Asbestos Mineralogy and Health Effects
Fibers and fibrous minerals, for example, the asbestos minerals, erion-ite
(one of the many natural and synthetic zeolite species) (1), fiber¬glass, or
other silica forms (diatoms) have been shown to be extremely hazardous. Their
airborne character is paramount, and the specific gravity of the species, the
size, and an appropriate morphology that permits suspension are of primary
consideration. Asbestos as a ubiq¬uitous natural resource refers to several
types of fibrous minerals formed by earth processes and made up of microscopic
bundles of fibers. The dangers associated with inhalation of asbestos fibers
have been known for more than 30 years. Asbestos is known as a group A human
carcinogen. The potential hazards of exposure to asbestos mate¬rials are of
concern worldwide. There are several modes of exposure to airborne fibers
including occupational exposure and the erosion of natural deposits in
asbestos-bearing rocks. Asbestos may also be dis¬persed in water from a number
of sources, including erosion of natural deposits, corrosion, and disintegration
of asbestos materials.
Governments and industries have introduced regulatory measures requiring safety
controls throughout the product life cycle to limit asbestos exposure to the
general public and workers. Although asbestos materials have been well
documented as to their physical and chemical characteristics, they remain under
investigation both by min¬eralogists studying geologic aspects and by
pathologists/epidemiolo-gists studying medical aspects. The term asbestos may be
well known, but the precise definition, safe level of exposure, duration of
exposure, and asbestos types of these fibrous materials still raise questions
and often lead to differences of opinions and arguments as well as legal
disputes (2).
Mineralogy of Asbestos Group Minerals
The six different types of asbestos fibers are divided into two mineral groups
based upon the crystalline structures: serpentine and amphi-bole asbestos.
Asbestiform minerals are not always found with a
fibrous habit. Tremolite, for example, occurs naturally in three distinct
morphologic forms or mineral habits. It may occur as asbestos, splin¬tery
fibers, or in massive crystalline deposits. Any mechanical manip¬ulation of
asbestos rocks rapidly produces many long, thin fibers/ fibrils, since for the
most part, asbestos fibrils are easily separable because of translocation along
a twin plane, which produces a much-reduced cohesion. A lot of data have been
accumulated that suggest that amphibole asbestos and its nonasbestos analogues
possess very different biologic potential. Davis et al (3) demonstrated that
although asbestiform tremolite was extremely carcinogenic when injected into the
peritoneal cavities of rats, nonasbestiform tremolite samples had little or no
carcinogenic potential. These observations suggest that the tremolite
contamination of any material may present a concern only if thin asbestiform
fibers are present.
Serpentine Group Asbestos Minerals
Serpentine group asbestos mineral is chrysotile. Chrysotile fibers are found as
veins in serpentines, in serpentinized ultramafic rocks, and in serpentinized
dolomitic rocks. Chrysotile is one of the three poly-morphs of serpentine group
minerals that have sheet or layer structure. It is a hydrated magnesium silicate
and its stoichiometric chemical composition may be given as
Mg3Si2O5
(OH)4. Most
of the industrial chrysotile fibers are extracted from deposits where fiber
length can reach several centimeters. Fiber growth may occur in massive
serpen-tinite at a right angle to the walls of cracks, which are referred to as
cross-vein chrysotile or cross-fibers, or inclined or parallel to the vein axes
called slip fibers, or as dispersed aggregates of short fibers with no
preferential orientation, which are called mass-fiber deposits.
Among three principal serpentine minerals, the distinction between asbestos and
nonasbestiform varieties is that the nonasbestiform anti-gorite and lizardite
are arranged to form a sheet structure, and the crys¬tals are platy, that is,
they have one short dimension and two longer dimensions, like a saucer. The
crystal structure of chrysotile, always in fibrous form, is discretely distinct
from that of the amphiboles. Chrysotile has an octahedral brucite layer
(Mg6O4(OH)8)-4
intercalated between each silicate tetrahedral sheet. In the
asbestiform variety of serpentine, chrysotile sheets
(Si4O10)-4
are rolled up
tightly to form fibers.
The serpentine’s theoretical formula is
(Mg3-x-y Rx2
+
Ry3
+)
(Si2-y
Ry3
+)
O5
(OH)4
where R2+ is
Fe2+, Mn2+, or Ni2+; and R3+ is Al3+
or Fe3+.
In the octahedral brucite layer, magnesium can be substituted by several
divalent ions, such as
Fe2+,
Mn2+, or Ni2+. In the tetrahedral layer, silicon
may be replaced by
Al3+
or Fe3+. The other two polymorphs are known as
antigorite and lizardite. Their composition is
Mg3Si2O5
(OH)4. The essential
difference of the three minerals is 1:1 layers in the struc¬ture. The silicate
and brucite layers share oxygen atoms. The distance is 0.305nm in the silicate
layer and 0.342 nm in the brucite layer (4).
This mismatch of O—O distances induces curvature and 1:1 layers are
concentrically coiled, producing hollow tubes parallel to the a-axis in
chrysotile. The concentric sheets forming fibers have a curvature radius from
2.5 to 3.0nm for the internal layers up to approximately 25nm for the external
layers (5). Electron microscopy studies indicate that the unit fiber (fibril)
cross section appears in a concentric or spiral arrange¬ment. In the lizardite,
these layers are planar, which is characteristic of sheet silicates. Antigorite
structure is corrugated.
