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Substance: CU/S-02.13 - CU/D-02.27 SCOEL/SUM/94-final June 2002 Recommendation from Scientific Committee on Occupational Exposure Limits (SCOEL) for Silica, Crystalline (respirable dust) Chemical name SiO2 modifications silicon dioxide, crystalline Molecular formula Molecular weight Synonyms quartz, a-quartz, low quartz CAS number 14808-60-7 Synonyms cristobalite, a-cristobalite, low cristobalite CAS number 14464-46-1 Synonyms tridymite, a-tridymite, low tridymite CAS number 15468-32-3 SiO2 60.09 Quartz Cristobalite Tridymite Temperature at which the a-modification is transformed into the high-temperature pmodification Melting point Density at 20C (g/m3) Crystal form 573C 1610C 2.65 g/cm3 trigonal 270C 1713C 2.33 g/cm3 tetragonal 130C -- 2.27 g/cm3 monoclinic Occurrence/use Silica (silicon dioxide (SiO2)), occurs in either a crystalline or non-crystalline (amorphous) form. Crystalline silica may be found in more than one form (polymorphism), depending on the orientation and position of the tetrahedra (i.e., the three-dimensional basic unit of all forms of crystalline silica). The natural crystalline forms of silica are a-quartz, a-,p1-, and p2-tridymite, aand p-cristobalite, coesite, stishovite, and moganite (IARC, 1997). The most common form of naturally occurring crystalline silica are quartz (CAS No. 14808-60-7), Cristobalite (CAS No. 14464-46-1) and tridymite (CAS No. 15468-32-3), but they can also be created during industrial processes, such as the calcination of diatomaceous earth, ceramics manufacturing, foundry processes, silicon carbide manufacturing, and any other process in which quartz is heated to high temperature. Quartz is a colourless, odourless, non-combustible solid and a component of many mineral dusts. It is insoluble in water. When quartz is cut, ground, or milled, the crystal is fractured, and Si and Si-O radicals may be generated on the cleavage surfaces. Trace metal impurities, such as iron and aluminium, can modify the surface reactivity of quartz. Quartz is abundant in most rocks, sands, and soils. The extensive natural occurrence of quartz and the wide uses of the materials than contain quartz are directly related to potential occupational exposures to quartz for workers in many industries and occupations. Virtually any process that involves movement of earth (e.g., quarrying and tunnelling), disturbance of silica-containing products such as masonry or use of sand and other silica-containing products (e.g., foundry processes) may potentially expose a workers to quartz. Health significance Introduction In humans the main effect of the exposure to respirable silica dust is silicosis. Silicosis has been detected by X-ray, lung-function testing and computed tomography. Other non-neoplastic pulmonary effects in humans are inflammation, lymph node fibrosis, chronic air flow limitation, emphysema and "extrapulmonary silicosis". Epidemiological studies reveal an association between exposure to crystalline silica dust and an increased probability of developing lung cancer. Administration of crystalline silica to rats by inhalation or intratracheal instillation also led to the development of lung tumours. Therefore crystalline silica is classified by IARC as a Group 1 carcinogen to humans. The epidemiological studies show that the incidence of lung cancer is increased especially in workers with silicosis. The first step in reducing the cancer risk, therefore, must be the prevention of silicosis. Mechanism of crystalline silica toxicity The mechanism for the development of silicosis and lung tumours in man and animals exposed to crystalline silica is still unclear. The mechanism of the toxic action of crystalline silica and other SiO2 modifications involves a direct interaction of the surface of the crystalline silica particles with cell membranes or cell fluids. Treatment of crystalline silica by heating, corrosion with chemicals or milling can alter the surface properties of the crystalline silica particles and therefore alter their toxicity (Fubini 1998, Fubini et al. 1995). The binding to trivalent ions such as Al3+ or Fe3+ can reduce the effects of crystalline silica on cell membranes (Nolan et al. 1981). The study of the physicochemical properties of the various SiO2 modifications is a very complex area of research (reviewed by Fubini 1998, Fubini et al. 1989, 1995). The functional groups which have been suggested to be involved in interactions of the surface of crystalline silica particles confer a hydrophilic or hydrophobic character, or result in charged groups or the formation of reactive radicals on the particle surfaces and affect the facility with which hydrogen bonds are formed (Fubini 1998). This indicates that crystalline silica particles of different sources, age and preparation modes differ in their inflammatory potencies. Further research will help to better differentiate between the different crystalline silica species and the biological potencies. Crystalline silica can accumulate in the lungs. With increasing levels of deposited crystalline silica