Document 1wMY6GXqQV37JNyMGp1rvoEa

ssrvice by Pfizer Laboratories Pfizer Labs // 'f// - J Volume 6 Issue 3 ROBLEMS E , MD,JD, Co-editor Fiber Toxicology and Occupational Health: The Integration of Research And Health Programs William B. Bunn, MD, JD, MPH Senior Director, Health, Safety and Environment: and Vice President, Manville Sales Corporation Denver, Colorado Joel R. Bender, PhD, MD Vice President, Health, Safety and Environment Owens-Cowme Fiberglas Toledo, Ohio 1 he potential toxic consequences involved in the manufacture and use of manmade fibers (especially fiber glass and other man-made vitreous fibers) in voke the sense that we have been here before. But the manmade fibers are physicochemically unique; they differ from the mineral fibers and from each other. Unlike the problems associated with asbestos, in which the untoward properties became apparent only after the long and widespread use of the min eral. there is continuing and worldwide investigation of the epidemiology and toxicology of many of the manmade fi bers. The questions recently raised about the advisability of removing remainant asbestos from the environ ment has focused the attention of phy sicians and scientists on the potential for a new epidemic of occupational and environmental lung diseases caused by the newer fibers. iiucKorounb There is growing contention about the risk of exposure to asbestos and the rationale for asbestos removal. This was recently pointed out by an article in Sci ence (1990:247:294) by Brooke T. Mossman and her colleagues. They raised the question of whether there is a potential for a third wave of asbestosrelated disease among persons neither engaged in manufacturing asbestos nor among its end users. The article was hotly debated in the letters to the edi tor of that publication. The paper concerned the relative risks of removing chrysotile (the pre dominant form), crocidolite, and other forms of asbestos from buildings. The Editor's Comment It is premature to write an epilogue for the chronicle of asbestosis. There are chapters yet to be written and precepts begging formulation. But the lessons already at hand need to be indelibly taken to heart by every physi cian and by every member of society. It is clearly established that exposure to amphibole asbestos fibers imparts an important risk for fibrosing lung disease, and an important and specific risk for mesothelioma. Furthermore, there is little room for debate regarding the synergy for bronchogenic carcinoma when such an exposure coincides with cigarette smoking. To establish these tenets as "facts" required more than a genius for clinical investigation: it required zeal and perseverance on behalf of the worker at fsk1 to convince the skeptic and overcome the inertia inherent in any attempt to shift moneys from profits to welfare. We have come that far. Asbestos exposure in the industrial setting is regulated; no more than two fibers in 10 mL of air is permissible. Furthermore, we have held perpetra tors of exposure accountable after the "fact" for events that occurred before the "fact"--levels of accountability measured in tens of billions of dollars (Continued on page 2) 1 PLAINTIFF'S EXHIBIT PLAINTIFF'S EXHIBIT Editor's Comment (Continued from page 1) that drove such corporations as Johns Manville and Raybestos into bank ruptcy to deal with the process.2 Such is our collective guilt. But here the issue doesn't rest. The same zeal drives extrapolations from these "facts": 1. What stochastic imperative defines the "permissable risk? How does one balance cost with conscience? 2. Most asbestos mined is not amphibole but serpentine fibers; more particularly, 90% or more of the world's asbestos mining yields chrysotile, a serpentine fiber. These fibers have far less toxicity than amphibole fibers. In fact, it has been argued that the risk is negligible3 and that our national mandate to remove asbestos from public buildings is a waste of money and, possibly, a hazard4 regardless of the fiber. ' These issues engender debates that are fueled by emotion5 wherein con viction supplants data. But conviction supplants data of necessity. Epidemi ology can cope with rare events but only if they cluster or if they are qualitatively unique. Otherwise, so much goes on in any complex system, such as a population of people, that all manner of influences perturb the likelihood of a rare event.6'7 The lingering debates about asbestos will rage until all spleens are vented, and data is not likely to come to the rescue. Knowing the asbestos saga, how can we be prescient regarding other and new fibers that are taking their places in our environment? Addressing that question was my charge to Dr. Bunn and his co-authors. Dr. Bunn, my co editor, and Dr. Bender are responsible for health and environment at two of the largest fiber manufacturers in the US. If any of us needs to learn lessons from the asbestos story, they do. We want to share their insights. Nortin M. Hadler, MD, FACP Professor of Medicine and Microbiology!Immunology University ofNorth Carolina at Chapel Hill Chapel Hill, North Carolina References y 1. Nicholson WJ, Perkel G, Selikoff IF: Occupational exposure to asbestos: popula tion at risk and projected mortality--1980-2030. Am J Ind Med 1982;3:259-311. ,2. Morgan WKC: The adversary system: Cui bono? Ann Intern Med 1982:97:919921. / 3. Mossman BT, Gee JBL: Asbestos-related diseases. N Engl J Med 1989:320:1721^ 1730. 