Stacking of the tetrahedral and octahedral sheets in the chrysotile structure
has been shown to yield three types of chrysotile fibers:
1. Clino-chrysotile: Monoclinic stacking, x-axis is parallel to the fiber axis
2. Ortho-chrysotile: Orthorhombic stacking, x-axis is parallel to the fiber axis
3. Para-chrysotile: 180-degree rotation of two-layer structure, y-axis is
parallel to the fiber axis
Amphibole Group Asbestos Minerals
The chemical composition of amphibole group asbestos minerals can vary widely
and reflects the complexity of the environment in which they formed. The
commercially used asbestiform amphiboles are actin-olite, tremolite,
anthophyllite, amosite, and crocidolite. They are all hydrated silicates, which
have double tetrahedral chains with
Si8O22 composition that extend along the
c-axis. Amphiboles are distin¬guished from one another by the number of the
cations
Ca,
Fe, Mg, and Na that they contain.
The amphibole group has the general chemical formula of
A0-1B2C5T8O22(OH,
F, CI, O)2
where A represents zero to one Na+ or K+ in the A site, two ions of
Mg2+,
Fe2+,
Mn2+,
Ca2+,
Na+,
or
Li+ enter the M4 sites, five ions of
Mg2+,
Fe2+,
Mn2+, Al3+, Fe3+,
Cr3+, or Ti4+ enter M1, M2, and M3 sites, and eight ions of Si4+ or Al3+
enter the T site. The remaining entry in the formula (OH, F, Cl, O) indicates
anions that occupy another site. Complete ionic sub¬stitution may take place
between Fe3+ and Al, and between Ti and other c-type cations, and there is
partial substitution of Al for Si in the tetra-hedral chains. Thus, from their
respective composition, amphibole fibers can be viewed as a series of minerals.
For example, the magne¬sium in tremolite is partly replaced by divalent iron in
the c-position to yield actinolite.
The theoretical formulas for the amphibole group of asbestos min¬erals are as
follows:
Actinolite: Ca2
(Mg, Fe2+)5 Si8 O22 (OH)2
Tremolite: Ca2 Mg5
Si8 O22 (OH)2 Anthophyllite: Mg7
Si8 O22 (OH)2
Amosite: (Fe2+)2 (Fe2+Fe3+,
Mg)5 Si8 O22 (OH)2
(Cummingtonite-Grunerite series)
Crocidolite: Na2 (Fe2+,
Mg)3 Fe3+2 Si8 O22 (OH)2
(Riebeckite)
The term amosite is applied to brown industrial asbestos; it is an acronym for
“asbestos minerals of South Africa” with the addition of the usual “-ite” suffix
to designate a mineral. The term crocidolite is applied to blue amphibole
asbestos. Asbestiform varieties of several other amphiboles have been
identified. Other minerals are similar to asbestos in their particle shape, but
they do not possess the character¬istics of asbestos.
The amphibole group of silicates is composed of very common min¬erals in igneous
and metamorphic rocks. The minerals show long pris¬matic or needle-like
(acicular) crystal habits or morphologies. Because of their peculiar structure,
the amphiboles have a distinctive cleavage that results in acicular or
needle-like morphology when the minerals are crushed. A tiny oblong form often
appears naturally in sedimen¬tary deposits if the primary rocks are eroded, or
when mined and milled as part of the extraction of other minerals. However, only
when amphiboles form fibers or adopt an asbestiform habit should they be
classified as asbestos (6).
Unlike chrysotile fiber, the atomic structure of amphibole does not inherently
lead to fiber formation; instead it results from multiple nucleation and
specific growth conditions. Asbestiform and nonas-bestiform amphiboles are
similar in their crystalline structure, but dif¬ferent in the macroscopic scale.
The asbestiform amphiboles tend to have a larger number of crystal defects such
as twinning, Wadsley defects, and chain width disorder than nonasbestiform
varieties.
Identification of Asbestos
Over the years much data have been accumulated about asbestos, which suggests
that amphibole asbestos and its nonasbestos analogues possess very different
biologic potential. Davis et al (3) demonstrated that although asbestiform
tremolite was extremely carcinogenic when injected into peritoneal cavities of
rats, nonasbestiform tremolite sam¬ples had little or no carcinogenic potential.
Therefore, it is important to distinguish between asbestiform and nonasbestiform
amphiboles and types of fibers in bulk, air, and tissue samples. There are some
problems related to the mineralogic techniques necessary to prepare and
characterize samples. The designation of the shape and size of fibrous materials
can be relatively easily revealed by optical examina¬tion. Optics became the
technique of choice to investigate the occur¬rence of inorganic fibrous airborne
particulates at occupational sites, in schools, or any buildings, and even
outdoors where filters could be set up to obtain a representative aliquot of the
air. However, the light (optical) microscope does not have enough spatial
resolution and so is not sufficient on its own for positive identification of
minerals. It is dif¬ficult to identify some fibers such as chrysotile in the
tissue samples under the optical microscope because of the small fiber sizes.
Since the small fiber size of chrysotile in the tissue samples preclude the use
of optical microscopes, morphologic, chemical, and structural identifications
are done by combinations of methods in order to make
unambiguous mineral identifications. The crystal chemical range of potentially
hazardous inorganic and mineral species should be accu¬rately identified.
Morphologic identifications can be performed by using transmission electron
microscopy (TEM) and scanning electron microscopy (SEM). Chemical information is
most commonly obtained by energy dispersive spectroscopy (EDS) or wavelength
dispersive spectroscopy (WDS), which is an integral part of SEM or TEM. A
rela¬tive error percentage for EDS is about 10% and for WDS is about 1%.
Therefore, EDS provides only semiquantitative information, but WDS provides more
quantitative information on chemical composition of the sample. Crystal
structures can be determined by electron diffraction (ED) on samples. Powder
x-ray diffraction (XRD) is a powerful tech¬nique providing that enough material
is available, but not for a mineral present at low percentage in tissue and air
samples. Certain regulations may require specific species of amphiboles; thus,
quantitative chemi¬cal data may be necessary. For example, substitution solid
solution series of amphiboles, such as a tremolite and an actinolite, must be
identified. The SEM studies combined with EDS may not be conclusive because of
the lack of information on the mineral structure.
