INORGANIC DUSTS
AOEC Teaching Module
2007
This educational module was produced by Michael Greenberg, MD, MPH, Arthur Frank, MD, PhD, and John Curtis, MD for The University of Texas
Health Science Center at San Antonio (UTHSCSA) Environmental Medicine Education Program and South Texas Environmental Education and Research Program (STEER-San Antonio/Laredo/Harlingen,Texas)Administrative support was provided by the Association of Occupational
and Environmental Clinics through funding to UTHSCSA by the Agency forToxic Substances and Disease Registry (ATSDR), U.S. Department of
Health and Human Services.Use of this program must include acknowledgement of the authors,
UTHSCSA and the funding support.For information about other educational modules contact the UTHSCSA
STEER office, Mail Code 7796, 7703 Floyd Curl Drive, San Antonio,Texas 78229-3900,(210)567-7407.
HISTORICAL PERSPECTIVE
• Dusty trades such as mining have been linked to potential health problems since antiquity– Pliny described problems associated with
mining nearly 2 thousand years ago
• A key recognition was that the dust itself could lead to lung problems (pneumoconioses)
Libby, Montana
• Vermiculite mining began in Libby in the 1920’s– The vermiculite ore was contaminated with
tremolite asbestos
• W.R. Grace Company controlled the mines beginning in the 1960’s
Libby Mine Site
Asbestos (tremolite)-containing Vermiculite
Why are we concerned about Libby, MT?
• Materials mined from the Libby area were actually shipped throughout USA
• Texas and other border areas did receive materials mined at Libby
From Libby to Texas
• More than 675,000 tons of vermiculite were sent from Libby area mines to dozens of locations in Texas between 1963 and 1992> 327,000 tons to Dallas
> 193,000 tons to Houston
> 103,000 tons to San Antonio
Health Effects
• Some studies have reported increased rates of lung cancer, asbestosis and mesothelioma in vermiculite exposed populations in and around Libby, MT– Miners– Families of those employed in the mines– Local population surrounding the mines
Toxicological Considerations for Inorganic Dusts
• Asbestos• Silica• Fiberglass• Vermiculite
Asbestos
• A group of hydrates silicates found as mineral fibers in natural rock formations
• 2 major groups (6 distinct types)– Serpentine
• Chrysotile
– Amphibole• Amosite, anthophyllite,
crocidolite, actinolite, tremolite
Asbestos - Occurrence
• Exists in natural deposits– Harmless if undisturbed
• Used in industry– Thousands of uses
including:• Fire-proofing
• Construction
• Automobile parts
• Durable and persistent in the environment
Tremolite Asbestos
Exposure
• Construction (now less frequent)
• Demolition of asbestos containing structures may result in aerosolization of fibers
• Drinking water may contain asbestos– Natural deposits– Cement pipes containing
asbestos
Potential Health Effects
• Nonmalignant– Asbestosis
• Malignant– Lung Cancer (bronchogenic carcinoma)– Mesothelioma– Possible association with non-pulmonary
Asbestosis related deaths by state:
Asbestosis
• When asbestos is deposited in the lungs– Biopersistence in lungs
varies with specific type of asbestos
– A fibrotic response may arise from retained fibers
• This may cause pulmonary problems in some cases
• Usually develops over 20-40 years
Rajagopol J and Mark E. N Engl J Med 2002;347:1262-1268
Active Fibrosis at the Edge of a Scar (Hematoxylin and Eosin, x125)
Asbestos body
Asbestosis - Clinical
• Symptoms may include dyspnea and cough
• Pulmonary function tests may reveal:– Reduced diffusing
capacity– Restrictive pattern on
PFTs
• Radiographic abnormalities may be seen Histopathologic view of asbestosis
Asbestosis - Radiographic Findings
• Chest radiography:– Small irregular opacities in lower lobes
• Upper lobe disease less likely
– Pleural plaques• Indication of exposure ONLY• Does NOT indicate clinical disease• Only 10-15% of plaques are visible radiographically
– Pleural Effusions– Fibrosis
• Curvilinear plural lines• Thickened inter- and intra-lobular lines
• CT scan may show “honeycombing”
Asbestosis
• Note:– Pleural plaques– Fibrosis
Amphibole Asbestos and Cancer
• Increased risk of bronchogenic carcinoma - up to 5 times relative risk in some studies– SYNERGISTIC effect
with tobacco smoking that may increase relative risk up to almost 50
Scanning electron micrograph of lung cancer cells
Mesothelioma• Cancer arising from the epithelium or sub-
epithelium of pleura, peritoneum or pericardium
• May have increased incidence in populations with long-term, high concentration amphibole asbestos exposure– Reported odds ratios vary in different trades– No excess risk from chrysotile asbestos– Some exposures may involve multiple types of
asbestos with co-existent amphibole and chrysotile forms
Robinson B and Lake R. N Engl J Med 2005;353:1591-1603
Clinical and Computed Tomographic (CT) Features of Malignant Mesothelioma
Mesothelioma presenting as a pleural mass
Mesothelioma encircling the intrathoracic space
Subcutaneous extension of mesothelioma
Mesothelioma
• Does occur in patients with no asbestos exposure
• May be difficult to diagnose• Long latency period
– Averages 30-40 years following exposure
• Difficult to treat/poor prognosis– Chemotherapy– Radical thoracic surgery
Dvorak A. N Engl J Med 2001;345:424
Electron micrograph of tumor showing several characteristics of mesothelioma
Mesothelioma
• Survival from time of diagnosis varies according to several prognostic factors– Usually less than 20 months– No effective curative therapy– Surgery is mainly palliative– Chemotherapy may prolong survival
