Preview
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NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023
EXHIBIT 136
FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020
NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023
Consensus report
Scand J Work En viron Health 1997;23:31 1-6
Asbestos, asbestosis, and cancer: the Helsinki criteria for diagnosis and
altribu tion
The International Expert Meeting on Asbestos, Asbesto- tos-induced lung cancers are estimated to occur anilually
sis, and Cancer was convened in Helsinki on 20-22 in the population of approxiinately 800 million people.
January 1997 to discuss disorders of the lung and pleura In general, reliable work histories provide the most
in association with asbestos and to agree upon state-of- practical and useful measure of occupational asbestos
the-art criteria for their diagnosis and attribution with exposure. Using structured questionnaires and checltlists,
respect to asbestos. The group decided to name this doc- trained interviewers can identify persons who have a
ument Tlze Helsirzlci Criteria. work history compatible with significant asbestos expo-
The requirement for diagnostic criteria was perceived sure. Dust measurements can be used in the estimation of
in part because of new developinents in diagnostic meth- past fiber levels at typical worltplaces and in the use of
ods, with better identification of asbestos-related disor- asbestos-containing materials. A cumulative fiber dose,
ders. Such developments enhance awareness of health as expressed in fiber-years per cubic centimeter, is an
hazards imposed by asbestos, lead to practical preven- important parameter of asbestos exposure.
tion and appropriate compensation, and also provide an The clinical diagnosis of asbestos-related diseases is
opportunity to carry out international comparisons. They based on a detailed interview of the patient and occupa-
also provide possible models for the risk assessment of tional data on asbestos exposure and appropriate latency,
other mineral dusts. signs and symptoms, radiological and lung physiology
The meeting was attended by 19 participants from findings, and selected cytological, histological and other
8 countries not produciilg asbestos. The chairmen were laboratory studies. Histopathological confirmation is re-
Professor Douglas W Henderson (Flinders Medical quired for suspected asbestos-related malignancies and
Centre, Australia) and Professor Jorma Rantanen (Finn- for the resolution of differential diagnoses. A multidis-
ish Institute of Occupational Health, Finland). The ciplinary approach is suggested for the evaluation of
group was a multidisciplinary gathering of pathologists, probletn cases.
radiologists, occupational and pulmonary physicians, The chest radiograph is the basic tool for identifying
epidemiologists, toxicologists, industrial hygienists, and asbestos-related diseases such as asbestosis, pleural ab-
clinical and laboratory scientists specializing in tissue normalities, lung cancer, and mesothelioma. The limita-
fiber analysis. Collectively, the group has published over tion of the chest radiograph in the detection of asbestosis
1000 articles on asbestos and associated disorders. This and asbestos-associated pleural abnormalities is widely
document is based on a more co~nprehensivereport pro- recognized. Computed tomography (CT) and high reso-
viding scientific evidence for the conclusions and rec- lution computed tomography (HRCT) can facilitate the
ommendations (People arzd Work Research Reports, no detection of asbestosis and asbestos-related pleural ab-
14, Finnish Institute of Occupational Health, Helsinki, normalities, as well as asbestos-related malignancies;
1997). they are not recoinmended as a screening tool but may be
The meeting was scieiltifically supported by leading invaluable for individual clinical evaluation and research
institutions in the field of asbestos research, and it was purposes. Examples are the detection of pleural abnor-
funded by the Ministry of Social Affairs and Health and malities in suspected cases of asbestosis and the detec-
the Finnish Work Environment Fund. tion of parenchy~naldisease obscured on the chest film
and also use as an aid to differential diagnosis. As new
imaging techniques such as digital radiography are evolv-
General considerations
ing, standard images and iilterpretations must be devel-
Occupational exposures to asbestos dust have been wide- oped. The place of other imaging techniques (ultrasound,
spread in all industrial countries and continue as a conse- magnetic resonance imaging, gallium scanning, ventila-
quence of "in-place" materials. In detailed interviews tion-perfusion studies, positron-emission tomography)
about 20% to 40% of adult men report some past occupa- has yet to be established, and they are not currently
tions and jobs that may have entailed asbestos exposure recommended for the clinical diagnosis of asbestos-re-
at work. In Western Europe, North America, Japan, and lated disorders.
Australia the use of asbestos peaked in the 1970s, and Analysis of lung tissue for asbestos fibers and asbes-
cussently about 10 000 mesotheliomas and 20 000 asbes- tos bodies can provide data to supplemeilt the occupa-
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NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023
Consensus report
tional history. For clinical purposes, the following guide- Smoking effects should be considered in the evalua-
lines are recommended to identify persons with a high tion of early asbestosis, lung function tests, and respira-
probability of exposure to asbestos dust at work: over 0.1 tory symptoms.
nill lion amphibole fibers (>5 ym) per gram of dry lung A histological diagnosis of asbestosis requires the
tissue o r over 1 million amphibole fibers (>I pm) per identification of diffuse interstitial fibrosis in well inflat-
gram of dry lung tissue as measured by electron micro- ed lung tissue remote from a lung cancer or other mass
scopy in a qualified laboratory o r over 1000 asbestos lesion, plus the presence of either 2 or more asbestos
bodies per gram of dry tissue (100 asbestos bodies per bodies in tissue with a section area of 1 cm2 or a count of
gram of wet tissue) o r over 1 asbestos body per milliliter uncoated asbestos fibers that falls into the range recorded
of bronchoalveolar lavage fluid, as measured by light for asbestosis by the same laboratory.
inicroscopy in a qualified laboratory. In order to achieve reasonable comparability between
Each laboratory should establish its own reference different studies, a standardized system for the histologi-
values. The median values for occupationally exposed cal diagnosis and grading of asbestosis is required. The
populations should be substantially above the reference Roggli-Pratt modification of the CAP-NIOSH system is
values. Efforts to standardize analytical methods for recommended as a reasonably simple and reproducible
fiber burden analyses by different laboratories are rec- scheme for this purpose.
