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Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis

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  • EpidStat Institute

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Background: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis. Methods: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I 2 estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures. Results: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61–1.05) with significant heterogeneity (P-H
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© e Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.
•  1
RE VIEW
Mesothelioma among Motor Vehicle
Mechanics: An Updated Review and
Meta-analysis
David H.Garabrant
1,2
*, Dominik D.Alexander
1
, Paula E.Miller
1
,
Jon P.Fryzek
1
, PaoloBoea
3
, M. J.Teta
4
, Patrick A.Hessel
5
, Valerie
A.Craven
6
, Michael A.Kelsh
7
and MichaelGoodman
8
1.EpidStat Institute, 2100 Commonwealth Blvd, Suite 203, Ann Arbor, MI 48105, USA;
2.University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA;
3.e Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai,
One Gustave L. Levy Place, Box 1133, New York, NY 10029, USA;
4.Department of Health Sciences, Exponent, Inc., 420 Lexington Avenue, New York, NY 10170, USA;
5.EpiLung Consulting, #25, 26204 Township Road 512, Spruce Grove, Alberta, Canada T7Y 1C5;
6.Exponent, Inc., 500 12th Street, Suite 220, Oakland, CA 94607, USA;
7.Amgen, Inc One Amgen Center Drive, ousand Oaks, CA 91320, USA;
8.Emory University School of Public Health, 1518 Clion Road, Atlanta, GA 30322, USA
*Author to whom correspondence should be addressed. Tel:734-929-9150; e-mail: david@epidstat.com
Submied 10 February 2015; revised 8 May 2015; revised version accepted 21 July 2015.
ABSTRACT
Background: We published a meta-analysis of the association between work as a motor vehicle mechanic
and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. us,
to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis.
Methods: A comprehensive PubMed literature search through May 2014 was conducted to identify
studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in gen-
eral), and those who were engaged in brake repair (specically). Studies were scored and classied
based on study characteristics. Random-eects meta-analyses generated summary relative risk esti-
mates (SRREs) and corresponding 95% condence intervals (CI). Heterogeneity of results was exam-
ined by calculating Q-test P-values (P-H) and I
2
estimates. Sub-group and sensitivity analyses were
conducted for relevant study characteristics and quality measures.
Results: Ten case-control studies, one cohort study, and ve proportionate mortality ratio (PMR)/
standardized mortality odds ratio (SMOR) studies were identied and included in the quantitative
assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically signicant
increases in mesothelioma were observed. e SRRE for all studies was 0.80 (95% CI: 0.61–1.05) with
signicant heterogeneity (P-H <0.001, I
2
=62.90). Asimilar SRRE was observed among the ve Tier
1 studies with the highest quality ratings (SRRE=0.76, 95% CI: 0.46–1.25), with no heterogeneity
Ann. Occup. Hyg., 2015, 1–19
doi:10.1093/annhyg/mev060
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among studies (P-H=0.912, I
2
=0.00). Meta-analysis of the Tier 2 (n=5) and Tier 3 (n=6) studies
resulted in SRREs of 1.09 (95% CI: 0.76–1.58) and 0.73 (95% CI: 0.49–1.08), respectively. Restricting
the analysis to Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72–1.29). e SRRE
specic to brake work (n=4) was 0.64 (95% CI: 0.38–1.09).
Conclusions: is meta-analysis of the epidemiologic studies provides evidence that motor vehicle
mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma.
KEYWORDS: asbestos epidemiology; auto repair; brake dust; cancer epidemiology; chrysotile;
mesothelioma
INTRODUCTION
Studies of motor vehicle repair activities and brake
repair activities provide an opportunity to examine
the risks of mesothelioma in seings in which chry-
sotile exposure is not accompanied by exposure to
commercial amphibole products. Exposure to short
chrysotile bers can occur during installation and
repair of asbestos-containing brakes, clutches, and
gaskets. In the past, automobile brakes typically con-
tained chrysotile asbestos embedded in a solid binder
(Jacko et al., 1975). In the USA, EPA banned the
manufacture, importation, and processing of brake
linings and pads containing asbestos in 1993 (EPA,
1989). Although the phase-out of asbestos-containing
brakes likely began in the 1980s, brakes that were in
place in 1993 continued to be replaced aer the ban
took eect. e process of brake replacement involves
three potential opportunities for release of asbestos
bers: (i) small amounts of chrysotile asbestos (usu-
ally <1%) may be present in the brake wear debris
(Lynch, 1968; Hickish and Knight, 1970; Anderson
et al., 1973; Jacko and DuCharme, 1973; Rowson,
1978; Williams and Muhlbaier, 1982; Cha etal., 1983;
NIOSH etal., 1989), (ii) asbestos can be released dur-
ing sanding, grinding, and beveling of new asbestos
brake linings or pads, and (iii) asbestos can be released
during handling of new brakes and packaging materi-
als (Madl etal., 2008).
Some authors (Freeman and Kohles, 2012; Lorimer
etal., 1976), regulatory agencies (EPA, 1986b), and
trade organizations (World Trade Organization,
2000) have opined in the past that motor vehicle
mechanics are likely to be at increased risk of asbes-
tos-related disease, most notably mesothelioma.
ese opinions were based primarily on the assumed
opportunity for asbestos exposure during brake work
(Paustenbach et al., 2004; Madl et al., 2008; IARC,
2012) and on case reports of mesothelioma among
brake repair workers (EPA, 1986a,b, 1989; Lemen,
2004). However, case reports and case series cannot
quantify associations and are not adequate for assess-
ing causality (Hennekens and Buring, 1987). Case
reports and case series become even less informative
in the presence of analytic studies.
When the EPA conducted its evaluation ~30years
ago (EPA, 1986a,b), the epidemiologic information
on mesothelioma among vehicle mechanics was lim-
ited to only three studies (McDonald and McDonald,
1980; Teta etal., 1983; Spirtas etal., 1985). Our pre-
vious meta-analysis (Goodman etal., 2004) included
11 studies. In the past 10years, ve additional epide-
miologic studies (Rake et al., 2009; Aguilar-Madrid
etal., 2010; Rolland etal., 2010; Merlo etal., 2010;
Roelofs etal., 2013) and four updates of previous stud-
ies (McElvenny etal., 2005; Milham, 2011; NIOSH,
2011; Health and Safety Executive, 2013) have exam-
ined the risk of mesothelioma among motor vehicle
mechanics or brake workers. erefore, an updated
systematic review is warranted.
Our objective was to conduct an updated system-
atic review and quantitative meta-analysis of the epi-
demiologic literature examining the relative risk (RR)
of mesothelioma among workers engaged in motor
vehicle repair and, when possible, among workers
occupationally exposed to brake dust. e specic
aims were to: (i) estimate summary relative risk esti-
mates (SRREs) between motor vehicle mechanics and
mesothelioma; (ii) conduct sub-group and sensitivity
analyses by relevant study characteristics (e.g. study
design and type of population) to identify potential
sources of heterogeneity; (iii) estimate the inuence
of each study on the overall eect size; (iv) examine
potential trends of associations for certain study fac-
tors (study quality, study period) using meta-regres-
sion; and (v) evaluate the potential for publication
bias.
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METHODS
Literature search and study selection
A comprehensive literature search was conducted
using PubMed and Embase to identify studies evaluat-
ing mesothelioma risk among motor vehicle mechan-
ics. e literature search was conducted through May
2014, with no lower date truncation. Keyword searches
were conducted in PubMed and Embase for terms
including ‘mesothelioma, ‘pleural neoplasms’, ‘pleura
tumor, ‘occupational exposure, ‘occupational dis-
eases’, ‘asbestos’, ‘motor vehicles’, ‘automobiles’, ‘auto-
mobile industry, ‘mechanics’, ‘case control studies,
odds ratio, ‘risk factors’, ‘mortality/trends’, ‘registries’,
‘incidence, ‘epidemiology, and ‘population surveil-
lance. References from relevant studies, review arti-
cles, and previous meta-analyses were also screened.
Additional electronic searches were conducted to
identify relevant studies that were not published in
the peer-reviewed literature, including government
documents. When information was missing from
published reports, aempts were made to contact the
authors to obtain it. Search results were screened by
two individuals to determine relevancy, with no dis-
crepancies between reviewers (Fig.1). To be included
in the meta-analysis, studies were required to meet the
following criteria: (i) cohort or case-control design
reporting incidence or mortality, or studies based on
analyses of proportions [proportionate mortality ratio
(PMR)/proportional incidence ratio (PIR)/stand-
ardized mortality odds ratio (SMOR) analyses]; (ii)
analysis of an adult human population; (iii) meso-
thelioma risk analyzed among subjects involved in
motor vehicle repair (if a study reported results only
on the broad category of general mechanics, it was not
included in the meta-analysis); and (iv) mesothelioma
RR estimates and variance measures either reported in
the original publication or calculated based on the data
obtained from the authors or reported in the papers.
