Single Intratracheal Quartz Instillation Induced Chronic Inflammation and Tumourigenesis in Rat Lungs.

Crystalline silica (quartz) is known to induce silicosis and cancer in the lungs. In the present study, we investigated the relationship between quartz-induced chronic inflammation and lung carcinogenesis in rat lungs after a single exposure to quartz. F344 rats were treated with a single intratracheal instillation (i.t.) of quartz (4 mg/rat), and control rats were treated with a single i.t. of saline. After 52 or 96 weeks, the animals were sacrificed, and the lungs and other organs were used for analyses. Quartz particles were observed in the lungs of all quartz-treated rats. According to our scoring system, the lungs of rats treated with quartz had higher scores for infiltration of lymphocytes, macrophages and neutrophils, oedema, fibrosis, and granuloma than the lungs of control rats. After 96 weeks, the quartz-treated rats had higher incidences of adenoma (85.7%) and adenocarcinoma (81.0%) than control rats (20% and 20%, respectively). Quartz-treated and control rats did not show lung neoplastic lesions at 52 weeks after treatment. The number of lung neoplastic lesions per rat positively correlated with the degree of macrophage and lymphocyte infiltration, oedema, fibrosis, and lymph follicle formation around the bronchioles. In conclusion, single i.t. of quartz may induce lung cancer in rat along with chronic inflammation.

The use of Argentum-Quartz® solution in primary or recurrent perianal fistulas: first experience on three cases.

Primary perianal fistulous pathology represents a painful condition often noticeable in patients affected by Crohn's disease or Ulcerative colitis. It causes difficult defecation and can evolve in perianal abscess that should be urgently ascertained and drained. The present work aims to propose Argentum-Quartz® as valid non-surgical therapeutic treatment in order to reach a more comfortable perianal fistula healing. In fact, our preliminary data allow us to consider Argentum Quartz® ideally employable for treatment of perianal fistulas associated or not with IBDs, representing a reliable sphincter-sparing solution.

Organosilane-Based Coating of Quartz Species from the Traditional Ceramics Industry: Evidence of Hazard Reduction Using In Vitro and In Vivo Tests.

The exposure to respirable crystalline silica (RCS), e.g. quartz, in industrial settings can induce silicosis and may cause tumours in chronic periods. Consequently, RCS in the form of quartz and cristobalite has been classified as human lung carcinogen category 1 by the International Agency for Research on Cancer in 1997, acknowledging differences in hazardous potential depending on source as well as chemical, thermal, and mechanical history. The physico-chemical determinants of quartz toxicity are well understood and are linked to density and abundance of surface silanol groups/radicals. Hence, poly-2-vinylpyridine-N-oxide and aluminium lactate, which effectively block highly reactive silanol groups at the quartz surface, have formerly been introduced as therapeutic approaches in the occupational field. In the traditional ceramics industry, quartz-containing raw materials are indispensable for the manufacturing process, and workers are potentially at risk of developing quartz-related lung diseases. Therefore, in the present study, two organosilanes, i.e. Dynasylan® PTMO and Dynasylan® SIVO 160, were tested as preventive, covalent quartz-coating agents to render ceramics production safer without loss in product quality. Coating effectiveness and coating stability (up to 1 week) in artificial alveolar and lysosomal fluids were first analysed in vitro, using the industrially relevant quartz Q1 as RCS model, quartz DQ12 as a positive control, primary rat alveolar macrophages as cellular model system (75 µg cm-2; 4 h of incubation ± aluminium lactate to verify quartz-related effects), and lactate dehydrogenase release and DNA strand break induction (alkaline comet assay) as biological endpoints. In vitro results with coated quartz were confirmed in a 90-day intratracheal instillation study in rats with inflammatory parameters as most relevant readouts. The results of the present study indicate that in particular Dynasylan® SIVO 160 (0.2% w/w of quartz) was able to effectively and stably block toxicity of biologically active quartz species without interfering with technical process quality of certain ceramic products. In conclusion, covalent organosilane coatings of quartz might represent a promising strategy to increase workers' safety in the traditional ceramics industry.

