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Inhaled chrysotile asbestos or carbon dust that reaches the alveoli in guinea pig lungs is ingested by macrophages which move through the parenchyma of the lung toward the pleura. Some macrophages are eliminated from the lung by passing through blood vessel or bronchiolar walls. Those that reach the pleura are mainly aggregated in a few small areas. They may pass through the pleura. The active macrophages stain blue with Perls' reagent due to iron in the lysosomes. Occasionally, a macrophage may disintegrate while passing through the pleura and Perls-positive lysosomes become distributed over an area, presumably in the lymphatics.

A histological study of the lungs of guinea-pigs that inhaled carbon, chrysotile asbestos or crocidolite asbestos dust indicated that dust particles in macrophages move through alveolar walls towards the pleura. After some weeks accumulations of dust-filled macrophages were found near to pulmonary blood vessels. Macrophages that ingested carbon appeared to be much less mobile than those that ingested carbon appeared to be such less mobile than those that ingested asbestos. In sections from the animals that inhaled asbestos, macrophages were found that were penetrating the wall of blood vessels, dust is transferred to extrapulmonary sites by macrophages in the blood

In histological sections asbestos bodies in human lungs may be either transparent, yellow, strongly Perls-positive structures as described in published reports, or opaque, black structures, the ferroprotein coating having been converted into haemosiderin. The transparent asbestos bodies fragment into segments; the black asbestos bodies disintegrate into a mass of haemosiderin granules that accumulate as dense deposits, particularly near to blood vessels. The presence of haemosiderin granules indicates that asbestos bodies have broken down. When a patient has died with a mesothelioma there is little evidence of phagocytic activity in many areas of the lung. When exposure to asbestos ceased many years before a mesothelioma developed there may be few recognisable asbestos bodies remaining in the lung.

The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies. The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos. Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 mum long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to normal. THIS CLEARANCE MECHANISM IS INHIBITED BY OTHER FACTORS: quartz dust may almost completely inhibit asbestos body formation; tobacco smoke has a considerable effect, and even very heavy loads of carbon may act similarly. The normal lung appears able to efficiently eliminate small loads of both nonfibrous and fibrous dust, including the carcinogenic asbestos fibers. The capacity is not unlimited, however, and when the load is heavy there is a much greater probability that fibers will not be detoxicated. In addition, other factors such as silica dust and tobacco smoke may remove the protective mechanism in the lungs.

Carbon fibre, manufactured from a polyacrylonitrile fibre precursor, is used to reinforce plastic in the aircraft industry. When carbon fibre was fed into a hammer mill, only low concentrations of dust of respirable size could be produced and less than 1% of the respirable carbon particles were fibrous. The dust cloud contained a few transparent fibres, probably glass, of respirable size. When the dust was inhaled by guinea pigs nonfibrous particles were phagocytosed. The few carbon fibres found in the lung that were longer than 5 microns were still extracellular after 27 weeks and they were uncoated. No free transparent fibres were found in the lungs but fibre bodies with a ferruginous coating were probably derived from the transparent fibres. No pathological effects were observed.

Poly(2-vinylpyridine 1-oxide) inhibits the cytotoxic effects of quartz in cell cultures but the syndiotactic polymer behaves differently from the isotactic and atactic polymers. In each case approximately 1-0 mg/m2 of the polymer represents the adsorption maximum. No difference has been found between the adsorption isotherms of the stereoisomeric polymers or the stability of the adsorbed layers. The layers are not removed by repeated washing. The observations do not support the theory that the poly(2-vinylpyridine 1-oxide) is active because it coats the quartz surface.

1. Poly(2-vinylpyridine 1-oxide) counteracts the pathogenic effects normally produced when quartz is injected into or inhaled by animals and the cytotoxic effects when quartz is added to macrophage cultures. The protective action of this polymer has been attributed variously to the formation of an adsorbed layer on the quartz particles, complex formation with monosilicic acid produced by the dissolution of quartz, and strengthening of the membranes or microstructures of the cells.2. Stereoregular forms of poly(2-vinylpyridine 1-oxide), some alkyl derivatives of poly(2-vinylpyridine 1-oxide), poly(3-vinylpyridine 1-oxide) and poly(4-vinylpyridine 1-oxide), a copolymer of 2-vinylpyridine 1-oxide and 2-n-propenylpyridine 1-oxide, some poly(1-methyl-2-vinylpyridinium) quaternary salts, and poly(1-methoxy-2-vinylpyridinium iodide), which had previously been synthesized and studied with respect to their viscosities and interaction with silicic acid, were tested for their ability to counteract the cytotoxic effects of quartz in macrophage cultures. The tests were effected both by pretreating the quartz with polymers, and by pretreating the cells.3. Every polymer proved active in one or other of these conditions, but several were active in one test but inactive in the other. Some polymer quaternary salts, which do not contain the N-oxide group, were found to be active. A remarkable difference in activity was found between the two stereoregular forms of poly(2-vinylpyridine 1-oxide). Pretreatment of the quartz with some of the polymers increased its cytotoxicity significantly.4. Most of the results could be interpreted on the hypothesis that the polymers form an adsorbed layer on the quartz surface, but it is difficult to apply this explanation to two polymers which are inactive when used to pretreat the macrophages but are active when adsorbed on quartz.