Study quality scoring methodology
All studies retained for quantitative assessment under-
went formal evaluation and were assigned a quality
score according to their methodological strengths and
limitations, based on the methods used in our previous
Figure1 Flow diagram of study selection.
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paper (Goodman etal., 2004) and those recommended
in the Meta-analysis Of Observational Studies in
Epidemiology (MOOSE) (Stroup et al., 2000) and
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) (Moher etal., 2009) guide-
lines. Each study was awarded a point for fullling each
methodological criterion and a score of zero for failing
to do so. e scoring used the following 12 criteria:
• Overall study design: PMR/PIR studies or
death certicate-based SMOR studies=0;
else (cohort or case–control studies)=1.
• Asbestos exposure: Job title based=0 (e.g.
car mechanic’); task specic=1 [e.g. ‘brake
repairmen’ or industrial hygiene (IH) based].
• Was age taken into account? no=0; yes=1.
• Lifetime asbestos exposure history obtained:
no=0; yes=1.
• Did study methods or analysis address
confounding in any way? no=0; yes=1.
• Exposure-response analysis performed?
no=0; yes=1.
• Was latency taken into account? no=0; yes=1.
• For cohort studies, duration of follow-up:
<30years=0; ≥30years=1.
• For case-control studies, response rate <80%
or not reported:=0; ≥80%=1.
• Information bias: possible=0; unlikely/
addressed=1 (e.g. in case–control studies
using recorded occupational histories).
• Selection bias: possible=0 (e.g. in hospital-
based case-control studies); unlikely/
addressed=1 (e.g. in cohort studies or
population-based case-control studies).
• Cases conrmed by pathologic review:
no=0; yes=1.
Scoring was used as a formal approach to classify
studies into three equal sized tiers. Studies with scores
of seven or above were included in Tier 1 and consid-
ered to have the strongest study design and analysis
and less opportunity for bias. Tier 2 included studies
with a score of ve or six, which were considered less
informative due to methodological limitations. Tier 3
included studies that scored four or less. It should be
noted that many of the scoring criteria related to inher-
ent strengths or limitations of the study design and the
underlying data, and not necessarily to the methodo-
logical decisions of the original investigators.
Data extraction and statistical analysis
Information extracted from each study using a stand-
ard form included rst author, publication year, study
design, nature of cohort, geographic location of study,
exposure denition, source of cases, comparison
group, sample size, number of cases, years of follow-
up, population demographic characteristics, outcome
classication, measures RR and 95% condence inter-
vals (CIs) for each relevant exposure group and worker
classication, statistical adjustments, and the method-
ological factors on which scoring was based. If more
than one article from the same study population was
published, data from the publication with the longest
follow-up and/or the most completely adjusted risk
estimate wasused.
Random-eects models were used to calculate
SRREs and 95% CIs. e study weights were equal to
the inverse of the variance of each studys eect estimate
(DerSimonian and Laird, 1986). Measures of RR [e.g.
odds ratios (ORs), rate ratios, standardized mortality
ratios(SMRs)] and associated measures of variance (e.g.
95% CIs) were used as input parameters in the meta-
analysis models. Four case-control studies (McDonald
and McDonald, 1980; Woitowitz and Rodelsperger,
1994; Agudo etal., 2000; Aguilar-Madrid etal., 2010)
did not report the results in terms of ORs but provided
information from which ORs and 95% CIs could be cal-
culated using SAS 9.3 (Cary, NC, USA). Two propor-
tional mortality studies (Milham and Ossiander, 2001;
NIOSH, 2011) did not report 95% CIs, but provided
numbers of observed and expected cases, from which
95% CIs were calculated based on the Poisson distribu-
tion (Breslow and Day, 1987).
Primary meta-analysis models were used to gen-
erate SRREs for case-control and cohort studies of
motor vehicle mechanics and mesothelioma overall
and by study tiers. e base model included all eligi-
ble studies, and separate models were created for each
study quality tier. Sub-group and sensitivity analyses
were conducted to examine paerns of associations
and to identify potential sources of heterogeneity
overall and for groups of studies. ese included analy-
ses by study design, geographic location, and asbestos
exposure history ascertainment. One-study-removed
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sensitivity analyses were conducted to determine the
relative inuence of each study on the overallmodel.
Heterogeneity was assessed quantitatively using the
Cochrans Q-test with the corresponding P-value (P-
H) and by calculating the I
2
statistic, which indicates
the percentage of variation aributable to between-
study heterogeneity (Higgins and ompson, 2002).
e presence of publication bias was assessed visually
by examining a funnel plot measuring the standard
error as a function of eect size, as well as perform-
ing Eggers regression method (Rothstein etal., 2005).
We generated forest plots for models of motor vehicle
mechanics and mesothelioma by study quality tiers.
Meta-regression analyses were performed to evaluate
the paerns in summary eect sizes based on relevant
factors (modeled as continuous variables), such as
increasing study quality and study period. Statistical
analyses were conducted using Comprehensive
Meta-Analysis Soware (version 2.2.046; Biostat,
Englewood, NJ, USA), SAS 9.3 (SAS Institute, Cary,
NC, USA), and STATA statistical soware (Stata
Corporation, College Station, TX, USA).
RESULTS
Ten case-control studies, one cohort study, and ve
PMR/SMOR studies published between 1980 and
2013 were included in the meta-analysis (Table1). Since
RRs could not be calculated for three cohort studies of
motor vehicle mechanics (two from Sweden and one
from Denmark) that provided information on meso-
thelioma (Jarvholm and Brisman, 1988; Hansen, 1989;
Gustavsson etal., 1990), these studies were not included
in the meta-analysis. Five studies were of higher method-
ological quality (Tier 1), ve studies were of moderate
methodological quality (Tier 2), while six studies were
of lower methodological quality (Tier 3)(Table2).
Overview of studies included in meta-analysis
Tier1
McDonald (McDonald and McDonald, 1980) com-
pared histologically conrmed mesothelioma cases in
the USA and Canada to matched controls that had pul-
monary metastases from non-pulmonary malignancies.
Lifetime occupational histories were obtained through
interviews with relatives. Of the 156 cases and 156
controls who worked in occupations thought to entail
asbestos exposure but not previously recognized as
associated with mesothelioma risk, 11 cases and 12 con-
trols were ‘garage’ workers, from which we calculated an
OR of 0.91 (95% CI: 0.35–2.34). is study had a large
sample size and a high next-of-kin response rate for
both cases (95%) and controls (91%). Hospital-based
cancer cases may not have been representative of the
source population of cases (i.e. possible selection bias).
However, the choice of controls with other cancers may
have reduced recall bias. e use of the highest asbestos
exposure to characterize each participant’s occupational
history likely decreased potential confounding by other
asbestos exposures.
Teta (Teta et al., 1983) compared pathologi-
cally conrmed cases from the Connecticut Tumor
Registry and from a Veterans Administration hospi-
tal with controls from Connecticut death certicate
les. Occupational histories were obtained from death
certicates and city directories and did not include
information specic to brake work. ere were 147
total cases and 464 controls with 1 exposed case and 5
exposed controls included in the analysis. e OR for
subjects employed in ‘automobile repair and related
service’ was 0.65 (95% CI: 0.08–5.53). e choice of
population controls, the completeness of occupational
records (job titles were obtained for 98% of cases and
99% of controls) and the histological conrmation of
cases were methodological strengths. Shortcomings
were a lack of information on brake repair work and
lack of control for confounding by other potential
sources of asbestos exposure. e OR estimate was
based on relatively few observations and did not take
into account exposure-response or latency.
Hessel (Hessel et al., 2004) updated a previous
National Cancer Institute (NCI) case-control study
(Spirtas etal., 1985, 1994). Pathologically conrmed
denite or probable mesothelioma cases in the Los
Angeles County Cancer Surveillance Program, the
New York State Cancer Registry (excluding New York
City) and 39 Veterans Administration hospitals were
included (n=147). Controls included patients who
died of causes other than cancer, respiratory disease,
suicide, or violence (n= 358). Interviews requested
lifetime occupational history and information spe-
cically on brake lining installation or repair. Hessel
calculated an OR of 1.04 (95% CI: 0.46–2.22) for the
occupational category ‘brake installation or repair’.
However, aer adjusting for any of eight occupations
with potential asbestos exposure, the OR became 0.82
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Table1. Summary of mesothelioma studies and corresponding RR estimates included in the meta-analysis.
