Summary.-Two experiments in which SPF Wistar rats were exposed by inhalation to dust clouds of the UICC standard reference samples for periods of between one day and 2 years are described. All the samples of asbestos produced asbestosis which continued to progress after removal from exposure but only a little fibrosis was observed in control rats. Lung tumours, ranging in severity from adenomata to squamous carcinomata, were produced by all samples but in the controls there were only a few adenomata and none of the more serious tumours. Of the 20 tumours which metastasized, 16 occurred after exposure to one or other of the 2 chrysotile samples. In addition, a total of 11 mesotheliomata occurred, 4 of which were with crocidolite and 4 with Canadian chrysotile. Two of the mesotheliomata occurred with only one day's exposure to asbestos. There was a positive association between asbestosis and lung tumours.WAGNER, Berry and Timbrell (1973) reported the results of experiments in which rats were inoculated intrapleurally with samples of asbestos. In the discussion it was mentioned that two experiments in which rats had been exposed to dust clouds of the UICC reference samples had been carried out, and the results of these are now presented. Some preliminary results of one of these experiments were reported by Wagner (1972).In both experiments the rats were exposed to similar dust concentrations and the dose varied by exposing rats for various lengths of time. The main aim was to establish the relationship between the development of malignant tumours in the lungs and the dose and type of asbestos dust but, additionally, the amount of fibrosis was assessed.
MATERIALS ANI) METHODSCaesarean derived rats of the Wistar strain were used which had been bred at the Unit from SPF stocks given to us by the Imperial Chemical Industries, Pharmaceutical Division at Alderley Edge, Cheshire in 1964 and 1968.The asbestos samples used consisted of the 5 UICC standard reference samples (Timbrell, Gilson and Webster, 1968) which were prepared following recommendations of the UICC. These samples are of 3 amphibole types amosite, anthophyllite and crocidolite-and 2 chrysotiles-a Canadian and a Rhodesian sample.The rats were exposed in 1e4 m3 inhalation chambers (Timbrell et al., 1970) which contained 8 cages, each of which could hold 6 rats, or, for a short period with young rats, there was room for a seventh. Five chambers were used, one for each type of asbestos. The chambers were constructed so that the rats could be tended without the chambers being opened.The dust clouds were generated using a specially devised dispenser (Timbrell, Hyett and Skidmore, 1968). The clouds were generated for 7 hours a day and 5 days per week. The respirable dust concentrations were measured using size selective gravimetric dust samples (Cassella Type 114A). The collected samples were evaluated at the end of each daily session. In order to achieve the required dosage, calculated as the product of concentration and time, variations occurring in the concentr...