4. Mossman BT, Bignon J, Com M, et al: Asbestos: scientific development and implications for public policy. Science 1990;247:294-301. J 5. The Association of Occupational and Environmental Clinics: Letter to the Editor (in response to Reference 3). N Engl J Med 1991;324:195-196. 6. Feinstein AR: Scientific standards in epidemiologic studies of the menace of daily life. Science 1988:242:1257-1263. 7. Diamond GA, Forrester JS: Clinical trials and statistical verdicts: probable grounds for appeal. Ann Intern Med 1983;98:385-394. authors questioned current risk-assess ments on the grounds they were too conservative: the public faces a greater hazard in removal, they said, than in maintenance. Furthermore, the cost of removal programs, estimated at over $100 billion, might be better spent on primary asbestosis-prevention programs. Finally, there was some concern raised regarding the potential toxicity of as bestos substitutes. The debate extended beyond Science and rapidly reached the public. It is un likely the issue will soon be resolved scientifically, but. we may assume, even without such resolution, asbestos will be removed and the ban on asbestosrelated products will continue, with or without modification. Medical (and legal) practitioners will have to adopt positions in this debate: asbestosis and other pneumoconioses are difficult to diagnose in the early stages and often occur in the setting of other insults, such as smoking. Epidemiologic methods are less pow erful in such a circumstance. Society and medicine both are wont to draw causal inferences from prominent indi vidual cases. The result is that anecdote and emotion drive political, regulatory, and judicial activity at least as effectively as does science. The recent quandary faced by physi cians over asbestos-related disease in troduces the need for the medical com munity to understand pulmonary toxic ity and fiber (or particulate) toxicology. These issues are not only controversial today, but, it must be re-emphasized, developing technology will have future impact. The pneumoconioses in historical perspectite Asbestosis, the scarring of the lung, was known early in the 20th Century and perhaps as early as the 1890s. Because of the need to insulate ships rapidly dur ing World Wars I and H, its incidence increased greatly. Although the associa tion of asbestos exposure an3 lung cam* ~cer (lung tumors and mesothelioma) was "once a matter of debate, the recogni tion ot the association occurred 3uring "the 1950s and 'bUsi Thd moSt-recent ' research concerns the reduction of Hbnoccupational exposures~sfemriiihg "from removal of asbestos containing products from buildings. Perhaps the greatest lesson to be learned is that it is imperative that we anticipate the health effects of exposure to fiber. We still do not fully under stand fiber toxicity, but the past hun dred years of scientific scrutiny and pub lic response must serve to guide con sideration of other naturally occurring or man-made fibers and particulates. The recognition of the relationship to cancer in the '50s and '60s spurred a reaction that included regulations by the Occupational Safety and Health Admin istration (OSHA) and, in the '70s, liti gation that has been going on since. In the '80s, concern for a low level of risk led to the removal of asbestos from pub lic schools and other buildings and to a ban on asbestos-containing products. These latter measures have led to the current scientific debate. Fibers are not the only fibrogenic pul monary toxins. For example, that crys talline silica causes lung scarring has been known since the time of Hippocrates. Silicosis gained general at tention after the Gauley Bridge inci dent in 1937, resulting in acute silicotic 2 reaction in a group of miners.* That attention led to social reform in occu pational health regulations and compen sation (primarily Worker's Compensa tion) for silicotic disease processes. Coal workers' pneumoconioses have been well recognized since the early 1800s, but it took a century to awaken the public conscience--and then only after the Farmington mine disaster of 1968. The high-water mark of mine safety in the US was reached with the enactment of the Black Lung Act of 1969. Other pulmonary diseases, such as byssinosis and berylliosis, have been the subject of regulation, litigation, and debate for many years. issue is somewhat clouded by the fact that other fibers--including asbestos-- are present in these areas. In animals, erionite appears to be a more-potent mesotheliomogenic agent than is asbes tos. No consensus has been reached on acceptable levels of occupational expo sure to the fiber, so no recommenda tions have been made: nor have defini tive regulatory reviews been conducted for erionite, wollastonite, or attapulgite. W nllaslonil' In such products