Four-week inhalation toxicity study with Ludox colloidal silica in rats: pulmonary cellular responses.
This study was designed to complement a traditional subchronic inhalation toxicity study with Ludox colloidal silica. CD rats were exposed nose-only for 2 or 4 weeks at concentrations of 0, 10, 50, and 150 mg/m3 Ludox (dried SiO2). Additional groups of rats exposed for 4 weeks were given a 3-month recovery period. Following exposure and/or recovery, fluids and cells were recovered from the lungs by bronchoalveolar lavage (BAL) and measured for cellular and biochemical parameters. Additional groups of animals were processed for cell labeling studies or lung deposition studies. Inhaled doses of Ludox colloidal silica were measured after 4-week exposures and were found to be 489 micrograms/lung (10 mg/m3 group), 2418 micrograms/lung (50 mg/m3), and 7378 micrograms/lung (150 mg/m3), respectively. Results showed that exposures to 150 mg/m3 Ludox for 2 or 4 weeks produced pulmonary inflammation along with increases in BAL protein, LDH, and alkaline phosphatase values (p less than 0.05) and reduced macrophage phagocytosis. Inflammatory responses, evidenced by increased numbers of neutrophils, were also measured in the lungs of the 50 mg/m3 group following 2 and/or 4 weeks of exposure. Most biochemical parameters for all groups returned to control values following a 3-month recovery period. Autoradiographic studies demonstrated that the labeling indices of terminal bronchiolar and lung parenchymal cells were generally increased in the 50 and 150 mg/m3 groups after 2 and 4 weeks of exposure but, with one exception, returned to normal levels following a 3-month postexposure period. No significant alterations in any measured parameters were detected in rats exposed to 10 mg/m3 Ludox at any time postexposure. The determination of a no-observable-effect level (NOEL) of 10 mg/m3 was consistent with results obtained by conventional toxicology methods and affirms the utility of these biochemical, cellular, and autoradiographic techniques for providing a predictive screen to assess the toxicity of inhaled particles.
Warheit
D B
DB
Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company, Newark, Delaware 19714.
Carakostas
M C
MC
Kelly
D P
DP
Hartsky
M A
MA
D000280:Administration, Inhalation; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000201:enzymology; D007501:Iron / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000032:analysis / Q000633:toxicity*
D012822:Silicon Dioxide; D007501:Iron; D000469:Alkaline Phosphatase