First author Year Design Exposure denition Source of cases Comparison group RR estimate (95% CI)
a
Tier 1 studies
b
McDonald 1980 Case-control Garage workers Hospital records Non-pulmonary cancers 0.91 (0.35–2.34)
Teta 1983 Case-control Automobile repair and related
services
CT Tumor Registry Connecticut decedents 0.65 (0.08–5.53)
Teschke 1997 Case-control Vehicle mechanics British Columbias
Cancer Registry
Randomly selected from
voters lists
0.8 (0.2–2.3)
Brake lining installation or
repair
0.3 (0.0–1.4)
Vehicle mechanics (ever
employed in at-risk
occupations excluded)
0.4 (0.0–3.2)
Hessel 2004 Case-control Brake lining installation or
repair, all other asbestos
exposures controlled
NY Cancer Registry,
LA County Cancer
Surveillance Program,
VA Hospitals
Deaths from causes other
than cancer, respiratory
disease, suicide or violence
0.82 (0.36–1.80)
Rake 2009 Case-control Vehicle maintenance involving
work with brakes or gaskets
Hospital records, National
Cancer Research Network,
healthcare providers
Randomly selected from
Health Authority registers
0.4 (0.1–1.7)
Tier 2 studies
c
Agudo 2000 Case-control Mechanics, motor vehicles Hospital records Patients with non-asbestos-
related conditions
0.62 (0.11–2.36)
Hansen 2003 Case-control Repair of motor vehicles and
motorcycles
Danish Cancer Registry All other occupations
combined
0.8 (0.4–1.5)
Aguilar-Madrid 2010 Case-control Automobile mechanics Two hospitals Randomly selected active
and retired workers in the
Mexican Institute of Social
Security database
0.74 (0.08–6.68)
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First author Year Design Exposure denition Source of cases Comparison group RR estimate (95% CI)
a
Merlo 2010 Cohort Bus maintenance workers Employees of Azienda
Municipalizzata Trasporti
Ligurian male population 1.27 (0.66–2.43)
Rolland 2010 Case-control Motor vehicle mechanics National Mesothelioma
Surveillance Program
Randomly selected from
the 1999 census
1.50 (0.76–2.95)
Tier 3 studies
d
Woitowitz 1994 Case-control Motor vehicle repair workers Not specied Lung resection patients
and population controls
0.87 (0.43–1.70)
Denitely engaged in brake
service
0.89 (0.31–2.47)
McElvenny 2005 Proportionate
mortality
Motor mechanics British mesothelioma
register
General population of Great
Britain
0.48 (0.37–0.62)
Milham 2011 Proportionate
mortality
Automobile mechanics and
repair workers
Washington State
residents
All other occupations
combined
0.73 (0.50–1.11)
NIOSH 2011 Proportionate
mortality
Auto mechanics National Occupational
Mortality Surveillance
database
All other occupations
combined
0.82 (0.50–1.27)
Health and
Safety Executive
2013 Proportionate
mortality
Motor mechanics; auto
engineers
British mesothelioma
register
General population of
Great Britain
0.41 (0.30–0.55)
Roelofs 2013 Standardized
morbidity
Automobile mechanics Massachuses Cancer
Registry
Patients with cancers not
associated with asbestos
2.1 (1.1–4.0)
a
RR estimates are shown as reported by each study or are rounded to two decimal places if they were calculated based on data obtained from the authors or reported in the papers.
b
Studies of higher methodological quality.
c
Studies of moderate methodological quality.
d
Studies of lower methodological quality.
Table1.  Continued
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(95% CI: 0.36–1.80). In addition, when cases and
controls with a history of employment in any of these
occupations were removed from the analysis, the OR
for occupational brake installation and repair became
0.62 (95% CI: 0.01–4.71). An exposure-response
analysis showed no evidence of increasing risk of
mesothelioma with increasing duration of brake work.
Subjects whose only brake work was non-occupa-
tional (i.e. do-it-yourself) were not at increased risk
of mesothelioma. ese NCI data have several impor-
tant features: (i) exposure was dened specically
as brake installation and repair, (ii) confounding by
other occupational exposures was addressed, and (iii)
information on duration of employment allowed an
exposure-response analysis. Alimitation of this data
set was the relatively low response rate (74% among
cases’ next-of-kin, 79% among controls’ next-of-kin).
Teschke etal. (1997) compared pathologically con-
rmed mesothelioma cases from the British Columbia
Cancer Agency to matched controls selected from
voter registration lists. Lifetime occupational and
exposure histories were obtained, whenever possible,
directly from cases and controls. e OR for ‘vehicle
mechanics’ was 0.8 (95% CI: 0.2–2.3). e OR for the
Table2. Quality scores of studies evaluating the association between mesothelioma risk and 
employment as a motor vehicle mechanic.
Quality criteria Study
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Overall study design: PMR/PIR/SMOR=0; SMR/
OR=1
1 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0
Asbestos exposure: Job title (e.g. ‘car
mechanic’)=0; Task specic (e.g. brake repairman
or IH-based)=1
0 0 1 1 1 0 1 0 0 0 1 0 0 0 0 0
Was age taken into account adequately?: no=0;
yes=1
1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1
Lifetime asbestos exposure history: no=0; yes=1 1 1 1 1 1 1 0 1 0 1 1 0 0 0 0 0
Was any aempt made to control for confounding?:
no=0; unlikely/addressed=1
1 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0
Exposure-response analysis performed? no=0;
yes=1
0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0
Was latency taken into account? no=0; yes=1 0 0 1 0 1 0 1 0 1 0 0 0 0 0 0 0
For cohort studies: follow-up <30 yr=0;
≥30years=1
1 0 0 0 0 0
For case–control studies: response rate:
<80% or not reported=0; ≥80%=1
1 1 1 0 0 1 1 0 0 0
Information bias: possible=0; unlikely/
addressed=1
1 1 0 0 1 0 1 1 1 1 0 1 1 1 1 0
Selection bias: possible=0; unlikely/addressed=1 0 1 0 1 1 1 0 0 1 0 0 1 1 1 1 0
Cases based on pathology review: no=0; yes=1 1 1 1 1 1 1 0 1 0 1 1 0 0 0 0 1
Total score 7 7 8 8 10 6 6 5 6 5 4 3 3 3 3 2
1, (McDonald and McDonald, 1980); 2, (Teta etal., 1983); 3, (Teschke etal., 1997); 4, (Hessel etal., 2004); 5, (Rake etal., 2009); 6, (Agudo etal., 2000);
7, (Hansen and Meersohn, 2003); 8, (Aguilar-Madrid etal., 2010); 9, (Merlo etal., 2010); 10, (Rolland etal., 2010); 11, (Woitowitz and Rodelsperger,
1994b); 12, (McElvenny etal., 2005); 13, (Milham, 2011); 14, (NIOSH, 2011); 15, (Health and Safety Executive, 2013); 16, (Roelofs etal., 2013).
Page 8 of 19 Mesothelioma among motor vehicle mechanics
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category ‘brake lining installation or repair’ was 0.3
(95% CI: 0.0–1.4). Aer removing cases and controls
with at-risk occupational asbestos exposures, the OR
for ‘vehicle mechanics’ was 0.4 (95% CI: 0.0–3.2).
e results did not change aer taking into account
20+ years of latency and, in fact, the rst exposure for
all of the vehicle mechanics and brake workers was
>20years prior to diagnosis. Information bias is a con-
cern in this study due to the dierence in proportion
of next-of-kin interviews among cases (33.3%) com-
pared with controls (13.6%). Although fairly small in
size, this study was methodologically strong because:
(i) it considered other asbestos exposures, (ii) speci-
ed exposure as ‘brake lining installation or repair,
(iii) considered latency, and (iv) had a high response
rate (88% among cases, 81% among controls).
Rake etal. (2009) conducted a case-control study
of 622 mesothelioma patients (92% histologically con-
rmed) and 1420 age-matched population controls in
England, Wales, and Scotland. Cases were identied
through chest physicians, surgeons and nurses, the
National Cancer Research Network, and English and
Scoish hospital records. Apostal questionnaire and
telephone interview assessed lifetime occupational
and residential history, do-it-yourself activities, and
other possible environmental exposures for living
cases and controls. is included work with gaskets
and brake linings. e OR for vehicle maintenance
involving work with brakes or gaskets was 0.4 (95% CI:
0.1–1.7). ough this study used only living cases and
controls, the response rates diered between the cases
(73%) and controls (60%). is study was methodo-
logically strong because the authors accounted for the
impact of other high-risk jobs and examined latency
and duration of exposure.