Computer-automated silica aerosol generator and animal inhalation exposure system.

Inhalation exposure systems are necessary tools for determining the dose response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this study was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of uniformly dispersed airborne silica particles. An acoustical aerosol generator was developed which was capable of re-suspending particles from bulk powder. The aerosolized silica output from the generator was introduced into the throat of a venturi tube. The turbulent high-velocity air stream within the venturi tube increased the dispersion of the re-suspended powder. That aerosol was then used to expose small laboratory animals to constant aerosol concentrations, up to 20 mg/m(3), for durations lasting up to 8 h. Particle distribution and morphology of the silica aerosol delivered to the exposure chamber were characterized to verify that a fully dispersed and respirable aerosol was being produced. The inhalation exposure system utilized a combination of airflow controllers, particle monitors, data acquisition devices and custom software with automatic feedback control to achieve constant and repeatable exposure environments. The automatic control algorithm was capable of maintaining median aerosol concentrations to within ±0.2 mg/m(3) of a user selected target concentration during exposures lasting from 2 to 8 h. The system was able to reach 95% of the desired target value in <10 min during the beginning phase of an exposure. This exposure system provided a highly automated tool for conducting inhalation toxicology studies involving silica particles.

Argentum-quarz solution in the treatment of anorectal fistulas: is it possible a conservative approach?

Patients suffering from chronic intestinal diseases (Crohn's disease, Ulcerative Colitis, Indeterminate Colitis) are prone to the development of pyogenic complications. These complications are most commonly in the form of perianal or intraabdominal abscesses and/or fistulas. The treatment of these complications are managed differently but, after an initial treatment based on medical or minimally invasive management, the solution of the pathological condition is always achieved by a surgical procedure. In the last few years prospective studies have proposed an alternative conservative therapeutic approach based on application of fibrin glue in the healing of patients with fistulas-in-ano. In this paper we suggest and discuss the therapeutic potential of silver and quarz in the conservative treatment of anorectal fistulas pointing out their role in modulating particular steps of the pathogenetic process which characterizes this pathological condition.

Acute and subchronic airway inflammation after intratracheal instillation of quartz and titanium dioxide agglomerates in mice.

This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compounds were the two micro-size reference quartzes, SRM1878a and DQ12, a micro- and nano-size rutile titanium dioxide (TiO2), a nano-size anatase, and an amorphous TiO2. Particles were administered by a single i.t. instillation in mice at a fixed dose of 5, 50, and 500 micrograms, respectively. Inflammation was evaluated from the bronchoalveolar lavage fluid (BALF) content of inflammatory cells, the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), as well as from lung histology. Evaluations were at 24 h (acute effects) and 3 months (subchronic effects) after instillations. Both types of quartz induced a dose-dependent acute increase of neutrophils, IL-6, and total protein in BALF. Limited subchronic inflammation was observed. All types of TiO2 induced a dose-dependent acute increase of neutrophils in BALF. In the acute phase, micro- and nano-size rutile and nano-size amorphous TiO2 induced elevated levels of IL-6 and total protein in BALF at the highest dose. At the nano-size rutile and amorphous TiO2, subchronic lung inflammation was apparent from a dose-dependent increase in BALF macrophages. Histology showed little inflammation overall. The two types of quartz showed virtually similar inflammatory effects. Nearly similar effects were observed for two sizes of rutile TiO2. Differences were seen between the different polymorphs of nano-size TiO2, with rutile being the most inflammogenic and amorphous being the most potent in regard to acute tissue damage.

Toxicity of a quartz with occluded surfaces in a 90-day intratracheal instillation study in rats.

