Tuesday, August 25, 2015
Properties of Asbestos Associated with Carcinogenic Potential
The carcinogenic potential of asbestos fibers has been linked to their
geometry, size, and chemical composition. Because of the increased
potential of long (>5mm) fibers to cause mesothelioma and fibrosis after
intrapleural or intraperitoneal administration to rodents , health
concerns for long respirable fibers [World Health Organization (WHO)
criteria: length >5mm, diameter <3mm] are considerable .
In addition to size, the chemical composition of fibers plays an important
role in determining the durability, biopersistence, and biodegradability
of asbestos types. The greater durability of amphiboles
compared to chrysotile appears to be one of the principal reasons for
their greater carcinogenic potential. Amphibole fibers persist at sites of
tumor development and may serve as stimuli for neoplastic growth of
cells . Studies on the retention of asbestos fibers in lung tissues
of asbestos workers show that concentrations of amphibole fibers
increase with durations of exposure, whereas chrysotile concentration
does not . Studies also indicate that the lung fiber content of amphiboles
is less than that required for chrysotile in the induction of
mesothelioma . The persistence of the amphibole fibers at the site
of tumor formation is important to both tumor induction and promotion
because the mean latency period between initial exposure to
asbestos and the development of mesothelioma is around 30 to 40 years
Properties of Asbestos Fibers
Asbestos is a naturally occurring group of fibers, each with its own
unique structure and chemical composition . There are two
subgroups: the serpentine group, consisting of chrysotile; and
the amphiboles, a group of rod-like fibers including crocidolite,
amosite, tremolite, anthophyllite, and actinolite . Asbestos fibers are
ubiquitous in certain geographic areas and become problematic to
human health when they are inhaled. It is unclear how they get to the
pleura to cause mesothelioma.
Epidemiology of Asbestos-Induced Mesotheliomas
The most important causal factor for the development of human
mesothelioma is exposure to asbestos, primarily the amphiboles crocidolite
and amosite. Malignant mesothelioma is presently a worldwide .
Although mesothelioma is a rare disease, with an annual
incidence in the United States of 2000 to 3000 cases, a steady rise in
cases has been reported . In Europe, the incidence of malignant
pleural mesothelioma has risen for decades and is expected to peak
between the years 2010 and 2020 . In Germany, a study conducted
on 1605 patients in the mesothelioma register (1987–1999), found that
70% had a history of exposure to asbestos . In the United Kingdom,
asbestos reportedly accounts for some 600 cases of mesothelioma and
100 cases of bronchial carcinoma per year
Asbestos-Induced Mesothelioma
Asbestos, a group of chemically and physically distinct fibers, is one of
the most notorious carcinogens in the lung and pleura. The National
Institutes of Health in 1978 estimated that approximately 11 million
individuals had been exposed to asbestos in the United States since
1940. Although widely employed in World Wars I and II, the use of
asbestos has undergone major changes in recent decades, with severe
restrictions in most countries on amphiboles. In developed countries,
with the exception of Japan, asbestos production is controlled or
banned, while in developing countries, consumption has leveled off or
increased . Between the 1940s and 1970s, asbestos was utilized extensively
in insulation applications (primarily in the building construction
industry), and in asbestos-cement pipes. Current usage is generally
confined to chrysotile in four products: asbestos cement, friction materials,
roof coating and cements, and gaskets. In 1992 approximately 28
million tons of asbestos-cement products were produced in approximately
100 countries .
The History of Mesothelioma
Ian Webster, who was J.C. Wagner’s brother-in-law and a well respected
pulmonary pathologist, still stated that there were unsolved
problems in the relationship between asbestos and malignancy in a
paper he published in February 1973 in the South African Medical
Journal. Webster remained skeptical as to why this previously rare
tumor seemed to be found primarily only in direct relationship to crocidolite
exposure. Webster suggested that some other factor, possibly
mineral, must be present to explain the high incidence of mesothelioma
in a very localized area of South Africa. He looked at exposure to
asbestos and the association with 232 cases of pleural mesothelioma.
Almost all the individuals had been exposed to Cape Blue asbestos and
only two miners had been exposed to amosite as far as could be discerned.
Thirty-two cases occurred where there was no evidence of any
asbestos exposure, presumably having environmental exposure. There
were only two cases related to exposure to amosite out of 232 confirmed
cases of mesotheliomas. He stated, “Furthermore, it is difficult to conceive
of amosite in the intermediate group of asbestos fibers causing
malignancy, as suggested by Wagner et al when there are so few cases
in the employees of the amosite mines.” He goes on to say, “The production
of amosite far exceeded that of Cape Blue asbestos. It is suggested
that more attention should be paid to the determination of the
nature of the substance of the Cape Blue areas and not in the Transvaal
Blue, and apparently limited to the areas where amosite is mined.” The
same opinion had been offered earlier, in 1969, by George Wright,
one of America’s most respected investigators in occupational pulmonary
disease, who in his review, “Asbestos and Health in 1969,”
stated, “That something other than, or in addition to, asbestos plays a
role in mesothelioma formation seems inescapable.” Wright accepted
asbestos as a cause of mesothelioma but felt there was a “tolerable level
of airborne asbestos fiber which does not cause an undue risk of development
of mesothelioma.” He later states that “the tolerable level was
substantial.”
The Doubters and the Role of Other Forms of Asbestos
My first impression is that there is now less certainty that asbestos inhalation
is associated with pulmonary neoplasia than there was 10 or 20 years ago
Perhaps this is due to greatly reduced dust exposures. Asbestos may after all
prove to be carcinogenic only in overwhelming dosage. Thus, the high prevalence
of neoplasia which was reported several decades ago may be a function
of the severity of exposure rather than an indication of high carcinogenic
potency. I suspect that in the final analysis the carcinogenicity of asbestos will
be rated as of low order. Perhaps carcinogenicity will prove to be a correlate of
asbestosis rather than a specific biological function of the mineral asbestos. This
may be the crux of the matter. In all cases of asbestos-associated lung cancer
that I have personally studied (the number now exceeds two dozen), there
invariably was well-established asbestosis. Not only was the asbestosis of
marked degree in the areas where the cancer arose, but there generally was
evidence from serial chest x-rays that asbestosis had been present in the lungs
.for a protracted period.
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