the alveolar macrophages and epithelial cells become activated. This results in increased release of cytokines, bioactive lipids, growth factors, proteases and reactive oxygen and nitrogen oxide species. The sequel can be a chronic inflammatory reaction. Oxidative stress can induce mutations in epithelial cells. Activation of nuclear transcription factors, increased expression of proinflammatory genes and oncogenes and the induction of nuclear transcription factors and mutations in tumour suppresser genes can be caused by reactive oxygen species (Donaldson and Borm 1998, Fubini 1998, Hojo etal. 1998, Knaapen et al. 1999, Shi et al. 1998). In vitro, crystalline silica induces DNA damage in cell-free systems and micronuclei and cell transformation in mammalian cells. It is, however, doubtful whether the DNA damage demonstrated with very high crystalline silica concentrations in unphysiological milieu in vitro also occurs in vivo. In an in vivo micronucleus test in the mouse, crystalline silica had no effects. Toxicokinetics Crystalline silica dust is practically insoluble in body fluids and can be deposited in the lungs. In addition, the macrophage-mediated mechanical clearance of crystalline silica particles can be disturbed because crystalline silica dust is cytotoxic for macrophages. Therefore, in the presence of high levels of crystalline silica dust, the transport of particles out of the lungs by this means is minimal. Cigarette smoking can reduce the clearance of crystalline silica . Autopsy reports for persons who had been exposed to crystalline silica revealed wide range of levels of crystalline silica retention in the lungs. For example, lung loads of 264 mg per lung were found in employees exposed during work with rock for per 14 to 36 years (Greim 1999). Crystalline silica dust has been detected in bronchoalveolar macrophages and in the saliva of persons suffering from silicosis. Genotoxicity Crystalline silica dust induced cell transforming activity in vitro in mammalian cells. High concentrations of crystalline silica induced DNA damage in cell-free systems and also micronuclei in mammalian cells in vitro. In contrast, after intraperitoneal injection into mice, no micronuclei were detected in vivo. The hprt mutations detected in vitro in the alveolar epithelial cells of rats exposed to crystalline silica dust are probably the result of indirect genotoxic effects. This could be explained by the production of reactive oxygen and nitrogen species which can be formed on reactive SiO2 surfaces or by activation of alveolar macrophages (IARC 1997). In the alkaline single cell gel/comet assay, crystalline silica (Min-U-Sil 5) induced DNA damage i.e., DNA migration) in cultured Chinese hamster lung fibroblasts (V79 cells) and human embryonic lung fibroblasts (Hel 299 cells) at concentrations ranging from 17.2 to 103.4 pg/cm2 (Zhong et al., 1997, Liu et al. 1996, 1998). Experimental conditions (i.e., Chinese hamster lung fibroblasts challenge with dusts pre-treated with a phospholipid surfactant) were applied recentes to simulate the condition of particles immediately after deposition on the pulmonary alveolar surface. Results of the experiments showed that untreated Min-U-Sil 5 and Min-U-Sil 10 induced micronucleus formation in a dose-dependent manner, but surfactant pre-treatment suppressed that activity (Liu et al., 1996). A subsequent experiment found that surfactant pre-treatment suppressed crystalline silica-induced DNA damage in lavaged rat pulmonary macrophages, but DNA-damaging activity was restored with time as the phospholipid surfactant was removed by intercellular digestion (Liu et al., 1998). Recent in vivo studies found that crystalline silica induced micronuclei in pulmonary alveolar macrophages of male Wistar rats in a time-dependent (Leigh et al. 1998) and dose-dependent manner (Wang et al., 1997). Fibrosis and tumour induction It is not clear whether fibrosis is a precondition for the development of tumours. Fibrosis develops in different target cells (fibroblasts) than do the lung tumours (epithelial cells). It seems likely that the chronic inflammatory processes play an important role in the development of both fibrosis and lung tumours. A hypothetical mechanism for the development of tumours in a rat is shown in the documentation of the MAK-Commission (see Figure 2 in Greim, 2000; Donaldson and Borm 1998, Driscoll et al. 1998, IARC 1997, Shi et al. 1998, Vallyathan et al. 1998). It is not clear whether the same mechanism could also be responsible for the development of lung tumours in man because the inflammatory processes seen in persons exposed to crystalline silica are less severe. There are numerous studies of persons with silicosis for whom this has been recognized as an occupational disease. In the IARC document (IARC 1997) most emphasis is placed on two studies (Amandus et al. 1991, Partanen et al. 1994) in each of which the causes of death in a cohort of persons with silicosis was studied. One cohort was made up of 655 dusty trade workers in whom silicosis was diagnosed after 1940 in North Carolina (Amandus