as ceramics, insula tion, and wallboard. wollastonite-- a monocalcium silicate fiber--is used useful for assessing its hazards. Overall, the data suggests that two risk-profiles exist, one for origin the other for fiber length. The data on exposure is vari able, but dust levels for certain opera tions approach the standards for nui sance dust (15 mg/m' total, 5 mg/m' respirable). >1' 'Mi tii VITREOUS FIRELr For more than 50 years, the man-made vitreous fibers (MMVFs) have been pro duced and used in a wide variety of applications. They are synthetic, inor- THE EPIDEMILOGY AND TOXICOLOGY OE FIBERS Natural fiber' Asbestos is a naturally occurring min eral fiber the toxicologic and epi demiologic effects of which have been well documented. Standards for work place exposure and work practices exist in most developed countries. However, there is a need to evaluate the risk posed by other naturally occurring fibers (eg, erionite). A body of information is emerging on these fibers, but specific regulations exist in only a few countries. Erionite Zeolite is a naturally occurring, crystal line, hydrated aluminosilicate; erionite is a crystalline, fibrous form. It is found naturally in the western United States, Turkey, South Africa, and elsewhere. Erionite has very limited commercial application, but exposure occurs because it is a contaminant in the min ing and manufacture of other zeolites (which do have commercial value, as molecular sieves and in ion-exchange processes). Erionite can produce tumors, particu larly mesothelioma, in mice and rats that inhale it. Villages near Turkish erionite deposits have been found to have high incidences of mesotheliomas, but the ' Al Gauley Bridge. West Virginia, workers were exposed to high levels of crystalline silica when tunnelling through a mountain with a high quartz content. The minimum exposure necessary to produce silicosis was then thought to be two years, but a num ber of workers with less than two years' exposure developed an acute pulmonary process and many died. The event led to the recognition of acute silicosis and trig gered a deeper scrutiny of the chronic ef fects of crystalline silica. ` `Mat hi laae fibetx /un r simila:' irritant effects the extent of which depends on the diameter and flexihility of the fiber. as an asbestos replacement. It is a durable fiber, but it has less tensile strength than asbestos. Toxicologic stud ies of wollastonite are limited: the only inhalation study in animals failed to pro duce a significant tumor-response. Injection and in vitro studies suggest that wollastonite is less toxic than asbestos. Epidemiologic studies of the neoplastic potential of wollastonite have not been conducted, and studies of its ftbrotic potential are limited. Overall, the health studies of wollas tonite are sparse. Exposure levels vary widely with the application and the in dustry: fiber levels of up to 40 to 50 fibers/cc (f/cc) have sometimes been reported. Attapulgite A fibrous aluminum silicate and mag nesium silicate, attapulgite is used as a thickening agent and an absorbent, as in pet litter. It is mined primarily in the United States. The fibers are short and relatively thin, although the size varies with the geographic region of the deposit. The effect of attapulgite in ani mals has varied significantly from study to study. These differences appear to be related to the origin of the fiber. Inhalation studies in animals suggest that the longer the fiber the greater the toxicity. This result is consistent with injection and in vitro studies, although there is considerable variability. The epidemiologic data on attapulgite is very limited and does not yield data ganic, and amorphous; the family is sometimes referred to as "man-made mineral fibers" (MMMFs), but, techni cally, MMVF is more correct. These fibers are all created from molten masses of raw material under highly controlled conditions. Fiber glass is one MMVF, which also includes rock/slag (mineral) wool and refractory ceramic fiber (RCF). Much more is known of the epide miology of vitreous fibers than is known of other man-made fibers or non asbestos natural fibers. In addition, chronic inhalation and other toxicologic testing has been performed. Specific standards do not exist in the United States (except as nuisance dust), but broader standards are currently under consideration and multiple international bodies have already reviewed the sci entific literature on man-made vitreous fibers. Fiber glass Two basic forms of fiber glass are in general use: wool-type fibers and tex tile fibers. Fiber glass was originally developed in the early 1930s for use in home panel filters and home insulation; textile fibers appeared commercially in the late 1930s, followed by fine-diam eter glass fibers in the early 1940s. Wool fiber-glass is generally used in thermal and acoustical insulation. These products include air-duct insulation, pipe insulation, ventilation-system airfilters, roof insulation, and insulation for 3 'X'^-v^vV f^B IJ. homes, automobiles, aircraft, cooling ap pliances, and refrigerators. Glass fibers are also manufactured with diameters of less than one p. This fmediameter material is produced in the United States in limited quantities that constitute less than 1% of the total fiber glass production. Special-purpose, fine fi ber is limited to use in specialty filter pa pers, battery components, and sophisti cated aerospace insulations. Textile fiber-glass finds wide application as a component of curtains, industrial fab rics, electrical yams, roofing shingles, and reinforcement for plastics, papers, rubber, and other materials. It is generally not of respirable size. Hcnlth diet1!