Limit values. The current occupational exposure limit (MAC) for glass fibers or dust in the Netherlands is 10 mg/m3, defined as an 8 hour time weighted average (TWA). No limits have been set for the other MMMF. The ACGIH in the USA recommends the same limit for fibrous glass dust and mineral wool fibers. NIOSH/USA has recommended a limit for fibrous glass and other man-made fibers of 3 respirable fibers per ml (f/ml), TWA-8 h, and for total fibrous glass of 5 mg/m3, TWA-8 h. Germany has a TRK-Standard for MMMF of 0.5 f/ml.The occupational exposure limit for synthetic inorganic fibers in Sweden is 1 f/ml. Standards in the United Kingdom are: Maximum Exposure Limit for airborne respirable fibers 2 f/ml, for superfine fibers 1 f/ml and for inhalable dust 5 mg/m3. Toxicokinetics. Fibers differ in general from particulates in their deposition behaviour in the various regions of the respiratory tract. Retention times at the deposition sites and clearance pathways may also differ. Deposition. Like other fibrous materials, MMMF may be deposited in the respiratory airways by processes such as impaction, interception and sedimentation. These processes are governed by the aerodynamic diameter of the fibers. For MMMF the aerodynamic diameter is close to three times the nominal fiber diameter. Clearance and translocation. Within one day after deposition fibers in the tracheobronchial lung region are carried proximally along the surface of the mucous to the larynx, to be swallowed and passed into the gastrointestinal tract. Clearance of fibers deposited in the non-ciliated airspaces beyond the terminal bronchioles is slower. The half time of MMMF in the tracheobronchial part of the lung is estimated to be less than one day and in the alveolar region between 60 and 90 days. These figures do not apply to fibers longer than 20 um. Dissolution. The solubility of MMMF in the lungs of rats was found to depend on fiber size and composition. Glass fibers shorter than 10 um dissolve to a much lesser extent than fibers longer than 30 um. The dissolution of long fibers with a diameter of 1.5 um is quite variable. For rock wool fibers of 20 um in length, e.g., no change in fiber dimensions was observed during a period of six months following deposition. In general, MMMF deposited in lungs are better soluble than asbestos fibers. Effects. Human data show that skin conditions are the major problem of MMMF during handling. The fibers in themselves are not sensitising, but contact with finishers such as uncured resins, hardeners and accelerators may induce sensitisation in workers involved in MMMF production. Inhalable but non-respirable MMMF (with diameters larger than 4-5 um) may induce transient irritation of the skin, eyes and upper respiratory tract. The results from in vitro assays of cytotoxicity of insulation wools are contradictory. Cytotoxicity was shown to be a function of fiber size distribution. Refractory ceramic fibers displayed a somewhat lower degree of cytotoxicity than amosite asbestos. The cytotoxicity of special purpose glass fibers increases with fiber length and inversely increases with fiber diameter. ln most of the assays fibrous glass with relatively large fiber diameters appeared to be less cytotoxic than chrysotile and crocidolite. Studies on fibrogenicity of respirable insulation wool fibers and special purpose glass fibers show equivocal results. Respirable refractory ceramic fibers may cause mild lung fibrosis in rats. In cross-sectional epidemiological studies no substantial non-malignant effects of longterm exposure to MMMF on the respiratory tract were found. Several reports with results from retrospective cohort mortality studies of workers occupationally exposed to MMMF are available. In none of these an excess mortality due to mesothelioma was reported. With respect to lung cancer the three largest and most informative studies were carried out in the insulation wool production industry in Western Europe, the United States and Canada and produced the following results. Glass and rock wool production workers did not show a statistically significantly elevated lung cancer mortality as compared to the local population mortality rates in the European- and US-cohorts. In a Canadian study a statistically significant higher lung cancer mortality was seen in glass wool workers than in the local population. However, the mortality increase was not related to exposure duration or time since first exposure. Among mineral wool production workers, lung cancer mortality was slightly higher for workers with 20-29 years since first exposure than was expected from regional population mortality data. The use of a particular type of slag wool, containing arsenic, may have been responsible for the excess of respiratory cancer. A case-control study of lung cancer deaths in a cohort of workers potentially exposed to slag wool fibers in the US individually matched with controls selected from the remaining deaths in the cohort, showed no association between length of exposure or cumulative exposure to slag wool and lung cancer risk, after adjustment for smoking habits. A highly statistically significant association was found in this study between smoking habits and increased risk of lung cancer. All cases in this study were cigarette smokers. Only one epidemiological study on the health risk of persons exposed to refractory ceramic fibers is available. Slight lung aberrations were seen in the exposed workers. This effect was associated with age and smoking habits but not with cumulative exposure to RCF. There was some evidence of an association between the effect and time spent in industry. The committee considers properly conducted inhalation studies with rats, using fibers of appropriate, i.e. rat-respirable size, useful for assessing human health hazards for lung cancer and interstitial fibrosis from inhaled fibers. In none of the inhalation