et al. 1991). The SMR for lung carcinoma for these persons with silicosis compared with the population of the USA was 2.56. In this publication it is stated that 18 of the 33 persons who died with lungcarcinoma were smokers (SMR 3.4) and 5 were non-smokers (SMR 1.7). For the remaining 10 persons who died (SMR 2.2) there were no data for smoking habits. The authors suggested that their results be interpreted with caution because the calculation of the SMR values was based on official statistics which did not differentiate between smokers and non smokers. In this study it is conspicuous that the proportion of non-smokers among the cases of lung carcinoma is relatively high (at least 5 of 33, i.e. 15 %). In this study the SMR did not increase with the time after the diagnosis of silicosis. Among 811 Finnish workers for whom silicosis had been diagnosed, the incidence of lung carcinoma was increased (SIR 2.89) (Partanen et al. 1994). The smoking habits were known for 41 of the 101 cases of lung carcinoma. One patient said he had never smoked, 25 were active smokers (SIR 6.67) and 15 were ex-smokers (SIR 1.89). In this study, unlike in that of Amandus et al. (1991), the SMR increased with the time after the diagnosis of silicosis. During the first two years, the disease was diagnosed in one patient. In the years 2-9, 32 cases were observed (SIR 2.73) and after 10 years another 68 cases had been diagnosed (SIR 3.27). In a meta-analysis of the question of a relationship between silicosis and lung carcinoma, a total of 23 studies were analysed (Smith et al. 1995). The two studies described above from the USA and Finland were among these 23. In the studies a total of 882 cases of lung carcinoma were included. The relative overall risk was given as 2.2; the relative risk for the cohort studies was 2.0 and for the case-control studies 2.5. Seen as a whole, the data indicate that the relative lung cancer risk is increased for persons with silicosis. At present there are no studies available which provide an explanation of the mechanism by which lung tumours develop and the possible role of silicosis. Dose-response relationship for the carcinogenic activity of crystalline silica dust It was shown that lung cancer risk tended to increase with: cumulative exposure to respirable silica (i.e., Checkoway et al., 1993, 1996) duration of exposure (i.e., Costello & Graham, 1988; Merlo et al., 1991, Partenen et al., 1994; Costello et al., 1995; Dong et al., 1995) peak intensity of exposure (Burgess et al., 1997; Cherry et al., 1997; McDonald et al., 1997) the presence of radiographically defined silicosis (Amandus et al., 1992; Dong et al., 1995) length of follow-up time from date of silicosis diagnosis (Partanen et al., 1994) The existence of dose-response relationship was studied in three investigations. While the study of gold miners in the USA (Steenland and Brown 1995) and the study of English ceramics workers (Winter et al., 1990) did not reveal any dose-response for lung cancer mortality and different classes of exposure, Checkoway et al., (1997, 1999) revealed a statistically significant doseresponse relationship with relative lung cancer risks of 1.0, 0.96, 0.77, 1.26 and 2.15 for cumulative exposure of < 0.5, 0.5-1.1, 1.1-2.1, 2.1-5.0, 3 5.0 mg/m3 x years for the diatomaceous earth industry workers. Further analysis of the dose-response relationship yielded an increased relative risk for lung cancer per 1000 particle years or per 0.06 mg respirable crystalline silica dust mP x year of 1.023 (95% CI: 1.005-1.042) for South African gold miners (Hnizdo and Sluis-Cremer, 1993). In a case-control study was shown that the lung cancer risk was increased with increasing exposure (Meijers et al., 1990). In another case-control study the OR for lung cancer increased with exposure to crystalline silica (McLanghlin etal., 1992). No relationship between the exposure level and the risk of developing lung cancer could be demonstrated in a case-control study of employers without silicosis who worked in quarries and in the ceramics industry (Ulm et al., 1999). In summary there is evidence that the incidence of lung cancer increases with increasing cumulative exposure to respirable crystalline silica dust and that the relative lung cancer risk is increased for persons with silicosis.. It is not clear from which exposure value the relative lung cancer risk is increased. The studies differ with respect to exposure levels and durations, with respect to the type of crystalline silica and also the occupational cofounders such as simultaneous exposure to radon. Recently, Steenland et al. (2001) performed dose-response analyses and risk assessment for lung cancer in a pooled cohort of 65 980 silica-exposed workers (44 610 miners and 21 820 non miners) with 1 972 lung cancer deaths observed (663 in miners and 409 in non miners). Categorical analyses by quintile of cumulative exposure showed for miners and not miners the odds ratios and 95% confidence intervals reported in the table. Quintiles of cumulative exposure (mg/m3) <0.07 0.07-0.21 0.21-0.41 0.41-1.36 >1.36 (median 