title: The behavior of glass fibers in the rat following intraperitoneal injection.
abstract: Potential carcinogenicity of fibers is believed to be determined by three factors: the dose, dimensions and durability of the fibers concerned. Currently there is considerable debate on the appropriateness of using results from intraperitoneal (i.p.) injection studies to predict the potential carcinogenicity of airborne fibers following inhalation. For 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. Preliminary 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 fibers (> 20 microns) were observed to decline at a rate consistent with their exposure to a neutral pH environment. The diameter of shorter fibers declined much more slowly, consistent with exposure to a more acidic environment such as is found in the phagolysosomes of alveolar macrophages. In the peritoneal cavity all fibers, regardless of length, dissolved at the same rate as short fibers in the lung. The effect of dose on the distribution of fibers in the peritoneal cavity was investigated 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 proportion to their surface area. This uptake was complete 1-2 days after injection. At higher doses, the majority of the material in excess of this 1.5 mg formed clumps of fibers (nodules) which were either free in the peritoneal cavity or loosely bound to peritoneal organs. These nodules displayed classic foreign body reactions with an associated granulomatous inflammatory response. The findings on both durability in the peritoneal cavity and the presence of two distinct populations of material following i.p. injection have implications for the justification of the use of i.p. injections to assess potential carcinogenicity of fibers following inhalation.
authors.affiliation: Biomedical Research, AEA Technology, Didcot, Oxon, United Kingdom.
authors.forename: C G
authors.initials: CG
authors.lastname: Collier
authors.forename: K J
authors.initials: KJ
authors.lastname: Morris
authors.forename: K A
authors.initials: KA
authors.lastname: Launder
authors.forename: J A
authors.initials: JA
authors.lastname: Humphreys
authors.forename: A
authors.initials: A
authors.lastname: Morgan
authors.forename: W
authors.initials: W
authors.lastname: Eastes
authors.forename: S
authors.initials: S
authors.lastname: Townsend
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D005260:Female; D005898:Glass / Q000032:analysis; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D010529:Peritoneal Cavity / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D013997:Time Factors
chemical_list: C009753:fiberglass