ommended. There is evidence that rare cases of asbestosis occur
without significant numbers of asbestos bodies. These
cases are recognizable - and distinguishable from idio-
Asbestosis
pathic pulmonary fibrosis - only by analysis of the
Asbestosis is defined as diffuse interstitial fibrosis of uncoated fiber burden. Rare cases of asbestosis in rela-
the lung as a consequence of exposure to asbestos dust. tion to the inhalation of pure chrysotile can occur, with a
Neither the clinical features nor the architectual tissue prolonged interval between the last exposure and the
abnormalities sufficiently differ from those of other diagnosis and few or no detectable asbestos bodies and a
causes of interstitial fibrosis to allow confident diag- low fiber burden. The existence of such cases is specula-
nosis without a history of significant exposure to asbes- tive and, if the diagnosis can be made, it must be done
tos dust in the past or the detection of asbestos fibers or from other compelling clinical or radiological grounds
bodies in the lung tissue greatly in excess of that com- combined with exposure data.
monly seen in the general population. Symptoms of as- Fibro-inflammatory patterns other than conventional
bestosis include dyspnea and cough. Common findings asbestosis have also been described for workers with
are inspiratory basilar crackles and, less commonly, occupational exposure to asbestos, including a pattern
clubbing of the fingers. Functional disturbances can in- resembling desquamative interstitial pneumonia (DIP),
clude gas exchange abnormalities, a restrictive pattern, the occurrence of granulomatous inflammation, a picture
and obstructive features due to small airway disease. that resembles lymphocytic interstitial pneumonia, and
Asbestosis is generally associated with relatively organizing pneumonia with bronchiolitis obliterans. Al-
high exposure levels with radiological signs of paren- though the DIP-like picture with asbestos bodies is prob-
chymal fibrosis. However, it is possible that mild ably asbestos-related, the other patterns have not yet
fibrosis may occur at lower exposure levels, and the been shown to be so related.
radiological criteria need not always be fulfilled in cases
of llistologically detectable parenchymal fibrosis. The
Pleural disorders
recognition of asbestosis by chest radiography is best
guided by standardized methods such as the classifi- Asbestos-related pleural abnormalities are divided into
cation of the International Labour Organisation (ILO) pleural plaques, mainly involving the parietal pleura,
and its modifications. Standard films must always be sometimes with calcification, and diffuse pleural thick-
used. For research and screening purposes, radiological ening, which is a collective name for pleural reactions
findings of small opacities, grade 110, are usually re- involving mainly the visceral pleura. These include be-
garded as an early stage of asbestosis. Inspiratory basi- nign asbestos-related pleural effusion, blunted costo-
lar sales, restrictive impairment, small airway ob- phrenic angle, crow's feet or pleuroparenchymal fibrous
struction, and gas exchange disturbances in pulmonary strands, and rounded atelectasis. Avoidance of the term
function are considered valuable information for clini- "pleural asbestosis" is recommended. Pleural plaques are
cal diagnosis, for occupational health practice, and for usually asymptomatic, and without clinically important
attribution purposes. HRCT can confirm radiological findings.
findings of asbestosis and show early changes not seen The specificity of pleural plaques according to the
on chest X rays, but should be performed only in ILO 1980 Classification of Radiographs of Pneumoconi-
selected cases. oses is low unless the plaques are radiographically well
31 2 Scand J Work Environ Health 1997, vol23, no 4
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Consensus report
defined. The most common differential diagnosis is sub- absence of such markers, a history of significant occu-
pleural fat. Radiographic findings are reliable for the pational, domestic, or environmental exposure to asbes-
diagnosis of asbestos-related pleural plaques when they tos will suffice for attribution. There is evidence that
are characteristic (eg, bilateral circumscribed plaques, peritoneal mesotheliomas are associated with higher
bilateral calcification, diaphragmatic plaques). levels of asbestos exposure than pleural mesotheliomas
Pleural plaques represent circumscribed areas of fi- are. In some circumstances, exposures such as those
brous thickening, typically of the parietal pleura, due to occurring among household members may approach oc-
the deposition of paucicellular collagenous tissue with a cupational levels.
laminar or basket-weave pattern; they may or may not The question is unresolved of whether or not a case
calcify. In regions where plaques are not endemic, 80- of mesothelioma for which the lung fiber count falls
90% of the plaques that are radiologically well defined within the range recorded for unexposed urban dwellers
are attributable to occupational asbestos exposure. The is related to asbestos. More information is needed re-
presence of pleural plaques may justify follow-up among garding the interpretation of fiber burdens in the pleura
occupationally exposed groups. or samples of tumor tissue before these measures can be
Diffuse pleural fibrosis designates noncircumscribed used for the purposes of attribution.
fibrous thickening of variable cellularity, which usually The following points need to be considered in the
affects the parietal, but mainly the visceral, layers. In the assessment of occupational etiology:
setting of occupational asbestos exposure, such diffuse
fibrosis is probably a result of benign asbestos pleuritis
. The great majority of mesotheliomas are due to asbes-
tos exposure.
with effusion. It may or may not be associated with
rounded atelectasis. Diffuse pleural thickening can be
. Mesothelioma can occur in cases with low asbestos
exposure. However, very low background environ-
associated with mild, or rarely moderate or severe, re-
mental exposures carry only an extremely low risk.
strictive pulmonary function defects.
Low exposures from work-related, household, and
. About 80% of mesothelioma patients have had some
occupational exposure to asbestos, and therefore a
natural sources may induce pleural plaques. For diffuse
careful occupational and environmental history should
pleural thickening, higher exposure levels may be re-
be taken.
quired.
An occupational history of brief or low-level exposure
should be considered sufficient for mesothelioma to
Mesothelioma be designated as occupationally related.
A minimum of 10 years from the first exposure is
Malignant mesothelioma affecting any serosal membrane
required to attribute the mesothelioma to asbestos ex-
may be induced by asbestos inhalation. The histological,
posure, though in most cases the latency interval is
immunohistochemical and ultrastructural markers for the
longer (eg, on the order of 30 to 40 years).
diagnosis of mesothelioma are well established. Expert
Smoking has no influence on the risk of mesothelio-
opinion should be sought on atypical cases, or on those
ma.
in which the diagnosis is uncertain because of discordant
findings or in which the amount of material available is
insufficient for definite diagnosis. Mesothelioma is fre-
Lung cancer
quently presented with pleural effusion, dyspnea, and
chest pain. All 4 major histological types (squamous, adeno-, large-
With the exception of certain histological types of cell and small-cell carcinoma) can be related to asbestos.
mesothelioma that are benign or of uncertain or border- The histological type of a lung cancer and its anatomic
line malignant potential (eg, multicystic mesothelioma, location (central or peripheral, upper lobe versus lower
benign papillary mesothelioma), all types of malignant lobe) are of no significant value in deciding whether or
mesothelioma can be induced by asbestos, with the am- not an individual lung cancer is attributable to asbestos.
phiboles showing greater carcinogenic potency than Clinical signs and symptoms of asbestos-related cancer
chrysotile. do not differ from those of lung cancer of other causes.
