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Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats
Authors:KATZ  GARY V; RENNER  EUGENE R  JR; TERHAAR  C J
Abstract:Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats.KATZ, G. V., RENNER, E. R., JR., AND TERHAAR, C. J. (1986).Fundam. Appl. Toxicol. 6, 498–505. Rats were exposed byinhalation, 6 hr/day, 5 days/week, to target vapor concentrationsof 2000, 1000, or 0 ppm of methyl isoamyl ketone (MIAK) for12 exposures spanning 16 days, and 2000, 1000, 200, or 0 ppmfor 69 exposures spanning 96 days. Body weights, hematology,and serum clinical chemistry determinations were comparableto controls in both inhalation studies. Clinical signs of toxicitywere lethargy and decreased aural response (2000 ppm, 2-weekstudy; 2000 and 1000 ppm, 90-day study) and nasal and eye irritation(2000 and 1000 ppm, 90-day study). In addition, the excretionof gel-like casts in seminal fluid was seen in males exposedto 2000 and 1000 ppm in both studies. increases in absoluteand relative liver and kidney weights were observed in bothsexes following exposure to 2000 and 1000 ppm in the 2-weekand 90-day studies. Liver weight increases were exposure dependentand in the 90-day study reflected hepatocyte hypertrophy observedon microscopic examination. Microscopic kidney changes werehyalin degeneration or hyalin droplet formation in males inthe 2-week (2000 and 1000 ppm) and 90-day (2000 ppm) studies;and minor to moderate regeneration of tubular epithelium (2000and 1000 ppm) in both studies. Minor tubular epithelium regenerationwas seen in females exposed to 2000 ppm for 90 days. The toxicityof MIAK following inhalation exposure was not as extensive orsevere as that resulting from a prior study in which male ratswere dosed orally with 2000 mg/kg/day (a dose comparable to2000 ppm) for 13 weeks. The 90-day inhalation exposure no-observed-effectlevel for toxicity was 200 ppm MIAK.
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