Document Jrn0abJBEkDpYOe54kQxM6YL6

06 12 <!' 1" ;)7 EA.X 3 L7 735 22S3 iXflU'lu* . ' -1 vo?' % a; _ ..j ENT HEALTH SCIENCE 012--01* 0 NVIRONMENT HEALTH PEF t 06/12/02 17:06 FAX 817 735 228DUNT HEALTH'SCIENCE 009/017 '.rj.'-o-'-. . ^ gnrirrmrrutntel Health. Perspectives Yl- PP- 313-31$, 1971 Jf- Tumorigenic Effect of Fibrous Dusts in Experimental Animals \*A C*5v - . by F. Pott,*^ F. Huth,* and K. H> Friedrichs* ,b^ NOVOE rruv n* Gotfo s Fibrous duau (chrysatUa, glass fiber*, nsmaHts, pajygorecite, md gypsum) and gruuUr duals (acti&olltc, biotits, hematite. neotollte, mnldina, tnd talcum) ware injected in- traparitoueoily into rats. The Qbrous dusts (othsr than gypsum) resulted in a hiah incidence at mesothelioma (30 - 67%). Qypsum produced only 6% and-granular dusts none at all. It la suggssted that the fibrous shape leads to a high multiplication rate of.cells and predispaass to tumor formation. FibeosU, in the othsr hand, doei not so proditposs- Milled ohrysatile with 99.8% fibers than Sum la length are carcinogenic in our experience. The carcinogenicity of glass fibers in our esperimenii! may have significance for occupational situations'. The starting point of our investigations was the question whether the tumorigenic effect of asbestos fibers depends on physicochemical properties of the fiber or the shape of the fibers which are characteristic for all kinds of asbestos. For this purpose chemically different fibrous forms were compared to chemically similar dusts having different forms. Dusts Tested Tables 1 and 2 list Che dusts tested in the animal experiments with respect to their chemical composition, particle shape, fiber length, and particle size. The fiber length and particle size were estimated by evaluation of electron micrographs. Experimental Methods The dusts were injected intraperitoneally in Wistar rats. We could not see any difference between the reaction of peritoneum and pleura. lr. addition, the injection did not essentially dis turb the general status of the animals. Table 1. Estimation offiber length offibrous dust by Electron microscopy. Dust Chemical composition Fiber length Chrv3'otile A Chrysotile (milled) Gl3 Gypsum Nemslite Paiygoracite Mg silicate 73,7 Mg silicate 914 Na, Ca borosiilcates 49.9 Ca sulfate 66.0 Mg hydroxide 91.5 Mg, A) silicates 37.5 93.9 99.8 72.6 75.0 96.4 70.0 Table 2. Efitimetion of particle *ize af gnus durU, by microscopy Dust " Chemical composition Particle size <2 am. % <&/xtn, Actinoiite Biotite Hematite Hematite Peetolin* Sanidine Talc Ca, Mg,- Fo silicates K. Ke. Mg, A1 silicataa Fe oxide (precipitated) Fe oxide (mineral) Ci, Na silicates K, Ai ailicatea Mg silicate a 86.5 A A 36.2 S5.6 a a 06.3 X a 98.4 97.2 a * No particle 31`ze analysis possible. `Medmr.irchea InsliLul far Lufthygiene und SUikosofor7chun^, Ilnive'-eitSt Dduseldarf, DUsKeidorf. Germany. The best experimental method would be the inhalation of the dusts, but this method leads to December 1974 Jfc < . x<j1:t t -! \i. *L. r;.. ;1 C M< 313 'O. ".Vi; .Ij\. 12. 5. '3:V )I * ' 06/12-'02 17:07 FAX 817 735 228-3 I'NT HEALTH SCIENCE @010/017 enormous technical difficulties. The time re Table 3. Tumor ram aJUr intraprriton*ol injection gf regem quired to produce tumours following injection of fibrous and granular duita. prolift dusts is already long. This time would be prolonged tremendously by an inhalation method, since it takes months to get an effective. dose at the vulnerable cell structures. The Dust Time required to Do3(i,p.)t produce first Tumor rate, mg tumor in animals * of irroup, days We wheth cells 1 irritai necessary concentration time of the dusts and the time to produce the tumors may even exceed normal life span. , The test dusts were suspended in 3aline solu tion at concentrations up to 25 mg/2 