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254 J. C. WAGNER, G. BERRY, J. W. SKIDMORE AND V. TIMBRELL Length of exposure 1 day 3 months 6 months 12 months 24 months Table I.--Number of Rats Exposed Amosite 49 52 24 25 21 Anthophyllite 49 52 24 28 19 Crocidolite 49 52 24 26 20 Chrysotile (Canadian) 49 52 24 23 24 Chrysotile (Rhodesian) Control 49 48 52 58 25 .) 27 t 48 20 I Length of exposure 1 day 3 months 6 months 12 months 24 months Table II.---Mean Respirable Dust Concentration (malm3]1 and Cumulative Dose (mgjm3 hours) Amosite 141 12-4 11-2 10-8 10-6 99 5000 8550 17000 33500 Anthophyllite 12-8 13-5 10-9 11-4 10-6 90 5240 8540 17100 33700 Crocidolite 12-5 12-6 10-7 10-6 10-3 88 5030 8430 17000 33200 Chrysotile (Canadian) 9-7 12-1 10-2 10-7 10-1 68 4930 8240 17100 33200 Chrysotile (Rhodesian) 14-7 12-3 10-7 10-9 10-1 103 507(1 85911 1710(1 3360O included in the 12-month groups and hence the numbei of rats in these groups is slightly higher, and in the 24-month groups slightly lower, than planned. In Table II the mean respirable dust concentrations and the cumulative doses, the products of concentration and time, are shown. The one-day exposure was 7 hours for all dusts. For the other 4 time intervals of exposure, there were slight variations in the number of hours required to achieve approximately equal doses but the mean times were 402, 788, 1574 and 3237 hours respectively. The mean concentrations were usually higher in Experiment 1 than Experi ment 2, and the 3-month group had an average dose of 60% of that of the 6-month group. Reasonable equality of dose between the dusts was achieved for all the lengths of exposure, except for the one-day which was too short to allow any adjustments. Interpretation of histological findings Classification of asbestosis.--The lesions seen in the lungs of rats exposed to all types of asbestos were similar to those described in guinea-pigs (Wagner, 1963, 1965). There were 2 main differences; firstly, asbestos bodies were never seen in the lung tissue of the rat although they are frequently seen in the pleural granulomata which follow the intra-pleural inoculation of amphibole fibres; secondly, there was a far greater production of granular pneumocytes (type II) alveolar epithelial cells in the rat. The lesions consist initially of a deposi. tion of asbestos fibres, alveolar macrophages and cell debris in the alveoli arising direetlv from the respiratory bronchioles. These deposits become organized firstly by being enmeshed in a thin reticulin network which coarsens with time and becomes replaced bv collagen fibres. The alveolar epithelium, reacts with replacement of the type I cells, and becomes completely lined by granular pneumocytes. In some of the alveoli the epithelium is shed into the lumina, in others there is a walling of the alveoli by these cells. This usually occurs at the bifurcations where groups of alveoli are closed off from the lumina of the respiratory bronchioles, giving the so-called pseudo-acinar ap pearance. In the guinea-pigs these small cystic spaces contained asbestos fibre and degenerating macrophages, but in the rats numerous granular pneumocytes were also present. The initial lesions were confined to occasional discrete individual respiratory bronchioles scattered throughout the lung substance. After further exposure, more and more respiratory bronchioles become involved and all the respiratory bronchioles arising from terminal bronchioles become thickened as the fibrous tissue network extends into the wall of the respiratory bronchiole, and this interstitial reaction spreads down into the peripheral elements of the primary unit, involving the alveolar ducts, atria and finally the air sacs and'alveoli. With progression, the individual lesions tend to coalesce, leading to the development of a