A lung fiber count exceeding the background range As examples, 1 year of heavy exposure (eg, manufac-
for the laboratory in question or the presence of radio- ture of asbestos products, asbestos spraying, insulation
graphic or pathological evidence of asbestos-related tis- work with asbestos materials, demolition of old build-
sue injury (eg, asbestosis or pleural plaques) or his- ings) or 5-10 years of moderate exposure (eg, construc-
topathologic evidence of abnormal asbestos content tion, shipbuilding) may increase the lung cancer risk 2-
(eg, asbestos bodies in histologic sections of lung) fold or more. In some circumstances of extremely high
should be sufficient to relate a case of pleural mesothe- asbestos exposure, a 2-fold risk of lung cancer can be
lioma to asbestos exposure on a probability basis. In the achieved with exposure of less than 1 year.
Scand J Work Environ Health 1997, "0123, no 4 313
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Consensus report
The relative risk of lung cancer is estimated to in- bestos exposure alone. Asbestosis diagnosed clinically,
crease 0.5--4% for each fiber per cubic centimeter per radiologically (including HRCT), or histologically can
year (fiber-years) of cumulative exposure. With the use be used to attribute a substantial causal or contributory
of the upper boundary of this range, a cumulative expo- role to asbestos for an associated lung cancer.
sure of 25 fiber-years is estimated to increase the risk of Pleural plaques are an indicator of exposure to asbes-
lung cancer 2-fold. Clinical cases of asbestosis may oc- tos fibers. Because pleural plaques may be associated
cur at comparable cumulative exposures. with low levels of asbestos exposure, the attribution of
A 2-fold risk of lung cancer is related to retained lung cancer to asbestos exposure must be supported by
fiber levels of 2 million amphibole fibers (>5 pm) per an occupational history of substantial asbestos exposure
gram of dry lung tissue or 5 million amphibole fibers or measures of asbestos fiber burden. Bilateral diffuse
(> 1 pm) per gram of dry lung tissue. This lung fiber pleural thickening is often associated with moderate or
concentration is approximately equal to 5000 to 15 000 heavy exposures, as seen in cases with asbestosis, and
asbestos bodies per gram of dry tissue, or 5 to 15 asbes- should be considered accordingly in terms of attribution.
tos bodies per milliliter of bronchoalveolar lavage fluid. A minimum lag-time of 10 years from the first asbes-
When asbestos body concentrations are less than 10 000 tos exposure is required to attribute the lung cancer to
asbestos bodies per gram of dry tissue, electron micro- asbestos.
scopic fiber analyses are recommended. Not all exposure criteria need to be fulfilled for the
Chrysotile fibers do not accumulate within lung tis- purposes of attribution. For example, the following can
sue to the same extent as amphiboles because of faster be considered: (i) significant occupational exposure his-
clearance rates; therefore, occupational histories (fiber- tory with low fiber burdens (eg, long exposure to chrys-
years of exposure) are probably a better indicator of lung otile and long lag-time between the end of exposure and
cancer risk from chrysotile than fiber burden analysis is. mineralogical analysis) and (ii) high fiber counts in lung
A lung fiber burden within the range recorded for or broncholavage fluid with an uncertain history or with-
asbestosis in the same laboratory should be assigned a out long-term duration (short exposures can be very in-
significance similar to that of asbestosis. For a patient tense).
with lung cancer and a fiber count that falls within the At very low levels of asbestos exposure, the risk of
range recorded for unexposed urban dwellers, the rela- lung cancer appears to be undetectably low.
tionship of the tumor to amphibole asbestos is doubtful Although tobacco smoking affects the total lung can-
at most. cer risk, this effect does not detract from the risk of lung
Estimates of the relative risk for asbestos-associated cancer attributable to asbestos exposure. No attempt has
lung cancer are based on different-sized populations. Be- been made in this report to apportion the relative contri-
cause of the high incidence of lung cancer in the general butions of asbestos exposure and tobacco smoking.
population, it is not possible to prove in precise deter-
ministic terms that asbestos is the causative factor for an
Prevention and screening
individual patient, even when asbestosis is present. How-
ever, attribution of causation requires reasonable medi- Screening of asbestos-exposed populations can be car-
cal certainty on a probability basis that the agent (asbes- ried out for practical and scientific purposes. There are
tos) has caused or contributed materially to the disease. 4 goals of screening: (i) to identify high risk groups, (ii)
The likelihood that asbestos exposure has made a sub- to target preventive actions, (iii) to discover occupational
stantial contribution increases when the exposure in- diseases, and (iv) to develop improved tools for treat-
creases. Cumulative exposure, on a probability basis, ment, rehabilitation and prevention. Screening should
should thus be considered the main criterion for the attri- aim to prevent asbestos-related diseases and therefore
bution of a substantial contribution by asbestos to lung lead to gained healthy years of life among the screened
cancer risk. For example, relative risk is roughly doubled or among those in similar risk situations. The benefits to
for cohorts exposed to asbestos fibers at a cumulative the individual person should be viewed cautiously. The
exposure of 25 fiber-years or with an equivalent occupa- substantial morbidity and mortality related to asbestos
tional history, at which level asbestosis may or may not exposure argue for continued efforts to increase the pre-
be present or detectable. Heavy exposure, in the absence ventive power of screening.
of radiologically diagnosed asbestosis, is sufficient to Any screening for purely scientific purposes requires
increase the risk of lung cancer. Cumulative exposures appropriate methods and criteria (eg, low cost and high
below 25 fiber-years are also associated with an increased predictive value). Before a screening program is initiat-
risk of lung cancer, but to a less extent. ed, the ethical, financial, and legislative aspects need to
The presence of asbestosis is an indicator of high be considered. These aspects may include patient notifi-
exposure. Asbestosis may also contribute some addi- cation, data protection, allocation of costs, and follow-up
tional risk of lung cancer beyond that conferred by as- of identified abnormalities. In addition, provision should
31 4 Scand J Work Environ Health 1997, vol23, no 4
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Consensus report
be made for epidemiologic analyses, quality control, pri- disease outcome or various biornarkers. Identified abnor-
mary and secondary prevention, and the assessment of malities should be followed by the best clinical and oc-
program effectiveness. cupational practices.