ml. For higher dosages, the injections were repeated once a week. The different test groups consisted- 40 rats. Pure saline was injected in 80 control' animals. The rats were observed until spon taneous death or sacrifice. All tumors were studied histologically. Results Chrysotile A Chrysotile A Chrysotile A Chrysotile A . {milled) Giaiis fibers Nemalite Fttlygontcitr. Gypsum Pectolite Sanidine Talcum Actinolite niotfte Hematite 6 25 .1X25 4X25 4 X 25 4X25 3 X 25 4 X 25 4 X 25 4 X 25 4 X 25 4X 25 4 X 25 4X25 343 276 270 400 197 249 257 546 569 743 537 _ -- __ 67.5 65 37.5 30 57.5 62.5 65 5 2,5 2.5 2.5 -- -- _ Fin duced as sta Even 30-4t that t degre The Pi Th. facto expei diam The UICC standard asbestos as well aB palygor9cite, nemalite, and glass fibers induced tumors in the abdominal cavity of 30-67% of che rats. Several dusts chemically closely (precipitated) Hematite (mineral) NaCl (control) 4X25 4 X 2 ml -- -- - sped by th has s The related to chrysotile (like actinolite, biotite, pec- and * I tolite, talcum), but of granular or platy shape with only a few fibers did not lead to the development of tumors except for a few cases. Calcium sulfate (gypsum) did show a fibrous tumors? We don't have a complete answer, bol, we.rio.w make the following speculation. Animal experiments and the histological investigation showed formation of tumors in the mesothelium c-inoi plete brell ah or shape but dissolved in the animal tissue and in in an overwhelming degree. Some authors have duce duced tumors only in 5% of the animals. Table 3 reported lung tumors following asbestos only shows the tumor rate within the different, ex application. In our experiments subcutaneous 99.8' perimental groups. Histologically nearly all the injection of chrysotile A in one case only led to also ii tumors were sarcomatous mesotheliomata. In current experiments the lowest effective dosage of glass fibers was 2 mg/rat. The glass fibers were uncoated. The average diameter of the glass fibers was about 0.5 /tm. With this tumors in the subcutaneous connective tissue space. In addition, the storage of fibers by the lymph nodes never induced tumors of the lymphatic system. These observations suggest that tissues have different vulnerabilities to can thar. dian duct dian ' dosage the first mesotheliomata occurred at 17 months. It seems of importance that 2 mg of fibrous du9ts. Epithelial and epithelium-like cells obviously conflict with fibrous dusts in an reac yet glass fibers induced only slight adhesions intensive degree; this intensive contact can be around the liver lobeB; 10 mg led to slight or well observed in cell cultures. Beck and Bruch medium adhesions and fibrous alterations, es pecially around the liver and the stomach; 50 mg of fiber dust induced tremendous adhesions on all abdominal organs with strong fibrosis. The fibrotic alterations generally could be differen tiated from the numerous tumors. With 100 mg glass fiber only 6.5 months were necessary for tumor induction in the first rat. (]) demonstrated by electron microscopy a par tial invagination of long asbestos and glass fibers by fibroblasts (L-cells) of mice. Although these cells can not phagocytose the fibers com pletely they remain dense around the foreign bodies. Such a relation between fiber and cells could support a chronically enhanced reproduc tion of cells within quickly regenerating Activity of Fibers within the Tissues epithelial and meaothelial cells. For decades it has been known that in epithelial organs like the We are confronted with the question: Why do liver and the respiratory tract chronically special shapes cf particles lead to formation of enhanced regeneration can change to abnormal I 314 :e:ved ::ve c-jn. a i-.wu. Environmental Health Perspectives 'x;n~ time ;2. `0?M De