-, of filler piass Skin irritation. Fiber glass may irritate the skin of some workers in glass-fiber manufacturing facilities and of some work ers who fabricate or install fiber-glass-con taining materials. The skin irritation and possible inflammation is a mechanical re action to sharp, broken ends of fiber that rub or become embedded in the outer layer of the skin. Skin reactions vary di rectly with the size and the stiffness of the fiber: those with diameters greater than 4 to 5 p are more likely to cause irritation than are finer-diameter fibers. When the diameter is less than 1.0 p, the fibers usu ally do not cause skin irritation. Normally, the irritation does not persist for long, and it can usually be relieved by using mild soap and warm water to gently wash the exposed areas. Most workers find that any irritation experienced when first working with fiber glass lessens over time. Allergic contact dermatitis has not been associated with exposure to fiber glass, but there have been reports of allergic reactions to the uncured-resin finishes that are used in some fiber-glass products. Some persons may be more affected by irritation from fiber glass than are others, and a few may be forced to seek other types of employment. The vast majority of workers, however, can control skin irri tation by using appropriate work practices. Man-made fibers have similar irritant ef fects the extent of which depends on the diameter and flexibility of the fiber. Upper respiratory irritation. Some work ers may experience a temporary upper res piratory irritation manifested as a scratchiness or burning of the nose or throat. This is especially likely if. during the manufac ture or handling of glass-containing prod ucts. more than 3 to 5 f/cc are released and if they are of large diameter (more than 5 to 6 p). Like skin irritation, upper respiratory irritation is a mechanical reac tion to sharp, broken fibers. Accidental exposures to high concen trations of airborne glass fiber may, like exposure to dust, produce a nonspecific, transitory, lung condition usually mani fested by coughing or wheezing. The effects subside soon after the worker is finer cias> cuk's noT sensitize the lung nor produce allergic reaction." removed from exposure, and there should be no further effect on the worker's health and well-being. Expo sure to fiber glass does not sensitize the lung nor produce allergic reaction. lipiciemioiouic studies Respiratory system diseases are the pri mary subjects of most epidemiologic studies involving fiber glass and other MMVFs. Tens of thousands of workers have been employed in manufacturing fiber glass since its initial development over 50 years ago, and two major stud ies have addressed the mortality of workers engaged in that production. Researchers at the University of Pitts burgh studied the mortality of almost 15,000 workers from 11 fiber-glass manufacturing facilities. This study has been expanded to include over 30,000 workers from 14 such facilities. The first results from the enlarged study will be available in 1992. In Europe, research ers at the International Agency for Research on Cancer (IARC) have con ducted a five-country study of mortality among almost 12.000 workers at six plants manufacturing fiber glass. An update of this study is under way. In 1984. Saracci et al published their study of the mortality of 23.609 work ers (including 11,852 workers produc ing fiber glass) in 13 European facto ries producing MMVFs. There were 2,836 deaths. That study was updated by Simonato et al in 1986. The authors reported that, compared to regional rates, glass workers suffered no excess mortality from lung cancer. However, they did report an "excess of lung can cer among rock-wool/slag-wool workers employed during an early technological phase before the introduction of dust suppressing agents." They concluded that "fiber exposure, either alone or in combination with other exposures, may have contributed to the elevated risk. More-recent studies have shown sev eral potential confounders in the min eral wool industry." The authors also reported that "no excess of the same magnitude was evident for glass-wool production." Also, "there was no evi dence of an increased risk for pleural tumors or nonmalignant respiratory dis eases." The University of Pittsburgh compre hensive mortality study of over 16,000 workers, many with long-term exposure (up to 40 years), was undertaken at 17 fiber-glass- and mineral-wool-manufacturing plants (14,800 fiber-glass work ers in 11 plants). The original report, published in 