Document 3NXnnab98g9q91kpMwGJ8amxE

*< V* i VDI Berichte Nr. 475,1983 291 tial of mineral fibres and to serve bs b sub stitute for animal studies. rely on medical research, including animal experiments, to assess the relative harmful effects of existing und new fibres. I believe that animal experiments, (which must be used because we cannot do direct exper iments exposing people to dust) may be giving us no Dr. HILLERDflL (Sweden)-------- Dr. MUHLE correct answers - even where we choose animals - like the rat - which do at least produce the same diseases Hice are not men, Bnd investigations of the after fibre exposure - as man does, i.e. asbestosis, clearance of various inhalants in "healthy" lung cancer - mesothelioma. smokers with chronic bronchitis actually show I would like to support my criticism of animal experi an increased clearance. So I doubt if your findings have any clinical importance for hu man beings. ments and in-vitro tests by the following examples where 1 believe they do not rank the asbestos fibre in the correct order of harmful effect in man. rt f! Dr. MUHLE ---------- Dr. HILLERDflL Amosite - was reported by Dr. DAVIS not to be carcino genic to rats and yet the SELIKOFF studies of U.S. in The long-term lung clearance (alveolar clear ance) investigated in our experiments result sulation workers and other studies show it to be high ly carcinogenic in man. 4 ed in a biological half-life of ca. 45 days. Crocidolite - gives in-vitro test results which show This important long-term clearance is also that it is not very haemolytic nor very cytotoxic to reduced in man after cigarette smoke inhala many cell systems and it is ranked (by DAVIS and oth tion, as indicate results of COHEN et al. (Sci ers) as only moderately carcinogenic to rats. Yet in ence 204 (1979), p. 514). The experimental re man, as shown by the studies in South African mines sults concerning the effect of cigarette smoke and also the Nottingham (England) gas mask workers, on the short-term clearance are contradictory. it is very carcinogenic and gives a very high rate of formation of mesothelioma. $l T l Chrysotile - by contrast - is shown by in-vitro tests to be very highly haemolytic, very cytotoxic to a num Dr. DUNNIGAN (Canada) ber of cell systems (phagocytic and non-phagocytic) and is shown by some animal injection and inhalation Does anyone know if adsorption of benzo(a)py- experiments (DAVIS et al.) to be the most carcinogenic rene, present in cigarette smoke, would change of all three commercial asbestos fibres. Yet human ex the geometry of fibres 7 perience shows that it is much less implicated in the I put this question in the light of the well causation of mesothelioma (by studies of Canadian min recognized combined effects of asbestos and ers ). Indeed many people believe that chrysotile does cigarette smoke. If the answer is no, then this not cause mesothelioma. ' would be another indication of the importance of surface chemistry of fibre reactivity These differences between man and animal need to be > mo XX > CT Dr. MUHLE discussed und investigated. I believe they may be ex The multiplying effect of cigarette smoke and asbestos gives no evidence of the impor tance of the surface chemistry. Other mecha nisms of the combined effect are possible, for example as described in our paper. plained by the differences in solubility and dispersa i- r* * m bility of the fibre in the lung. Chrysotile is much more easily eliminated, but the very short life-span of the animal compared to man may not allow normal clearance/solution mechanisms to operate as they do during the much longer life-span in man. Tumours are too e -h" o 03 rp to p 8~Oo 5 ro-- o Q > 73 generated only after a 20-40 year tine-span in man. In rats they are generated in 1-2 years. Hr. 6.F. HERON (Great Britain) 1 would like to suggest that this meeting gives more attention to the value and significance of animal ex periments and in-vitro tests. Those of us who manufac ture and sell asbestos products or their substitutes Dr. DAVIS 1 believe that it is incorrect to talk of "anomalies" in this context. 1 believe that we have only one anomaly. In animal studies chrysotile appears to be much more dangerous than suggested by human studies. 1000297? 292 VDI-Berichte Nr. 475, 1 If chrysotile is excluded, then 1 believe that ani Obviously it is extremely important to determine mal studies agree with human data and can be used to the results of animal studies using chrysotile ap predict the relative harmfulness of a new material. anomalous. At present, the most likely suggestion In support of this suggestion I would point out that that while chrysotile is potentially--the most car. animal experiments show crocidolite to be more car genic of the main asbestos types, it does not rem cinogenic than amosite. I would also cite Or. WAGNER's long enough in human lungs to produce tumours. Fu recent finding that erionite, which has produced an ture studies should aim to clarify this problem. epidemic of human mesotheliomas in Italy, has caused by far the largest, number of mesotheliomas so far found in an animal study. 10002980