BIOPERSISTENCE OF INSULATION GLASS FIBRES

Transcription

1 r ergamoil Ann. occup. Hyg., Vol. 41, Supplement 1, pp , British Occupational Hygiene Society Published by Elsevier Science Ltd. All rights reserved Printed in Great Britain /97 $ Inhaled Particles V1I1 PII: S (96)00049-X BIOPERSISTENCE OF INSULATION GLASS FIBRES M. A. Moore,* L. M. Hanna,t D. M. Grumm,t P. Turnham,t C. P. Yu$ and G. A. Jubb *Morgan Crucible Company pic, Windsor, U.K.; fsciences International Inc, Alexandria, Virginia, U.S.A.; ^State University of New York, Buffalo, New York, U.S.A.; and Morgan Materials Technology Ltd, Bewdley Road, Stourport-on-Severn DY13 8QR, U.K. INTRODUCTION Insulation fibres, often referred to as man-made vitreous fibres (MMVFs), are silicate glasses, widely employed in buildings, land, marine and air transport, consumer goods and industrial process equipment. The potential hazard to human health posed by respirable fibrous dust from these materials has been the subject of extensive scientific investigation and debate. Although the scientific issues are complex, toxicologists agree that the potential hazard depends on the lung burden of long, thin fibres (WHO, 1994). The lung burden (that is dose) of such fibres is determined by exposure time and airborne respirable fibre concentration and by the biopersistence of fibres in the lung. A direct measure of biopersistence is obtained from fibre clearance rates following a single or short-term administration of the fibre. Fibre solubility measured in vitro has been used as a surrogate for fibre biopersistence, but solubility is an incomplete descriptor of the relevant fibre properties determining biopersistence. Studies following the administration of fibres by inhalation (Bernstein, 1996), or intratracheal (IT) instillation (Bellmann and Muhle, 1995), have shown that, in addition to generally faster clearance rates for higher solubility fibres, fibres longer than 20 [Am may clear faster than shorter fibres (Fig. 1). Hypotheses to explain this disparity invoke either preferential breakage or preferential dissolution of long fibres in contrast to the macrophage-mediated clearance rate of shorter fibres (Morris et al., 1995; Bernstein et al., 1995; Eastes and Hadley, 1995, 1996). Preferential dissolution alone of long fibres is unable to account for observations in animals that the mean diameter of fibres recovered from the lungs may change little with residence time, whereas there is very rapid clearance of long fibres immediately post-administration accompanied by a short-term increase in the number of fibres < 20 urn in length (Bernstein et al., 1995; Bellmann and Muhle, 1995), (Fig. 2). Additionally, the observed clearance rates for long fibres are much faster than the times required for complete dissolution, estimated from in vitro dissolution rates (Christensen et al., 1994; Eastes and Hadley, 1995). Evident from in vivo and in vitro studies is that MMVFs are susceptible to local chemical attack and to preferential leaching of certain phases and constituents, which are detrimental to the strength and toughness of silicate glasses (Paul, 1990). 312

2 Biopersistence of insulation glass fibres 313 1,000 (0 (0 T3 i 3. O CM A -ongf : ibres I Short Fibres (5 jm<l<20 jm) T!4 - days Fig. 1. Comparison of in vivo clearance half-lives from rat lungs of long (> 20 \un) and short (5-20 nm) mineral fibres, inhalation; + IT instillation. Data from Bernstein (1996), for inhalation and Bellmann and Muhle (1995), for IT instillation. 0) Post Exposure Time - days Fig. 2. Early post exposure changes in number of fibres of length > and < 20 urn and mean fibre diameter for MMVFIO recovered from rat lungs after inhalation, - - number of fibres 720 /xm, + number of fibres < 20 /u.m, * mean fibre diameter. Data from RCC/TIMA study. 100

