Toxicity of calcium sodium metaphosphate fiber. II. Chronic inhalation and oncogenicity study.
Male and female Fischer 344 rats (80/sex/group) were exposed to CSM fiber 6 hr/day, 5 days/week at target-exposure levels of 0, 1, 5, or 25 mg/m3 for 24 months, corresponding to 0, 27, 80, and 513 fibers/cc, respectively. Number and size of the airborne fibers were determined during the course of the study. At 3 and 12 months, 10 rats/sex/group were euthanized and at 18 and 24 months 5 rats/sex/group were euthanized. In addition, 5 rats/sex/group were removed from exposure at 18 months and maintained for a 6-month recovery period. All animals surviving at the completion of the exposure period were maintained in a clean environment for up to 5 additional months. Clinical laboratory examinations were performed on 10 animals/sex/group at 3, 12, and 24 months. The number of fibers in the lung were also determined at 3, 12, 18, and 24 months. Body weight and survival did not appear to be affected by treatment. There were no biologically significant effects on clinical parameters. There was a dose-related increase in lung weight during the exposure period which was generally reversible during the recovery periods. There also was a dose-related increase in the number of fibers/milligram of lung, but no increase in lung fiber burden after the first 3 months. The number of fibers in the lungs of animals exposed to CSM fiber for 18 months and allowed 6-month recovery period showed a decrease especially at the high dose. No increase in tumors (benign or malignant) was observed in this study. Microscopic changes considered reflective of an irritant response were observed in the nasal turbinates notably at the 5 and 25 mg/m3 levels. Histological changes were also observed in the lungs at the 5 and 25 mg/m3 levels. The incidence and/or severity of histopathological changes in the 1 mg/m3 group was considered to be essentially comparable to controls.
Nair
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Monsanto Company, St. Louis, Missouri 63167.
Johannsen
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Bolte
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Newton
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Rinehart
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D000280:Administration, Inhalation; D000818:Animals; D001822:Body Burden; D001835:Body Weight / Q000187:drug effects; D002130:Calcium Phosphates / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D002130:Calcium Phosphates; D002273:Carcinogens