Current Asbestos Related Issues

Aparna Koppikar, M.D., Ph. D.koppikar.aparna@epa.gov

202-564-3242May 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

Some Links

www.epa.gov/swerrims/asbestos_ws/index.htmwww.getf.org/asbestosstrategies/reportwww.atsdr.cdc.gov/HAC/asbestospanel/