3.75) Odds ratio, (95%CI) Miners 1.0 0.90 (0.66-1.2) 0.81 (0.59-1.1) 1.2 (0.86-1.6) 1.4 (1.0-1.9) Odds ratio, (95%CI) Non-miners 1.0 1.2 (0.92-1.6) 2.1 (1.6-2.8) 1.7 (1.2-2,4) 1.5 (0.97-2.4) Odds ratio, (95%CI) Total 1.0 1.0 (0.85-1.3) 1.3 (1.1-1.7) 1.5 (1.2-1.9) 1.6 (1.3-2.1) They also estimated excess lifetime (through age 75) risk of lung cancer death for workers exposed to various concentrations of respirable crystalline silica for 45 years (age 20-65). For a US worker, at 0.10 mg/m3, resulting in a cumulative exposure of 3.0mg/m3 by age 65, the excess risk above background was 1.7% (95%CI 0.2%-3.6%).The lifetime excess risk at 0.05 mg/m3 (Steenland, 2002), using US rates after 45 years, assuming a 15 year exposure lag, is 1.5% (95% CI 0.2-3.7% ), above a background US rate for the non-exposed of 6%. Exposure limits to reduce silicosis It is widely accepted that a reduction in the prevalence of silicosis can contribute to reducing the cancer risk. In a review of the results of epidemiological studies of silicosis prevalence (WHO 1986) the threshold value suggested for the avoidance of silicosis was a time-weighted average concentration of respirable crystalline silica dust of 0.04 mg/m3 for an 8-hour shift, 40-hour week and 35-year working life. From the results of the studies reviewed by the MAK Commission (Greim 2000), a NOAEL for the respirable crystalline silica dust concentration can be derived, at best in the range below 0.020 mg/m3. This concentration, which is in the range of the detection limit of the currently used analytical method with personal sampling, was obtained mathematically by extrapolation from higher concentrations for shorter exposure periods to a working lifetime of 45 years. Use of a mathematical model without a threshold value predicts that reduction of the concentration of respirable crystalline silica dust to 0.05 mg/m3, measured as the average concentration during 40 years, corresponding to a cumulative exposure level of 2 mg/m3 x years, could reduce the cumulative silicosis risk below that resulting from higher level exposures. The findings of the three extensive studies of cohorts from gold mining (Hnizdo and Sluis-Cremer 1993, Muir et al. 1989a, 1989b, Steenland and Brown 1995a, 1995b) and from the ceramics industry (Cherry et al. 1998) are considered to be particularly meaningful. According to these studies, at a respirable crystalline silica dust concentration of 0.05 mg/m3 the silicosis risk could be kept to about 5 % to 10 %, whereby two of these studies (Hnizdo and Sluis-Cremer 1993, Muir et al. 1989a, 1989b) apply the restrictive exclusion criterion ILO 3 1/1. However, in mortality studies (Davis et al. 1983, McDonald and Oakes 1984 - only gold mines), at this concentration up to 1 % deaths from silicosis were found in each case. The estimated threshold limit values are based on working lifetime doses and thus on long-term exposure values. Therefore, the derived values for risk remain valid when the long-term exposure values are used as shift-related thresholds for which deviations above the threshold up to a factor of 2 are permissible for occasional shifts (DFG 1998). Similar to MAK-Commission, Finkelstein (2000 s. table 1) evaluated the results of a number of studies that investigated silicosis. They showed that the risk of silicosis (ILO category 1/1 or more) following a lifetime of exposure at the current OSHA standard of 0.1 is likely to be at least 5-10%. The exposure-response relation for silicosis looks nonlinear (Hnizdo and Sluis-Cremer 1993), and is probably sigmoidal, as it is for asbestosis (Finkelstein 1982). Lifetime exposure at 0.1 mg/m3 appears to put workers on the supra-linear portion of the exposure-response curve. Reduction of dust exposures would thus have a greater than linear benefit in terms of risk reduction. This evaluation suggests that 30 years exposure at 0.1 mg/m3 might lead to a lifetime silicosis risk of about 25%, whereas reduction of the exposure to 0.05 mg/m3 might reduce the risk to under 5% (Hnizdo and Sluis-Cremer 1993). ACGIH (2000) recommended a TLW-TWA for the alpha-crystalline silica from of crystalline silica of 0.05 mg/m3 as respirable dust on the basis of the data shown in table 2. An appropriate model for the effects of crystalline silica exposure on mortality from "Lung diseases other than cancer" (LDOC) was found to be the linear relative rate model, although the power model using log-transformed cumulative silica exposure performed almost as well (Park et al in press). It was estimated that based on the linear relative rate model, the excess lifetime risk at approximately 0.05 mg/m3 for the cristobalite form of silica was estimated to be over 5 percent. Even exposures at 0.01 mg/m3 may pose a risk, > 1 per 1000. This "Lung disease other than cancer" (LDOC) risk is in addition to the relative risk of lung cancer which has been shown to be increased for workers exposed to this form of silica (Park et al. in press). HSE (2001) based its assessment for risk of developing silicosis on the study of Buchanan et al (2001) s. table 3. The results of this