It is also very difficult to observe chrysotile through the electron microscope
because of its beam sensitivity. Analysts tend to measure fibers that are more
stable under beam conditions. Lung burden studies indicate that chrysotile is
often inhaled as a shorter fiber than amphi-boles. Therefore, in a tissue with
both amphibole and chrysotile, it is possible to make a misjudgment unless the
fibers are identified individually.
The levels of sensitivity using the high-resolution techniques now available
mandate that we follow up the reactions delineated as inter¬ference of inorganic
materials in the biologic environment. The infor¬mation on the inorganic fibrous
particulates can be matched with the equally high-resolution techniques applied
to analyses of tissues, with data gathered at the cellular and molecular levels.
The advances in techniques increase the possibilities that we can test
hypotheses and, it is hoped, gain greater understanding from the anatomic to the
genetic of the reactions that lead to induction of disease. Coordinating
ultra-microscopic levels with the health and mineralogic investigations for a
particular geographic area should enable us to refine the possibilities. The
exchange of information among the several disciplines is needed to advance our
knowledge.
Asbestos Materials and Their Properties
An environment-friendly product is defined as one that is made from simple
starting materials, produced by low-energy–consuming tech¬nology, has a long
useful service life and presents a low risk during its manufacture,
transportation, storage, use, and disposal. Asbestos fits the definition with
the exception of risk factors. The asbestos bundles have splaying ends and are
extremely flexible and can be woven. It pos¬sesses high tensile strength,
resistance to chemical and thermal degra-
dation, and high electrical resistance. Fibers are not volatile or soluble.
Asbestos has been mined for its useful properties for years.
Asbestos is commonly used in heat, thermal, and acoustic insulation; fire
proofing; and in other building materials, including floor and ceiling tiles,
wallboards, siding, pipes, adhesives, roofing shingles and felt, base flashing,
fire doors, electrical panel partitions, electrical cloth, textured
paintings/coatings, taping compounds, table tops, laboratory hoods, laboratory
gloves, fire blankets and curtains, joint compounds, spackling compounds,
packing materials, thermal paper products, chalkboards, elevator brake shoes,
HVAC duct insulation, boiler insu¬lation, breaching insulation, electric wiring
insulation, ductwork flexi¬ble fabric connections, cooling towers, pipe
insulation, heating and electrical ducts, vinyl wall coverings, and
high-temperature gaskets.
Today, only the chrysotile type of asbestos is used. The industry now markets
dense and nonfriable materials including chrysotile-cement building materials,
friction materials, gaskets, and certain plastics. Chrysotile and its nonfriable
products, such as chrysotile cement, are claimed to be used in complete safety
if properly controlled through¬out the product life cycle. However, there is
debate about the hazards of chrysotile.
Alternative Products
There are alternative products on the market. The manufacturing cost is 20% to
30% higher, and many of the products have been demon¬strated to be less
resistant to heat, humidity, and temperature contrasts (freeze-thaw), and they
are not as durable as chrysotile-reinforced products. These fibers, including
cellulose, are quite biopersistent, and thus require care during manufacture,
handling, and use. In addition, many of these asbestos-free materials have poor
technical performance or durability.
Replacement products contain natural or synthetic fibers that can be hazardous
as well. However, unlike chrysotile, few countries have introduced appropriate
regulations for these substitute materials. Thus, scientists have begun to raise
concerns over the health effects of some of the fibers used to replace
chrysotile.
Asbestos Exposures
Occupations involving a risk of exposure to asbestos include mining and milling
of minerals containing asbestos; manufacturing, stripping, repair, or
maintenance of materials or products containing asbestos; demolition or repair
of plants or structures containing asbestos; trans¬portation, storage, and
handling of asbestos or materials containing asbestos; and other occupations
involving a risk of exposure to airborne asbestos fibers.
Removal of asbestos insulation should be considered a last resort and it should
be undertaken only when the materials are beyond repair or at the time of major
renovation work or building demolition. Asbestos
removal is a very costly operation, which must be conducted by highly
specialized contractors. Hasty elimination of asbestos insulation con¬siderably
increases the probability that controls will not be adequately enforced, thus
presenting a source of risk not only for the workers, but for building occupants
as well.
Chrysotile, the most common serpentine fiber, is known to be con¬siderably less
hazardous than the amphibole varieties. It has curly fibers that are unlikely to
remain suspended in the air, and it does not stay in the lungs very long. Thus,
in general, chrysotile is a less dusty material and is more easily eliminated
from the human body than amphiboles. The controlled use of chrysotile allows its
continued use in high-density products, provided permissible exposure limits of
1.0F/cc or below (F is the degree of fineness of abrasive particles) are
recommend by a group of experts from the World Health Organization (WHO).
However, increasing evidence about the hazards of occupa¬tional and
environmental exposure to chrysotile was presented at a 3-day conference on
Parliament Hill, Ottawa, on September 12, 2003. The chrysotile producers of
Zimbabwe, Canada, Brazil, and Swaziland, which together account for 75% of world
exports of chrysotile fibers, have signed a Memorandum of Understanding (MOU),
the objective of which is to supply chrysotile fibers only to those companies
that demonstrate compliance with international rules and standards.
We can now ask more precise questions based on data accumulated over the many
years of scientific research. Potentially hazardous inor¬ganic and mineral
species have been accurately identified (7). The health responses are well
documented (8). The crossover of informa¬tion among the several disciplines will
be needed to advance our knowledge.
Occupational and Environmental Health Hazards Related to Asbestos Exposure
Three different types of diseases that are associated with the inhalation of the
various types of asbestos fibers have been identified: asbestosis (form of
fibrosis), lung cancer, and mesothelioma of the pleura (lining of the lung and
chest cavity) or peritoneum (lining of the abdomen). Asbestosis is characterized
by shortness of breath and cough. It may lead to severe impairment of
respiratory function and ultimately death because presently there is no cure for
the disease.