This 90-day study was aimed at characterizing the differences in biological activity between a crystalline ground reference quartz (DQ12) and a quartz with occluded surfaces (quartz isolate) obtained from a clay deposit formed 110 to 112 million years ago. In different test groups, rats were dosed with the same total mass and quartz level by intratracheal instillation, with a total high dose of 15.2 mg/kg (body weight, bw) or approximately 4.7 mg/rat of each quartz species in a saline suspension. The reference quartz was mixed with titanium dioxide to achieve a positive control mixture, which contained the same quartz content as in the quartz isolate. At 3 days post dosing, both quartz groups showed a significant inflammatory response based on total and differential cell counts from bronchoalveolar lavageate (BAL) analysis. At 28 and 90 days, the quartz isolate values were no longer statistically different from vehicle control group values; however, the positive control group values were approximately 12 and 65 times greater than those of the control group, respectively. After 28 days, histopathological evaluation showed moderate effects in the quartz isolate group compared to the saline control animals. These effects did not progress in severity at 90 days. In contrast, the positive control group exhibited more severe effects than the quartz isolate group and these effects showed a progression to a persistent and self-perpetuating inflammatory state. The toxicological properties of quartz particles can vary significantly dependent on their surface characteristics. Toxicity can range from a high-dose-induced, modest, transient inflammation from quartz with occluded surfaces, to a severe and persistent inflammatory state caused by ground quartz with fractured surfaces.

Physicochemical and mineralogical characterization of test materials used in 28-day and 90-day intratracheal instillation toxicology studies in rats.

Two recent intratracheal instillation toxicology studies in rats clearly show that a naturally occurring quartz, with occluded crystal surfaces (quartz isolate), produced significantly less inflammatory response than a crushed reference quartz (DQ12). Respirable-size quartz isolate was isolated from bentonite parent rock, without crushing or the use of chemicals, to ensure that the surface properties of the quartz particles were unaltered. The isolation technique utilized gentle mechanical dispersion followed by sedimentation in an aqueous medium. Extensive mineralogical and chemical characterizations were undertaken to define the physicochemical properties of the test materials. The characterizations showed significant, measurable physicochemical differences between the two quartz types. These differences may help to explain the difference in toxicological response associated with these materials. The evaluation methods and resulting data that characterized the chemical and physical properties of the instillation test materials are discussed. The data presented show that such characterizations are essential if meaningful correlations are to be made between test materials and their toxicological profiles.

Bioassay by intratracheal instillation for detection of lung toxicity due to fine particles in F344 male rats.

We have established and documented an in vivo bioassay for detection of hazards with intratracheally instilled fine particles, which can be used for risk assessment of toxicity of materials inhaled into deep lung tissue of humans (Yokohira et al. Establishment of a bioassay system for detection of lung toxicity due to fine particle instillation: sequential histopathological changes with acute and subacute lung damage due to intratracheal instillation of quartz in F344 male rats. J Toxicol Pathol 2005;18:13-8). For validation we here examined toxicity of fine particles from quartz, hydrotalcite, potassium octatitanate, palladium oxide and carbon black with this bioassay. A total of 108, 10-week-old F344/DuCrj male rats were randomly divided into 8 groups. Groups 1 to 5 underwent intratracheal instillation of the 5 test particles (4 mg/rat) suspended in 0.2 ml vehicle (saline or 10% propylene glycol and 1% sodium carboxymethyl cellulose in saline: PG-CMC) with a specially designed aerolizer, and subgroups of 7 rats were killed on Days 1 and 28 thereafter. Groups 6 and 7 similarly were exposed to saline and PG-CMC, respectively, as vehicle controls, while group 8 was maintained untreated. Using histopathological changes and immunohistochemically assessed bromodeoxyuridine (BrdU) labeling indices, inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3) levels as end points, the quartz treated group exhibited high toxicity, while the values for the other particle-treated groups pointed to only slight effects. Although additional efforts are needed to establish advantages and disadvantages with our bioassay, models featuring intratracheal instillation clearly can be useful for detection of acute or subacute lung toxicity due to inhaled fine particles by using histopathological scoring and markers like BrdU and iNOS for screening purposes in short-term studies.

