Current Asbestos Related Issues Aparna Koppikar, M.D., Ph. D May 21, 2003 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

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