As tools for screening, questionnaires and personal
interviews should include items related to asbestos expo-
Research needs
sure, smoking, and other contributing factors. Question-
naires should preferably be validated for smoking habits There are several issues that still require clarification and
and occupational histories. When possible, question- further study. The following list of recommendations
naires should be applied nationally to permit epidemio- and future directions is not intended to be exhaustive.
logic analysis of the results.
Improvement in the assessment and quantification of
Chest X-ray examinations can include frontal and
exposure to asbestos, to include specific worker
lateral roentgenograms. Appropriate lung function tests
groups, with collation of data and the development of
can measure respiratory flow volumes and rates. In
an international standardized protocol for the assess-
spirometry, attention should be given to careful calibra-
ment of exposure.
tion, acceptable performallce efforts, and reproducibility.
Further analysis of job-exposure data and further
The prevention strategies of asbestos-related diseases
studies on asbestos fiber burdens in tissue in relation
can be based on the identification of exposure sources
to various asbestos-related disorders.
and exposed people. There are 3 main targets for preven-
Studies on chrysotile fiber burdens in lung tissue rela-
tion: (i) an individual worker, (ii) a selected group of
tive to the risk of lung cancer (also to include experi-
workers, and (iii) the work environment. At the level of
mental investigations).
the individual worker, the tools for prevention include
Lung cancer relative to the lung tissue burdens of
health education and the introduction of safe work prac-
mineral fibers other than asbestos (eg, refractory ce-
tices, the avoidance of tobacco smoking, and careful
ramic fibers and zeolites).
follow-up of health by surveillance. The group level
Improvement of the ILO system for the radiological
methods are in part the same as at the individual level (ie,
diagnosis and categorization of pleural abnormalities.
health information, education, and recommendations in-
Development of a standardized system for the report-
cluding the use of respiratory protective equipment).
ing of HRCT scans of asbestos-related disorders,
The work environment is the most important target
analogous to the ILO system.
for preventive measures, starting from avoiding the use
Studies on the specificity of lesions of the pleura visu-
of asbestos, carefully controlling dust emissions using
alized by CT as markers of asbestos exposure and
wet techniques, and controlling passive smoking at the
studies on the prognosis of diffuse pleural abnor-
workplace. Many countries have prohibited the use of
malities.
asbestos, but there are still substantial amounts of asbes-
Improvement in ultrasound imaging of the pleura.
tos in consumer products and in buildings that can ex-
Development of new digital imaging techniques for
pose workers in repair and removal work. Some coun-
the investigation of asbestos-related diseases.
tries have permitted asbestos work only under special
Standardization of the approach to lung crepitations
authorization, training, and protective measures.
with the use of special auditory devices.
From the knowledge on potential exposures to asbes-
Investigation of mesothelioma as a potential outcome
tos, high-risk populations can be identified among per- of exposure to mineral fibers other than asbestos -
sons exposed 10 or more years ago. The availability of
such as refractory ceramic fibers - to include experi-
registers - union, workers' compensation, and employ- mental studies and a series of mesothelioma patients
ment records - can be explored for this purpose.
without exposure to asbestos or erionite, supported by
Subjects can be assigned to subgroups for interven-
lung tissue fiber analysis.
tion or screening as defined by their risk (eg, the current
Multicenter studies on biomarkers for the detection of
risk of lung cancer and risk projected to given time
early asbestos diseases and the assessment of the re-
windows in the future). Criteria for inclusion in each
sponse to new treatment modalities.
intervention or screening group should be established in
Investigation of asbestos-associated tumors other than
the study protocol. Subsequently, the members of each
lung cancer and mesothelioma (eg, laryngeal carcino-
subgroup can serve as separate targets for group-based
ma and renal carcinoma).
and individual intervention programs.
Further studies on the effectiveness of screening pro-
Protocols for intervention should be designed in such
grams.
a way that they serve each subject and subgroup optimal-
ly in terms of promoting individual health and the early Participants: Douglas W. Henderson (Flinders Medical
detection of asbestos-related diseases. Data on these sub- Centre, Australia), Jorma Rantanen (Finnish Institute of
groups can also form a basis for more specific studies of Occupational Health, Finland), Scott Barnhart (Universi-
Scand J Work Environ Health 1997, "0123, no 4 315
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NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023
Consensus report
ty of Washington, United States), John M Dement (Duke cal Center, United States), Klaus Rodelsperger (Justus-
University Medical Center, United States), Paul De Liebig University, Germany), Joachim Rosler (Justus-
Vuyst (Cliniques Universitaires de Bruxelles, Hopital Liebig University, Germany), Antti Tossavainen (Finn-
Erasme, Belgium), Gunnar Hillerdal (Karolinska Hospi- ish Institute of Occupational Health, Finland), Hans-
tal, Sweden), Matti S Huuskonen (Finnish Institute of Joachim Woitowitz (Justus-Liebig University, Germany).
Occupational Health, Finland), Leena Kivisaari (Helsin-
Reprint requests to Dr Antti Tossavainen, Department of
ki University Central Hospital, Finland), Yukinori Kusa-
Industrial Hygiene and Toxicology, Finnish Institute of
ka (Fukui Medical School, Japan), Aarne Lahdensuo
Occupational Health, Topeliuksenkatu 41 a A, FIN-
(Tampere University Hospital, Finland), Sverre LangLd
00250 Helsinki, Finland (free of charge).
(The National Hospital, Norway), Gunnar Mowe (De-
partment of Social Insurance Medicine, University of The reprint plus a copy of the conclusions and recommenda-
Oslo, Norway), Toshiteru Okubo (University of Occupa- tions (People and Work Research Reports, no 14) can be
tional and Environmental Health, Japan), John E Parker obtained from the Finnish Institute of Occupational Health,
(National Institute for Occupational Safety and Health, Suvi Lehtinen, Topeliuksenkatu 41 a A, FIN-00250 Helsinki,
United States), Victor L Roggli (Duke University Medi- Finland, for a price of FIM 80.00 t postage.