Tier2
In 1987, Olsen and Jensen published a proportionate
incidence ratio (PIR) analysis that linked cases from
the Danish Cancer Registry with occupational histo-
ries (Olsen and Jensen, 1987). ere were no cases of
mesothelioma for the occupational category ‘repair
of motor vehicles and motorcycles’ or for the indus-
try category ‘garage. e data were updated in a 2003
case-control study (Hansen and Meersohn, 2003).
For the category ‘repair of motor vehicles and motor-
cycles’ the OR was 0.8 (95% CI: 0.4–1.5), based on
10 mesothelioma cases. Limitations of this study were
lack of requirement of histological conrmation of
mesothelioma diagnosis for study inclusion, inability
to obtain a complete work history or detailed expo-
sure history regarding work with brakes specically,
and lack of latency analysis for repair of motor vehicles
specically. Its strengths included large sample size
and unlikeliness of reporting bias due to the coverage
of all cancer cases in Denmark by the registry.
Agudo etal. (2000), in a hospital-based case-con-
trol study in Spain, compared pathology-conrmed
cases of mesothelioma to population/hospital con-
trols. Acomplete occupational history was collected,
though information was not available on exposure to
brake repair specically. ere were three cases and
14 controls in the category ‘mechanics, motor vehi-
cle. e non-exposed category included 51 cases and
148 controls that had never worked in any of the at-
risk occupations. e crude OR for ‘mechanics, motor
vehicle’ was 0.62 (95% CI: 0.11–2.36). e compari-
son of motor vehicle mechanics that may have had
other potential asbestos exposure to persons without
exposure may have led to unmeasured confounding.
Because 44% of cases and <1% of controls had next-
of-kin interviews, information bias is possible. e
studys high response rate, methods of control selec-
tion, and complete occupational histories were among
its strengths.
Aguilar-Madrid (Aguilar-Madrid etal., 2010) con-
ducted a case-control study of 472 workers insured by
the Mexican Institute of Social Security including 119
histologically conrmed incident mesotheliomas and
353 matched hospital controls. In-person interviews
for both cases and controls assessed the complete
employment history and para-occupational exposures
including family members’ occupations and likely
environmental exposures though information was
not available on brake work specically. No next-of-
kin interviews were conducted. ere were one case
and four controls whose most frequent occupation
was ‘mechanic, automobile, resulting in an OR of 0.74
(95% CI: 0.08–6.68). is OR estimate was based
on relatively few observations, was not adjusted for
potential confounding by other occupational or non-
occupational exposures, and did not take into account
exposure-response or latency.
In Genoa, Italy, Merlo et al. (2010) conducted a
historical cohort mortality study among 9267 male
public transport workers of which 2073 were bus
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maintenance workers. Nine deaths from pleural
mesothelioma were observed among bus mainte-
nance workers, resulting in an SMR of 1.27 (95% CI:
0.66–2.43) when compared to the regional male pop-
ulation. is study did not obtain a lifetime asbestos
exposure history, control for potential confounding
by other exposures, assess exposure specic to brake
work, require pathologic review of cases, or perform
exposure-response analyses. is study did, however,
have a long duration of follow-up (1 January 1970 to
31 December 2005) and took latency into account
in the overall cohort but not among the bus mainte-
nance workers specically. Reporting or selection bias
was unlikely as the authors identied all subjects ever
employed at the public transport company inGenoa.
Rolland et al. (2005, 2010) conducted a popu-
lation-based case-control study of primary malig-
nant pleural tumors, nested within Frances National
Mesothelioma Surveillance Program (PNSM); 86.8%
of the cases were pathologically conrmed. A self-
administered survey and interviewer-administered
questionnaire assessed lifetime residential, educa-
tional, and occupational history, including specic job
tasks and do-it-yourself repair. No next-of-kin inter-
views were conducted. Of the 371 and 732 male cases
and controls, 17 cases and 22 controls were motor
vehicle mechanics. e OR for motor vehicle mechan-
ics was 1.50 (95% CI: 0.76–2.95). e authors did not
control for multiple occupational exposures despite
the fact that this information was included in the ques-
tionnaire. e response rate was low, with overall par-
ticipation under 50%.
Tier3
Woitowitz and Rodelsperger (1994) compared life-
time occupational histories of 324 pathology-con-
rmed mesothelioma cases in Germany with two
groups of controls: 315 hospital control patients who
underwent lung resection and 182 population controls.
Lung resection controls were used in order to obtain
lung tissue for ber analysis. Sixteen cases, 16 hospi-
tal controls and 12 population controls were listed as
motor vehicle repair workers’. ese data yielded an
OR of 0.97 (95% CI: 0.45– 2.12) using hospital con-
trols and an OR of 0.74 (95% CI: 0.32–1.75) using
population controls. For people denitely engaged in
brake service, the OR was 0.75 (95% CI: 0.25–2.23)
using hospital controls and 1.32 (95% CI: 0.30–6.51)
using population controls. e use of hospital con-
trols that were largely lung cancer patients raises the
possibility of confounding, whereas the population
controls were not subject to this issue. When the two
types of controls were combined for a larger sample
size, the OR was 0.87 (95% CI: 0.43–1.70) for motor
vehicle mechanics and 0.89 (95% CI: 0.31–2.47) for
persons denitely engaged in brake servicing. (ese
calculations were based on updated numbers pro-
vided by the authors, Prof. H.-J. Woitowitz and Dr
K. Rödelsperger, Justus-Liebig University Giessen,
Germany.) e strengths of this study were its ability
to examine the association with brake repair and its
high response rate. e most important shortcomings
included the lack of adjustment for age and an inad-
equate description of subject selection.
Roelofs et al. (2013) conducted a standardized
morbidity odds ratio (SMOR) analysis using inci-
dent mesothelioma cases in the Massachuses Cancer
Registry (MCR) from 1988 to 2003. Atotal of 80 184
cancer controls were used to compute SMORs for
each occupation and industry, controlling for gender
and age. Of the 564 mesothelioma cases coded for
occupation, 10 were identied as automobile mechan-
ics, resulting in an SMOR of 2.1 (95% CI: 1.1–4.0).
Although there were 1424 total cases of mesothelioma
in the MCR during the time period of interest, only
564 (40%) were able to be coded for ‘usual’ occupa-
tion. e majority of cases were identied as retired, of
unknown occupation, or disabled, and were excluded.
e authors did not obtain a lifetime asbestos expo-
sure history or brake work-specic exposure informa-
tion, did not perform exposure-response analysis, and
did not take latency into account. When calculating
the risk estimate for each occupation, they omied
subjects with occupations known to carry an increased
risk from the non-exposed group; however, similar
at-risk individuals could not be excluded from the
exposed group (only the usual occupation was coded).
us many occupations, including vehicle mechanics,
showed elevated risk estimates. e authors noted that
it was not possible to determine if the cases in their
study resulted from exposure to the reported usual
occupation.
Four studies included in this review and meta-
analysis were PMR analyses. Two of these studies took
place in Great Britain (McElvenny etal., 2005; Health
and Safety Executive, 2013) and two in the USA
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(Milham, 2011; NIOSH, 2011). ese studies did
not collect task-specic asbestos exposure histories
(i.e. brake repairman versus automobile mechanic) or
lifetime asbestos exposure histories. e PMR stud-
ies did not control for confounding by other asbestos
exposures and the reference group for each occupa-
tion was the general population, which included those
with known risk-related exposures to asbestos. ese
studies did not assess exposure-response or latency.
e cases of mesothelioma in these studies were not
necessarily based on pathologic review.
Meta-analysis results
Primary meta-analyses
Meta-analysis of all 16 eligible studies (all tiers com-
bined) of mesothelioma risk among motor vehicle
mechanics resulted in an SRRE of 0.80 (95% CI:
0.61–1.05), with statistically signicant heteroge-
neity [Q-test P-value (P-H) < 0.000, I
2
 = 62.90]
(Table3, Fig.2). Meta-regression by study quality
did not yield a statistically signicant eect (Fig.3).
e paerns of associations across tiers were rela-
tively similar with overlapping CIs (Fig.2). All ve
Tier 1 studies reported no increased risk of mesothe-
lioma among motor vehicle mechanics resulting in
an SRRE=0.76 (95% CI: 0.46–1.25), with no het-
erogeneity between studies (P-H=0.912, I
2
=0.00)
(Table3, Fig.2). In this model, the study by Hessel
contributed the most relative weight (38.18%),
while the study by Teta contributed the lowest
(5.51%). Meta-analysis of the ve Tier 2 studies
produced a non-signicant SRRE of 1.09 (95% CI:
0.76–1.58) with lile heterogeneity (P-H=0.637,
I
2
= 0.00). ree of the individual study ORs in
this model were below 1.0 and two were above 1.0
(none of which was statistically signicant) and all
CIs overlapped. Meta-analysis of the Tier 3 studies
resulted in an SRRE of 0.73 (95% CI: 0.49–1.08),
with statistically signicant heterogeneity (P-
H<0.000, I
2
=81.39). Of the six Tier 3 studies, ve
reported point estimates ranging between 0.41 and
0.87, while one study (Roelofs etal., 2013) reported
a point estimate of 2.10. e study by Roelofs etal.
was identied as an outlier (overall and within the
Tier 3 model) based on visual inspection of a funnel
plot of standard error by log OR. Removal of this
outlier study in a sensitivity analysis modied the
Tier 3 eect size to 0.59, which was statistically sig-
nicant (95% CI: 0.44–0.79).