1982, covered mortality from the 1940s to the end of 1977. The same group of workers was followed through 1982 (reported in October, 1986, with additional analyses in June, 1987). The 1987 report contained, for the first time, local area mortality sta tistics for each of the plants. The study was further updated through 1985, with publication in 1990. Through 1982, malignant respiratory disease had caused no statistically significant excess of deaths in any of the 11 fiber-glass plants, nor in any grouping that distin guished those plants on the basis of glass-wool or textile production (textile fibers are referred to as "glass filament" in the manuscript and by IARC). The update through 1985, however, did show a statistically significant excess of deaths from respiratory cancer among workers employed in glass-wool and mineral-wool plants. To see if the data were consistent with a cause-effect relationship specific for exposure to glass fibers, the researchers investigated possible associations of excess cancer deaths with length of employment, dose response, time from initial employment, and the manufacture of still-finer glassfibers (microfibers). There were no sta tistically significant findings in support of a relationship between respiratory disease and exposure to glass fibers. A recent case-control study was un dertaken in which those workers were studied who had manufactured fiber glass and who had participated in the University of Pittsburgh study. The in terview portion of the later study showed that smoking is the most-im portant nonworkplace factor in lung cancer among the fiber-glass-manufac turing employees. Smoking at the New ark. Ohio, plant in 1955 was significantly greater than in the rest of the US, sug gesting that cigarettes could account for 4 some of the excess lung cancer previ ously reported in the University of Pitts burgh study. Other than the statistically significant standardized mortality rate, no note worthy mortality findings--such as from nonmalignant respiratory disease or mesotheliomas--were associated with exposure to fiber glass. Morbidity among fiber-glass workers has also been studied. None of the major studies reported a consistent pat tern of respiratory disease: nor was any impairment found of the respiratory function of manufacturing workers, even among those with extensive exposure. In the most-comprehensive study. Weill reported on the respiratory health of 1.089 workers at five fiber-glass and two mineral-wool plants in the United States during 1979 and 1980. The researchers noted that the sub jects were generally healthy. However, small opacities did show on the chest x-rays of some workers. In summariz ing their findings, the authors noted that, in general, "the minimal evidence of respiratory effects detected in the in vestigation, which cannot, at present, be considered clinically significant, is en couraging concerning the question of potential health effects of exposure to man-made vitreous fiber." A follow-up study with controls, reported by Weill in 1985 and 1990. found no adverse pul monary effects associated with work in the MMVF industry. Experimental studies Researchers have studied the effects of surgically implanting fibrous material in the pleural and abdominal cavities of animals and of injecting fibers directly into the trachea. In 1977, it was found in such work that tissue changes, including cancer and scarring, were produced by specialty glass-fibers with diameters of less than 1.0 p. Other fiber-glass compo sitions, including those used in building insulation, did not produce such results. These experiments are valuable in the study of the mechanisms of tissue reac tions, but. because they are based on the introduction of large amounts of fiber by routes that bypass normal body-defensemechanisms, they do not justify the con clusion that inhalation of glass fiber is hazardous to workers. As a consequence, several inhalation studies in animals were initiated at independent research cen ters. Commercially available fiber-glass products and, more recently, specially prepared fibers with carefully specified lengths and diameters were used. None of these studies demonstrated tumor in duction or fibrosis by fibrous glass. Risi. evaluation International and US agencies have con ducted a number of reviews of the health aspects of glass fibers. These agencies included the National Institute for Occupational Safety and Health (1977). the World Health Organization (1984), and the National Academy of Sciences (1984). Recently, there have been two additional major reports pre pared on the health effects of glass fibers. In 1986, the International Agency for Research on Cancer (IARC) reviewed man-made mineral-fibers. After review ing the epidemiologic data on over 400 deaths from lung cancer among the 27,000 fiber-glass workers in the Euro pean study (by Simonato et al) and the US study (by Enterline and Marsh), the 1987 IARC working group of the World Health Organization stated that the evi dence was inadequate to conclude that either glass wool or glass filaments were carcinogenic to humans. No evidence of