Current Asbestos Related Issues Aparna Koppikar, M.D., Ph. D. koppikar.aparna@epa 202-564-3242

1. NCEA National Center for Environmental Assessment Current Asbestos Related Issues Aparna Koppikar, M.D., Ph. D. koppikar.aparna@epa.gov 202-564-3242 May 21, 2003

2. 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

3. 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

4. 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?

5. 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?

6. 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

7. 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

8. New Knowledge - Fiber TypeLung 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. Some Links www.epa.gov/swerrims/asbestos_ws/index.htm www.getf.org/asbestosstrategies/report www.atsdr.cdc.gov/HAC/asbestospanel/