Cancers of the larynx, pancreas, esophagus, colon, and kidney have also been
linked to asbestos exposure, but the increased risk is not as great as with the
respiratory system. It is possible to test for the pres¬ence of fibers in urine,
feces, or mucus.
At least from the diagnostic perspective, asbestos has another effect—it can
cause pleural lesions, visible some decades after expo¬sure. Calcified pleural
plaques (CPPs) and pleural thickening (PT) are the lesions. Epidemiologic
studies indicate that high frequency of malignant pleural mesothelioma (MPM),
CPP, and PT constitute important pulmonary health problems in some countries,
including
Italy (i.e., Corsica) (9,10), Greece (11), Turkey (12–15), Cyprus (16), and the
United Kingdom (17). It has been predicted that within a few years in the United
Kingdom, for example, mesothelioma will be the cause of death in 1 in 150 males
born between 1945 and 1950 (17). Dogan (18,19) suggested that although MPM cases
were not observed where low doses (0.054–0.1 fiber/mL in the air samples) of
long, but thick, splintery fibers, and short and thin mixed asbestos fiber
exposures are present, there is a high incidence of CPP and PT in Central
Anatolia in Turkey.
Asbestos and Mesothelioma
A layer of specialized cells called mesothelial cells lines the chest and
abdominal cavities, and the cavity around the heart. These cells also cover the
outer surface of most internal organs. The tissue formed by these cells is
called the mesothelium. The mesothelium helps protect the organs by producing
special lubricating fluid that makes the organs move around. Tumors of the
mesothelium can be benign (noncancer-ous) or malignant (cancerous). Malignant
mesothelioma is a cancerous tumor of the pleura or peritoneum. About three
fourths of malignant mesothelioma occurrences start in the chest cavity and are
known as pleural mesothelioma. Another 10% to 20% begin in the abdomen and are
called peritoneal mesothelioma. The mesothelium of the pericardial cavity is
called the pericardium. Cancer cells can invade and damage nearby tissues and
organs. They can also metastasize from their origi-nal site to other parts of
the body. The covering layer of the testicles is actually an outpouching of
peritoneum into the scrotum. It is subject to a rare form of cancer. The risk of
developing a mesothelioma is related to how much asbestos a person was exposed
to and how long this exposure lasted. People exposed at an early age, for a long
period of time, and at higher levels are most likely to develop this cancer.
Although the risk of developing mesothelioma rises with the amount of asbestos
exposure, it is clear that genetic factors also play a role in determining who
develops the disease (20,21). This explains why not all persons exposed to high
levels of asbestos dust develop mesothelioma.
Despite standard “dust” levels that have been in existence since the 1970s, in
some countries the number of cases of lung cancer and mesothelioma grows and the
controversy still persists.
The discovery that exposure to asbestos is linked to mesothelioma was first made
in 1960 (22) and again in 1965 (23); these studies docu¬mented the high
incidence of the disease among people working at or living near crocidolite
asbestos mines, as well as in household members of workers at these mines. From
the 1940s through the 1970s, crocido-lite and another amphibole, amosite, were
used extensively, either alone or in conjunction with chrysotile, in friable
insulation applica¬tions in the shipbuilding and construction industries,
primarily in North America and Europe. These sprayed-on applications have been
discontinued since the 1970s. To a lesser extent, amphiboles were also
used in the manufacture of asbestos-cement pipe. The amphibole hypothesis,
officially introduced in 1990 (24), states that chrysotile asbestos is not a
potent cause of malignant mesothelioma, supporting the findings of Doll and Peto
(25) and the U.S. Environmental Protec¬tion Agency (26). The amphibole
hypothesis has raised many crucial issues and served to focus research on still
partially unanswered ques¬tions of why different exposed populations have
experienced such dif¬ferent rates of major asbestos diseases. McDonald et al
(27), Stayner et al (28), and Cullen (29) also suggested that chrysotile may be
less potent than some amphibole asbestos minerals in causing mesothelioma. Some
publications, however, suggested that chrysotile asbestos is the main cause of
pleural mesothelioma in humans (30–33).
Whether chrysotile fibers on their own can ever cause mesotheliomas is still
debated. Other evidence of the connection between chrysotile exposure and
mesothelioma has been provided by the cohort study of Quebec chrysotile miners
(27), as reported at the September 12, 2003, Conference of Canadian Asbestos.
Epidemiologic studies have shown an excess of developing mesothe-lioma among
residents in Biancavilla, Sicily, Italy, and a new asbestos amphibole,
fluoro-edenite, appears responsible for the high incidence of malignant pleural
mesothelioma (34).
Mesothelioma is more common in people who have had serious lung diseases such as
tuberculosis. The median survival varies from 4 to 18 months in different
studies. However, the prognosis depends on the stage of the tumor.
Mesothelioma does not generally cause symptoms in the early stages. Symptoms of
mesothelioma in the lining of the lung can include shortness of breath, pain in
the lower back or the side of the chest, per¬sistent cough and hoarseness,
difficulty in swallowing, unexplained weight loss, and sweating. Symptoms of
mesothelioma in the abdom¬inal lining may include abdominal pain, swelling of
the abdomen, nausea and vomiting, loss of appetite, unexplained weight loss, and
change in bowel habits. These signs and symptoms usually indicate problems other
than cancer. However, people who have been exposed to asbestos who notice any
symptoms should see their doctor.
Differentiation of the tumor from other conditions of the pleura and other types
of cancer can be difficult. Since mesothelioma can affect the lungs and abdomen,
doctors may also carry out some of the tests commonly used to detect lung or
stomach cancer, such as chest x-ray, to show tumor and possibly pleural
effusion, thoracic com¬puted tomography (CT), cytology from pleural fluid, and
open lung biopsy.