study show a steeply rising non-linear exposure response curve for silicosis, and indicate that periods of average exposure to concentrations 3 2 mg/m3 even for a few months, incur high risks of silicosis. A 15 years exposure to 0.02 mg/m3 respirable crystalline silica results in 0.25% risk of developing silicosis (Category 2/1) 15 years past exposure. Recommendation : The main effect in human of the inhalation of respirable silica dust is silicosis. There is sufficient information to conclude that the relative lung cancer risk is increased in persons with silicosis (and, apparently, not in employees without silicosis exposed to silica dust in quarries and in the ceramic industry). Therefore preventing the onset of silicosis will also reduce the cancer risk. Since a clear threshold for silicosis development cannot be identified, any reduction of exposure will reduce the risk of silicosis. It was observed that the dose-response curve for silicosis appears to be sigmoidal and that maintenance of exposure below 0.05 mg/m3 would avoid being on the steeper part of the doseresponse curve, in the region where relatively small increases in exposure entail significant increases in silicosis risk. The reduction of exposure to 0.05 mg/m3 of crystalline silica is expected to reduce the prevalence of silicosis, ILO category 1/1, to about or less than 5% whereas an average respirable silica concentration of 0.02 mg/m3 reduces prevalence of silicosis to about 0.25 % or less. It arises that a OEL should lie below 0.05 mg/m3 of respirable silica dust. No STEL nor skin notation are needed. Key bibliography: Amandus HE, Castellan RM, Shy C, Heineiman EF, Blair A (1992) Reevaluation of silicosis and lung cancer in North Carolina dusty trades workers. American Journal of industrial medicine, 22:147-153. Amandus HE, Shy C, Wing S, Blair A, Heinemann EF (1991) Silicosis and lung cancer in North Carolina dusty trades workers. Am J Ind Med 20: 57--70 Buchanan D, Miller BG and Soutar CA (2001) Quantitative relationships between exposure to respirable quartz and risk of silicosis at one Scottish colliery. Institute of Occupational Medicine Edinburgh. Unpublished Research Report TM/01/03, an reported in HSE (2001) Burgess GL, Turner S, McDonald JC, Cherry NM (1997) Cohort mortality study of Staffordshire pottery workers: (I) Radiographic validation of an exposure matrix for respirable crystalline silica. Annals of occupational hygiene, 41 (Suppl. 1):403-407. Checkoway H., Heyer NJ, Demers PA, Breslow NE (1993) Mortality among workers in the diatomaceous earth industry. British journal of industrial medicine, 50:586-597. Checkoway H., Heyer NJ, Demers PA, Gibbs GW (1996) Reanalysis of mortality from lung cancer among diatomaceous earth industry workers, with consideration of potential confounding by asbestos exposure. Occupational and environmental medicine, 53:645 647. Cherry NM, Burgess GL, Turner S, McDonald JC (1998) Crystalline silica and risk of lung cancer in the potteries. Occup Environ Med 55: 779--785 Cherry NM, Burgess GL, Turner S, McDonald JC (1997) Cohort study of Staffordshire pottery workers: (II) Nested case referent analysis of lung cancer. Annals of occupational hygiene, 41 (Suppl. 1):408-411. Costello J. Graham WGB (1988) Vermont granite workers' mortality study. American journal of industrial medicine, 13:483-497. Costello J. Castellan RM, Swecker GS, Kullman GJ (1995) Mortality of a cohort of U.S. workers employed in the crushed stone industry, 1940-1980. American journal of industrial medicine, 27:625-640. Davis LK, Wegman DH, Monson RR, Froines J (1983) Mortality experience of Vermont granite workers. Am J Ind Med 4: 705--723 DFG (1988) List of MAK and BAT Values 1998. Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Report No. 34, Wiley-VCH, Weinheim Donaldson K, Borm PJA (1998) The quartz hazard: a variable entity. Ann Occup Hyg 42:287-294 Dong D; Xu G, Sun Y, Hu P (1995) Lung cancer among workers exposed to silica sust in Chinese refractory plants. Scandinavian journal of work, environment and health, 21 (Suppl. 2):69-72. Driscoll KE, Carter JM, Howard BW, Hassenbein D, Janssen YMW, Mossman BT (1998) Crocidolite activates NF-k B and MIP-2 gene espression in rat alveolar epithelial cells. Role of mitochrondrial-derived oxidants. Environ Health Perspect 106: 1171--1174 Finkelstein MM (2000) Silica, Silicosis, and Lung Cancer: A risk assessment. Am J Ind Med 38: 8-18 Finkelstein MM (1982) Asbestos in long-term employees of an Ontario asbestos-cement factory. Am Rev Resp Dis 125: 496-501 Fubini B (1998) Health effects of silica. The surface properties of silicas. In: Legrand AP (Ed) John Wiley, New York Fubini B, Bolis V, Cavenago A, Ugliengo P (1995) Physico-chemical properties of crystalline silica dusts and their possible implication in various biological responses. Scand J Work Environ Health 21: 9--21 Fubini B, Bolis V, Giamello E, Pugliese L, Volante M (1989) The formation of oxygen reactive radicals at the surface of the crushed quatz dusts as a possible cause of silica pathogenicity. In: Mossman BT, Begin RO (Ed) Effects of mineral dusts