Combination of the Tier 1 and Tier 2 studies
produced a non-signicant SRRE (0.96, 95% CI:
0.72–1.29) with no heterogeneity (P-H = 0.845,
I
2
=0.00). e Tier 1 studies provided ~36% of the
relative weight in this model. is model was robust
to the inuence of any single study as reected by our
one-study-removed sensitivity analyses where SRREs
ranged between 0.87 (Rolland removed) and 1.01
(Hansen removed).
Four studies reported data specic to brake
work; meta-analysis of these studies resulted in an
SRRE=0.66 (95% CI: 0.39–1.10), with no appreci-
able heterogeneity (P-H=0.472, I
2
=0.00) (Table3,
Fig.4). All four studies reported ORs below1.0.
Sub-group meta-analyses
Meta-analysis by study design generated SRREs <1.0
for both case-control and PMR/SMOR/cohort stud-
ies (Table 3). While no heterogeneity was apparent
for the model including only case-control studies
(P-H = 0.911, I
2
= 0.00), signicant heterogeneity
was found in the model including only studies that
used PMR/SMOR/cohort methods (P-H = 0.000,
I
2
= 83.86). Analysis of only PMR/SMOR studies
resulted in an SRRE of 0.71 (95% CI: 0.46–1.10) with
signicant heterogeneity. Summary results of studies
conducted in the USA/Canada (SRRE = 0.93, 95%
CI: 0.69–1.27) diered slightly from the non-US/
Canadian studies (SRRE=0.70, 95% CI: 0.49–1.00),
but the CIs largely overlapped and removal of Roelofs
in the US/Canada model resulted in an SRRE of 0.79
(95% CI: 0.60–1.04). Analysis including only stud-
ies that controlled for confounding by other asbestos
exposure resulted in an SRRE of 0.77 (95% CI=0.46–
1.28) with no apparent heterogeneity.
Publication bias assessment
Statistical testing for possible publication bias pro-
duced signicant observations. Egger’s regression
test—a test for funnel plot asymmetry on a linear
regression of a standard normal deviate—produced a
P-value of 0.05. If a meta-analysis captured all relevant
studies, it would be expected that the funnel plot would
be symmetric, and that the studies would be dispersed
equally on both sides of the overall eect (Rothstein
etal., 2005). us, the Duval and Tweedie trim and
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Table3.  Summary of meta-analysis results for mesothelioma among motor vehicle mechanics.
Model (number of studies) SRRE 95% CI P-value for 
heterogeneity, I
2
Notes
Primary analyses
All studies (n=16) 0.80 0.61–1.05 0.000, 62.90 Tier 1, 2, 3 studies included
All studies (n=16), adjusted data
from Teschke
0.79 0.60–1.05 0.000, 62.90 Teschke: Cases and controls
removed if ever held at-risk
occupations
All studies, Roelofs excluded
(n=15)
0.72 0.57–0.91 0.018, 48.44 Roelofs identied as an
outlier study, and had the
lowest study quality rating
Tier 1 studies (n=5) 0.76 0.46–1.25 0.912, 0.00 Studies with the highest study
quality rating
Tier 1 studies (n=5), adjusted
data from Teschke
0.74 0.43–1.26 0.885, 0.00 Teschke: Cases and controls
removed if ever held at-risk
occupations
Tier 2 studies (n=5) 1.09 0.76–1.58 0.637, 0.00 Studies determined to be of
moderate quality
Tier 3 studies (n=6) 0.73 0.49–1.08 0.000, 81.39 Studies determined to be of
low methodological quality
a
Tier 1 and 2 studies combined
(n=10)
0.96 0.72–1.29 0.845, 0.00 Tier 1 and 2 studies included
Studies specic to brake work
(n=4)
0.64 0.38–1.09 0.486, 0.00 Analysis of studies that
reported data specically for
brake work
Sub-group analyses
Case-control studies
(n=10)
0.89 0.66–1.20 0.911, 0.00 Analysis of case-control stud-
ies only
SMOR/PMR/cohort studies
(n=6)
0.77 0.51–1.18 0.000, 83.86 Analysis of SMOR/PMR and
cohort studies
SMOR/PMR studies
(n=5)
0.71 0.46–1.10 0.000, 84.30 Analysis of SMOR/PMR
studies
Studies conducted in the
USA/Canada (n=7)
0.93 0.69–1.27 0.253, 23.12 Studies conducted in the
USA/Canada
Studies conducted in the
USA/Canada (n=6),
Roelofs excluded
0.79 0.60–1.04 0.998, 0.00 Roelofs identied as an out-
lier study, and had the lowest
study quality rating
Non-US/Canadian studies
(n=9)
0.70 0.49–1.00 0.004, 64.60 Studies conducted in Europe,
with the exception of one
(Mexico)
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ll method (Duval and Tweedie, 2000) imputes data
to account for variable results between studies. Eight
data points were imputed using this method, result-
ing in a change of the overall model SRRE from 0.80
(95% CI: 0.61–1.05) to 0.52 (95% CI: 0.39–0.69),
further reinforcing the evidence of lack of an increased
risk of mesothelioma among motor vehicle mechanics
(Supplementary Fig. S1).
DISCUSSION
Our results indicate that mesothelioma risk is not asso-
ciated with either motor vehicle repair or with brake
repair work. e SRREs of mesothelioma showed no
trend either upward or downward according to study
quality. ere have been a number of studies published
since 2004, when we last reviewed this topic, including
four studies in Tiers 1 and 2 (Rake etal., 2009; Aguilar-
Madrid etal., 2010; Merlo etal., 2010; Rolland etal.,
2010), a new study in Tier 3 (Roelofs et al., 2013),
and updates to PMR studies (Milham, 2011; Health
and Safety Executive, 2013). e addition of this sub-
stantial body of scientic evidence did not change
the previously reported conclusion (Goodman etal.,
2004) of no association between mesothelioma and
either motor vehicle repair or brake repair work. e
single study that showed a signicantly increased risk
Figure2 Meta-analysis of mesothelioma risk among motor vehicle mechanics by study tier.
Model (number of studies) SRRE 95% CI P-value for 
heterogeneity, I
2
Notes
Studies that controlled for confounding
by other asbestos exposures (n=4)
0.77 0.46–1.28 0.809, 0.00 Analysis of studies that con-
trolled for confounding due
to asbestos exposure outside
of motor vehicle repair
Lifetime asbestos exposure history
ascertained (n=9)
0.92 0.66–1.28 0.868, 0.00 Analysis of studies that
obtained information on
prior history of potential
asbestos exposure
a
ese studies were determined to be of lower quality but provided risk estimates for motor vehicle mechanic workers and mesothelioma, and were
evaluated in the context of ‘results consistency’ with other studies.
Table3.  Continued
Mesothelioma among motor vehicle mechanics •  Page 13 of 19
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of mesothelioma (Roelofs et al., 2013) had several
methodological deciencies and received the lowest
quality score. Moreover, analyses of heterogeneity
indicated that this study was appreciably dierent than
the entire body of literature on thistopic.
It should be emphasized that this body of research
was conducted using dierent study designs, in dif-
ferent populations in Europe and North America, by
dierent teams of researchers, and over a period span-
ning three decades. ese dierent circumstances
yielded consistent results with no appreciable hetero-
geneity. Although it can be argued that not all motor
vehicle mechanics are engaged in brake repairs, clearly
many are. While in theory exposure misclassication
at the occupational title level could miss an associa-
tion if the exposure was low level or of low frequency,
we sought to minimize this possibility by focusing on
studies that reported brake, clutch, and gasket repairs
specically and on studies that examined duration of
exposure. Moreover, the studies that examined brake
repairs specically (Woitowitz and Rodelsperger,
1994; Teschke etal., 1997; Hessel etal., 2004; Rake
etal., 2009) provided results that were not appreciably
dierent than the results for motor vehicle mechan-
ics across all studies. us, the lack of association
seen in the studies specic to exposure to brakes was
not meaningfully dierent than studies that were less
specic. is was not unexpected as brake repair is
a very common activity among vehicle mechanics.