Patients with mesothelioma usually had a rapid demise (within a year in many
cases), in spite of the fact that the exposure to asbestos may have been
relatively mild and taken place over 30 years (25). Malignant mesothelioma
affects men more frequently than women (35). Sustained exposure to asbestos or
erionite is the main risk factor. It can take 15 to 40 years following these
fiber exposure for mesothe-lioma to develop. However, smoking dramatically
increases the risk among the toxic fiber exposed. Mesothelioma may also develop
follow-
ing exposure to radiation from a substance called thorium dioxide, which was
used to create x-rays of blood vessels until 1955. Other sus¬pected causes
include biogenic silica fibers, chronic irritation stemming from tuberculosis
and other factors.
Simian virus 40 (SV40) has been detected in human tumors in over 40
laboratories, and many of these reports linked SV40 to mesothe-liomas. The
presence of SV40 in mesothelioma and other human tumor types has been reported
by negative findings (36). However, three independent panels established a
positive link between SV40 in human mesothelioma and brain tumors (37,38).
Mechanisms of the Potentially Hazardous Minerals
It is generally accepted that to be pathogenic to the lung or pleura, fibers
must be long, thin, and durable. Researchers still debate the safe level of
exposure, but it is known that the greater and the longer the exposure, the
greater the risk of contracting an asbestos-related disease. Investigators
suggested mechanisms of disease induction that went beyond physical trauma.
Fiber chemistry may also be significant. The body has multifunctional chemical
cascades that are only partially understood. Some investigators suggested that
health causation mech¬anisms could be small differences in the morphology of the
particulates or in the chemical character of the particulates, and particularly
the sur¬faces of the asbestos materials. One of the hypotheses came with the
investigations on crocidolite, and in the series of
tremolite-actinolite-ferroactinolite (39). The presence of Fe, both Fe2+ and
Fe3+, states in the amphibole could initiate a cascade of cell responses leading
to an acti¬vated oxygen ligand thought to be a carcinogenic agent. For example,
asbestiform species within the tremolite-ferroactinolite series is present at
Libby, Montana, where the mining of vermiculate has an accompa¬nying fibrous
Fe-containing amphibole species in the gangue. Libby’s population has a high
incidence of mesothelioma.
Some individuals appear to be more susceptible while others develop cancer after
only limited exposure. There is evidence of a genetic disposition among the
affected population (20,40).
Research into the potential causative effects of these diseases, includ¬ing
exposure to fiberglass, suggests that the inorganic materials were foreign
bodies in the biologic environment. The longer a foreign sub¬stance persists in
the body, the more likely it is to cause cellular damage and lead to accelerated
cell reproduction and chromosomal damage, which are associated with tumor
growth. Many studies using intrapleural or intraperitoneal injection have
demonstrated that long and thin fibers were the most effective in producing
mesotheliomas, once they were within the body cavities (41–44). Fibers longer
than 20mm are more potent than fibers shorter than 10mm with respect to the
induction of pulmonary tumors and fibrosis by inhalation (45,46). Dodson et al
(47) confirmed that the most dangerous fibers were more than 8mm in length and
less than 0.25mm in diameter. However, both
the chrysotile and amphibole fibers in the pleura/plaques of all of these
studies have been reported as consistently shorter than those in the parenchyma
itself. Repeated episodes of cell tissue injury followed by proliferation and
genetic damage may give rise to a tumor that prolif¬erates autonomously (48).
The identification of a particular hazardous species from areas where disease,
such as mesothelioma, is endemic showed that minerals other than those
originally designated could be present (49,50). Both amphi-bole- and
chrysotile-type mineral fibers in lung tissue from several mesothelioma cases
and some controls were studied by Jones et al (51), McDonald et al (52), Mowe et
al (53), Gaudichet et al (54), McDonald et al (55), Rogers et al (56), and
Rodelsperger et al (57).
It has been accepted that amphiboles are more toxic than chrysotiles. The
greater toxicity of amphiboles is linked to durability in the lung. Chrysotile
fibers dissolve relatively quickly, but amphiboles persist at sites of tumor
development and serve as the stimulus for euplastic (new tissue) growth (58,59).
The kinetics for amphiboles and chrysotile fibers are different in human lung
tissue (60–62). Amphibole fiber con¬centrations increase with the duration of
exposure, whereas chrysotile concentrations do not. In addition to the
biopersistence of amphiboles, the Fe content of particles appears to trigger an
oxidative stress process—the generation of active oxygen species (AOS), which
some researchers believe can cause membrane damage, induce the release of
inflammatory compounds, which can lead to fibrosis and lung cancer, and even
cause DNA strand breaks. Fe-containing particles can produce AOS by an oxidation
mechanism.
Wagner et al (63) and Davis et al (64) also have amplified the impor¬tance of
the numbers of very fine fibers for determination of chrysotile pathogenesis.
Brooke Mossman, of the University of Vermont College of Medicine, suggests that
the lower amounts and bioavailability of Fe in chrysotile fibers may render them
less biologically active over time. It may be that asbestos causes cancer by
physically irritating cells rather than by chemical effects. Other studies have
confirmed the importance of fiber length and geometry in the generation of AOS
by alveolar macrophages. Longer fibers and particles are generally relatively
inac¬tive (65). When fibers are inhaled, most are cleared from the nose, throat,
trachea, or bronchi. Fibers are cleared by sticking to mucus inside air passages
and being coughed up or swallowed. The long, thin fibers are less readily
cleared, and they may reach the ends of the small airways and penetrate into the
pleural lining of the lung and chest wall. These fibers may then directly injure
mesothelial cells of the pleura, and eventually cause mesothelioma.
