Document 165npVyNLjxYv4wYVJyzrKBj

'. * i * !' J. ~ ; i; l ' i Sr i : * S Federal Register / Voi. 51, No. 119 / Friday, June 20, 1986 / Rules and Regulations 22629 and Kuschner (Ex. 84-210) injected established that shorter fibers are (see Exs. 84-193, 84-195) should be asbestos intratracheally into guinea pigs readily engulfed by lung macrophages reassessed. He argues (Ex. 227-A, Table and found fibrosis only with fibers and transported to the mucociliary 4) that this hypothesis assumes that all jonger than 10 um (Ex. 84-128). NIOSH escalator or to the lymph system (Exs. comminution methods merely reduce the (Platek et a!., Ex. 84-240) conducted . 86-3, 86-4, 236-A, 321, TV, 7/9, pp/ 5-6). dimensions of the fibers without altering inhalation studies in rats with chrysolite Several researchers (Exs. 86-3, 84-210, other fiber characteristicsi'To illustrate ' fibers less than 5 um in length and did 86-4, 236-A, 321, Tr. 7/9, pp. 5-6) have that this may not be the case, Dr. not find increased incidences of theorized that the greater biological Dunnigan (Ex. 91-15-2) cites a 1978 pulmonary fibrosis or tumors compared with incidences in controls. Since activity of longer fibers may be due to the inability of the macrophage to study by Arthur Longer that showed that "ball milling of experimental (asbestos) NIOSH has difficulty in generating completely engulf the fiber. This may samples results in important changes in fibers with an aspect ratio of 3:1 or lead to the release of lysosomal the structural and surface greater by the ball milling method and in enzymes and oxygen-free radicals from characteristics of asbestos fibers, and counting the fibers, the NIOSH results the macrophage, damaging alveolar reduces their effects on all membranes" only suggest that, short fibers do not epithelial cells and initiating fibrosis. In (Ex. 19-15-2, p. 393). He also cites a 1980 induce pulmonary fibrosis or tumors. addition, the fibers may disrupt the report done by Dr. Spumy in Germany However, studies conducted by Koler normal proliferation and differentiation that concluded that "milling procedures (1982) and Pott et al. (1972,1976), as of lung fibroblasts either by directly change not only the size distribution, but discussed by the National Research Interacting with the fibroblast or as a also the shape and crystal structure of Council (Ex. 321, p. 182), suggest that result of macrophage secretions. asbestos fibers" (Ex; 19-15-2, p. 393). amorphous asbestos and fibers shorter Since the November proposal, OSHA In a further elaboration of the than 5 um can induce mesothelioma in has received much comment and evidence against the fiber size theory, rodents, a finding that contrasts with the testimony regarding the relative Dr. Dunnigan cited a study done by . findings of other animal studies importance of fiber size, aspect ratio, Poole et al. (1983) that shows erionite reviewed above. and surface chemistry of the fiber to fibers (In a concentration of 150 f/ug One problem with the studies carcinogenic potential. Most of these mineral] of the "pathogenic" size range conducted by Stanton et al. (Exs. 84-193, commenters expressed the view that the are more reactive than a larger number 84-195) was the difficulty in generating ' surface chemistry of the fiber iB an (1.6x10s f/ug) of similarly sized asbestos samples with fibers of uniform Important determinant of disease. Dr. crocidolite fibers (Ex. 227-A-4, p. 12). lengths; because of this difficulty, the Dunnigan of the Universite de Studies by Suzuki (1980), Wagner. authors could not conclude that short Sherbrooke (Ex. 91-15, p. 391, (1982), and Maltpni.et al. (1982) were asbestos fibers were safe despite the attachment) cited studies and comments also cited by Dr. Dunnigan (Ex. 227-A-4) finding that exposure to shorter fibers of several investigators that were as evidence'that fibrous erionite is the were associated with lower tumor presented at the World Symposium on most powerful mesothelioma-producing incidences in animals. At the hearing, Asbestos (1982) that point to chemical agent, suggesting that these fibers may Dr. Davis (Tr. 7/9, pp. 29-28) discussed factors rather than geometric or physical display disruptive or catalytic properties some of his findings from rat inhalation factors as the important determinant of not shared equally by other types of and injection studies that used carefully asbestos fiber effects on the cell fiber. prepared long- and short-fiber samples membrane. They postulated that OSHA believes that the animal of amosite. For the inhalation' asbestos fiber interaction with cell studies discussed above, in particular experiment, rats were exposed for 12 membrances.causes cell homolysis. the recent work by Dr. Davis, point to a months by inhalation to amosite ' Mossman et al. (Ex. 321, p. 39) found clear relationship between fiber samples ofvarying fiber lengths. asbestos-induced cell damage to be dimension and disease potential. The Animals were observed for their full initiated by the reaction of the fiber with finding in these studies that thin fibers lifespans. Davis observed 13 tumors, as the plasma membrane, which causes cell (Le., having an aspect ratio of at least . well as extensive lung scarring, in 40 lysia or phagocytosis; The National 3:1) greater than 5 um in length are animals exposed to the long-fiber dust. Research Council, National Academy of associated with.elevated incidences of No tumors or scarring was found among Sciences (Ex. 321) cites the work of cancer and lung fibrosis is also animals exposed to the short-fiber dust Wilkinson (1976) and Stossel (1972), who consistent, with current knowledge (Tr. 7/9 p. 26). The amosite samples found that recognition of the asbestos regarding lung clearance mechanisms, were also injected into the peritoneal fiber by phagocytes and their l.e., that shorter fibers are easily cavities of groups of 25 rats. The long- subsequent ingestion of the fiber may be phagocytized and removed from lung fiber sample produced mesotheliomas in due to physicochemical affinities tissue. OSHA also acknowledges recent 95 percent of the animals treated, while between the fiber and the phagocyte. A - findings that interactions between fibers the short-fiber sample produced only study done by Light and Wei (Ex. 91-15) and cell surfaces, in part, may also one mesothelioma tumor. Dr. Davis stated that "fiber dimensions are determine the course of asbestos-related concluded from these studies that short important in determining whether. disease. However, the mechanisms of asbestos fibers were . . unable to . ' asbestoB fibers are able to reach sites fibercell Interactions and their role in damage tissues" (Tr. 7/9, p. 28). where critical cellular interactions take disease causation are not clearly Researchers (Ex. 88-4) have also place, and thus could govern whether understood at this time. found that a significantly.higher the potential biological activityof fibers Some chemists have also suggested percentage.of long fibers (greater than 5 due to their surface charge is displayed" that the biochemically active sites or the um) are retained in the lungs of (Ex. 91-15, p. 391, attachment). electrical charge of the chemical groups mesothelioma and asbestosis victims.' Dr. Dunnigan (Ex. 91-15-2, p. 393) on the asbestos fiber surface can be Morgan (Ex, 86-3) showed that contended that, in view of studies modified to reduce the hazardous . anthophyllite fibers,less'than 5 uiin.in suggesting that modification of the fiber potential of the fiber (Ex. 84-333). In length were more easily cleared from rat structure affects the biological reactivity vitro tests of modified asbestos fibers lung than larger fibers. It has been well of the fiber, the "Stanton Hypothesis" . have shown decreased toxicity GLEASON-000877