Toxicity of calcium sodium metaphosphate fiber. I. In vitro and in vivo degradation and clearance studies.
In an experiment to ascertain the degradability of calcium sodium metaphosphate (CSM) fiber in vitro, 32P-labeled CSM fiber was incubated in media with or without rat lung epithelial cells (LEC) or rat alveolar macrophages (RAM). The amount of radioactivity appearing in the filtrate of the media in the presence of cells minus the radioactivity in the media in the absence of cells was considered to reflect cell-aided dissolution of the fiber. LEC and RAM cells increased the degree of dissolution two- and sevenfold, respectively, compared to their respective media controls in a 7-day time period. In a separate experiment, male Fischer rats were given 32P-labeled CSM fiber either by intraperitoneal injection or by intratracheal instillation and the amount of radioactivity appearing in the urine and feces was measured over a period of 60 days. Selected animals from this experiment were also subjected to whole-body autoradiography 0, 1, 5, 15, 30, and 60 days postexposure. After intraperitoneal injection, approximately 0.9% of the administered dose appeared in the urine. A similar percentage of the dose was eliminated in the urine when the fibers were administered by intratracheal instillation; however, the amount of radioactivity in the feces after intratracheal instillation, i.e., 11.6% of the administered dose, was much higher than that after intraperitoneal dose, i.e., 0.24% of the administered dose. Whole-body autoradiographs showed a time-related increase in radioactivity at a site other than the site of administration, and the location of this radioactivity appeared to be exclusively associated with mineralized tissue. The clearance of nonradiolabeled CSM fiber (approximately 200,000 fibers) from rat lung after intratracheal inhalation (IH) and intratracheal instillation (IT) was monitored. Approximately 93% of the initial fiber load after IH and approximately 84% of the initial fiber load after IT was cleared from the lung in 6 months. Histological and biochemical evaluation of the rat lungs did not reveal any indication of fibrosis up to a period of 6 months. All the studies discussed indicate that CSM is degradable in biological systems and is cleared from the lung after IT and IH administration. These attributes of CSM fiber should reduce the potential for chronic adverse effects in the lung after inhalation.
Nair
R S
RS
Monsanto Company, St. Louis, Missouri 63167.
Li
A P
AP
Shiotsuka
R N
RN
Wilson
A G
AG
D000818:Animals; D001345:Autoradiography; D001673:Biodegradation, Environmental; D002130:Calcium Phosphates / Q000493:pharmacokinetics / Q000633:toxicity*; D002478:Cells, Cultured; D004333:Drug Administration Routes; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010761:Phosphorus Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D014132:Trachea
D002130:Calcium Phosphates; D010761:Phosphorus Radioisotopes; C077456:metaphosphoric acid, calcium sodium salt