Similarly, vehicle mechanics were commonly exposed
to asbestos from clutch and gasket repairs. e lack of
mesothelioma risk across studies indicates that vehicle
mechanics’ work with asbestos-containing clutches
and gaskets does not increase the risk for mesothe-
lioma. It is unlikely that the healthy worker eect
biased the results. Anumber of the studies compared
Figure3 Regression of log odds ratio on study quality. e circle size represents the weight in the regression analysis.
Figure4 Meta-analysis of mesothelioma risk among workers involved with brake repair.
Page 14 of 19 Mesothelioma among motor vehicle mechanics
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vehicle mechanics to other working populations or
were case-control studies. Moreover, mesothelioma
has a very long latency and is oen diagnosed aer the
exposed workers have retired—it is dicult to imag-
ine a healthy worker eect exists 40+ years aer start-
ing work and into retirement.
Although some of the individual studies had limited
power to detect a statistically signicant association,
the meta-analysis had greatly increased study power as
reected in the narrow CIs. Furthermore, the SRREs
indicated associations near and slightly below 1.0.
us, power to detect a statistically signicant positive
association in individual studies was irrelevant.
In general, the relevant exposure periods of the
study populations coincided with the timeframe in
which chrysotile asbestos was used in brakes. In addi-
tion, the studies had adequate elapsed time from rst
exposure to case identication to detect mesothelioma
if this outcome had been causally related to brake expo-
sures. is is of particular importance because of the
long latency period of mesothelioma. For example,
in Woitowitz (Woitowitz and Rodelsperger, 1994),
the median rst date of exposure was 1949 for both
cases and controls, and case ascertainment occurred
between 1988 and 1994. In the study by Teschke etal.
(1997), where latency was considered, all of the vehi-
cle mechanics and brake workers began their exposures
prior to the minimum latency period (i.e. 20years).
Both study design and statistical heterogeneity are
important considerations in a rigorous meta-analytic
approach. Indeed, we made an eort to conduct an
objective and transparent study quality scoring exer-
cise based on recommendations by the MOOSE
(Stroup et al., 2000) and PRISMA (Moher et al.,
2009) guidelines. is facilitated several additional
meta-analyses based on parameters such as study
design, potential bias, the inuence of confounding,
and the specicity of exposure designations. SRREs
by study design, study quality, study region, and
ascertainment of lifetime asbestos exposure were cal-
culated. However, virtually all analyses produced the
same results—no association between mesothelioma
risk and either motor vehicle repair or brake repair.
Some study designs are inherently weaker than oth-
ers, such as PMR studies, which are not designed to
include lifetime occupational histories, task-specic
Table4. Summary of mesothelioma studies and corresponding RR estimates not included in the 
meta-analysis.
First author Year Design RR estimate 95% CI Reason for exclusion
Malker
a
1985 Cohort 2.4 (P<0.01) NA Exposure dened as
mechanics’
Jarvholm 1988 Cohort NA (1 case) NA Unable to calculate
relative risk
Schiman 1988 Case-control 0 (no cases, 2 controls) NA Exposure dened as
mechanics’
Hansen 1989 Cohort NA (1 case) NA Unable to calculate
relative risk
Gustavsson 1990 Cohort NA (2 cases) NA Unable to calculate
relative risk
Pan
b
2005 Case-control 1.02 0.66– 1.57 Exposure dened as
mechanics, not specied’
Welch 2005 Case-control 1.50 0.43– 5.26 Exposure dened as ‘Tire
or brake lining work’
CI, condence interval; NA, not available; RR, estimate of relative risk.
a
Of the 16 mechanics with mesothelioma in this study, only one was likely to be an auto mechanic (W. Blot, personal communication, 2003).
b
Mechanics were not restricted to motor vehicle mechanics (D. Garabrant, personal communication, 2014).
Mesothelioma among motor vehicle mechanics •  Page 15 of 19
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information, duration of employment, latency, or
covariates for other sources of exposure. ese types
of studies received zero scores on all of these criteria,
as they should. In the PMR studies, the results for
motor vehicle mechanics are below 1.0 but sometimes
are above other occupations. is likely reects the
fact that mechanics may be more likely than workers
in other occupations (e.g. farmers, teachers, clerical
workers) to have worked in other asbestos-exposed
jobs. For this reason, we believe the analyses that con-
trolled for other sources of asbestos exposure (Hessel
etal., 2004; Rake etal., 2009) provide a more reliable
estimate of RR and warrant great analytical weight.
ere were seven potentially relevant studies that
could not be included in the meta-analysis (Table4).
ree were excluded because no measures of associa-
tion were provided or could be calculated. Jarvholm
and Brisman (1988) reported a single case of meso-
thelioma in a cohort of 21 905 Swedish car mechanics
born between 1890 and 1945, and followed through
1979. Hansen (1989) reported a single case of meso-
thelioma in a cohort of 21 800 Danish auto mechanics
and followed from 1970 to 1980, accumulating 192
000 person years. Gustavsson etal. (1990) reported
two cases of mesothelioma among 695 Stockholm
bus garage workers followed from 1958 to 1994.
ree other studies (Malker et al., 1985; Schiman
etal., 1988; Pan etal., 2005) reported mesothelioma
risks for ‘mechanics’, but could not be included in the
meta-analysis because occupations were not restricted
to motor vehicle mechanics (W. Blot and H.Malker,
2003, personal communication; D. Garabrant and
M. Shenker, 2013, personal communication). e
seventh study (Welch etal., 2005), which compared
cases of peritoneal mesothelioma to cases of appen-
diceal cancer, was excluded because it grouped brake
installation and repair with tire installation and repair
and did not report brake repair activities or work as
a motor vehicle mechanic. ese studies did not pro-
vide evidence of mesothelioma risks among motor
vehicle mechanics.
e observed lack of association between work
as a motor vehicle mechanic or brake mechanic and
mesothelioma may result from several factors. First,
the asbestos bers found in dust and airborne sam-
ples of vehicle mechanics workplaces or simulated
workplaces are generally short (<5 μm) chrysotile
bers (Hatch, 1970; Anderson et al., 1973; Rohl
etal., 1976; Roberts and Zumwalde, 1982; Williams
and Muhlbaier, 1982; Cha etal., 1983; Rodelsperger
et al., 1986; Rodelsperger, 1987; NIOSH et al.,
1989). ere appears to be increasing consensus that
short bers, particularly those <5μm in length, are
associated with lile (if any) pathologic response,
including risk of lung cancer and mesothelioma
(Platek etal., 1985; Eastern Research Group, 2003;
Berman, 2011; Bernstein etal., 2013). In an analysis
of dust obtained from sanding brake drums manu-
factured with chrysotile, no signicant pathological
response was shown following short-term inhalation
in rats (Bernstein etal., 2014). Secondly, asbestos b-
ers in brake pads are embedded in resin (Weir and
Meraz, 2001) and therefore are less likely to become
airborne. irdly, much of the chrysotile in brake
pads is transformed to forsterite during the brak-
ing process (Anderson etal., 1973). Forsterite does
not appear to have asbestos ber properties and
is not considered carcinogenic in humans (Wong,
1992). More importantly, Langer demonstrated that
chrysotile’s biological activity becomes virtually nil
hundreds of degrees below the forsterite transforma-
tion temperature. us, complete transformation of
the mineral is not required to result in loss of activ-
ity (Langer, 2003). A large body of IH literature
indicates the mean time weighted average asbestos
exposure during brake servicing was ~0.04 bers per
cubic centimeter during the post-1974 time period
(Weil and Delpire, 1985).
Two studies addressed the risk of mesothelioma
among bystanders (i.e. persons presumed to be indi-
rectly exposed to asbestos) and do-it-yourself mechan-
ics (Hessel etal., 2004; Rake etal., 2009). Both studies
reported no association in these circumstances. If
workers whose occupation involving low-level chry-
sotile exposure are not associated with an increased
risk of mesothelioma, it follows that co-habitants of
these workers also would not have an increased risk
of mesothelioma (Goswami etal., 2013). Take-home
exposure from friction products has been estimated to
be lower than the exposures of automobile mechanics
(0.0001 f/cc versus 0.04 f/cc) (Goswami etal., 2013).
An association between an exposure and a disease
should clearly exist before a determination of causa-
tion is made (Hill, 1965). Even in the absence of an
association between employment as a motor vehi-
cle mechanic and mesothelioma, our meta-analysis
Page 16 of 19 Mesothelioma among motor vehicle mechanics
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allowed evaluating some key considerations of a causal
relationship such as strength of association and con-
sistency of ndings. All of the studies with the excep-
tion of Roelofs et al., 2013 provided homogeneous
eect estimates showing no association. e SRREs
do not support an increased risk of mesothelioma.