3 314 M. A. Moore et al. Glasses are brittle materials, having very limited plasticity, which fail (break) at stresses much lower than their theoretical strength because of the presence of inherent flaws. They fail catastrophically when the stress intensity at a flaw, which is proportional to o.a 1/2, where a is the applied stress and a is the flaw size, reaches a critical value. Additionally, in aqueous environments silicate glasses demonstrate time-dependent failure at stresses below their catastrophic fracture strength; a phenomenon known as stress-corrosion cracking and illustrated in Fig. 3 (Wiederhorn and Bolz, 1970), for three glasses having very similar catastrophic fracture strengths, but for which the stress-corrosion effect is most pronounced in the more chemically active soda-lime glass. The mechanism of stress-corrosion failure in glasses involves ion exchange and, therefore, depends on the availability of exchangeable cations present as silicate network modifiers (typically the alkali and alkaline earth metals), the ph and the kinetics of ion exchange. The effect on failure time of ph depends on glass composition as shown in Fig. 4 (Wiederhorn and Johnson, 1973). The time to failure for silicate glasses, at a specific sub-critical stress, is described by: where v, is the initial crack velocity, a t is the initial flaw size (usually the depth of a surface flaw) and (3 depends on glass chemistry and the environment. The initial crack velocity v, oc exp(p.o.a^), where o is the applied stress. Values of v, in glasses typically range from less than 10~ 10 m.s." 1 to greater than 10~ 4 m.s" 1, depending on the applied stress, initial flaw size, specific glass and the environment. As the flaw enlarges by sub-critical growth the crack velocity increases, until the flaw size is large enough to satisfy the criterion for catastrophic failure, which is: K IC = o(n.a)», where K IC (the materials-dependent critical stress intensity factor) for silicate glasses has a value of ~ 1 MN.m~ 3/2. The cumulative probability of catastrophic failure, POF, as a function of applied stress, is determined by the statistical distribution of flaw sizes, which is a feature of all glases, such that: POF = 1 - exp-(o/o n ) w, where m is known as the Weibull modulus, with a value which increases as the flaw size distribution decreases (typically in the range 5-15 for glasses) and o n is a normalising stress (usually taken to be the mean of the failure stress distribution and, therefore, a material property). Thus, if breakage of long fibres is a significant contributory mechanism, the clearance rate should be a function of the stress on the fibre and of time. Assuming that long fibres in the lung are subject to bending forces, F, the stress on the fibre is: F.l.d -3

4 Biopersistence of insulation glass fibres Failure Time - days Fig. 3. Time dependent failure of glasses in distilled water, silica, aluminosilicate, soda-lime. After Wiederhorn and Bolz (1970). Silica glass 99.8%; aluminosilicate 57% silica, 20% alumina; soda-lime 72% silica, 14% soda, 7% calcia. <L> a: 1, Solution ph Fig. 4. Time dependent failure of glasses in aqueous solutions of different ph, silica, - soda-lime. After Wiederhorn and Johnson (1973). Silica glass 99.8%; soda-lime, 72% silica, 14% soda, 7% silica.

5 316 M. A. Moore et al Exposure Time - hrs Fig. 5. Time dependent breakage of a glass fibre exposed to simulated body fluid. After Bauer (1995). where / and d are the fibre length and diameter, respectively. Bauer (1995) has demonstrated in vitro time-dependent fracture of a silicate glass fibre exposed to simulated body fluid, (Fig. 5). The cumulative probability of failure, the number of ends per initial fibre in his data, may be represented as an exponential function of time for the early stages of exposure (up to 400 h). This is consistent with the general equations for glass failure if the applied stress were less than the critical stress to cause catastrophic failure at the largest flaw present at time zero, but sufficient to provide failure of many of the fibres within a few hundred hours by sub-critical crack growth. Combining the principles of the sub-critical time to failure equation with the cumulative probability of failure equation and subsuming fibre diameter distribution with flaw size distribution, we have curve fit > 20 um long fibre clearance data for MMVFs 10, 11, 21 and 22 (RCC/TIMA durability studies post inhalation by rats) to expressions of the form: POF = 1 - NJN 0 = 1 - exp-b(0-/, where N t and JV 0 are the number of fibres of length / at time t and time 0, respectively (Fig. 6). We have found that the time-dependent coefficients b(f), determined from these fits, are best described by the kinetic expression commonly known as the Michaelis-Menten equation:

6 Biopersistence of insulation glass fibres Fibre Length - jm Fig. 6. Cumulative probability of failure against fibre length curve fits at various post exposure times for MMVF10. 5 days curve fit, O 5 days data; 31 days curve fit, * 31 days data; - 91 days curve fit, 91 days data; 546 days curve fit, O 546 days data. b(0 = Q>.t/(Ci + t), where C x is the kinetic half-life to reach one half the maximum C o, as shown in Fig. 7. Values of C o and C x for each MMVF are given in Table 1. The small differences in the C o values for the four fibres are consistent with fibre failure rates after long periods being both low and relatively independent of the initial fibre properties when most of the glass network modifiers have been depleted, whereas the differences in the Q values are consistent with early post-administration fibre failure rates being both high and dependent on fibre properties. Specifically, C\ values rank with measured in vitro fibre dissolution rates at near-neutral ph (Fig. 8); this correlation is not because dissolution itself is causing fibres to fail, but because dissolution rate is a measure of ion exchange kinetics. Thus, the most soluble and chemically active fibres, MMVF 10 and 11, have the lowest C l values and highest early fibre breakage rates, or shortest time to failure, consistent with the general stress-corrosion failure of glasses discussed earlier. It is reasonable to assume that long fibres start to break by this mechanism immediately post-deposition, providing an "apparent" early and rapid clearance, although the fragments will remain to be cleared by other mechanisms, such as complete dissolution or phagocytosis, and may include further breakage. At long postdeposition times the analysis indicates that some long fibres may remain; the cumulative probability of failure is less than 1, determined by the C o coefficient, but approaches 1 more closely for the longest fibres. This suggests that a few fibres neither have a large enough sub-critical flaw to fail, nor do they disappear by complete dissolution, within several hundreds of days post deposition.