Prognostic factors in oncology assist in the selection of patients who are more
likely to benefit from clinical treatment. These factors in mesothelioma were
studied in the past two decades by Chahinian et al (66), Samson et al (67),
Antman et al (68), Calavrezos et al (69), Spirtas et al (70), Tammilehto (71),
Boutin et al (72), De Paugher Manzini et al (73), Ruffie et al (74), Currau et
al (75), Herndon et al (76), and Edwards et al (77). It is hoped that these
studies will provide insight into the biology of cancer. Recently, gene therapy
studies including suicide gene
therapy, genetic immunopotentiation, and suicide gene plus allogenic vaccine
were reported (78–81).
The particles initiated cellular responses to an unexpected trauma, and a normal
repair mechanism was the deposition of a fibrous protein, collagen, in excessive
concentrations at the site of trauma. This reaction is also encountered with
other trauma such as the invasion of bacteria, for example, in the lung
environment or when cuts are healing in the skin. The physical rejection of the
particles can be envisioned, but the local reactions that lead to scarring
depend not only on the fiber reach¬ing the delicate tissues of the alveoli deep
within the lung but also on local cell responses.
Conclusion
Asbestos, characterized as a group A human carcinogen, is a generic name given
to the fibrous variety of six naturally occurring minerals: chrysotile,
actinolite, tremolite, anthophyllite, amosite, and crocidolite. The permissible
exposure limits recommended by WHO is 1.0F/cc or below. The identification of
asbestos fibers can be performed through morphologic, crystal structural, and
compositional analyses. It is widely accepted that asbestos fibers can be
associated with asbestosis, lung cancer, and mesothelioma. Despite extensive
cancer studies in humans, certain controversies remain about asbestos exposure
and cancer. Today, only chrysotile is used as an asbestos material because it is
considered to be less potent. The key questions concern whether or not, and to
what extent, exposure to chrysotile asbestos, including its natural contaminant
tremolite, causes mesothelioma. Many compa¬nies ceased production of
asbestos-containing insulations, plasters, ceiling tiles, and cement products
because of liability issues. However, there is a continued demand for
inexpensive and durable construction materials.
Acknowledgment
We acknowledge Prof. Robert L. Brenner of the Department of Geo-science, the
University of Iowa, for critically reading an earlier version of the manuscript.
References
1. Dogan AU. Mesothelioma in Cappadocian Villages. Indoor Built and Environment
2003;12(6):367–375.
2. Carbone M, Setlak P, Bocchetta M, et al. Genetic susceptibility to
mesothe-lioma. In: Peters GA, Peter BJ, eds. The Asbestos Legacy—The Sourcebook
on Asbestos Diseases, vol 23. LexisNexis 2001;151–168.
3. Davis JMG, Bolton RE, Miller BG, Nieven K. Mesothelioma dose-response
following intrapertoneal injection of mineral fibers. Int Exp Pathol 1991;
72:263–274.
4. Skinner HCW, Ross M, Frondel C. Asbestos and Other Fibrous Materials.
NewYork: Oxford University Press, 1988.
5. Yada K. Study of microstructure of chrysotile asbestos by high resolution
electron microscopy. Acta Crystallography 1971;27:659–664.
6. United States Environmental Protection Agency. Master Testing List.
Washington, DC: Office of Prevention, Pesticides and Toxics, USEPA, 1992.
7. Wiley AG, Verkouteren JR. Amphibole asbestos, Libby, Montana. Am Mineralogist
2000;85:1540–1542.
8. Finkelmen R, Skinner HCW, Plumlee GS, Bunnell JE. Medical geology. Geotimes
2001;46:20–23.
9. Boutin C, Viallat JR, Steinbauer J, Massey DG, Charpin D, Mouries JC.
Bilateral pleural plaques in Corsica: a non-occupational asbestos exposure
marker. Eur J Respir Dis 1986;69:4–9.
10. Rey F, Boutin C, Steinbauer J, Viallat JR, et al. Environmental pleural
plaques in an asbestos exposed population of northeast Corsica. Eur Respir J
1993;6:978–982.
11. Constantopoulos SH, Goudevenos JA, Saratsiz N, Langer AM, Selikoff IJ,
Moutsopoulos HM. Metsova lung: pleural calcification and restrictive lung
function in northwestern Greece. Environmental exposure to mineral fiber as
etiology. Environ Res 1985;38:319–331.
12. Barıs YI. Asbestos and erionite related chest diseases. Ankara, Turkey:
Semih Ofset Matbaacılık Ltd., 1987.
13. Coplu L, Dumortier P, Demir AU, et al. An epidemiological study in an
Anatolian Village in Turkey environmentally exposed to tremolite asbestos. J
Environ Pathol Toxicol Oncol 1996;13(I):1–7.
14. Karakoca Y, Emri S, Cangir AK, Baris YI. Enviromental pleural plaques due to
asbestos and fibrous zeolite exposure in Turkey. Indoor Built Enviroment
1997;6:100–105.
15. Yazicioglu S, Ilcayto R, Balci K, Sayli BS, Yorulmaz B. Pleural
calcification, pleural mesotheliomas and bronchial cancers caused by tremolite
dust. Thorax 1980;35:564–569.
16. McConnochie K, Simonato L, Mavrides P, Chritofides P, Pooley FD, Wagner JC.
Mesothelioma in Cyprus: the role of tremolite. Thorax 1987;42:342–347.
17. Peto J, Decarli A, La Vecchia C, Levi F, Negri E. The European mesothe-lioma
epidemic. Br J Cancer 1999;79:566–572.
18. Dogan M. Environmental health problems related to mineral dusts: exam¬ples
from Central Anatolia, Turkey. Environ Geol 2002;41(5):571–579.
19. Dogan M. Sources and types of mineral dust in regions of Turkey with endemic
malignant mesothelioma. Indoor and Built Environment 2003;12: 377–383.
20. Carbone M, Kratzke RA, Testa JR. The pathogenesis of mesothelioma. Semin
Oncol 2002;29(1):2–17.