fibrosis or other morbidity was found by the IARC panel. Despite seven negative inhalationstudies in animals, implantation of microfibers of two special-purpose glasses induced cancer. This is the basis for the determination by the IARC that glass wool is "2B"--a possible human carcinogen. Continuous-filament fiber glass was designated "Group 3"--it is "not classifiable as to human carcino genicity." In 1987, a second major, international evaluation of the safety of glass fibers by the World Health Organization (WHO), led to the report of the Inter national Programme on Chemical Safety (IPCS): "The overall picture indicates that the possible risk of cancers among the general public is very low, if there is any at all, and should not be a cause for concern if the current low level of exposure continues." The IPCS does allow the weighting of evidence, and the inhalation studies in animals were given greater weight in their analysis. In 1988, the US Environmental Pro tection Agency announced its agree ment with the IPCS conclusion when it stated that the evidence for the carci nogenicity of fiber glass "is considered inadequate." Mineral wool The fibers known as "mineral woof are produced by spinning or blowing mol ten basalt or the slag obtained from refining ores. These latter consist of metal silicates--silicates of aluminum, boron, calcium, iron, sodium--and vari ous metal oxides. Depending on the source, the average fiber-diameter ranges from 3 to 15 p. Ma.ior apniicaiioi In the early 1900s, mineral wool was developed as insulation. The fiber is generally supplied in three basic forms: loose wool, wool bonded into a batt or blanket, and acoustical tile and panels. Today, mineral wool is widely used to control temperature and sound. Its major applications are in commercial insulation, acoustical control products, pipe insulation, and insulation for auto mobiles, ships, mobile homes, refrigera tors, domestic cooling appliances, and a wide variety of other appliances and equipment. Health effects The skin, eye, and upper respiratory ir ritations of mineral wool are similar to those of fiber glass. Animal studio Several inhalation studies with animals have been done at independent research centers. Commercially avail able mineral-wool was used. In two of these studies, the animals were exposed to high concentrations of fiber for one year or more and then allowed to live out the rest of their lives. Compared to the controls, none of the test animals demonstrated fibrogenesis, carcino genesis, or permanent changes of the respiratory system: nor did the expo sure reduce life expectancy to a signifi cant degree. Other studies of implanted, injected, or instilled mineral wool have shown that virtually all fibrous materials can, at very high dosages and regardless of physical or chemical makeup, have adverse effects. However, evidence from other experiments indicates that mineral wool is attacked by the fluids normally present in the lung. This may cause fragmentation into shorter fibers that may be biologically less active or may even lead to the total disappear ance of very fine fibers Epidemiologic studies Thousands of workers have been em ployed in plants that manufactured min eral wool during the 50 years since its development. A number of epi demiologic studies of workers have been done, but the two major mortality stud ies were those discussed above in the fiber-glass section. The excess lung can cer found in slag- and rock-wool work ers was the most-disturbing finding, but that excess might be related to early production phases and to confounding 5 exposures to such carcinogens as lead, asbestos, or arsenic. In addition, the studies were difficult to control for other factors--smoking, for example--that could have contributed to the excess. There are three broad categories of refractory ceramic fiber (RCF): kaolinbased fibers, in which the clay is obtained by mining; blends of alumina, silica, and a refractory metal oxide (eg, zirconia); and high-purity products that are a blend of alumina and silica pro cessed to limit the levels of impurities that are found in other RCF products. The fibers are produced by spinning molten mixtures. The average diameter of the fibers produced in this manner is in the range of 1.2 to 3.5 |X Fiber length can be varied from long fibers down to p-sized. and no effects were found in the lungfunction tests of nonsmokers. Among current and former cigarette-smokers, the results of lung function tests were consistent with minimal obstruction associated with cigarette smoking and also, but to a lesser extent, with expo sure to ceramic fiber. Some symptoms of dry cough and breathlessness were also found. Small opacities were present on 13% of 594 chest x-rays. Primarily, these were related to age and to smoking hab its and there was some evidence of an association with time spent in the industry (but not with cumulative exposure to RCF). It is not clear what the long-term biological significance may be of the small effects apparently related to ceramic fibers, and the study is likely to be continued. Results from the US study will soon `'Recall studies on animals may affect the risk evaluation for RCFs." Major application be available. Preliminary reports indi Applications vary, but all are used in cate a decrease in pulmonary function high-temperature, specialty environ that is not clinically significant and a ments. Blankets are used primarily as possible increase in pleural plaques furnace and kiln-wall liners; loose fiber among RCF-exposed workers. The is used as a filler in packing voids and latter findings may have been con expansion joints; custom-molded shapes founded by exposure to asbestos. are widely used in metal molding and as furnace combustion-chamber liners. Inhalation studies Health effects There have been four known investiga tions of the effects that high concentra Skin irritation and upper respiratory tions of airborne RCF have on animals. irritation are largely the same as those In one. 48 rats were exposed to RCF by found with fiber glass. inhalation for seven hours a day, five days After-service effects a week, for 32 weeks. Fibers longer than 5 phad airborne levels of95 f/cc. Animals RCF that has been in service at elevated sacrificed at the end of the study had temperatures (greater than 1,800F) interstitial fibrosis in an average of 5% of will undergo partial conversion to cristo- the lung area: eight rats had pulmonary balite. a form of crystalline silica that tumors, of which three were carcinomas; can cause silicosis. there was also one peritoneal mesothelioma. Lpidemiolopic studio In contrast, inhalation work at Los There are no published reports dealing Alamos showed no cancer and little pul with the health experience of people monary fibrosis in rats: 50 hamsters who work with RCFs. Two investiga showed one mesothelioma but no fibrosis. tions. one in Europe and the other in The exposures were conducted at 200 the United States, are studying the f/cc. six hours a day, five days a week, for health of workers engaged in the manu 24 months. One of 157 control animals facture of RCFs. In October. 1989. a unexposed to fiber developed a sponta preliminary report from the European neous tumor. study of over 650 RCF-plant workers In June. 1988, to help clarify some of was made available. It noted that no the uncertainties, a two-year inhalation evidence was found of pneumoconiosis I study in rats and hamsters was begun by TIMA (Thermal Insulation Manufactur ing Association). Groups of rats were exposed for six hours per day, five days a week, to 30 mg/m3 of four different types of RCF: kaolin, zirconia, high purity, or "after service" (ie, a kaolin-based, ce ramic fiber, containing 27% crystalline silica that had previously been exposed to high temperatures). Approximately 200 to 250 f/cc were greater than 5 pin length. Hamsters were exposed only to kaolin RCFs. In both the rat and the hamster studies, positive controls inhaled 10 mg/ m3 of chrysotile asbestos and negative controls received filtered air. A total of 35% ofthe hamsters exposed to the kaolin RCF-fibers developed mesotheliomas. A nonmalignant mesothelial proliferation was found in the pleura of one of the asbestos-exposed hamsters; negative-control hamsters had no lung lesions. Cytologic examination of the lungs of the kaolin-exposed hamsters revealed pulmonary fibrosis in the termi nal airways and pleura. In the RCF-exposed rats, pathological studies revealed lung tumors (some be nign), pulmonary tumors, and mesotheliomas. In asbestos-exposed rats, benign and malignant lung tumors were reported; the final results are not yet available. Cytologic examination of the rats sacrificed at one year showed that exposure to kaolin RCF, zirconia RCF, high purity RCF, "after service" RCF, and asbestos all resulted in pulmonary fibrosis. After the first year, the fibrosis progressed more slowly. Risk evaluation In 1987, IARC designated RCF as Group 2B, "possibly carcinogenic to hu mans," on the basis of animal studies. IPCS evaluated RCF with other MMVFs. Crystalline silica in the form of cristobalite has been classified by IARC as 2A, "probably carcinogenic to humans." MMVF reputations Although no US regulatory guidelines exist for any fibers, save asbestos, there are multiple recommendations. NIOSH (the National Institute for Occupational Safety and Health) recommended a 3 f/cc or 5 mg/m3 guideline in 1977. Fiber glass and mineral wool manufac turers recommend a standard of 1 f/cc, based on irritation. The Safety and Health Committee of the Building and Trades Department of the AFL-CIO also rec ommends a standard of 1 f/cc. An OSHA proposal is expected for fiber glass, mineral wool, and refractory ce ramic fibers over the next year. Recent studies on animals may affect the risk evaluation for RCFs. 6 Control of levels of respirable particles 'in' titfilf itif" the perspective and scientific overview or fibers is accomplished by a combina The family of polyolefin fibers consists that will allow physicians to make tion of engineering changes, work prac of polypropylene, polyethylene, and informed judgments about the risks cur tices, and protective equipment. In addi polycarbonate fibers. The major uses are rently