316 Scand J Work Environ Health 1997, vol23, no 4
Preview
FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020 NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023 EXHIBIT 136 FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020 NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023 Consensus report Scand J Work En viron Health 1997;23:31 1-6 Asbestos, asbestosis, and cancer: the Helsinki criteria for diagnosis and altribu tion The International Expert Meeting on Asbestos, Asbesto- tos-induced lung cancers are estimated to occur anilually sis, and Cancer was convened in Helsinki on 20-22 in the population of approxiinately 800 million people. January 1997 to discuss disorders of the lung and pleura In general, reliable work histories provide the most in association with asbestos and to agree upon state-of- practical and useful measure of occupational asbestos the-art criteria for their diagnosis and attribution with exposure. Using structured questionnaires and checltlists, respect to asbestos. The group decided to name this doc- trained interviewers can identify persons who have a ument Tlze Helsirzlci Criteria. work history compatible with significant asbestos expo- The requirement for diagnostic criteria was perceived sure. Dust measurements can be used in the estimation of in part because of new developinents in diagnostic meth- past fiber levels at typical worltplaces and in the use of ods, with better identification of asbestos-related disor- asbestos-containing materials. A cumulative fiber dose, ders. Such developments enhance awareness of health as expressed in fiber-years per cubic centimeter, is an hazards imposed by asbestos, lead to practical preven- important parameter of asbestos exposure. tion and appropriate compensation, and also provide an The clinical diagnosis of asbestos-related diseases is opportunity to carry out international comparisons. They based on a detailed interview of the patient and occupa- also provide possible models for the risk assessment of tional data on asbestos exposure and appropriate latency, other mineral dusts. signs and symptoms, radiological and lung physiology The meeting was attended by 19 participants from findings, and selected cytological, histological and other 8 countries not produciilg asbestos. The chairmen were laboratory studies. Histopathological confirmation is re- Professor Douglas W Henderson (Flinders Medical quired for suspected asbestos-related malignancies and Centre, Australia) and Professor Jorma Rantanen (Finn- for the resolution of differential diagnoses. A multidis- ish Institute of Occupational Health, Finland). The ciplinary approach is suggested for the evaluation of group was a multidisciplinary gathering of pathologists, probletn cases. radiologists, occupational and pulmonary physicians, The chest radiograph is the basic tool for identifying epidemiologists, toxicologists, industrial hygienists, and asbestos-related diseases such as asbestosis, pleural ab- clinical and laboratory scientists specializing in tissue normalities, lung cancer, and mesothelioma. The limita- fiber analysis. Collectively, the group has published over tion of the chest radiograph in the detection of asbestosis 1000 articles on asbestos and associated disorders. This and asbestos-associated pleural abnormalities is widely document is based on a more co~nprehensivereport pro- recognized. Computed tomography (CT) and high reso- viding scientific evidence for the conclusions and rec- lution computed tomography (HRCT) can facilitate the ommendations (People arzd Work Research Reports, no detection of asbestosis and asbestos-related pleural ab- 14, Finnish Institute of Occupational Health, Helsinki, normalities, as well as asbestos-related malignancies; 1997). they are not recoinmended as a screening tool but may be The meeting was scieiltifically supported by leading invaluable for individual clinical evaluation and research institutions in the field of asbestos research, and it was purposes. Examples are the detection of pleural abnor- funded by the Ministry of Social Affairs and Health and malities in suspected cases of asbestosis and the detec- the Finnish Work Environment Fund. tion of parenchy~naldisease obscured on the chest film and also use as an aid to differential diagnosis. As new imaging techniques such as digital radiography are evolv- General considerations ing, standard images and iilterpretations must be devel- Occupational exposures to asbestos dust have been wide- oped. The place of other imaging techniques (ultrasound, spread in all industrial countries and continue as a conse- magnetic resonance imaging, gallium scanning, ventila- quence of "in-place" materials. In detailed interviews tion-perfusion studies, positron-emission tomography) about 20% to 40% of adult men report some past occupa- has yet to be established, and they are not currently tions and jobs that may have entailed asbestos exposure recommended for the clinical diagnosis of asbestos-re- at work. In Western Europe, North America, Japan, and lated disorders. Australia the use of asbestos peaked in the 1970s, and Analysis of lung tissue for asbestos fibers and asbes- cussently about 10 000 mesotheliomas and 20 000 asbes- tos bodies can provide data to supplemeilt the occupa- FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020 NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023 Consensus report tional history. For clinical purposes, the following guide- Smoking effects should be considered in the evalua- lines are recommended to identify persons with a high tion of early asbestosis, lung function tests, and respira- probability of exposure to asbestos dust at work: over 0.1 tory symptoms. nill lion amphibole fibers (>5 ym) per gram of dry lung A histological diagnosis of asbestosis requires the tissue o r over 1 million amphibole fibers (>I pm) per identification of diffuse interstitial fibrosis in well inflat- gram of dry lung tissue as measured by electron micro- ed lung tissue remote from a lung cancer or other mass scopy in a qualified laboratory o r over 1000 asbestos lesion, plus the presence of either 2 or more asbestos bodies per gram of dry tissue (100 asbestos bodies per bodies in tissue with a section area of 1 cm2 or a count of gram of wet tissue) o r over 1 asbestos body per milliliter uncoated asbestos fibers that falls into the range recorded of bronchoalveolar lavage fluid, as measured by light for asbestosis by the same laboratory. inicroscopy in a qualified laboratory. In order to achieve reasonable comparability between Each laboratory should establish its own reference different studies, a standardized system for the histologi- values. The median values for occupationally exposed cal diagnosis and grading of asbestosis is required. The populations should be substantially above the reference Roggli-Pratt modification of the CAP-NIOSH system is values. Efforts to standardize analytical methods for recommended as a reasonably simple and reproducible fiber burden analyses by different laboratories are rec- scheme for this purpose. ommended. There is evidence that rare cases of asbestosis occur without significant numbers of asbestos bodies. These cases are recognizable - and distinguishable from idio- Asbestosis pathic pulmonary fibrosis - only by analysis of the Asbestosis is defined as diffuse interstitial fibrosis of uncoated