21. Powers A, Carbone M. The role of environmental carcinogens, viruses, and
genetic predisposition in the pathogenesis of mesothelioma. Cancer Biol Ther
2002;1(4):350–355.
22. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos
exposure in the north western Cape Province. Br J Ind Med 1960; 17:260–271.
23. Newhouse ML, Thompson H. Mesothelioma of pleura and peritoneum following
exposure to asbestos in the London area. Br J Ind Med 1965; 22(4):261–269.
24. Mossman BT, Bignon J, Corn M, Seaton A, Gee JB. Asbestos scientific
devel¬opment and implications for public policy. Science 1990;247:294–301.
25. Doll R, Peto J. Asbestos-effects on health exposures and mortality among
chrysotile asbestos workers. Part 1: exposure estimates. Am J Med 1985;
26:31–447.
26. United States Environmental Protection Agency. Airbone asbestos-health
assessment update. Document No: EPA-600/8-84003F. Washington, DC: Environmental
Protection Agency, Office of Health and Environment Assessment, 1986.
27. McDonald JC, Liddell FD, Dufresne A, McDonald AD. The 1891–1920 birth cohort
of Quebec chrysotile miners and millers: mortality 1976–88. Br J Ind Med
1993;50(12):1073–1081.
28. Stayner LT, Dankovic DA, Lemen RA. Occupational exposure to chrysotile
asbestos and cancer risk: a review of the amphibole hypothesis. Am J Public
Health 1996;86:179–186.
29. Cullen MR. The amphibole hypothesis of asbestos related cancer. Am J Public
Health 1996;86:179–186.
30. Kohyama N, Suzuki Y. Asbestos in insulation workers. Ann NY Acad Sci
1991;27–52.
31. Huncharek M. Asbestos and cancer. Epidemiological and public health
controversies. Cancer Invest 1994;12:214–222.
32. Nicholson WJ, Landrigan PJ. The carcinogencity of chrysotile asbestos. Adv
Modern Environ Toxicol 1994;22:407–423.
33. Smith AH, Wright CC. Chrysotile asbestos is the main cause of pleural
mesothelioma. Am J Ind Med 1996;30:252–266.
34. Cardile V, Renis M, Scifo C, et al. Behaviour of the new asbestos amphi-bole
fluoro-edenite in different lung cell systems. Int J Biochem Cell Biol
2004;1–12.
35. Testa JR, Carbone M. Mesothelioma. In: Schwab M, ed. Encyclopedic Reference
of Cancer. New York: Springer-Verlag, 2002;545–550.
36. Strickler HD. The International SV40 Working Group. Cancer Epidemiol Biomed
Prevent 2001;10:523–532.
37. Rizzo P, Bocchetta M, Powers A. SV40 and the pathogenesis of mesothe-lioma.
Semin Cancer Biol 2001;11:63–71.
38. Carbone M, Pass HI, Miele L, Bocchetta M. New developments about the
association of SV40 with human mesothelioma. Oncogene 2003;22:5173– 5180.
39. Verkouteren JR, Wylie AG. The tremolite-actinolite-ferroactinolite series:
systematic relationships between cell parameters, optical properties, and habit,
and evidence of discontinuities. Am Mineralogist 2000;85:1239–1254.
40. Roushdy-Hammady I, Siegel I, Emri S, Testa JR, Carbone M.
Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian
region of Turkey. 2001;357(9254):444–445.
41. Pott F, Huth F, Friedrichs HK. Tumors in rats after intraperitoneal
injection of asbestos dusts. Naturwissenschaften 1972;59:318–332.
42. Pott F, Huth F, Fredrichs KH. Tumorigenic effect of fibrous dusts in
exper¬imental animals. Environ Health Perspect 1974;9:313–315.
43. Stanton MF, Wreinch C. Mechanism of mesothelioma induction with asbestos and
fibrous glass. J Natl Cancer Inst 1972;48:797–821.
44. Stanton MF, Layard M, Tegeris A, Miller MM, Kent E. Carcinogenecity of
fibrous glass: pleural response in the rat in relation to fiber dimension. J
Natl Cancer Inst 1977;58:587–603.
45. Davis JMG. Mineral Fibre Carcinogenesis: Experimental Data Relating to the
Importance of Fiber Type, Size, Deposition, Dissolution, and Migration.
International Agency for Research on Cancer 1989;33–35.
46. Davis JMG, Addison J, Bolton RE, Donaldson K, Jones AD, Smith T. The
pathogenicity of long versus short fiber samples of amosite asbestos
administered to rats by inhalation and intraperitoneal injection. Br J Exp
Pathol 1986;67:415–430.
47. Dodson RF, O’Sullivan M, Corn CJ, McLarty JW, Hammar SM. Analysis of
asbestos fibers in lung tissue from mesothelioma patients. Ultrastruct Pathol
1997;21:321–336.
48. Antoniades HN. Linking cellular injury to gene expression and human
proliferative disorders: examples with the PDGF genes. Mol Carcinogen
1992;6:175–180.
49. Barıs YI, Artvinli M, Sahin AA. Environmental mesothelioma in Turkey. Ann
Acad Sci 1979;330:423–432.
50. Wiley AG, Huggins CW. Characterization of winchite-asbestos from Allamore
Talc District, Texas. Canad Mineralogist 1980;18:101–107.
51. Jones JSP, Roberts GH, Pooley FD, et al. The pathology and mineral content
of lung in cases of mesothelioma in the United Kingdom in 1976. In: Wagner JC,
ed. Biological Effects of Mineral Fibers. Lyon, France: IARC, 1980;187–199.
52. McDonald AD, McDonald JC, Pooley FD. Mineral fiber content of lung in
mesothelial tumors in North America. Ann Occup Hyg 1982;26:417–422.