associated with man-made and tion, regular medical surveillance of ex in home furnishings such as rugs, mineral fibers. posed populations is recommended. upholstery, curtains, and bedding. These fibers are generally not respirable even Special thanks to Thomas W. S'l'V.'TTTr' riBEk. Aramid Hikt- though fine fibers are used for light weight, insulating clothing and for air filtration. There has been one subchronic inha Hesterherg, PhD. Senior Toxicolo gist, and Gerald R. Chase. PhD. Chief BiostatisticianlEpidemiologist, of the Manville Technical Center, Aromatic polyamides constitute the lation study with sized polypropylene Denver, Colorado. They also contrib aramid fibers, which are durable and fibers; it showed biologic activity at 90 uted to this article. have high tensile strength. These fibers days, but no fibrosis. Variable, low lev generally fall outside the respirable range, but certain of them have fibrils that may break off and become respi rable. It is not clear that fabrication gen erates either a fibrous or particulate els of toxicity were found with injection and in vitro studies. No epidemiologic studies or data on workers exposed to polyolefin fibers have been published. Suggested Reading International Agency for Research on Can cer (IARC). IARC Monographs on the Evaluation of Carcinogenic Risks to Hu respirable component. Only a single experimental study of chronic exposure to aramid fibers has been conducted. Thin aramid fibers at a concentration of 100 f/cc produced fibrosis and rat-specific tumors. Short term inhalation studies suggest that respirable organic fibers do generate a tissue response in animals; intraperitoneal injection studies have shown a slight increase in the incidence of tumors and of fibrosis. Exposures mea sured at manufacturing locations indi cate fiber levels ranging from undetect able to less than 1.0 f/cc. SUMMARY This review of the scientific data shows that, in terms of physiologic effects, there are major differences from one man-made or natural fiber to the next. Most of the data is reassuring, but we do need to reduce levels of exposure and to detect disease at an early stage. Personal risks and workplace protec tion-programs may become the subject of judicial or regulatory scrutiny. In that context, it is worth noting that, histori cally, the recognition of occupational pulmonary disease has come only after the fact, from the study of mortality pat mans. Man-Made Mineral Fibres and Ra don. Lyon, France. Vol 43, 1988. International Programme on Chemical Safety (IPCS). Man-Made Mineral Fibres. Environmental Health Criteria 77. World Health Organization, Geneva, Switzerland, 1988. Bunn W, Hesterberg T, Chase G, et al: Man-made mineral fibers. In Medical Toxi cology of Hazardous Materials. Sullivan J, Kriegel G (ed). Williams and Wilkins, Bal timore (in press). US Environmental Protection Agency (USEPA). Health Hazard Assessment of Carbon fibers The term "carbon fibers" refers to both carbon and graphite fibers. They are terns. This retrospective approach is no longer morally or sociopolitically accept able. This paper, we hope, will supply Nonasbestos Fibers. Health and Environ mental Review Division, Office of Toxic Substances, Washington, DC, 1988. synthetic fibers prepared by the high- MEDILEGAL BULLETINtemperature processing of poly- acrylonine, pitch, or rayon. They are characterized by light weight, high ten sile strength, and flexibility. The aver age diameter of the fiber is 5 to 8 p, but up to 25% of the fibers are respi rable by humans. Regulation of the Manufacture and Use There have been two short-term Of Potentially Hazardousinhalation studies, one subchronic and Substancesone chronic, of carbon-based fibers. Unfortunately the studies were con ducted with materials that had large pro portions of particulate matter or fibers that were not respirable by rats. William B. Bunn, MD, JD, MPH Injection studies have not shown a Senior Director, Health, Safety and Environment; and significant increase in tumors, but in Vice President, Manville Sales Corporation vitro tests have shown both genotoxic Denver, Colorado and cytotoxic effects. Dermal studies have not shown statistically significant increases in tumors. in the United States, the evaluation standards for full evaluation and regu There have been only limited stud and regulation of the health effects of latory review; appropriate testing is ies of exposed populations, and epi commercial products is both intensive mandated before a new product can be demiologic data is not available for risk and comprehensive; internationally, approved. For chemicals, petroleum assessment. What data there is on re scrutiny is increasing. Before a new products, and other new commercial spirable carbon-fibers in the occupa commercial product is introduced, it introductions, regulatory review is tional setting indicates only minimal undergoes several levels of review. required by the Toxic Substances Con exposure. For pharmaceuticals, pesticides, and trol Act (TSCA). Regulatory authorities | consumer products, there are specific may also require special studies of po- 7