Document NeMKm1d065L6Zr88OZ5kwZDOb

' Confidential report 29-55 MELLON INSTITUTE Special Report R: 7-8-66 /ff'J 7^lb 12 pages v1^ ft (I1 The Fibrogenic Potential of Asbestos Products via Intraperitoneal Injection in Guinea Pigs, Rats and Rabbits .and by the Intratracheal Route in the Rat Chemicals Division, Union Carbide CorporationIndustrial Fellowship 274-29 The results of intraperitoneal administration indicate that the asbestos products studied produced fibrotic lesions of the visceral organs in rats and guinea pigs regardless of fiber length. Of the three products, CMS-100 (refined fiber), produces the most severe reaction. JT-100 (standard fiber) and JM-3K (Johns Manville screened fiber) produced similar but less severe reactions. The results on rabbits were inconclusive. Both JT-100 and CMS-100 produced specific lesions in rats by the intra tracheal route but with JT-100 they were more severe. No lesions were found in the rats which received JM-3K fibers. These results indicate that these three asbestos fibers may be fibrogenic by either route. No specific lesions were observed 'in the lungs of the JM-3K intratracheal rats, but only two rats survived to be examined. Samples The following samples were shipped to Mellon Institute at the request of Mr. Paul W. McDaniel who furnished the descriptive information. Designation of Asbestos Product . Sonrce Quan tity M. I. Date Sample Received / Number *CTS-100 Fiber (same as JT-100 Fiber) Sterling Forest "Standard Fiber" containing impuri ties in the form of clay and magne tite. A short fiber. 8 oz. 8-14-63 26-220 *CMS-100 Fiber "Refined Fiber" with Sterling Forest lesser impurities than JT-100. A short fiber. 8 oz. 8-14-63 26-219 A2v03C * The individual fibers for most part had lengths of 0.9 to 10 microns, but there were some as long as 30 microns and some that were less than 0.5 micron. The diameters of the fiber were generally 0.3 to 1.2 microns, but there were smaller sizes noted. The clay-magnetite particles were mostly 0.5 to 3.0 microns in diameter but there were some present as small as 0.08 micron (by electron microscope). > Designation of Asbestos Product JM-3K Fiber. "Long Fiber" (Brushed through screen to reduce fiber length to 1 mm.' or less before injecting.) Source Manville, N.J. Report 29-55 Page 2 Quantity Date Received M. I. Sample Number 8 oz. 8-26-63 26-227 Intraperitoneal Injections Methods The JM-3K asbestos was brushed through a 1 nun. screen to reduce its fiber length to < 1000 micra (1.0 mm.) in order to facilitate dosing. The CMS-100 and JT-100 asbestos samples were used as received. Each asbestos product was pre pared as a 2.52 (W/V) suspension in 0.85Z saline. All needles, syringes and suspensions were sterilized prior to use. The animals were divided into three groups--each consisting of eleven male albino guinea pigs (P), six male albino rats (R), and two male albino New Zealand rabbits (H) . The guinea pigs and rab bits received intraperitoneal injections of 2 ml. (50 mg.) and the rats, 1 ml. (25 mg.) of the respective asbestos suspensions. Eleven guinea pigs and six rats received control intraperitoneal injections of saline. There were no rabbit controls. All injections were made in the lower right quadrant of the abdomen. Tables 29-92 through 29-95 contain the results on individual`animals. Results CMS-100 produced the most severe reaction in the form of granulomas with giant cells in six of the seven guinea pigs examined micropathologically. Typical granulomas with giant cells were observed in three of four rats and the one rabbit JT-100 asbestos fiber produced a granulomatous reaction in all of the 8 guinea pigs as well as the one rat subjected to micropathological examination. The rabbits had incidental lesions unrelated to the asbestos fibers. The JM-3K asbestos fibers produced granulomas with fibers visible in five of the five guinea pigs examined. One of two rats had granuloma formation which was visible on gross examination. Methods Intratracheal Injections One per cent (W/V) suspensions of JT-100, CMS-100 JM-3K and a 0.52 suspension of CMS-100 were prepared in 0.85% saline as for the intraperitoneal Inj ections. A 2 -4 0 3 3 Report 29-55 \ Page 3 Female albino rats weighing in excess of 200 grams were given 1 ml. of the respective asbestos suspensions by intratracheal injection. The rats were anesthetized with saturated vapor of anhydrous diethyl ether. The trachea was exposed by blunt dissection and the injection was made directly.and the incision closed with a Michael Wound Clamp. . Eight rats were injected with 1 ml. of a 1Z JT-100 suspension (10 mg. asbestos). Eight rats were injected with 1 ml. of a-1% JM-3K suspension (10 mg. asbestos). Because of the flocciilent properties of CMS-100, only three rats were dosed with 1 ml. of a 1Z suspension (10 mg. asbestos). Eight rats were injected with 1 ml. of a 1% CMS-100 suspension (5 mg-, asbestos). Six rats injected with physiological saline served as controls. Tables 29-96 through 29-99 contain results on individual animals. Results Specific lesions were found in most of the rats given CMS-100 and JT-100 that consisted of marked granuloma formation with bluish foreign body material present (magnetite?).. Marked bronchiolitis obliterans was noted in most rats, also with bluish foreign body material within the lesions. The JT-100 rats had a more severe fibrotic reaction to this foreign material. Multinucleate giant cells were a common feature with the granulomas of the JT-100 rats but were conspicu ously absent in the lungs of the rats given CMS-100. Micropathology was performed on only two rats receiving JM-3K asbestos. Neither of these animals had lesions similar to JT-100 or CMS-100. . - Edwin R. Kinkead, B.S. . Research Associate Approved: Acknowledgments: Technical Assistance Pathological Examination Data in Book 868, pp. 63 to 90 and 99-109. Typed: July 11, 1966 - aid Urbano C. Pozzani, M^ Senior Fellow Charles P. Carpenter Assistant Administr^1 Fellow Charles C. Haun, B.S., Junior Fellow John M. 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