Two studies evaluated the duration of work and nei-
ther found a positive association in the group with
the longest duration of work (Hessel etal., 2004; Peto
etal., 2009). Further, a positive dose-response paern
would be unlikely given the fact that few studies (and
of lower quality) reported risks above 1.0. Finally,
study-specic risk estimates were consistent across
studies. We sought to nd an eect by analyzing the
data in a number of alternative ways to ensure that the
results were not overly inuenced by any single study
or group of studies. erefore, based on this compre-
hensive quantitative assessment of the totality of epi-
demiologic literature, neither work as a motor vehicle
mechanic nor work in brake repair is associated with
an increased risk of mesothelioma. is conclusion is
clearly supported by the data reported in a large group
of studies spanning decades of research across multi-
ple study populations using a variety of study design
and exposure assessment methods.
SUPPLE MENTARYDATA
Supplementary data can be found at hp://annhyg.
oxfordjournals.org/.
ACKNOWLEDGEMENTS
ere was no direct nancial support for this work.
No one other than the listed authors prepared the
research material, wrote, reviewed, or approved the
submied manuscript. D.H.G, D.D.A., M.J.T., P.A.H.,
V.A.C., and M.K.have provided legal testimony and/
or consultancy on behalf of companies that manufac-
ture automobiles, brakes, clutches, and automotive
gaskets. P.B. has provided legal testimony in a case
of asbestos exposure in the manufacture of synthetic
polymers and risk of mesothelioma.
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... The EPA failed to discuss the work of Bernstein et al. (2018Bernstein et al. ( , 2020aBernstein et al. ( , 2020b, which showed that fibers soaked in resin seem to lack biological activity. Beyond ignoring those studies and the meta-analyses of the epidemiology studies involving mechanics (Wong 2001; Goodman et al. 2004;Garabrant et al. 2016), the EPA also failed to cite many historically important studies that show that short fiber chrysotile lacks biologic activity (Davis and Coniam 1973;Stanton 1973;Stanton et al. 1977;Platek et al. 1985 The Agency relied on the Hamra et al. (2017) paper to respond to public comments regarding the lack of toxicity of shorter fibers versus longer asbestos fibers (EPA 2020c, p. 137). The premise of the Hamra article was that unregulated asbestos fibers, described as those not meeting the definition of an OSHA fiber -i.e. a diameter greater than 0.25 mm, a length greater than 5 lm, and having an aspect ratio of 3:1 or greater -posed a lung cancer hazard in the North Carolina and South Carolina textile mill cohorts described in Elliott et al. (2012). ...
... They happen to be an ideal cohort for evaluating the risks of exposure to brake dust and gaskets. If they had considered the studies, they would have found, based on a weight of the evidence approach, that no increased risk of mesothelioma is present in these workers (Garabrant et al. 2016;Paustenbach and Brew 2020). a. EPA's Response: "Following the SACC recommendation, EPA evaluated the quality of the studies of auto-mechanics for both lung cancer and mesothelioma and found deficiencies in exposure assessment and other aspects of the design of these studies (see Supplemental File to this Summary of Comments and Disposition). ...
... This study included 138,559 Danish vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)), and found that compared to other Danish workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n ¼ 47 cases) (ageadjusted and calendar-year-adjusted HR ¼ 0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR ¼ 1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR ¼ 1.50 (95% CI 1.10 to 2.03)), and a chronic obstructive pulmonary disease risk close to unity (HR ¼ 1.02 (95% CI 0.99 to 1.05)) ( Thomsen et al. 2021). The mesothelioma results of this study were no surprise, as it supported decades of epidemiological studies of vehicle mechanics which found similar results (Wong 2001; Goodman et al. 2004;Garabrant et al. 2016). ...
Article
Full-text available
From 2018 to 2020, the United States Environmental Protection Agency (EPA) performed a risk evaluation of chrysotile asbestos to evaluate the hazards of asbestos-containing products (e.g. encapsulated products), including brakes and gaskets, allegedly currently sold in the United States. During the public review period, the EPA received more than 100 letters commenting on the proposed risk evaluation. The Science Advisory Committee on Chemicals (SACC), which peer reviewed the document, asked approximately 100 questions of the EPA that they expected to be addressed prior to publication of the final version of the risk assessment on 30 December 2020. After careful analysis, the authors of this manuscript found many significant scientific shortcomings in both the EPA’s draft and final versions of the chrysotile risk evaluation. First, the EPA provided insufficient evidence regarding the current number of chrysotile-containing brakes and gaskets being sold in the United States, which influences the need for regulatory oversight. Second, the Agency did not give adequate consideration to the more than 200 air samples detailed in the published literature of auto mechanics who changed brakes in the 1970–1989 era. Third, the Agency did not consider more than 15 epidemiology studies indicating that exposures to encapsulated chrysotile asbestos in brakes and gaskets, which were generally in commerce from approximately 1950–1985, did not increase the incidence of any asbestos-related disease. Fourth, the concern about chrysotile asbestos being a mesothelioma hazard was based on populations in two facilities where mixed exposure to chrysotile and commercial amphibole asbestos (amosite and crocidolite) occurred. All 8 cases of pleural cancer and mesothelioma in the examined populations arose in facilities where amphiboles were present. It was therefore inappropriate to rely on these cohorts to predict the health risks of exposure to short fiber chrysotile, especially of those fibers filled with phenolic resins. Fifth, the suggested inhalation unit risk (IUR) for chrysotile asbestos was far too high since it was not markedly different than for amosite, despite the fact that the amphiboles are a far more potent carcinogen. Sixth, the approach to low dose modeling was not the most appropriate one in several respects, but, without question, it should have accounted for the background rate of mesothelioma in the general population. Just one month after this assessment was published, the National Academies of Science notified the EPA that the Agency's systematic review process was flawed. The result of the EPA’s chrysotile asbestos risk evaluation is that society can expect dozens of years of scientifically unwarranted litigation. Due to an aging population and because some fraction of the population is naturally predisposed to mesothelioma given the presence of various genetic mutations in DNA repair mechanisms (e.g. BAP1 and others), the vast majority of mesotheliomas in the post-2035 era are expected to be spontaneous and unrelated in any way to exposure to asbestos. Due to the EPA’s analysis, it is our belief that those who handled brakes and gaskets in the post-1985 era may now believe that those exposures were the cause of their mesothelioma, when a risk assessment based on the scientific weight of evidence would indicate otherwise.
... Such findings seem counter intuitive and the purpose of this review is to consider this relationship between chrysotile release from friction products and mesothelioma. The inten- tion is not to perform a repeat of previous analysis to deter- mine relative risk of MM in mechanics as recent and excellent analysis exists ( Garabrant et al. 2016a). Instead the purpose is to explore if physicochemical modification of chrysotile liberated from friction products provides a toxico- logical basis for altered toxicity of chrysotile. ...
... Further, meta-analysis studies of the available data have simi- larly endorsed a lack of casual relationship. One of the most recent analyses of relative risk estimates for MM in mechanics was published in 2016 by Garabrant et al. (2016a). This meta- analysis was based upon screening of the broader literature using a range of search terms intended at capturing informa- tion on MM incidence in mechanics more generally, as well as brake repair more specifically. ...
... Summary relative risk estimates (SRREs) for all studies was 0.80 (95% CI: 0.61-1.05) leading them to conclude no statistically significant increases in MM among mechanics ( Garabrant et al. 2016a). Such findings are in line with values determined by Wong (2001) of six studies (shown in Table 1 An updated summary of findings from studies addressing MM among automobile mechanics from Kelsh et al. (2007) is presented in Table 1. ...
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The global use of “asbestos” in various commercial products has led to a wide range and pervasive legacy of disease. One such use of chrysotile asbestos was brake pads and was utilized commonly in automobiles and heavy vehicles. The result of incorporation of chrysotile into brake pads is associated with the exposure of mechanics fitting and servicing vehicles to liberated chrysotile fibers. Despite the proven exposure, the relative risk of malignant mesothelioma (MM) in this occupational population is broadly seen as low. The toxicity of particulates, including fibers such as chrysotile, is driven by a combination of dose and physicochemical properties. As such, it is plausible that chrysotile released from brake pads may have undergone modification, thereby altering the pathogenicity profile. The impact of high sheer stress causing shortening of long fibers, heat modification, binding of resin matrix to the fiber surface on the relative toxicity of brake debris with regards to MM is considered. It is apparent that released chrysotile can undergo significant modification, reducing the long fiber dose although not all modifications may lead to reduced toxicity.