fiber burden. Rare cases of asbestosis in rela- the lung as a consequence of exposure to asbestos dust. tion to the inhalation of pure chrysotile can occur, with a Neither the clinical features nor the architectual tissue prolonged interval between the last exposure and the abnormalities sufficiently differ from those of other diagnosis and few or no detectable asbestos bodies and a causes of interstitial fibrosis to allow confident diag- low fiber burden. The existence of such cases is specula- nosis without a history of significant exposure to asbes- tive and, if the diagnosis can be made, it must be done tos dust in the past or the detection of asbestos fibers or from other compelling clinical or radiological grounds bodies in the lung tissue greatly in excess of that com- combined with exposure data. monly seen in the general population. Symptoms of as- Fibro-inflammatory patterns other than conventional bestosis include dyspnea and cough. Common findings asbestosis have also been described for workers with are inspiratory basilar crackles and, less commonly, occupational exposure to asbestos, including a pattern clubbing of the fingers. Functional disturbances can in- resembling desquamative interstitial pneumonia (DIP), clude gas exchange abnormalities, a restrictive pattern, the occurrence of granulomatous inflammation, a picture and obstructive features due to small airway disease. that resembles lymphocytic interstitial pneumonia, and Asbestosis is generally associated with relatively organizing pneumonia with bronchiolitis obliterans. Al- high exposure levels with radiological signs of paren- though the DIP-like picture with asbestos bodies is prob- chymal fibrosis. However, it is possible that mild ably asbestos-related, the other patterns have not yet fibrosis may occur at lower exposure levels, and the been shown to be so related. radiological criteria need not always be fulfilled in cases of llistologically detectable parenchymal fibrosis. The Pleural disorders recognition of asbestosis by chest radiography is best guided by standardized methods such as the classifi- Asbestos-related pleural abnormalities are divided into cation of the International Labour Organisation (ILO) pleural plaques, mainly involving the parietal pleura, and its modifications. Standard films must always be sometimes with calcification, and diffuse pleural thick- used. For research and screening purposes, radiological ening, which is a collective name for pleural reactions findings of small opacities, grade 110, are usually re- involving mainly the visceral pleura. These include be- garded as an early stage of asbestosis. Inspiratory basi- nign asbestos-related pleural effusion, blunted costo- lar sales, restrictive impairment, small airway ob- phrenic angle, crow's feet or pleuroparenchymal fibrous struction, and gas exchange disturbances in pulmonary strands, and rounded atelectasis. Avoidance of the term function are considered valuable information for clini- "pleural asbestosis" is recommended. Pleural plaques are cal diagnosis, for occupational health practice, and for usually asymptomatic, and without clinically important attribution purposes. HRCT can confirm radiological findings. findings of asbestosis and show early changes not seen The specificity of pleural plaques according to the on chest X rays, but should be performed only in ILO 1980 Classification of Radiographs of Pneumoconi- selected cases. oses is low unless the plaques are radiographically well 31 2 Scand J Work Environ Health 1997, vol23, no 4 FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020 NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023 Consensus report defined. The most common differential diagnosis is sub- absence of such markers, a history of significant occu- pleural fat. Radiographic findings are reliable for the pational, domestic, or environmental exposure to asbes- diagnosis of asbestos-related pleural plaques when they tos will suffice for attribution. There is evidence that are characteristic (eg, bilateral circumscribed plaques, peritoneal mesotheliomas are associated with higher bilateral calcification, diaphragmatic plaques). levels of asbestos exposure than pleural mesotheliomas Pleural plaques represent circumscribed areas of fi- are. In some circumstances, exposures such as those brous thickening, typically of the parietal pleura, due to occurring among household members may approach oc- the deposition of paucicellular collagenous tissue with a cupational levels. laminar or basket-weave pattern; they may or may not The question is unresolved of whether or not a case calcify. In regions where plaques are not endemic, 80- of mesothelioma for which the lung fiber count falls 90% of the plaques that are radiologically well defined within the range recorded for unexposed urban dwellers are attributable to occupational asbestos exposure. The is related to asbestos. More information is needed re- presence of pleural plaques may justify follow-up among garding the interpretation of fiber burdens in the pleura occupationally exposed groups. or samples of tumor tissue before these measures can be Diffuse pleural fibrosis designates noncircumscribed used for the purposes of attribution. fibrous thickening of variable cellularity, which usually The following points need to be considered in the affects the parietal, but mainly the visceral, layers. In the assessment of occupational etiology: setting of occupational asbestos exposure, such diffuse fibrosis is probably a result of benign asbestos pleuritis . The great majority of mesotheliomas are due to asbes- tos exposure. with effusion. It may or may not be associated with rounded atelectasis. Diffuse pleural thickening can be . Mesothelioma can occur in cases with low asbestos exposure. However, very low background environ- associated with mild, or rarely moderate or severe, re- mental exposures carry only an extremely low risk. strictive pulmonary function defects. Low exposures from work-related, household, and . About 80% of mesothelioma patients have had some occupational exposure to asbestos, and therefore a natural sources may induce pleural plaques. For diffuse careful occupational and environmental history should pleural thickening, higher exposure levels may be re- be taken. quired. An occupational history of brief or low-level exposure should be considered sufficient for mesothelioma to Mesothelioma be designated as occupationally related. A minimum of 10 years from the first exposure is Malignant mesothelioma affecting any serosal membrane required to attribute the mesothelioma to asbestos ex- may be induced by asbestos inhalation. The histological, posure, though in most cases the latency interval is immunohistochemical and ultrastructural markers for the longer (eg, on the order of 30 to 40 years). diagnosis of mesothelioma are well established. Expert Smoking has no influence on the risk of mesothelio- opinion should be sought on atypical cases, or on those ma. in which the diagnosis is uncertain because of discordant findings or in which the amount of material available is insufficient for definite diagnosis. Mesothelioma is fre- Lung cancer quently presented with pleural effusion, dyspnea, and chest pain. All 4 major histological types (squamous, adeno-, large- With the exception of certain histological types of cell and small-cell carcinoma) can