on cells. NATO ASI Series H30, Springer-Verlag, Berlin, Heidelberg, p 205-214 Greim (2000) Occupational Toxicants, Critical Data Evaluation for MAK Values and Classification of Carcinogens, Vol 14, Wiley-VCH, Weinheim Hnizdo E, Sluis-Cremer GK (1993) Risk of silicosis in a cohort of white South African gold miners. Am J Ind Med 24: 447--457 Hojo S, Fujita J, Yamadori I, Kamei T, Yoshinouchi T, Ohtsuki Y, Okada H, Bandoh S, Yamaji Y, Takahara J, Fukui T, Kinoshita M (1998) Heterogeneous point mutations of the p53 gene in pulmonary fibrosis. Eur Respir J 12: 1404--1408 IARC (International Agency for Research on Cancer) (1997) Silica, some silicates, coal dust and para-aramid fibrils. Lyon: IARC Mongraphs on the evaluation of carcinogenic risks to humans, Vol 68, Lyon Knaapen M, Seiler F, Schilderman PAEL, Nehls P, Bruch J, Schins RPF, Borm PJA (1999) Neutrophils cause oxidative DNA-damage in alveolar epithelial cells. Free Rad Biol Med 27: 234-240 Leigh J, Wang H, Bonin A, Peters M (1998) In vivo genotoxicity of silica evidenced by progressive development of micronuclei in alveolar macrophages. In: Chiyotani K, Hosoda Y, eds. Advances in the prevention of occupational respiratory diseases. Amsterdam, Elsevier Science, pp. 520-525 (Excerptta Medica Supplement 53). Liu X, Keane MJ, Zhong B-Z, Ong T, Wallace WE (1996) Micronucleus formation in V79 cells treated with respirable silica dispersed in medium and simulated pulmonary surfactant. Mutation research, 361:89-94. Liu X, Keane MJ, Harrison JC, Cliento EV, Ong T, Wallace WE (1998) Phospholipid surfactant adborption by respirable quartz and in vitro expression of cytotoxicity and DNA damage. Toxicology letters, 96, 97:77-84. McDonald JC, Burgess GL, Turner S., Cherry NM (1997) Cohort study of Staffordshire pottery workers: (III) Lung cancer, radiographic changes, silica exposure and smoking habit. Annals of occupational hygiene, 41 (Suppl. 1):412-414. McDonald JC, Oakes D (1984) Exposure-response in miners exposed to silica. In: BergbauBerufsgenossenschaft (Ed) Sixth international pneumoconiosis conference 1983, Bochum, Germany, 20-23.9.1983, Meeting Report Wirtschaftsverlag NW, Verlag fur neue Wissenschaft, Bremerhaven: 114-123 McLaughlin JK, Jing-Qiong C, Dosemeci M, Rong-An C, Rexing SH, Zhien W, Hearl FJ, McCawley MA, Blot WJ (1992) A nested case-control study of lung cancer among silica exposed workers in China. British hournal of industrial medicine, 49:167-171. Muir DCF, Shannon HS, Julian JA (1989a) Silica exposure and silicosis among Ontario hardrock miners: I. Methodology. Am J Ind Med 16: 5--11 Muir DCF, Shannon HS, Julian JA (1989b) Silica exposure and silicosis among Ontario hardrock miners: III. Analysis and risk estimates. Am J Ind Med 16: 29--43 Nolan RP, Langer AM, Harington JS, Oster G, Selikoff IJ (1981) Quartz hemolysis as related to its surface functionalities. Environ Res 26: 503--520 Park R, Rice F, Stayner L, Smith R, Glbert S, Checkoway H (in press) Crystallina silica exposure, silicosis and lung disease other than cancer in diatomaceous earth industry workers: in quantitative risk assessment. Partanen T, Pukkala E, Vainio H, Kurppa K, Koskinen H (1994) Increased incidence of lung and skin cancer in Finnish silicotic patients. J Occup Med 36: 616--622 Shi X, Castranova V, Halliwell B, Vallyathan V (1998) Reactive oxygen species and silicainduced carcinogenesis. J Toxicol Environ Health 1: 181--197 Smith AH, Lopipero PA, Barroga VR (1995) Meta-analysis of studies of lung cancer among silicotics. Epidemiol 6: 617--624 Steenland K, Brown D (1995a) Mortality study of gold miners exposed to silica and nonasbestiform amphibole mineral: an update with 14 more years of follow-up. Am J Ind Med 27: 217--229 Steenland K, Brown D (1995b) Silicosis among gold miners: exposure-response analyses and risk assessment. Am J Publ Health 85: 1372-1377 Steenland K, Mannetje A. Boffetta P, Stayner L, Attfield M, Jingqiong Chen, Dosemeci M, DeKlerk N, Hnidzo E, Koskela R, Checkoway H. Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica exposed workers: an IARC multicentre study, Cancer Causes Control 2001;12:773-784. Stenland N.K. (2002) Personal Communication Vallyathan V, Shi X, Castranova V (1998) Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis. Environ Health Perspect 106: 1151--1155 Wang H. Leigh J, Bonin A, Peters M (1997) Silica induced micronuclei in pulmonary alveolar macrophages in vivo. Annals of occupational hygiene, 41 (Suppl. 1):434-439. WHO (1986) Recommended health-based limits in occupational exposure to selected mineral dusts (silica, coal). Technical Report Series 734, WHO, Geneva Zhong B, Whong W., Ong T (1997) Detection of mineral-dust-induced DNA damage in two mammalian cell lines using the alkaline single cell gel/comet assay. Mutation research. 