7 318 M. A. Moore et al Q) 'o i o o Time, t - days Fig. 7. The time dependence of the cumulative probability of failure (POF) of fibres of length /, b(0 in the equation POF = 1 - exp-b(t)./. MMVF10, MMVF11, MMVF21, - MMVF22. Many chemically active fibres do not dissolve in the lungs in a uniform and congruent manner, but rather the silicate network modifiers are leached from the structure leaving a residual skeletal form which may be similar in dimensions to the original fibre, Bauer (1995). If such fibres do not fail during depletion of the glass network modifiers, the remaining, relatively insoluble silicate skeletal structure will be resistant to both stress-corrosion failure and to complete dissolution. The analysis suggests that the biopersistence of long fibres depends on general or local dissolution providing the ion exchange for stress-corrosion cracking, thereby increasing the probability of failure. Hence, clearance rates are not alternately described by either dissolution or simple mechanical breakage, but rather by a process integrating these two mechanisms, both of which are time-dependent. In the case of the MMVFs studied, the relatively small change in diameter suggests that stress-corrosion failure of the fibres dominates, whereas other fibres may be more resistant to stress-corrosion failure and may dissolve, resulting in diameter reduction leading to complete disappearance of the fibre or to increased Table 1. Comparison of C o and C\ coefficients Fibre type MMVF10 MMVF11 MMVF21 MMVF22 Co C x

8 Biopersistence of insulation glass fibres 319 DQ Dissolution Rate - ng/cm 2 /hr Fig. 8. The half-life for time-dependent long fibre breakage (coefficient Cl) correlated to in vitro dissolution rate for MMVFs 10, +; 11, ; 21, #; and 22, *. Dissolution rates are NAIMA values. probability of breakage. We are currently undertaking analysis of other fibre types to understand these phenomena in terms of specific fibre properties. REFERENCES Bauer, J. F. (1995) Glass Fiber in the Lung A Materials Science Perspective. Meeting of the American Ceramic Society, New Orleans. Bellmann, B. and Muhle, H. (1995) Biopersistence of Various Types of Mineral Fibres in the Rat Lung after Intratracheal Application. Bundesanstalt fur Arbeitsschutz, Dortmund. Bernstein, D. M. (1996) RCC study results presented at various European regulatory meetings. Research and Consulting Co. Ltd, Geneva. Bernstein, D. M., Morscheidt, C, Tiesler, H., Grimm, H-G., Thevenaz, P. and Teichert, U. (1995) Evaluation of the biopersistence of commercial and experimental fibers following inhalation. Inhal. Toxicol. 7, Christensen, V. R., Lund Jensen, S., Guldberg, M. and Kamstrup, O. (1994) Effect of chemical composition of man-made vitreous fibers on the rate of dissolution in vitro at different phs. Environ. Health Perspect. 102 (suppl. 5), Eastes, W. and Hadley, J. G. (1995) Dissolution of fibers inhaled by rats. Inhal. Toxicol. 7, Eastes, W. and Hadley, J. G. (1996) A mathematical model of fiber carcinogenicity and fibrosis in inhalation and intraperitoneal experiments in rats. Inhal. Toxicol. 8, Morris, K. J., Launder, K. A., Collier, C. G. and Morgan, A. (1995) In Vivo and In Vitro Comparisons of the Dissolution of Calcium Magnesium Silicate Fibres. 5th Int. Inhalation Symp., Hanover. Paul, A. (1990) Chemistry of Glasses, 2nd edn. Chapman and Hall, London. WHO (1994) Validity of Methods for Assessment of Carcinogenicity of Fibres. WHO European Regional Office, Copenhagen. Wiederhorn, S. M. and Bolz, L. H. (1970) Stress corrosion and static fatigue of glass. J. Am. Ceram. Soc. 53, Wiederhorn, S. M. and Johnson, H. (1973) Effect of electrolyte ph on crack propagation in glass. /. Amer. Ceram. Soc. 56,