53. Mowe G, Gylseth B, Hartveit F, et al. Fiber concentration in lung tissue of
patients with malignant mesothelioma: a case-control study. Cancer 1985;
56:1089–1093.
54. Gaudichet A, Janson X, Manchaux G, et al. Assessment by analytical
microscopy of the total lung fiber burden in mesothelioma patients matched with
four other pathological series. Ann Occup Hyg 1988;32: 213–223.
55. McDonald JC, Armstrong B, Case BW, et al. Mesothelioma and asbestos fiber
type: evidence from lung tissue analyses. Cancer 1989;63:1544–1547.
56. Rogers AJ, Leigh J, Berry G, et al. Relationship between lung asbestos fiber
type and concentration and relative risk of mesothelioma. A case-control study.
Cancer 1991;67:1912–1920.
57. Rodelsperger K, Woitowitz HJ, Bruckel B, et al. Dose-response relationship
between amphibole fiber lung burden and mesothelioma. Cancer Detect Prev
1999;23:183–193.
58. Jaurand MC, Bignon J, Sebastian P, Goni J. Leaching of chrysotile asbestos
in human lungs. Environ Res 1979;14:245–254.
59. Jaurand MC, Gaudichet A, Halpern S, Bignon J. In vitro biogradation of
chrysotile fibres by alveolar macrophages and mesothelial cells in culture—
comparison with a pH effect. Br J Ind Med 1984;41:389–395.
60. Wagner JC, Chamberlain M, Brown RC, et al. Biological effects of tremo-lite.
Br J Cancer 1982;45:352–360.
61. Wagner JC, Skidmore JW, Hill RJ, Griffiths DM. Mesotheliomas in rats. Br J
Cancer 1986;51:727–730.
62. Sebastien P, McDonald JC, McDonald AD, Case B, Harley R. Respiratory cancer
in chrysotile textile and mining industries. Br J Ind Med 1989; 46:180–187.
63. Wagner JC, Berry G, Skidmore JW, Pooley FD. The comparative effects of three
chrysotile by injection and inhalation in rats. In: Wagner JC, ed. Bio¬logical
Effects of Mineral Fibers. IARC Publication 30. Lyon: International Agency
Research on Cancer 1980;363–373.
64. Davis JMG, Addison J, Bolton RE, Donaldson K, Jones AD. Inhalation an
injection studies in rats using dust samples from chrysotile asbestos pre¬pared
by a wet dispersion process. Br J Exp Pathol 1986;67:113–129.
65. Hansen K, Mossman BT. Generation of superoxide (O-2) from alveolar
macrophages exposed to asbestiform and nonfibrous particles. Cancer Res
1987;47:1681–1686.
66. Chahinian AP, Pajak TF, Holland JF. Diffuse malignant mesothelioma. Ann
Intern Med 1982;96:746–755.
67. Samson MK, Wasser LP, Borden EC, et al. Randomized comparison of
cyclophosphamide, imidazole carboxamide, and Adriamycin versus cyclo-phosphamide
and Adriamycin in patients with advanced stage malignant mesothelioma. A Sarcome
Intergroup Study. J Clin Oncol 1987;5:86–91.
68. Antman KH, Shemin R, Ryan L. Malignant mesothelioma: prognostic vari¬ables
in a registry of ISO patients, The Dana-Farber Cancer Institute and Brigham and
Women’s Hospital experience over two decades, 1965–1985. J Clin Oncol
1988;6:147–153.
69. Calavrezos A, Koschel G, Huselman H, et al. Malignant mesothelioma of the
pleura. Klin Wochenschr 1988;66:607–613.
70. Spirtas R, Connelly RR, Tucker MA. Survival patterns for malignant
mesothelioma: The SEER experience. Int J Cancer 1988;41:525–530.
71. Tammilehto L. Malignant mesothelioma: prognostic factors in a prospec¬tive
study of 9 patients. Lung Cancer 1992;8:175–184.
72. Boutin C, Rey F, Gouvernet J, et al. Thoroscopy in pleural malignant
mesothelioma: a prospective study of 188 consecutive patients. Cancer
1993;72:394–404.
73. De Pangher Manzini V, Brollo A, et al. Prognostic factors of malignant
mesothelioma of the pleura. Cancer 1993;72:410–417.
74. Ruffie P, Feld R, Minkin S, et al. Diffuse malignant mesothelioma of the
pleura in Ontario and Quebec: a retrospective study of 188 consecutive patients.
Cancer 1993;72:410–417.
75. Currau D, Sahmoud T, Therasse P, et al. Prognostic factors in patients with
pleural mesothelioma: the European Organization for Research and Treat¬ment of
Cancer experience. J Clin Oncol 1998;16:145–152.
76. Herndon JE, Green MR, Chahinian AP, et al. Factors predictive of survival
among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer
and Leukemia Group B. Chest 1998;113:723–731.
77. Edwards JG, Abrams KR, Leverment JN, et al. Prognostic factors for
malig¬nant mesothelioma in 142 patients: validation of CALGB and EORTC
prog¬nostic scoring systems. Thorax 2000;55:731–735.
78. Schwarzenberger P, Harrison L, Freeman S, et al. Treatment of three patients
with malignant mesothelioma with the gene modified cell line PA1-STK. Proc Am
Soc Clin Oncol 1998;17:447a.
79. Sterman DH, Kaiser LR, Albelda SM. Advances in the treatment of malig¬nant
pleural mesothelioma. Chest 1999;116:504–520.
80. Mukherjee S, Haenel T, Himbeck R, et al. Replication-restricted vaccinia as
a cytokine gene therapy vector in cancer: persistent transgene expression
despite antibody generation. Cancer Gene Ther 2000;7:663–670.
81. Nowak AK, Lake RA, Kindler HL, Robinson BWS. New approaches for
mesothelioma: biologic, vaccines, gene therapy, and other novel agents. Semin
Oncol 2002;29(1):82–96.