Toxicological Considerations for Inorganic Dusts
• Asbestos• Silica• Fiberglass• Vermiculite
Silica
• Refers to the chemical compound silicon dioxide– Crystalline silica exists in
several forms• Alpha quartz (often simply
referred to as quartz)• Other forms (beta quartz,
keatite, coesite etc.) less common
– Noncrystalline (amorphous)
Silica - Occurrence
• Common component of soil and rock– Crystalline silica is a
component of nearly every mineral deposit
Silica Exposure
• NIOSH indicates that > 1.7 million U.S. workers may be exposed to silica
• Various occupations may result in exposure– Construction– Sandblasting– Mining
• Most exposures are to mixed dust with variable silica content
Health Consequences
• Estimated 200-300 deaths per year due to silica exposure
• In some cases silica exposure may result in:– Silicosis
• Some have suggested an association between silica and other medical conditions including– Lung cancer– Increased risk of tuberculosis– Autoimmune disease
Mycobacterium tuberculosis
Classical Silicosis
• Irreversible fibrotic disease of lungs
• May develop only after decades (chronic) of occupational exposure to silica
• Preventable with proper precautions
Silicosis with Fibrosis
Chronic (classic) silicosis
• Develops over many years (as long as 45 yrs or longer)
• Radiographic findings include:– Nodular opacities in upper lobes– Lymph node calcification (egg-shell pattern)– Lower-lobe hyperinflation or bullae
• Restrictive pattern seen on pulmonary function tests (PFTs)
Accelerated silicosis
• Accelerated silicosis– Develops more rapidly (in the range of 15
years)– Follows more intense exposure– Similar radiographic appearance
Acute silicosis• Extremely uncommon• Requires SUBSTANTIAL exposure over
relatively short time frame• May develop in less than 1 year• Symptoms: dyspnea, fever, weight-loss, chest
pain, rapidly progressive respiratory failure• Radiographic appearance:
– Ground-glass appearance– Linear opacities– Hilar lymph node enlargement
• Biological mechanisms for the development of this disease may differ from other forms
Hawk’s Nest Disaster
• 1931-1932; near Gauley Bridge, West Virginia
• Largest American epidemic of acute silicosis
• More than 400 workers died• Federal hearings determined that rock
blasting was conducted at this site through rock > 90% pure silica
Silicosis Treatment
• Avoidance of exposure
• Inhaled corticosteroids
• Supportive care
Silica and Lung Cancer
• There is evidence of carcinogenicity in some animal models
• Controversial in human populations -– Current IARC classification
• 1 (known human carcinogen)
– Other reviews report no evidence of causation between silicosis and lung cancer
Other manifestations
• Pulmonary tuberculosis– Occurs more frequently
in silicosis patients
• Some have posited association with autoimmune disease– Rheumatoid arthritis (RA)– Scleroderma– Progressive systemic
sclerosis
Toxicological Considerations for Inorganic Dusts
• Asbestos• Silica• Fiberglass• Vermiculite
Fiberglass
• Colloquial term/trade name for fibrous glass products made from molten glass or sand
• Used as thermal and sound insulation
• Known to cause irritative symptoms of the skin, upper airways, mucous membranes following unprotected exposure
Health Effects
• Limited animal evidence of carcinogenicity– Usually at doses and routes of exposure
not expected to be clinically relevant, i.e. extraordinarily high exposures for long time period
• IARC (2001) states fibrous glass is “not classifiable” as to carcinogenicity
Toxicological Considerations for Inorganic Dusts
• Asbestos• Silica• Fiberglass• Vermiculite
Vermiculite
• Naturally occurring mineral– Expands when
heated– Light-weight– Fire-resistant– Absorbent– Odorless
Vermiculite Uses
• Attic insulation• Packing material• Garden products
Health Issues
• May be contaminated with amphibole (tremolite) asbestos
• Health effects determined by degree of amphibole exposure
General Principles of Inorganic Dust Exposure
• Determining exposure
• Anticipation of health effects
• Reducing exposure and preventing disease
Exposure/Dose
• EXPOSURE is simply the opportunity for contact with a chemical or substance
• DOSE is how much of a material actually enters the body
• Some mistake the concept of exposure thinking it is synonymous with dose
• There is a clear difference between EXPOSURE and DOSE
Exposure• Determined by:
– Degree of aerosolization of particles and fibers
• Sanding, dusting, demolition, construction
– Adequacy of ventilation• Closed spaces result in
greater levels of exposure
– Proper use of personal protective equipment (PPE)
• Masks and filters decrease exposure
Principles of Dust-Related Disease
• Inorganic dusts only cause pulmonary disease following long-term, high intensity exposure
• Confounding factors may include:– Exposure to multiple other agents– Concomitant exposure to carcinogens– Tobacco use– Genetic issues
Disease Prevention
• Identify populations potentially at-risk– Workers– Those near uncontrolled,
heavy use– Families of workers
• Evaluation of working environment– Air quality evaluation– Wet work versus dry work– Use of proper PPE
Clinical Problem Solving Scenario
• Two male workers, ages 67 and 52, present to a local clinic following diagnosis with pleural mesothelioma
Relevant History
• What are the key features of an appropriate:– History of present illness (HPI)?– Past medical history?– Past surgical history?– Occupational history?– Social history?– Family history?