393:181-187. Silicosis Risk Table 1: Summary of Findings from the Silicosis Studies (Finkelstein 2000) Study (and endpoint) Muir (ILO 3 1/1) Hnizdo (ILO 3 1/1) Ng (ILO 3 1/1) Steenland certificate) (Death Kreiss (ILO 3 1/1) Rosenman (ILO 3 1/0) Miller (ILO 3 2/1) Hughes (ILO 3 1/0) Silicosis Risk at 2 mg/m3years cumulative exposure (%) 0.4 5 6 (at least 2 readers) 8 11 2 6 1.1 (low intensity <0.5 mg/m3) 3.7 (High intensity) Silicosis risk at 4 mg/m3 -years cumulative exposure (%) 12 52 15 53 53 10 30 4 (Low intensity) 12 (High intensity) Table 2: Relationship between respiratory silica exposure and risk of silicosis (ACGIH 2000) Study Muir et al. (1989) Graham et al. (1991) Hnizdo and Sluis-Cremer(1993) Steenland & Brown (1995) Kreis and Zhen(1996) Length of Follow-up Since 1st Exposure No follow-up after retirement No follow-up after retirement Yes; Follow-up after retirement Yes; Follow-up after retirement Yes; Follow-up after retirement Average Respirable Silica Concentration in mg/m3 0.1 0.06 0.05 0.01 0.025 to 0.05 Risk of Silicosis 1.2% 0.7% 5% 1% 13% ILO Categor y Used 1/1 1/0 1 / 1 1 / 1 1 / 0 Table 3: Relationship between respiratory silica exposure and risk of silicosis (Buchanan et al 2001) 15 years exposure to respirable crystalline silica mg/m-3 (8-hrTWA) 0.02 0.04 0.1 0.3 Cumulative exposure mg/m-3 years 0.3 0.6 1.5 4.5 Risk of developing silicosis (Category 2/1) 15 years post-exposure 0.25% 0.5% 2.5% 20% CERAME-UNIE BUREAU DE LIAISON DES INDUSTRIES CERAMIQUES EUROPEENNES LIAISON OFFICE OF THE EUROPEAN CERAMIC INDUSTRY Rue des Colonies 18-24 - B-1000 BRUXELLES Tel. +32(0)2 511 30/ 511 70 25 - Fax +32(0)2 511 51 74 - E-mail : sec@cerameunie.net CU/S-02.35 Brussels, 20 December 2002 Comments concerning the SCOEL position for an OEL for respirable crystalline silica (RCS) dusts (SCOFT./SUM/94-final. June 2002) 1. Exposure Limits to Reduce Silicosis. 2. SCOEL's recommendation on page 8 of SCOEL/SUM/94-final that "It arises that an OEL should lie below 0.05mg/m3 of respirable silica dust" appears to be based on the dose(exposure)-response data discussed on pages 6 and 7. The majority of the exposure-response data discussed are derived from studies in which the indicator of silicosis is determined to be a radiographic change of ILO category 1/0 or 1/1 (see tables 1 and 2). In many assessors opinion, see for example UK Health & Safety Executive1, category 1/0 represents only a minor radiographic abnormality, not necessarily indicative of the development of silicosis, and for category 1/1 there is a particularly high degree of inter-reader variability making its assignment unreliable. In contrast, ILO category 2/1 is less subject to reader variability and has been shown to be a more specific indicator of the presence of silicosis in those with a history of occupational exposure to RCS. It is our firm view that SCOEL's recommendation for an OEL for respirable crystalline silica dust should be based on exposure-response data for which the reliable indicator of silicosis is ILO category 2/1. In this case, and adopting the criteria to reduce the prevalence of silicosis to about or less than 5%, an appropriate OEL derived from the most reliable data2, as presented in table 3 of the SCOEL/SUM, would certainly have to be greater than 0.05mg/m3. In this respect we want to point out that existing standards at national level remain considerably above the limit you propose. 3. Variable Biological Potency of Respirable Crystalline SilicaContaining Dusts. On page 3 the SCOEL/SUM notes that "crystalline silica particles of different sources, age and preparation modes differ in their inflammatory potencies", and comments that "Further research will help to better differentiate between the different crystalline silica species and the biological potencies". Other recent reviews1,2 have reached similar conclusions and one1 has gone further by developing a potency matrix. While these conclusions are welcome, it is disappointing that no attempts have been made to quantify potency such that it might be a part of the risk control recommendations. There is little doubt that further research will be necessary to quantify the potency of some RCS-containing dusts, but it is also the case that for many RCS-containing dusts there already exists evidence of low potency. If potency is defined as the magnitude, with respect to dose, of the biological activity, it would be appropriate for regulation to enable an OEL established for a high potency dust to be relaxed for lower potency exposures. A factor of 10 between the limits for highest and lowest potency exposures has been suggested3. For RCS-containing dusts of lower potency than that from which the "reference" OEL is derived, a mechanism to relax the OEL should be provided in risk control regulation. An OEL relaxation might apply only when justified by a clear demonstration of low potency; for example, based on epidemiology for dusts encountered in the heavy clay industry4, or animal studies for devitrified refractory ceramic fibres5,6 . We also feel that (research on) the differentiation between crystalline silica species has to be made before proposing OELs. In our industry the most innocent species of crystalline silica occur; any OEL should take account of such different species in order to do justice to specific circumstances. We object against any OEL proposal which does not take account of the situation occurring in our plants. 