Inflammatory effects of respirable quartz collected in workplaces versus standard DQ12 quartz: particle surface correlates.

In 1997, the IARC (International Agency for Research on Cancer) reevaluated its quartz classification from a class 2 carcinogen, to that of a class 1, stating sufficient evidence for carcinogenicity in both humans and experimental animals. However, tumor development did not occur across all occupational settings. It is probable that this is due to the considerable differences in toxicity between workplace quartz in comparison to quartz used in experimental studies. We therefore hypothesized that workplace quartz samples differ in toxicity from standard experimental quartz samples at equal mass. To test this hypothesis we compared 2 workplace quartz samples (RH1 and OM) with standard experimental quartz (DQ12) in several assays commonly used in particle toxicology. The sizes of the quartz samples were as closely matched as possible. The endpoints of this study were inflammation in the rat lung following intratracheal instillation (1000 microg or 250 microg for 3 or 14 days), release of soluble iron, cytotoxicity to cells in culture, and surface reactivity as assessed by hemolysis and ESR. The workplace samples did not cause inflammation at any dose or time point. DQ12 quartz caused marked inflammatory responses, as measured by an increased number of neutrophils in the lungs of instilled animals for both time points and doses. Protein in the bronchoalveolar lavage also increased in animals exposed to DQ12 but not the workplace samples. In vitro, DQ12 had the greatest hemolytic activity but only RH1 released substantial amounts of soluble iron. The increased inflammogenicity of DQ12 was not wholly explained by a greater surface area, by diameter, or by releasable iron. The hemolytic activity of DQ12, while not being informative in terms of understanding the mechanism of carcinogenicity, was the best in vitro predictor for in vivo activity. Therefore the surface reactivity of DQ12 appears to drive its inflammogenicity.

Clara-cell hyperplasia after quartz and coal-dust instillation in rat lung.

Bronchiolo-alveolar hyperplasia of type II cells in rat lungs after particle exposure is a well-known preneoplastic lesion. The Clara cell, stem cell of the bronchiolar epithelium and the main carrier of cytochrome P-450 isoenzyme system in the lung, has barely been evaluated with regard to this effect. The aim of this study was to examine Clara-cell hyperplasia after particle exposure and to characterize cell proliferation and its normal function. Female Wistar rats were intratracheally instilled with coal dust samples of variable quartz content, quartz (DQ12), titanium dioxide, or saline solution containing 0.5% Tween 80. After 126-129 wk, all coal mine dust- and quartz-exposed animals developed Clara-cell hyperplasia: up to 0.48% of the total lung area, which was significantly increased compared to titanium dioxide (p <.05) and control (p <.03) animals. Proliferation and hyperplasia of bronchiolar Clara cells by coal dusts was independent of their quartz content. The lack of proliferating cell nuclear antigen staining in most of the hyperplastic Clara cells suggests that following damage of alveolar epithelial cells, Clara cells migrate in and remodulate the alveolar epithelium. After the migration they keep their function in the xenobiotic metabolism, as shown by expansion of CYP2E1 active Clara cells. The minor development of Clara-cell hyperplasia in titanium dioxide-treated rats indicates that this is not a general particle effect, and is possibly due to its lower toxicity to epithelial cells.

Evidence of a no-effect level in silica-induced rat lung mutagenicity but not in fibrogenicity.

Exposure to silica can lead to fibrosis and the development of lung tumors in the rat. Based on these animal studies and on epidemiological data, silica has been classified as a human carcinogen. The initial mechanisms have not been finally clarified, but particle-induced tumor formation is at least closely associated with inflammation, the production of reactive oxygen species (ROS) and DNA damage. We investigated the dose-dependent effects of silica on the formation of the major DNA oxidation product 8-oxoguanine (8-oxo-Gua) in rat lung cells, on p53 (p53) and p53 mutant protein (p53 mut) synthesis, as well as on the amount of the surfactant phospholipids phosphatidylinositol (PI) and phosphatidylglycerol (PG) in the bronchoalveolar lavage fluids (BALF) as indicators of fibrotic processes in the lung. Rats were exposed by intratracheal instillation to various amounts of DQ12 quartz (0.15, 0.3, 0.6, 1.2, 2.4 mg/animal) and lungs were investigated after 21 and 90 days. PG decreased and PI increased quartz dose dependently. 8-oxoGua was significantly increased only after 1.2 and 2.4 mg quartz/animal. Cells expressing p53 protein were increased at 1.2 and 2.4 mg, p53 mutant protein only at 2.4 mg/animal. This indicates a no-effect level for mutagenicity at a low, but still fibrogenic quartz exposure.