Relevant HPI
• Presence of cardiopulmonary complaints– Dyspnea– Chest pain
• Systemic complaints– Weight-loss– Night sweats
Past Medical History
• History of:– Asthma– COPD– Cancer, especially lung cancer– Pulmonary disease
• Tuberculosis• Sarcoidosis
Past Surgical History
• Identify previous thoracic surgery– Pneumonectomy– Radiation to thorax– Previous lung biopsy
Occupational and Environmental History
• Current occupation– Job description– Length of employment– Job specifics, time spent at each activity
• Use of personal protective equipment– Type/level of PPE– How frequently is PPE used– Is PPE supplied and/or required by employer
• Previous employment– Construction, demolition, military service, foreign travel
etc.
Social History
• Thorough tobacco use history– Accurate assessment of smoking history
• Ethanol use– Evaluation of nutritional and immune status
• Illicit drug use– Especially inhaled drugs (e.g. marijuana, crack,
solvent inhalants, etc)
• Hobbies/home environment– Radon in home, hobbies that may result in
pulmonary exposure
Family History
• Lung cancer
• Mesothelioma
• Asthma/COPD
• Sarcoidosis
Important Physical Exam Findings
• Presence or absence of:– Abnormal lung sounds– Clubbing of digits– Cyanosis– Abnormal heart sounds– Peripheral edema– Wasting/cachexia
Appropriate Work-up
• Consider:– Laboratory Testing– Radiographic Evaluation– Lung Function Testing
Laboratory Testing
• Screening labs as indicated by history
• Possibly pre-operative labs if thoracic surgery is being considered
• Stool guaiac– Important consideration in this age group
• Urinalysis for blood– If indicated by history
Radiographic Evaluation
• Chest radiography– Standard part of evaluation of patients with
exposure history– May be evaluated according to several reading
protocols– Possibly serial X-rays to look for progression
• Computed tomography– As necessary, possibly to confirm diagnosis or
follow response to treatment
Lung Function Testing
• Spirometry
• Full pulmonary function testing– May identify element of reversible
bronchospasm amenable to treatment
Assessment and Plan
• How should these patients be treated?• How should these patients be followed?• Is this an unusual event?
– Clusters of unusual cases need close evaluation
• Does this represent an occupational exposure?• Should the work-place be investigated
– Which is the responsible agency?
• Should other workers be screened or monitored?
References
• Camus M et al. Nonoccupational Exposure to Chrysotile Asbestos and the Risk of Lung Cancer N Engl J Med 1998
• Beckett WS. Current Concepts: Occupational Respiratory Diseases. N Engl J Med 2000
• Steele JPC. Prognostic Factors for Mesothelioma. Hematol Oncol Clin N Am. 2005
• West SD, Lee YCG. Management of Malignant Pleural Mesothelioma. Clin Chest Med 2006
References
• Krug LM. An overview of the chemotherapy for mesothelioma. Hematol Oncol Clin N Am 2005
• Hessel PA et al. Asbestos, asbestosis, and lung cancer: a critical assessment of the epidemiological evidence. Thorax 2005
References
• http://www.atsdr.cdc.gov/DT/fibrous-glass.html
• http://www.osha.gov/SLTC/etools/silica/silicosis/silicosis.html
• Calvert et al. Occupational silica exposure and risk of various diseases: an analysis using death certificates from 27 states of the United States. Occup Environ Med. 2003; 60(2):122-9.
References
• Occupational, Industrial, and Environmental Toxicology. M Greenberg (ed.). Mosby, Inc 2003
• Yarborough. Chrysotile as a cause of mesothelioma: An assessment based on epidemiology. Crit Rev Toxicol. 36: 165-187. 2006