be related to asbestos. mesothelioma that are benign or of uncertain or border- The histological type of a lung cancer and its anatomic line malignant potential (eg, multicystic mesothelioma, location (central or peripheral, upper lobe versus lower benign papillary mesothelioma), all types of malignant lobe) are of no significant value in deciding whether or mesothelioma can be induced by asbestos, with the am- not an individual lung cancer is attributable to asbestos. phiboles showing greater carcinogenic potency than Clinical signs and symptoms of asbestos-related cancer chrysotile. do not differ from those of lung cancer of other causes. A lung fiber count exceeding the background range As examples, 1 year of heavy exposure (eg, manufac- for the laboratory in question or the presence of radio- ture of asbestos products, asbestos spraying, insulation graphic or pathological evidence of asbestos-related tis- work with asbestos materials, demolition of old build- sue injury (eg, asbestosis or pleural plaques) or his- ings) or 5-10 years of moderate exposure (eg, construc- topathologic evidence of abnormal asbestos content tion, shipbuilding) may increase the lung cancer risk 2- (eg, asbestos bodies in histologic sections of lung) fold or more. In some circumstances of extremely high should be sufficient to relate a case of pleural mesothe- asbestos exposure, a 2-fold risk of lung cancer can be lioma to asbestos exposure on a probability basis. In the achieved with exposure of less than 1 year. Scand J Work Environ Health 1997, "0123, no 4 313 FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020 NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023 Consensus report The relative risk of lung cancer is estimated to in- bestos exposure alone. Asbestosis diagnosed clinically, crease 0.5--4% for each fiber per cubic centimeter per radiologically (including HRCT), or histologically can year (fiber-years) of cumulative exposure. With the use be used to attribute a substantial causal or contributory of the upper boundary of this range, a cumulative expo- role to asbestos for an associated lung cancer. sure of 25 fiber-years is estimated to increase the risk of Pleural plaques are an indicator of exposure to asbes- lung cancer 2-fold. Clinical cases of asbestosis may oc- tos fibers. Because pleural plaques may be associated cur at comparable cumulative exposures. with low levels of asbestos exposure, the attribution of A 2-fold risk of lung cancer is related to retained lung cancer to asbestos exposure must be supported by fiber levels of 2 million amphibole fibers (>5 pm) per an occupational history of substantial asbestos exposure gram of dry lung tissue or 5 million amphibole fibers or measures of asbestos fiber burden. Bilateral diffuse (> 1 pm) per gram of dry lung tissue. This lung fiber pleural thickening is often associated with moderate or concentration is approximately equal to 5000 to 15 000 heavy exposures, as seen in cases with asbestosis, and asbestos bodies per gram of dry tissue, or 5 to 15 asbes- should be considered accordingly in terms of attribution. tos bodies per milliliter of bronchoalveolar lavage fluid. A minimum lag-time of 10 years from the first asbes- When asbestos body concentrations are less than 10 000 tos exposure is required to attribute the lung cancer to asbestos bodies per gram of dry tissue, electron micro- asbestos. scopic fiber analyses are recommended. Not all exposure criteria need to be fulfilled for the Chrysotile fibers do not accumulate within lung tis- purposes of attribution. For example, the following can sue to the same extent as amphiboles because of faster be considered: (i) significant occupational exposure his- clearance rates; therefore, occupational histories (fiber- tory with low fiber burdens (eg, long exposure to chrys- years of exposure) are probably a better indicator of lung otile and long lag-time between the end of exposure and cancer risk from chrysotile than fiber burden analysis is. mineralogical analysis) and (ii) high fiber counts in lung A lung fiber burden within the range recorded for or broncholavage fluid with an uncertain history or with- asbestosis in the same laboratory should be assigned a out long-term duration (short exposures can be very in- significance similar to that of asbestosis. For a patient tense). with lung cancer and a fiber count that falls within the At very low levels of asbestos exposure, the risk of range recorded for unexposed urban dwellers, the rela- lung cancer appears to be undetectably low. tionship of the tumor to amphibole asbestos is doubtful Although tobacco smoking affects the total lung can- at most. cer risk, this effect does not detract from the risk of lung Estimates of the relative risk for asbestos-associated cancer attributable to asbestos exposure. No attempt has lung cancer are based on different-sized populations. Be- been made in this report to apportion the relative contri- cause of the high incidence of lung cancer in the general butions of asbestos exposure and tobacco smoking. population, it is not possible to prove in precise deter- ministic terms that asbestos is the causative factor for an Prevention and screening individual patient, even when asbestosis is present. How- ever, attribution of causation requires reasonable medi- Screening of asbestos-exposed populations can be car- cal certainty on a probability basis that the agent (asbes- ried out for practical and scientific purposes. There are tos) has caused or contributed materially to the disease. 4 goals of screening: (i) to identify high risk groups, (ii) The likelihood that asbestos exposure has made a sub- to target preventive actions, (iii) to discover occupational stantial contribution increases when the exposure in- diseases, and (iv) to develop improved tools for treat- creases. Cumulative exposure, on a probability basis, ment, rehabilitation and prevention. Screening should should thus be considered the main criterion for the attri- aim to prevent asbestos-related diseases and therefore bution of a substantial contribution by asbestos to lung lead to gained healthy years of life among the screened cancer risk. For example, relative risk is roughly doubled or among those in similar risk situations. The benefits to for cohorts exposed to asbestos fibers at a cumulative the individual person should be viewed cautiously. The exposure of 25 fiber-years or with an equivalent occupa- substantial morbidity and mortality related to asbestos tional history, at which level asbestosis may or may not exposure argue for continued efforts to increase the pre- be present or detectable. Heavy exposure, in the absence ventive power of screening. of radiologically diagnosed asbestosis, is sufficient to Any screening for purely scientific purposes requires increase the risk of lung cancer. Cumulative exposures appropriate methods and criteria (eg, low cost and high below 25 fiber-years are also associated with an increased predictive value). Before a screening program is initiat- risk of lung cancer, but to a less extent. ed, the ethical, financial, and legislative aspects need to The presence of asbestosis is an indicator of high be considered. These aspects may include patient notifi- exposure. Asbestosis may also contribute some addi- cation, data protection, allocation of costs, and follow-up tional risk of lung cancer beyond