Effects of quartz addition on the mechanochemical dechlorination of chlorobiphenyl by using CaO.

Grinding a mixture of 3-chlorobiphenyl (BP-Cl) and CaO with or without the addition of quartz was conducted in air by a planetary ball mill to investigate the mechanochemical dechlorination of BP-Cl. The dechlorinating reaction proceeds with an increase in grinding time, and over 99% of BP-Cl is decomposed at 360 min. Washing the ground sample with different solvents results in different products. Addition of quartz to the grinding mixture facilitates dechlorination efficiency, especially in the case of a high weight ratio of BP-Cl to CaO.

Rat alveolar and interstitial macrophages in the fibrosing stage following quartz exposure.

Exposure to quartz induces pulmonary inflammation and development of fibrosis. In order to study the fibrosing process, we investigated morphology, function and phenotype of alveolar (AMs) and interstitial (IMs) macrophages at an early stage of fibrosis in rats. Rats were exposed by intratracheal instillations of 10 mg quartz (n=8) or saline (n=8) and studied 3 months later. AMs were obtained by bronchoalveolar lavage and IMs by mechanical fragmentation, followed by enzymatic digestion of lung tissue. Histology revealed subacute silicosis, with early focal fibrosis and alveolar lipoproteinosis. AM quartz exposure increased phagocytic activity and expression of major histocompatibility complex (MHC) Ia antigens, the latter being associated with cellular antigen presenting capacity. IM had an even more pronounced expression of MHC than AM after quartz exposure. Both macrophage fractions had a higher expression of OX-42 (complement receptor 3, CR3) than controls, but the increase in the IM fraction might be explained by the remaining AM in the IM fraction. Exposed AM adhered less to extracellular matrix components (vitronectin and fibronectin) than controls. In contrast, the adhesion of IM to vitronectin increased after exposure. Besides increased adhesion, the effects on IM were scarce. Our results therefore do not support the hypothesis that IM has a key role in the process of inflammation, including fibrosis.

Intratracheal instillation of zinc-cadmium sulfide (ZnCdS) in Fischer 344 rats.

The purpose of this study was to assess the bioavailability and pulmonary toxicity of ZnCdS in rats. Groups of 30 male Fischer 344 rats each were anesthetized and dosed via intratracheal instillation with 5 mg of either ZnCdS, quartz (positive control), or titanium dioxide (TiO(2), negative control) suspended in 0.5 ml saline. A vehicle control group received 0.5 ml saline. Ten animals from each test group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for bronchoalveolar lavage fluid (BALF) analysis and histopathology. The BALF was analyzed for alkaline phosphatase, acid phosphatase, lactate dehydrogenase (LDH), beta-glucuronidase (beta-glu), total protein, and cell counts. Two separate groups of 24 rats each were dosed as already described with either ZnCdS or saline. Eight rats from each group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for determination of cadmium (Cd) and zinc (Zn) concentrations in the lung, liver, kidney, and blood. Results indicate that at 1 day after dosing, all enzyme activities (except acid phosphatase) and cell counts in BALF from the quartz and ZnCdS groups were significantly higher than in the TiO(2) and saline groups. At 7 days after dosing, high enzyme activity persisted in the quartz group, while the ZnCdS group showed only LDH and total protein levels significantly higher than the saline group. At 14 wk after dosing, LDH, total protein, beta-glu, and cell counts in the quartz group were significantly higher than all other groups. Histologic examination revealed interstitial inflammation and accumulation of foreign material in the lungs and mediastinal lymph nodes of quartz-, TiO(2)-, and ZnCdS-treated rats. Metal analyses in tissues showed profuse Cd and Zn concentrations in the lung 1 day after dosing, followed by a successive decline at 7 days and 14 wk after dosing. A very small, but statistically significant, amount of Cd and Zn was found in the kidneys at 14 wk after dosing. In conclusion, ZnCdS appears to cause temporary lung inflammation, is cleared slowly, and is poorly bioavailable.