... As such, it would be expected that such a documented exposure may lead to an excess risk of MM. However, numerous epidemiological studies have yet to demonstrate an excess risk of 'asbestos'-related disease including MM within this exposure cohort (Wong 2001;Goodman et al. 2004;Laden et al. 2004;Garabrant et al. 2016). It is important to note however that such epidemiological conclusions are not universally shared (Egilman and Billings 2005) and furthermore, there are case studies describing MM in auto mechanics working with chrysotile containing friction products (Langer and McCaughey 1982;Finkelstein 2015). ...
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Grinding and drilling of chrysotile asbestos-containing brake pads during the 20th century led to release of chrysotile, resulting in varying levels of workplace exposures of mechanics. Despite exposures, excess risk of mesothelioma remains in doubt. Objectives: The toxicity of particulates is primarily derived through a combination of physicochemical properties and dose and as such this study aimed to determine properties of asbestos-containing brake debris (BD) which may influence pathogenicity and potential of mesothelioma. Materials and Methods: Chrysotile-containing brake pads were ground – to reflect occupational activities, aerosolized, and size-fractionated to isolate respirable fractions. Analysis of morphology, biodurability, surface charge, and interactions with macrophages were undertaken. Results: The respirable fraction of BD contained ∼15–17% free chrysotile fibers thereby constituting a small but relevant potential long fiber dose. Acellular biodurability studies showed rapid dissolution and fragmentation of chrysotile fibers that was consistent for pure chrysotile control and BD samples. Conclusions: The long, free, respirable chrysotile fibers were present in BD, yet were of low bio-durability; incubation in artificial lysosomal fluid led to destruction of free fibers.
... Several studies have shown that worker exposure to asbestos in occupations where routine exposure to ACM is expected (heavy construction equipment, automobile brakes, and plane parts) is consistent with the OSHA PEL [4] [5] [6] [7] [8]. Those findings are also consistent with the lack of epidemiological evidence for enhanced asbestos-related disease among motor vehicle mechanics and heavy equipment brake removal [9] [10]. ...
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Characterizes occupational disease in New York State, replicates and expands on a report by Philip Landrigan and Steven Markowitz (1987). Considers traditional and emerging occupational health threats. Elucidates occupational health disparities. Reviews costs and current level of services. Includes recommendations.
Article
Introduction The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems. Methods We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services). Results Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes. Conclusions We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.
Chapter
Malignant mesothelioma is an uncommon cancer arising from the serosa of the pleura, peritoneum, pericardium, and tunica vaginalis testis. There have been substantial recent developments in relation to optimizing its accurate diagnosis and distinction from its mimics, understanding its molecular pathobiology and characterizing its varied causes. However, over the past five decades, there have been only modest improvements in the median overall survival of patients with the disease. Despite a better understanding of prognostic factors, malignant mesothelioma remains an almost invariably fatal cancer despite treatment. The proportion of malignant mesothelioma cases attributable to asbestos varies considerably according to fiber type, occupation and industry, tumor site, and gender. It is important to be mindful of the recent scientific literature when evaluating mesothelioma causation in extrapleural sites, in women, and in young persons because most of these cases are not likely asbestos-related cancers. These minority cases contrast with the majority of pleural mesotheliomas in men which are primarily caused by asbestos, most typically commercial amphiboles following occupational exposures.
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Malignant Pleural Mesothelioma (MPM) is a rare by aggressive cancer, and early detection is associated with better survival. Mesothelin, fibulin-3, and osteopontin have been suggested as screening biomarkers. The study conducted a meta-analysis of the mean differences of mesothelin, osteopontin, and fibulin-3 in blood and pleural samples. PubMed searches were conducted for studies that measured levels of mesothelin, osteopontin, and fibulin-3 in participants with MPM compared to with malignancy, benign lung disease, or healthy participants. Thirty-two studies with mesothelin levels, 12 studies with osteopontin levels and nine studies with fibulin-3 levels were included in the meta-analysis. Statistically significant mean differences were seen between MPM patients and all other comparison groups for mesothelin blood and pleural levels. Statistically significant differences in blood osteopontin levels were seen between participants with benign lung disease and healthy participants compared to participants with MPM, but not when comparing cancer participants to MPM participants. There were not enough studies that reported osteopontin levels in pleural fluid to complete a meta-analysis. Statistically significant differences were seen in both blood and pleural levels of fibulin-3 in MPM patients compared to all other groups. Based on these results, mesothelin and fibulin-3 levels appear to be significantly lower in all control groups compared to those with MPM, making them good candidates for screening biomarkers. Osteopontin may be a useful biomarker for screening healthy individuals or those with benign lung disease, but would not be useful for screening patients with malignancies.
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Background The association of mesothelioma and asbestos exposure is well known, but some data suggest that probably many people are still being exposed to asbestos without knowing it. Methods Between 1993 and 1996, 132 cases (77% males) of histologically confirmed malignant pleural mesothelioma and 257 controls, residents in two provinces of Spain (Barcelona and Cádiz), were interviewed. They were classified according to their probability and intensity of occupational asbestos exposure by a panel of industrial hygienists, based on a detailed occupational history. Results Age and sex‐adjusted odds ratio (OR) for the highest probability of exposure to asbestos was 13.2 (95% confidence interval 6.4–27.3), and 27.1 (9.28–79.3) for high intensity. A dose–response trend was observed for both, probability and intensity. Overall, 61% of cases and 42% of controls had ever worked in an occupation with risk of asbestos exposure, with an OR of 2.59 (1.60–4.22). In our population 62% of cases could be attributed to occupational asbestos exposure. Conclusions A high risk of pleural mesothelioma due to occupational asbestos exposure is confirmed, but there is still a sizeable proportion for which no evidence of occupational exposure was found. Most of these cases could be due to other sources of asbestos exposure, mainly domestic or environmental. Am. J. Ind. Med. 37:159–168, 2000. © 2000 Wiley‐Liss, Inc.
Article
Ascertainment, through 7,400 pathologists, of all fatal malignant mesothelial tumors in Canada (1960–75) and the U.S.A. (1972) gave a total of 668 cases (272 in 1972). In Canada, the annual number of male cases rose from about 17 in 1966 to 25 in 1972 but the number of female cases remained fairly steady at a much lower level. The annual incidence in North America in 972 was estimated at 2.8 per million males and 0.7 per million females aged 15 years and over. Occupational histories were obtained “blind” for 480 of the 557 cases through 1972, and their matched controls; relative risks were as follows: insulation work, 46.0, asbestos production and manufacture, 6.1, heating trades (other than insulation) 4.4. For nearly half the male cases and for about 5% of female cases, the tumor could be attributed to occupational exposure to asbestos, of which a fifth were in shipyards. No indication was found of other possible causes (including man-made mineral fibers, tobacco smoking, or residence near zeolite deposits). Four subjects were men who had been employed in Quebec chrysotile mines and 3 were children of employees, but no other subject had lived in the mining area. The findings remain consistent with a much greater mesothelioma-producing potential for crocidolite and amosite than for chrysotile; however, further studies of factory workers exposed to chrysotile only are needed to confirm this. Mineral fiber analysis of lung tissue from patients and controls is in progress.
Book
The impetus for writing this textbook arose from our teaching experiences in epidemiology at Harvard Medical School and Boston University School of Public Health as well as at other schools of medicine and public health, both in the United States and abroad. Our students have consistently suggested that their learning would be enhanced by the availability of an accompanying textbook, to serve both as an aid during the course and, subsequently, as a reference resource. We have also delivered lectures and conducted seminars with groups ranging from predominantly health professionals, such as the American Heart Association and the American Cancer Society, to media representatives, to meetings of biochemists, pharmacologists, nutritionists and other investigators whose primary interest is in basic science or clinical research. The universal concerns expressed by all these diverse groups have been how to evaluate what they read in the medical literature, and how to determine its value to their particular areas. We believe these concerns to be both important and timely. The importance of gaining such insights is borne out by the fact that much of continuing medical and public health education is derived from current literature. The timeliness is reflected in the large quantity of information from the medical literature which is now widely and daily disseminated to the general public by the media. © 1987 by Charles H. Hennekens and Julie E. Buring. All rights reserved.
Conference Paper
A computer controlled brake emission test rig that simulated road braking operation of a front wheel disc brake and collected airborne wear debris was constructed. Representative braking cycles were programmed on this system to experimentally estimate brake emissions under a variety of braking conditions. Application of the asbestos emission rates to air quality models confirmed Williams and Muhlbaier's previous findings that about 1% of asbestos fibres in city core districts originated from disc brake wear. (from authors' abstract)