INORGANIC DUSTS AOEC Teaching Module 2007. This educational module was produced by Michael Greenberg, MD, MPH, Arthur Frank, MD, PhD, and John Curtis,

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