Pulmonary histopathology and alteration in cellular pattern of bronchoalveolar lavage fluid in experimental silicosis.

Pathogenesis of silicosis is still being evaluated. Cellular and histopathological changes in lung following acute and chronic exposure of quartz in rats have been investigated. Inbred wistar rats were given single intratracheal injection of quartz (10 mg in 0.05 ml saline) in groups of acute model, and inhalation of quartz (40 mg/m3 with air flow 5 l/hr in a simulation chamber, 6 hr/day) in groups of chronic model. The control groups were exposed to vehicles only. Rats were sacrificed on day 3, 5 and 7 of intratracheal injection and after 2, 4 and 8 weeks of inhalation. Total and differential cell counts (TC and DC) were performed in bronchoalveolar lavage fluid (BALF). Histopathology was done in the lungs. There was significant (P < 0.001) increase in TC and significant (P < 0.001) changes in percentage of inflammatory cell counts on DC in the BALF of silicotic rats. Histopathology showed progressive inflammatory and fibrotic response in quartz exposed lungs in both acute and chronic models. The results indicate duration dependent inflammatory changes in lungs of both the models. Changes in cell counts precede the histopathological changes and may serve as early biological marker for detection of silicosis.

Risks of respiratory disease in the heavy clay industry.

OBJECTIVES: Little information is available on the quantitative risks of respiratory disease from quartz in airborne dust in the heavy clay industry. Available evidence suggested that these risks might be low, possibly because of the presence in the dust of other minerals, such as illite and kaolinite, which may reduce the harmful effects of quartz. The aims of the present cross sectional study were to determine among workers in the industry (a) their current and cumulative exposures to respirable mixed dust and quartz; (b) the frequencies of chest radiographic abnormalities and respiratory symptoms; (c) the relations between cumulative exposure to respirable dust and quartz, and risks of radiographic abnormality and respiratory symptoms. METHODS: Factories were chosen where the type of process had changed as little as possible during recent decades. 18 were selected in England and Scotland, ranging in size from 35 to 582 employees, representing all the main types of raw material, end product, kilns, and processes in the manufacture of bricks, pipes, and tiles but excluding refractory products. Weights of respirable dust and quartz in more than 1400 personal dust samples, and site histories, were used to derive occupational groups characterised by their levels of exposure to dust and quartz. Full size chest radiographs, respiratory symptoms, smoking, and occupational history questionnaires were administered to current workers at each factory. Exposure-response relations were examined for radiographic abnormalities (dust and quartz) and respiratory symptoms (dust only). RESULTS: Respirable dust and quartz concentrations ranged from means of 0.4 and 0.04 mg.m-3 for non-process workers to 10.0 and 0.62 mg.m-3 for kiln demolition workers respectively. Although 97% of all quartz concentrations were below the maximum exposure limit of 0.4 mg.m-3, 10% were greater than this among the groups of workers exposed to most dust. Cumulative exposure calculations for dust and quartz took account of changes of occupational group, factory, and kiln type at study and non-study sites. Because of the importance of changes of kiln type additional weighting factors were applied to concentrations of dust and quartz during previous employment at factories that used certain types of kiln. 85% (1934 employees) of the identified workforce attended the medical surveys. The frequency of small opacities in the chest radiograph, category > or = 1/0, was 1.4% (median reading) and seven of these 25 men had category > or = 2/1. Chronic bronchitis was reported by 14.2% of the workforce and breathlessness, when walking with someone of their own age, by 4.4%. Risks of having category > or = 0/1 small opacities differed by site and were also influenced by age, smoking, and lifetime cumulative exposure to respirable dust and quartz. Although exposures to dust and to quartz were highly correlated, the evidence suggested that radiological abnormality was associated with quartz rather than dust. A doubling of cumulative quartz exposure increased the risk of having category > or = 0/1 by a factor of 1.33. Both chronic bronchitis and breathlessness were significantly related to dust exposure. CONCLUSIONS: Although most quartz concentrations at the time of this study were currently below regulatory limits in the heavy clay industry, high exposures regularly occurred in specific processes and occasionally among most occupational groups. However, there are small risks of pneumoconiosis and respiratory symptoms in the industry, although frequency of pneumoconiosis is low in comparison to other quartz exposed workers.

