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Accepted Manuscript
Title: How much does benzene contribute to the overall
burden of cancer due to occupation?
Authors: L. Rushton, T.P. Brown, J. Cherrie, L. Fortunato, M.
Van Tongeren, S.J. Hutchings
PII: S0009-2797(09)00478-5
DOI: doi:10.1016/j.cbi.2009.11.007
Reference: CBI 6050
To appear in: Chemico-Biological Interactions
Please cite this article as: L. Rushton, T.P. Brown, J. Cherrie, L. Fortunato, M.
Van Tongeren, S.J. Hutchings, How much does benzene contribute to the overall
burden of cancer due to occupation?, Chemico-Biological Interactions (2008),
doi:10.1016/j.cbi.2009.11.007
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How much does benzene contribute to the overall burden of cancer due to
occupation?
L Rushton1*, TP Brown2, J Cherrie3, L Fortunato1, M Van Tongeren3, SJ Hutchings1
1 Department of Epidemiology and Public Health, Imperial College London, UK
2 Institute of Environment and Health, Cranfield University, UK.
3 Institute of Occupational Medicine, Edinburgh, UK.
1Imperial College London, Department of Public Health and Epidemiology, Faculty of
Medicine, Norfolk Place, London W2 3PG, UK
l.rushton@imperial.ac.uk; l.fortunato@imperial.ac.uk; s.hutchings@imperial.ac.uk
2Institute of Environment and Health, Cranfield Health, Cranfield University, Cranfield,
MK43 0AL
Terry.Brown@cranfield.ac.uk
3Institute of Occupational Medicine, Research Avenue North, Riccarton, Edinburgh
EH14 4AP
John.Cherrie@iom.org.uk
Martie.van.Tongeren@iom.org.uk
* Corresponding author
Telephone: +44(0)2075941801
Fax: +44(0)2075943196
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1 Introduction
Work-related cancers are largely preventable. There is increasing interest in estimating
and comparing burdens of disease generally [1] and for cancer [2]. Estimates can
identify major risk factors and high risk populations, support decisions on priority actions
for risk reduction and provide an understanding of important contributions to health
inequalities. The overall aim of this project is to estimate the current burden of cancer in
Great Britain attributable to occupational factors and identify carcinogenic agents,
industries and occupations for targeting risk prevention. This paper presents the results
for benzene associated with leukaemia and discusses these in the context of results for
other leukaemogens and other carcinogens and cancers sites.
2 Material and methods
The methods have been described in detail elsewhere [3]. Briefly, attributable fractions
(AF) (i.e. the proportion of cases that would not have occurred in the absence of
exposure) and attributable numbers (AN) are estimated for cancer mortality and
incidence for all cancers, agents and occupations classified by the International Agency
for Research on Cancer (IARC) as group 1 (definite) and 2A (probable) occupationally-
related human carcinogens [4]. Benzene is classified as a group 1 carcinogen.
Estimation was carried out using 2005 data for mortality and 2004 for cancer incidence.
There are several methods for estimating the AF but all depend on knowledge of the risk
of the disease due to the exposure of interest and the proportion of the target population
exposed [5]. A latency of 0-20 years was assumed for leukemia and we defined the risk
exposure period (REP) for deaths occurring in 2005 as 1986-2005.
The Carcinogen Exposure database (CAREX) was used as the basis for estimating
proportions exposed over the REP in different industry sectors, taking account of
changing employment levels and employment turnover [6]. A review of exposure to
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benzene in different industries and occupations in the US and Europe showed that
benzene levels have been greatly reduced over time in occupations such as the
petrochemical industry, service station attendants, the coke oven industry, motor
mechanics, aviation workers and urban workers [7]. A typical arithmetic mean (AM)
value for long-term exposure is around 0.3mg/m3, approximately 0.1ppm (1ppm =
3.25mg/m3), although values vary between much lower for urban workers such as traffic
police and bus drivers (0.20mg/m3), to much higher for workers in coke plants
(1.79mg/m3). An average cumulative exposure, assuming 30 or 40 years at 0.1ppm
level would be between 3 and 4ppm-years. Intermittent and short term exposures can
be much higher than the average long term exposures in several industries, with several
jobs having AMs over 2mg/m3 and some having maximum short-term exposure levels
over 10mg/m3 (3ppm). These types of workers might thus have had cumulative
exposures between 5-10ppm-years. Historically it is thought that some workers in the
1960s and 1970s might have been accumulating exposures much higher than this, up to
100ppm-years. These results were used to allocate the industry sectors in the CAREX
database to a ‘higher’ or ‘lower’ level of exposure.
Risk estimates for acute non-lymphocytic leukemia (ANLL) were selected from the
published literature and assigned to industry sectors to reflect the broad levels of
exposure as described above: (i) RR=1.32 (95%CI 0.49-2.88) for land transport [8] (ii)
RR=2.17 (95%CI 0.9-5.2) for workers in industrial chemical manufacturing [9] (iii)
RR=1.11 (95%CI 0.3-2.83) for industry groups with low levels of benzene exposure [10].
Monte Carlo methods were used to obtain random error confidence intervals (CI) for the
AFs and attributable numbers were estimated for adults aged 15-84 in GB by applying
the AFs to total cancer specific deaths for 2005 and cancer registrations for 2004.
3 Results
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A total of 3102 people (2001 male, 1101 female) died in 2005 aged 15-84 years from all
leukaemias in GB, including 1681 ANLLs (1017 male, 664 women); in 2004 there were
5402 cancer registrations for all leukaemias (3333 male, 1869 female) including 2820
ANLLs (1807 male, 1013 female). The AF for ANLL attributable to occupational
exposure to benzene was 0.25% (95% confidence interval (CI) 0, 4.65) overall and
0.19% (95% CI 0, 3.28) for males and 0.34% (95% CI 0, 6.76) for females. The
attributable fractions are higher for females than males due to the larger numbers
exposed at low risk to benzene in industry sectors such as personal and household
services which includes repair services, domestic services, dry cleaning, photography
etc. There were 2 deaths and 3 registrations for both males and females. These
occurred in the following industry sectors: wholesale and retail trade, restaurants and
hotels which included bulk petrol sales and gasoline retail sites (1 death, 1 registration),
land transport (0 deaths, 1 registration), personal and household services (3 deaths, 5
registrations).
IARC has evaluated 9 carcinogenic agents or occupations in relation to leukaemia.
Three of these, boot and shoe manufacture, petroleum refining and the rubber industry,
have been included in the estimate for benzene. The attributable fractions, numbers of
deaths and registrations for the burden of leukaemia due to the other 5 are presented in
Table 1 together with the results for benzene and all leukaemias. The numbers of deaths
and registrations for ionizing radiation are based on a subset of leukaemias excluding
chronic lymphatic leukaemia, those for benzene are based on ANLL and those for the
other agents on all leukaemias. In Table 1 the AFs for benzene and ionizing radiation
are related to all leukaemias for comparison purposes. The highest AFs and numbers of
deaths and registrations are found for non-arsenical insecticides followed by
formaldehyde and benzene. The higher estimates for both non-arsenical insecticides
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