that conferred by as- of identified abnormalities. In addition, provision should 31 4 Scand J Work Environ Health 1997, vol23, no 4 FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020 NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023 Consensus report be made for epidemiologic analyses, quality control, pri- disease outcome or various biornarkers. Identified abnor- mary and secondary prevention, and the assessment of malities should be followed by the best clinical and oc- program effectiveness. cupational practices. As tools for screening, questionnaires and personal interviews should include items related to asbestos expo- Research needs sure, smoking, and other contributing factors. Question- naires should preferably be validated for smoking habits There are several issues that still require clarification and and occupational histories. When possible, question- further study. The following list of recommendations naires should be applied nationally to permit epidemio- and future directions is not intended to be exhaustive. logic analysis of the results. Improvement in the assessment and quantification of Chest X-ray examinations can include frontal and exposure to asbestos, to include specific worker lateral roentgenograms. Appropriate lung function tests groups, with collation of data and the development of can measure respiratory flow volumes and rates. In an international standardized protocol for the assess- spirometry, attention should be given to careful calibra- ment of exposure. tion, acceptable performallce efforts, and reproducibility. Further analysis of job-exposure data and further The prevention strategies of asbestos-related diseases studies on asbestos fiber burdens in tissue in relation can be based on the identification of exposure sources to various asbestos-related disorders. and exposed people. There are 3 main targets for preven- Studies on chrysotile fiber burdens in lung tissue rela- tion: (i) an individual worker, (ii) a selected group of tive to the risk of lung cancer (also to include experi- workers, and (iii) the work environment. At the level of mental investigations). the individual worker, the tools for prevention include Lung cancer relative to the lung tissue burdens of health education and the introduction of safe work prac- mineral fibers other than asbestos (eg, refractory ce- tices, the avoidance of tobacco smoking, and careful ramic fibers and zeolites). follow-up of health by surveillance. The group level Improvement of the ILO system for the radiological methods are in part the same as at the individual level (ie, diagnosis and categorization of pleural abnormalities. health information, education, and recommendations in- Development of a standardized system for the report- cluding the use of respiratory protective equipment). ing of HRCT scans of asbestos-related disorders, The work environment is the most important target analogous to the ILO system. for preventive measures, starting from avoiding the use Studies on the specificity of lesions of the pleura visu- of asbestos, carefully controlling dust emissions using alized by CT as markers of asbestos exposure and wet techniques, and controlling passive smoking at the studies on the prognosis of diffuse pleural abnor- workplace. Many countries have prohibited the use of malities. asbestos, but there are still substantial amounts of asbes- Improvement in ultrasound imaging of the pleura. tos in consumer products and in buildings that can ex- Development of new digital imaging techniques for pose workers in repair and removal work. Some coun- the investigation of asbestos-related diseases. tries have permitted asbestos work only under special Standardization of the approach to lung crepitations authorization, training, and protective measures. with the use of special auditory devices. From the knowledge on potential exposures to asbes- Investigation of mesothelioma as a potential outcome tos, high-risk populations can be identified among per- of exposure to mineral fibers other than asbestos - sons exposed 10 or more years ago. The availability of such as refractory ceramic fibers - to include experi- registers - union, workers' compensation, and employ- mental studies and a series of mesothelioma patients ment records - can be explored for this purpose. without exposure to asbestos or erionite, supported by Subjects can be assigned to subgroups for interven- lung tissue fiber analysis. tion or screening as defined by their risk (eg, the current Multicenter studies on biomarkers for the detection of risk of lung cancer and risk projected to given time early asbestos diseases and the assessment of the re- windows in the future). Criteria for inclusion in each sponse to new treatment modalities. intervention or screening group should be established in Investigation of asbestos-associated tumors other than the study protocol. Subsequently, the members of each lung cancer and mesothelioma (eg, laryngeal carcino- subgroup can serve as separate targets for group-based ma and renal carcinoma). and individual intervention programs. Further studies on the effectiveness of screening pro- Protocols for intervention should be designed in such grams. a way that they serve each subject and subgroup optimal- ly in terms of promoting individual health and the early Participants: Douglas W. Henderson (Flinders Medical detection of asbestos-related diseases. Data on these sub- Centre, Australia), Jorma Rantanen (Finnish Institute of groups can also form a basis for more specific studies of Occupational Health, Finland), Scott Barnhart (Universi- Scand J Work Environ Health 1997, "0123, no 4 315 FILED: ERIE COUNTY CLERK 03/17/2023 09:21 PM INDEX NO. 815818/2020 NYSCEF DOC. NO. 347 RECEIVED NYSCEF: 03/17/2023 Consensus report ty of Washington, United States), John M Dement (Duke cal Center, United States), Klaus Rodelsperger (Justus- University Medical Center, United States), Paul De Liebig University, Germany), Joachim Rosler (Justus- Vuyst (Cliniques Universitaires de Bruxelles, Hopital Liebig University, Germany), Antti Tossavainen (Finn- Erasme, Belgium), Gunnar Hillerdal (Karolinska Hospi- ish Institute of Occupational Health, Finland), Hans- tal, Sweden), Matti S Huuskonen (Finnish Institute of Joachim Woitowitz (Justus-Liebig University, Germany). Occupational Health, Finland), Leena Kivisaari (Helsin- Reprint requests to Dr Antti Tossavainen, Department of ki University Central Hospital, Finland), Yukinori Kusa- Industrial Hygiene and Toxicology, Finnish Institute of ka (Fukui Medical School, Japan), Aarne Lahdensuo Occupational Health, Topeliuksenkatu 41 a A, FIN- (Tampere University Hospital, Finland), Sverre LangLd 00250 Helsinki, Finland (free of charge). (The National Hospital, Norway), Gunnar Mowe (De- partment of Social Insurance Medicine, University of The reprint plus a copy of the conclusions and recommenda- Oslo, Norway), Toshiteru Okubo (University of Occupa- tions (People and Work Research Reports, no 14) can be tional and Environmental Health, Japan), John E Parker obtained from the Finnish Institute of Occupational Health, (National Institute for Occupational Safety and Health, Suvi Lehtinen, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, United States), Victor L Roggli (Duke University Medi- Finland, for a price of FIM 80.00 t postage. 316 Scand J Work Environ Health 1997, vol23, no 4