POCK model simulations of pulmonary quartz dust retention data in extended inhalation exposures of rats.

In recent years, a physiology-oriented multicompartmental kinetics (POCK) model was developed to simulate pulmonary retention data of biopersistent, noncytotoxic aerosols in long-term inhalation exposures of rats. Experimental data were successfully simulated for submicrometer-sized aerosols like carbon black, diesel soot, and titanium dioxide and for a micrometer-sized xerographic toner aerosol (Stöber et al., 1994, 1995). This article describes for various rat strains successful POCK model simulations of experimental pulmonary retention data of micrometer-sized aerosols of biopersistent cytotoxic SiO2 modifications like quartz and quartzite. In the past, the POCK model was not applied to cytotoxic aerosols and dusts. Cytotoxicity was considered incompatible with the model assumption of a constant macrophage lifetime independent of the macrophage aerosol load. The few relevant experimental retention studies with biopersistent silica found in the open literature showed particulate lung burdens up to some 15 mg per rat lung. Apparently, at these loads, pulmonary burdens could be simulated because the fraction of alveolar macrophages killed by the cytotoxic particles was possibly still small compared to the total number of viable macrophages. Of necessity, however, the classical alveolar clearance in these studies was exclusively performed by alveolar macrophages that were burdened with cytotoxic particles, and the cells appeared to suffer from a substantial initial decrease of their inherent mobility. Thus a sizeable reduction of the alveolar clearance rate coefficient in comparison to nontoxic aerosol was found. The results for the model parameters of several different exposure studies are shown and interpreted in comparison to nontoxic titanium dioxide retention parameters.

Risks of silicosis in coalworkers exposed to unusual concentrations of respirable quartz.

OBJECTIVES: To describe the radiographic changes in coalworkers exposed to unusual concentrations of respirable quartz during the 1970s, and to relate these to exposure measurements. METHODS: Men who had worked at one Scottish colliery during the 1970s were invited to a health survey. Chest radiographs were taken from 547 subjects. Classifications of these films under the International Labour Organisation (ILO) 1980 scheme were related, by logistic regression, to existing data on individual men's exposures to respirable dust and quartz. RESULTS: Taking the median of the three readers' results on profusion of small opacities, 203 men (38%) showed progression of at least one profusion category on the 12 point scale, from the various 1970s surveys to the follow up in 1990-1. A total of 158 men (29%) had a profusion of at least 1/0, and 47 (8.6%) of at least 2/1 at the follow up survey. Large opacities were recorded as present by at least two readers for 14 (2.6%) of the men. Profusion of small opacities was strongly related to exposures experienced in the 1970s, and more strongly for quartz than for the non-quartz fraction of the dust. Estimates of risk are presented over the range of quartz exposures experienced. CONCLUSIONS: The quartz exposures experienced by some men at this colliery have caused considerable progression of radiographic abnormalities since exposure ended. The data accumulated offer opportunities for further more detailed analyses to inform debate on occupational limits for quartz exposures, both in collieries and in other industries where there is exposure to quartz in mixed dust.