studies conducted with experimental animals exposed to glass wool, rock wool or slag wool a significant excess of lung tumours was observed. The significance of the results of animal studies in which fibers were not administered by inhalation but in other ways, like intratracheal, intrapleural and intraperitoneal injection, are difficult to interprete. The unnatural mode of administration, which bypasses the early defence mechanisms results in such a high local concentration of fibers, that a tissue response may be triggered. Furthermore, injected fibers may be deposited at sites that cannot be reached by inhaled fibers, resulting in responses not relevant for the quantitative evaluation of a lung cancer risk associated with the inhalation of MMMF. In contrast to insulation wool fibers, refractory ceramic fibers do cause lung cancer and mesothelioma in some animal studies. Risk assessment. Continuous filament fiber glass. Continuous filament fiber glass is considered to be non-respirable due to the large diameters of the fibers (far above 4-5 um). Continuous filament fibers may cause mechanical irritation to the skin, eyes and respiratory tract; the potential for irritation is found to increase with fiber diameter. The committee cannot determine a health based recommended occupational exposure limit (HBR-OEL) based on this effect. It recommends to reduce exposure as far as possible. Glass wool fibers. Based on the currently available epidemiological data and animal studies the committee concludes that occupational exposure to glass wool fibers does not pose a carcinogenic hazard. The committee has identified lung fibrosis to be the critical effect. The no observed adverse effect level (NOAEL) for this effect in rats is found to be 5 mg/m3 (48 respirable fibers per ml). Using a safety factor of 10 for the extrapolation of animal data to man, this results in a health based recommended occupational exposure limit (HBR-OEL) of 4.8 respirable fibers per ml, averaged over an 8 hour working day (TWA-8 hour). Rock wool fibers. Based on the currently available epidemiological data and animal studies the committee concludes that occupational exposure to rock wool fibers does not pose a carcinogenic hazard. The committee has identified lung fibrosis to be the critical effect. The NOAEL for this effect of rock wool in rats after two-years exposure, is 3 mg/m3 (33 respirable fibers per ml). Using a safety factor of 10 for the extrapolation of animal data to man, this results in a HBR-OEL of 3.3 respirable fibers per ml, TWA-8 hour. Slag wool fibers. Based on the currently available epidemiological data and animal studies the committee concludes that occupational exposure to slag wool fibers does not pose a carcinogenic hazard. The committee has identified lung fibrosis to be the critical effect. The NOAEL for this effect of slag wool in rats after two-years exposure, was 30 mg/m3 (209 respirable fibers/ml). Using a safety factor of 10 for extrapolation of animal data to man, this results in a HBR-OEL of 21 respirable fibers per ml, TWA-8 hour. Special Purpose Glass Fibers. Based on the currently available epidemiological data and animal studies the committee concludes that occupational exposure to special purpose glass fibers does not pose a carcinogenic hazard. The committee has identified irritation and infection of the nasal mucuous membrane to be the critical effects. The minimal observed adverse effect level (MOAEL) for these effects in rats after two-years exposure, is 5 mg/m3 (332 respirable fibers per ml). Using a safety factor of 50 (10 for interspecies differences and 5 for applying the safety factor to a minimal effect level instead of to a no effect level), this results in a HBR-OEL of 6.6 respirable fibers per ml, TWA-8 hour. Overall HBR-OEL. The critical effects of the MMMF wool types and special purpose glass fibers discussed above are very similar. Also, the difference in the derived HBR-OELs is not large in view of the differences in design between the critical animal studies for each fiber type and the variation in fiber (sub)types used in these studies. Therefore, the committee recommends an identical occupational exposure limit for each type of Man Made Wool Fibers and Special Purpose Glass Fibers. Using the lowest figure obtained, viz. 3.3 respirable fibers per ml for rock wool, the committee recommends an overall HBR-OEL of 3 respirable fibers per ml, TWA-8 hour. Non-respirable fibers (i. e. fibers with diameters greater than 4-5 um) of these types of MMMF may cause mechanical irritation to the skin, eyes and respiratory tract. A health based recommended occupational exposure limit (HBR-OEL) cannot be determined for these effects. The committee recommends to reduce exposure to nonrespirable fibers as far as possible. Refractory Ceramic Fibers. Based on some positive animal studies, refractory ceramic fibers are considered to be potentially carcinogenic. However, the mechanism underlying the carcinogenicity is unclear. The committee has considered two situations, that both lead to comparable results: if a non-genotoxic mechanism underlies the carcinogenic potential, the committee derives a HBR- OEL of 1 respirable fiber per ml, TWA-8 hour; this value is based on a NOAEL of 25 fibers/ml and a safety of 25 taking into account the seriousness of the critical effect (cancer); if a genotoxic mechanism underlies the carcinogenic potential, the committee assumes a linear relationship between dose and response. Based on 40 years of occupational exposure an excess cancer risk of 4x10-3 appears to be associated with an exposure to 5.6 respirable fibers per ml. A cancer risk of 4x10-5 is associated with an exposure to 0.056 respirable fibers per ml. Applying a linear extrapolation, daily (8 h) occupational exposure to 1 respirable fiber per ml for 40 years appears to be associated with a cancer risk of 7xl0-4. (Shortened)