Comparison of biopersistence of experimental glass fibres in the lung and peritoneal cavity.

Thirty three female Fischer-344 rats were intra-peritoneally (IP) injected with 5 mg of an experimental glass fibre designated X7753. This fibre type had an in vitro dissolution rate of 600 ng cm-2h-1. Groups of three rats were killed at various times up to one year after injection. The diaphragm and any fibre nodules were removed from the carcass and separately digested using hypochlorite solution, to recover the fibres. The number and morphometry of the fibres was measured using phase contrast optical microscopy (PCOM) and semi-automatic image analysis. The data obtained were compared to the previous studies of the durability of the X7753 fibres in the lung.

The durability and distribution of glass fibres in the rat following intra-peritoneal injection.

Intra-peritoneal (IP) injection is being recommended as a means of assessing potential carcinogenicity of MMF following inhalation. Little is known of the behaviour of fibres in the peritoneal cavity or its relevance to the lung. This study considered both the biopersistence and the distribution of dose following IP injection of fibres. Biopersistence of fibres in the peritoneal cavity has been compared with that observed previously in the lung. Marked differences were found, with long fibres (> 20 microns) being more durable in the peritoneal cavity than in the lung. Breakage could not account for this finding, whereas differences in dissolution could. The behaviour of fibres and powders and their distribution in the peritoneal cavity following injection of different masses is reported. Distribution of dose depended on injection mass, with masses of < 1.5 mg showing even uptake onto the surfaces of the peritoneal organs, and higher masses resulting in the development of nodules of injection material, free in the peritoneal cavity, or loosely bound to the peritoneum. With fine powder, some clearance was observed over the first 48 h after IP injection, but not with fibres. The findings on both durability and distribution of dose following IP injection have implications on the justification for the use of IP injections in assessment of potential carcinogenicity of fibres following inhalation.

Preliminary data from investigations of the in vivo biopersistence of three experimental glass fibres of varying chemical composition.

The durability of three experimental glass fibres (X7753, X7484, and X7779) was investigated in vivo. These fibres had in vitro dissolution rates of 600, 150, and 2 ng cm-2 hour-1, respectively. Three groups of female Fischer-344 rats were intratracheally instilled with a 1.2 mg suspension of one of each of the fibre types. All fibres had previously been neutron activated, to produce radioactive 24Na within the glass, which served as a radiotracer. At 2 days post instillation (PI) about 1 x 10(6) glass fibres were within the pulmonary region of the lung. Animals were killed at various time points from 2 to 360 days PI. Fibres were recovered from the animal lungs by hypochlorite digestion. The retention and morphometry of these fibres was investigated, and preliminary results are presented. After 360 days in the lung, the number of X7753 and X7484 fibres fell respectively to 10% and 50% of those present at 2 days PI. There was no detectable reduction in the number of X7779 fibres in the lung over this period. Morphometric analyses demonstrated a 53% and 22% reduction in the mean length of the X7753 and X7484 fibres, after 360 days in the lung. Reduction in diameter was apparent after only 28 days for the these fibre types. No change in the mean size of the X7779 fibres was observed during the study. The fibre morphometry data suggested that short fibres dissolved at a slower rate than long fibres. In general the in vivo fibre retention and morphometry data reflected the measured in vitro dissolution rate.

The behavior of glass fibers in the rat following intraperitoneal injection.

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.

A radioactive tracer technique to determine in vivo the number of fibers in the lungs of rats following their administration by intratracheal instillation.

A radioactive tracer technique is described which enables the total number of fibers present in the lungs of rats to be estimated following administration of the fibers by intratracheal instillation. The glass fiber used in the study was irradiated with thermal neutrons to induce radioactive 24Na. A suspension of the radioactive fiber was administered to eight rats by intratracheal instillation and to two additional rats by intraesophageal instillation. The 24Na radioactivity in the rats was counted in vivo at 24 and 48 hr after administration, after which they were killed. The amounts of fiber in the lungs, in the gastrointestinal tracts, and excreted in feces were estimated radiometrically. On average 93% of the administered fiber was accounted for. The lungs were digested with sodium hypochlorite solution and aliquots of the resulting digest filtered through membrane filters which were clear for examination by phase-contrast optical microscopy (PCOM). The numbers of fibers in the lungs, estimated by PCOM, were well correlated with the in vivo counting rates at 48 hr, indicating that the latter can be used to provide an accurate index of the number of fibers retained in the lung at that time.