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Current Asbestos Related Issues
Aparna Koppikar, M.D., Ph. [email protected]
202-564-3242May 21, 2003
National Center for Environmental Assessment National Center for Environmental Assessment
What is asbestos?• There is a fibrous form and a nonfibrous form type of asbestos• Asbestos is a term generally used to describe the fibrous
forms of a family of hydrated metal silicate minerals• Widely accepted definition of asbestos includes the six fibrous
habits of these minerals which are currently federally regulated:– Serpentine: chrysotile - polymeric sheets which tend to wrap into
tubular fibers that are curved and flexible
– Amphibole: actinolite, amosite, anthophylite, rocidolite, tremolite
Consists of two ribbons separated by a band of cat ion
• Accepted definition of fiber: length of >5 µm and diameter of <3 µm with an aspect ratio of 3:1
Health Effects of Asbestos Exposure
Asbestos is a known human carcinogen• Asbestos warts• Benign pleural plaques• Asbestosis• Lung cancer• Mesothelioma
– pleural
– peritoneal
– other sites
• Gastrointestinal cancers
Current Issues• For both lung cancer and mesothelioma
– Influence of fiber type.
– Influence of fiber length.
– Does carcinogenic potency vary with fiber type and fiber length (suggestive evidence from animal studies)?
– Do fibers <5 µm cause any effects?
– Is potency a function of fiber diameter, aspect ratio, and/or surface properties (other than the fiber type and length)?
– Are cleavage fragments toxicologically significant?
– Are other amphiboles equally toxic as the five federally regulated ones?
Current Exposure Issues
• Are exposure estimates from epidemiologic studies reliable?
• Which Lab method is reliable and useful for exposure measurement?
• Should fibers <5 µm in length be counted?
• The old fiber definition of fiber length of >5 µm and diameter of <3 µm with an aspect ratio of 3:1 is still valid?
New Knowledge - Fiber Diameter
• Epidemiologic data suggest that fibers with diameter of 0.5 µm to 0.7 µm can reach the respiratory zone of the lungs. In animals fibers with a diameter of 0.4 µm are critical based on rat data
• There is some indication from epidemiologic data that fibers with a diameter as high as 1.5 µm can reach the respiratory zone of the lungs in mouth breathers
• Thus, fibers with a diameter of <0.5 µm to 1.5 µm are considered to be relevant as they can reach the respiratory zone of the lungs in humans
New Knowledge - Fiber Length
• Inhalation of fibers longer than 10 µm presents a considerably greater risk for lung cancer but the exact size cut-off for the length and magnitude of relative potency is uncertain
• There are two schools of thought about cancer toxicity of fibers <5 µm in length: – present a very low risk, possibly zero for cancer based on human
data
– cause inflammation and may potentiate the pulmonary reaction to long fibers based on animal data and in vitro studies
• For mesothelioma, greater weight should be assigned to thinner fibers and fibers in the 5 µm to 10 µm in length range
New Knowledge - Fiber Type
Lung Cancer• There are different opinions about the relative potency of
chrysotile vs amphiboles for lung cancer based on epidemiologic data
• Some assert that amphiboles are 5 times more toxic than chrysotile for lung cancer
• Others assert that no real difference is observed in statistical analysis of epidemiolgic data
• The additional review of epidemiologic data to identify other factors such as industry in which exposure occurred might shed some light
New Knowledge - Fiber Type Mesothelioma
• It is becoming apparent that there are different relative carcinogenic potencies for different fiber types
• The available epidemiologic data provides compelling evidence that potency of amphiboles is at least two orders of magnitude greater than that of chrysotile (ATSDR)
• Time since first exposure is an important factor for occurrence of mesothelioma
• Duration and intensity of exposure is also found to be important in epidemiologic studies
New Knowledge - Cleavage Fragments
• Data indicate that durability and dimension are critical to pulmonary pathogenesis
• There are little data directly addressing similarities and dissimilarities between the original fibers and cleavage fragments for pulmonary pathogenesis
• Evidence suggests that it is prudent at this time to assume equivalent potency for lung cancer in the absence of other information
• Similarly, evidence implies that for mesothelioma, thin diameter fibers and fibers >5 µm in length are found to be more important, thus, cleavage fragments that do not meet these criteria are not expected to contribute to the risk of mesothelioma
New Knowledge -Other Amphibole Fibers
• Currently there are no data available either in humans or in animals about the toxicity of other amphiboles (e. g., winchite and richterite)
• Other amphibole fibers with similar durability and dimension would be expected to result in similar pathogenicity
• Thus, it may be prudent to consider potency of currently regulated and unregulated amphiboles to be similar
Current Knowledge - Exposure Issues
• Historic exposure measurements in epidemiologic studies have too many uncertainties - measurements by PCM or MI
• Exposures to specific types of fibers or the % of each fiber type in mixture is unknown
• Information is usually lacking about other risk factors such as work processes, cigarette smoking, minerological, geological, and industrial hygiene data
• The fibers <5 µm in length should be counted
• The old fiber definition of fiber length of >5 µm and diameter of <3 µm is not valid
• Although minerolgy is considered to be important for toxicity, an aspect ratio of 3:1 is considered not to be relevant for toxicity
Exposure Measurement Methods
• MI: Midget impinger• PCM: Phase contrast microscopy• SEM: Scanning electron microscopy• TEM: Transmission electron microscopy• EDS: Energy dispersive x-raydetection• PLM: Polorized light microscopy
Some Links
www.epa.gov/swerrims/asbestos_ws/index.htm
www.getf.org/asbestosstrategies/report
www.atsdr.cdc.gov/HAC/asbestospanel/