THE BEHAVIOR OF GLASS-FIBERS IN THE RAT FOLLOWING INTRAPERITONEAL INJECTION

Potential carcinogenicity of fibers is believed to be determined by th ree factors: the dose, dimensions and durability of the fibers concern ed. Currently there is considerable debate on the appropriateness of u sing results from intraperitoneal (ip) injection studies to predict th e potential carcinogenicity of airborne fibers following inhalation. F or ip results to have any significance to potential inhalation hazards , there should be some relation between the biopersistence, dose, and dose distribution of fibers in the serosal cavity and in the lung. Pre liminary results on the durability of one experimental glass fiber in the peritoneal cavity suggest differences in dissolution when compared with durability in the lung. In the lung, the diameters of the long f ibers (> 20 mu m) were observed to decline at a rate consistent with t heir exposure to a neutral pH environment. The diameter of shorter fib ers declined much more slowly, consistent with exposure to a more acid ic environment such as is found in the phagolysosomes of alveolar macr ophages. In the peritoneal cavity all fibers, regardless of length, di ssolved at the same rate as short fibers in the lung. The effect of do se on the distribution of fibers in the peritoneal cavity was investig ated using similar experimental glass fibers and compared with that of a powder made from ground fibers. For both materials at doses up to 1 .5 mg, material was taken up by the peritoneal organs roughly in propo rtion to their surface area. This uptake was complete 1-2 days after i njection. At higher doses, the majority of the material in excess of t his 1.5 mg formed clumps of fibers (nodules) which were either free in the peritoneal cavity or loosely bound to peritoneal organs. These no dules displayed classic foreign body reactions with an associated gran ulomatous inflammatory response, The findings on both durability in th e peritoneal cavity and the presence of two distinct populations of ma terial following ip injection have implications for the justification of the use of ip injections to assess potential carcinogenicity of fib ers following inhalation. (C) 1994 Academic Press, Inc.