4. Detection Limits for Airborne Respirable Crystalline Silica Concentrations. On page 6 the SCOEL/SUM claims that "0.02 mg/m3 (of RCS) is in the range of the detection limit of the currently used analytical method with personal sampling". Personal sampling is carried out using a cyclone attached to a filter cassette, but there are no standard methods, for example CEN or ISO, agreed either in Europe or internationally. Cyclones in common use for respirable dust sampling have flow rates of about 2 litres/min, and, hence, should sample just less than 1 m3 in an 8 hr period. However, as Kenny et al7. reported, there is extensive variation between the performance of sampling instruments, such that the sampling of this volume of air in an 8 hr period cannot be relied upon. If samplers performed reliably at flow rates of 2 litres/min for a RCS concentration of 0.02 mg/m3, they would deposit 20 pg on the filter in an 8 hr sampling period. This mass is above the highest limit of detection for quartz (but not necessarily for other RCS polymorphs or for mixed mineral dusts generated from RCS-containing raw materials) of 10 pg determined by NIOSH2 using XRD or IR Spectrophotometry analytical methods, and, again, there are no internationally agreed, CEN or ISO, analytical methods for determination of RCS Although the claim made in the SCOEL document is theoretically achievable, it does not take account of the need when setting a regulatory concentration level for that level to be reliably and consistently detectable. In this regard NIOSH12, for example, has reported on the efficacy of sampling and analytical methods for measuring concentrations that meet the NIOSH accuracy criterion8. Its report concludes that samplers with flow rates of about 2 litres/min would deliver 8-hr sampled masses enabling a RCS concentration of not less than 0.1 mg/m3 4to5 *b*e determined with acceptable confidence limits, but that a sampler of flow rate 4 litres/min would be required to determine a RCS concentration of 0.05 mg/m3 with acceptable confidence limits. Such samplers are available, although not in common use, but have yet to be validated in laboratory and field trials. Therefore, in conclusion, our summary comments on the SCOEL/SUM recommendation "that a OEL should tie below 0.05 mg/m3 of respirable silica dust" are: The proposed exposure limit has been derived from exposure-response data that depend on an unreliable indicators of silicosis. For the more reliable indicator of ILO category 2/1, an appropriate OEL would have to be considerably greater than 0.05mg/m3. It is disappointing that no attempts have been made to quantify potency such that it might be a part of the risk control recommendations, because for many RCS-containing dusts there already exists evidence of low potency. It is unacceptable that a uniform OEL is proposed for crystalline silica without taking account of the diversity of crystalline silica species occurring in our plants. The recommended OEL cannot be implemented until lower detection limit and greater accuracy sampling and analytical methods are developed and proven, for the wide range of RCS-containing dusts encountered in occupational exposure sampling. We trust SCOEL members will take account of these comments in their further consideration of OELs to be proposed for RCS dusts. 1. Health & Safety Executive; Respirable Crystalline Silica Phase 1 - Variability in fibrogenic potency and exposure-response relationship for silicosis; Hazard assessment document EH75/4; 2002; HSE Books, UK. 2. National Institute for Occupational Safety and Health; Health Effects of Occupational Exposure to Respirable Crystalline Silica; 2002; DHHS (NIOSH) Publication No. 2002-129; NIOSH, Cincinnati, USA. 3. Organisation for Economic Co-operation and Development; Harmonised Integrated Classification System for Human Health and Environmental Hazards of Chemical Substances and Mixtures; 2001; ENV/JM/MONO(2001)6. 4. Love, R.G., Waclawski, E.R., Maclaren, W.M., Wetherill, G.Z., Groat, S.K., Porteous, R.H. & Soutar, C.A.; Risks of respiratory disease in the heavy clay industry; Occup. Environ. Med., 1999, vol 56, pp 124-133. 5. Bunn, W.B., Bender, J.R., Hesterberg, T.W., Chase, G.R. & Konzen, J.L.; Recent studies of man-made vitreous fibres - Chronic animal inhalation studies; J. Occup. Med., 1993, vol 35, pp 101-113. 6. Jones, A.D., Miller, B.G., Searl, A., Soutar, C.A., Bolton, R.E., Buchanan, D., Cullen, R.T., Davis, J.M.G. & Donaldson, K.; Man Made Mineral Fibre Biopersistence and Carcinogenicity; 1998; Report No. TM/98/01; institute of Occupational medicine, Edinburgh, UK. 7. Kenny, L.C., Aitken, R., Chalmers, C., Fabries, J.F., Gonzalez-Fernandez, E., Kromhout, H., Liden, G., Mark, D., Riedeger, G. & Prodi, V.; A collaborative European study of personal inhalable aerosaol sampler performance; Ann. occup. Hyg., 1997, vol 41, pp 135-153. 8. National Institute for Occupational Safety and Health; Guidelines for Air Sampling and Analytical Method Development and Evaluation; 1995; DHHS (NIOSH) Publication No. 95-117; NIOSH, Cincinnati, USA.