-a-r -s -
0-4
2 0.06 3333
I
I Ll 1 0.05 2000
5-9 2 0.06 3333
I 1-5 2 0.11 1818
10-19 2 0.10 2000
;I >5
3 0.19 1578
20-29 0 0.09
I
II
.T.o.t.a.l.e.....6......0...3.1....1.9.3.5............II...........6.....0...3.1....1935
REFERENCES
1) E . P a c i , E . B u i a t t i e t a1 (1988) Leukemia a p l a s t i c anaemia and other cancer mortality (submitted f o r pubblication)
2) M.Coleman, A.Douglas e t a1 Cohort s t u d y a n a l y s i s w i t h a f o r tan computer program (1986) Xnt.J.Epid.15,134-137
0 1988 Ekevi~~r c 1 i Sosrru in OCEupati C. Hoytedt, C. Rei
mKrALrrY IN
GILus PARADI Department of
man 300 A, M
school of occ
1
A historic determine whe disease, l m g
'%
arployed at t. G7 y e a r s a s o f J
u n t i l death, frun prwinci. cenputed u s i r reference.
The total : of 94.0% of t i this'cohort wi population (( exL3esses in m
SMR=109: 95% c 95%CI:95-118 -92; 95%CStatistically disease and f c length of erp-
for cixudatofor ischemic I with less tlm
we concludc
m y eqeriencc findings for A eweess iseherm
PROGRESS IN OCCUPATIONAL EPIDEMIOLOGY
Proceedings of the Sixth International Symposium on Epidemiology in Occupational Health, Stockholm, Sweden, 16-19 August 1988
Editors: Christer Hogstedt
Departments of Occupational Medicine, Karolinska Hospital and National Institute of Occupational Health Solna. Sweden
Christina Reuterwall Department of Occupational Medicine National Institute of Occupational Health Solna, Sweden
@J1988-
EXCERPTA MEDICA, Amsterdam - New York - Oxford