UICC Chrysotile Research Articles

Characteristics of peritoneal macrophages induced by asbestos injection

The effect of single intraperitoneal injections of UICC crocidolite, UICC chrysotile, and a latex control particulate on the induced murine peritoneal macrophage population was measured. Spreading, Fc receptor avidity, and phagocytosis were measured 3, 18, and 70 days after injection. When activation of the induced macrophage populations was found at all three times with asbestos, but not with latex, experiments were undertaken to determine whether the asbestos-activated macrophages had attained the full tumoricidally activated state. An in vitro assay measuring macrophage cytotoxicity to tumor cells revealed that the tumoricidal potential of asbestos-activated macrophages was low at 3 and 5 days and negligible by 35 days after injection. An in vivo assay measuring the effect of asbestos on tumor growth generally supported the contention that asbestos-activated macrophages were not tumoricidal, although one dose of UICC chrysotile did produce a small, significant reduction in growth of a concomitant tumor. It was concluded that a single intraperitoneal asbestos injection in mice induces activated macrophages which do not become fully tumoricidal.

Control of human classical complement pathway C3 convertase: inhibition of C3 cleavage by C3a

Products of the oxidative metabolism of polymorphonuclear leukocytes (PMN), namely hydrogen peroxide and superoxide, may play a role in tissue injury at sites of inflammation. Oxidant production by PMN was measured by the luminol-enhanced chemiluminescence (CL) of cells exposed in vitro to asbestos fibers. Human peripheral blood PMN were incubated with 1–1000 μg/ml of UICC chrysotile B asbestos fibers opsonized with either normal or heat-inactivated human serum. CL was measured over 210 min and revealed a peak response at 45 min; this response was delayed in comparison to control CL induced by Staphylococcus aureus (5–10 min) and represented approximately 50% of that of the latter. Although maximal CL was generated by asbestos concentrations of 100–500 μg/ml, significant CL was observed at concentrations as low as 0.5–1 μg/ml. Opsonization of asbestos fibers with heat-inactivated serum markedly depressed CL responses, suggesting that complement activation by asbestos fibers may be important in the generation of CL by PMN. In view of the previously reported accumulation of PMN in the lungs of asbestos-exposed animals, this study suggests that oxidant production by PMN may mediate some of the pathological effects of asbestos fibers.

The influence of external aerodymanic factors on the measurement of the airborne concentration of asbestos fibres by the membrane filter method.

This paper describes experiments carried out in the laboratory to clarify interpretation of the role of sampling flow rate and wind speed on the efficiency of sampling airborne asbestos fibres in workplaces. The experiments were carried out with test clouds of UICC amosite and UICC chrysotile with aerodynamic characteristics sufficiently close to those of workplace dusts to allow direct comparison to be made, at least as far as the immediate aims of this enquiry are concerned. It was shown unambiguously, for conditions of practical interest, that there were no significant effects of sampling flow rate and wind speed on the measurement of fibre mass concentration and fibre number concentration respectively. Thus, any observed bias in the measurement of fibre concentration by manual counting must instead be attributable to psychological effects relating to the density of fibres on the filter. On the basis of these results, it is suggested that recommended procedures which impose limitations on sampling flow rate or face velocity are unnecessarily restrictive. Rather it is preferable to tighten up the prescribed limits on fibre density on the filter.

TRANSLOCATION OF MINERAL FIBRES THROUGH THE RESPIRATORY SYSTEM AFTER INJECTION INTO THE PLEURAL CAVITY OF RATS

The translocation of various inorganic fibres (UICC chrysotile A, UICC crocidolite and JM 104 glass fibres) has been studied after their intrapleural injection into rats. Fibres were recovered from all organs removed at necropsy 90 days after injection. The kinetics of the number and mass of fibres recovered from mediastinal lymph nodes were determined. Translocation ratios in terms of number and of mass were calculated for fibres recovered from the lung parenchyma. The mean length of the fibres remaining in the lung parenchyma increased with time for all types of injected fibres. Various possible mechanisms for the clearance of fibres from the pleural cavity are discussed.

Early biochemical reactions in the lung of sheep exposed to asbestos: evidence for cyclic AMP accumulation in bronchoalveolar lavage fluids.

A conscious sheep model which allows sequential analysis of the bronchoalveolar milieu was used to investigate the early biochemical events following asbestos exposure. Segmental bronchoalveolar lavages (BAL) were performed in a group of 15 sheep exposed to repeated doses of UICC chrysotile B asbestos (0–128 mg) over a six month period. BAL cell population was analysed and various humoral components including total proteins, albumin, alpha1-globulins (α1), alpha2-globulins (α2), beta + gamma globulins (β+γ) and adenosine 3′,5′-cyclic monophosphate (cAMP) were determined in cell free supernates. All animals were also studied by pulmonary function tests (PF) and transbronchial lung biopsies (LB). Exposure to asbestos (up to 128 mg/month) did not cause any significant alteration of pulmonary functions and lung histology. However, analyses of the BAL effluent revealed that BAL fluids of sheep exposed to asbestos contained higher levels ofα1-globulins and cyclic AMP as compared to controls. Furthermore this phenomenon was observed without overall change of BAL cell population except for a significant eosinophilia in the asbestos-exposed animals. These data demonstrate that the early biochemical response of sheep exposed to asbestos is characterized by a significant eosinophilia and increases ofα1-globulins and cyclic AMP in the bronchoalveolar milieu. These biochemical events may be involved in the chronic inflammatory reaction to asbestos and possibly in the fibrogenic response.

Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres.

The carcinogenicity of untreated UICC chrysotile A, of acid (oxalic and hydrochloric)-leached UICC chrysotile A, of crocidolite and of JM 104 glass fibres has been studied by intrapleural injection into rats. This experiment, carried out on 304 animals, demonstrated that when more than 80% of the Mg had been leached from chrysotile fibres by either hydrochloric or oxalic acid, the proportion of pleural mesotheliomas was either nil or dramatically lower than that obtained with untreated chrysotile. The carcinogenic effect of crocidolite was higher than that of 43.7% oxalic acid-leached chrysotile. The proportion of mesotheliomas observed in animals injected with JM 104 glass fibres was similar to that in animals injected with fibres from which 63.8% had been leached with oxalic acid. These results indicate that with regard to the induction of pleural carcinogenicity by chrysotile fibres, not only size characteristics but also parameters such as chemical composition and physiochemical properties must intervene.

Recovery of ingested asbestos fibers from the gastrointestinal lymph in rats

Using the transmission electron microscope, asbestos fibers have been assessed in lymph fluid collected from the thoracic lymph duct in five groups of rats previously exposed to asbestos fibers (by ingestion). Ten rats were gavaged a single dose weighing approximately 20 mg. Five were given pure UICC chrysotile A while another group of five had pure UICC crocidolite. All the rats of the chrysotile group were positive animals with recovery rate values ranging from 6.9 × 10 −7 to 3 × 10 −5 (90% of the fibers being recovered during the first 16 hr following the gavage). The crocidolite group had only three positive animals and lower recovery rate values of 5.7 × 10 −8 to 5.6 × 10 −7. A third group was fed a synthetic diet containing 1%, by weight, chrysotile with a majority of short fibers (90% below 4 μm). Of the 15 rats comprising this group, 13 were positive with maximum daily recovery rates ranging from 2.1 × 10 −7 to 2.1 × 10 −6. A group of eight rats fed the same kind of diet but containing a higher proportion of long fibers, showed only four positive animals, however, they had higher daily recovery rates ranging from 1.9 × 10 −5 to 2.1 × 10 −4. No fibers were encountered in the samples of the two control rats. This study demonstrates the passage of chrysotile and crocidolite fibers across the gastrointestinal wall, with the passage rate being higher for long fibers than short ones.

Biological effects of chrysotile after SO 2 sorption : II. Effects on alveolar macrophages and red blood cells

An experimental study has been carried out using different biological and biochemical in vivo and in vitro tests for assessing the toxicity of natural UICC (A) chrysotile and SO 2-sorbed UICC (A) chrysotile and for detecting a possible synergistic effect. For in vivo studies, rabbits received an intratracheal injection of chrysotile fibers suspended in physiological saline (PS). The control group received only PS; all animals were sacrificed after 68 hr. The alveolar free cells were harvested by pulmonary lavage. The results have shown that chrysotile induces a decrease in the free cell population but there was no significant difference in the number of viable cells or in the nature of cells harvested between the two chrysotile groups. Enzymatic activities of the alveolar macrophages from animals injected with SO 2-sorbed chrysotile showed a significant increase of the enzymes LDH and acid phosphatases. The LDH increase could be related to the affinity of the enzyme regarding some chemical forms of SO 2. In vitro studies using alveolar macrophages harvested by pulmonary lavage have shown no differences between the two chrysotile groups when cell viability and enzyme release were studied. The toxic effect was due to chrysotile fibers (decrease of 38% in cell viability and increase in cellular enzyme release when compared with control). When rabbit red blood cells were used, both natural and SO 2 chrysotile fibers showed the same hemolytic activity. The failure to detect high differences between the two chrysotile groups may be related to the chemical form of sorbed SO 2.

The generation and evaluation of UICC asbestos clouds in animal exposure chambers.

When carrying out animal inhalation experiments using UICC asbestos it was found necessary to modify the dust cloud generation technique described by Timbrell, to obtain a stable, well-dispersed cloud at concentrations from 1 to 10 mg/m3. The MRE gravimetric dust sampler type 113A recommended by Timbrell as a routine monitoring instrument, was found to undersample at high chrysotile concentrations, and an alternative system was developed using a vertical elutriator. Fibre number counts of the clouds were obtained and correlated with mass concentrations. A Royco particle counter model 225 and Sibata digital dust indicator model AP.3 were tested, and their usefulness at the prevailing high concentrations assessed. Fibre length distributions for clouds of UICC chrysotile A, amosite and crocidolite asbestos are reported.