Subchronic inhalation toxicity of methyl isoamyl ketone in rats.

Rats were exposed by inhalation, 6 hr/day, 5 days/week, to target vapor concentrations of 2000, 1000, or 0 ppm of methyl isoamyl ketone (MIAK) for 12 exposures spanning 16 days, and 2000, 1000, 200, or 0 ppm for 69 exposures spanning 96 days. Body weights, hematology, and serum clinical chemistry determinations were comparable to controls in both inhalation studies. Clinical signs of toxicity were lethargy and decreased aural response (2000 ppm, 2-week study; 2000 and 1000 ppm, 90-day study) and nasal and eye irritation (2000 and 1000 ppm, 90-day study). In addition, the excretion of gel-like casts in seminal fluid was seen in males exposed to 2000 and 1000 ppm in both studies. Increases in absolute and relative liver and kidney weights were observed in both sexes following exposure to 2000 and 1000 ppm in the 2-week and 90-day studies. Liver weight increases were exposure dependent and in the 90-day study reflected hepatocyte hypertrophy observed on microscopic examination. Microscopic kidney changes were hyalin degeneration or hyalin droplet formation in males in the 2-week (2000 and 1000 ppm) and 90-day (2000 ppm) studies; and minor to moderate regeneration of tubular epithelium (2000 and 1000 ppm) in both studies. Minor tubular epithelium regeneration was seen in females exposed to 2000 ppm for 90 days. The toxicity of MIAK following inhalation exposure was not as extensive or severe as that resulting from a prior study in which male rats were dosed orally with 2000 mg/kg/day (a dose comparable to 2000 ppm) for 13 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative acute and subchronic toxicity of ethylene glycol monopropyl ether and ethylene glycol monopropyl ether acetate.

The acute toxicity of ethylene glycol monopropyl ether (EGPE) and ethylene glycol monopropyl ether acetate (EGPEA) was determined in a series of standardized tests. The oral LD50 in rats was 3089 and 9456 mg/kg EGPE and EGPEA, respectively. Skin irritation was slight following an occluded single dose application of either compound to the guinea pig abdomen. The dermal LD50 for guinea pigs was 1 to 5 mL/kg and greater than 20 mL/kg EGPE and EGPEA, respectively. EGPE produced a very weak positive sensitization response in one of five guinea pigs. No positive response was elicited when 10 guinea pigs were similarly challenged with EGPEA. EGPE produced transient moderate to severe eye irritation in rabbits while EGPEA produced slight eye irritation. Subchronic toxicity was determined in a series of oral and inhalation studies. Groups of 10 male rats were dosed with 15, 7.5, 3.75 or 1.88 mmole/kg EGPE and 30, 15 or 7.5 mmole/kg EGPEA by gavage 5 days/week for 6 weeks. Hemoglobinuria was seen at least once at all dose levels of both compounds. EGPE had little effect on feed consumption or body weight gain, while body weight gain was reduced in the two high dose groups exposed to EGPEA and feed consumption was reduced at all dose levels. Hematologic changes were seen at all dose levels of both compounds. Absolute and/or relative spleen weights were increased at all but the lowest EGPE dose level and at all EGPEA dose levels. Gross and histopathologic examinations revealed significant effects on the spleen of animals exposed to EGPE and on the spleen, liver, kidney and testes of animals exposed to EGPEA. The no-observed effect level (NOEL) for splenic changes was 1.88 mmole/kg EGPE. A NOEL for hematology was not established. The NOEL for liver and testicular changes were 15 and 7.5 mmole/kg EGPEA, respectively while a NOEL for hematologic, splenic and renal changes was not established. Groups of 10 rats (5M, 5F) were exposed to 800, 400, 200 or 100 ppm EGPE or EGPEA 6 hr/day, 5 days/week for a total of 11 exposures. Body weight gains in all exposure groups were comparable to controls. Hemoglobinuria was seen only after the first or second exposure in males and females exposed to 800 ppm EGPE and in males exposed to 400 ppm EGPE. Males and females exposed to 800 ppm EGPEA and females exposed to 400 and 200 ppm EGPEA also exhibited hemoglobinuria.(ABSTRACT TRUNCATED AT 400 WORDS)

Nervous system degeneration produced by the industrial solvent methyl n-butyl ketone.

Because of a number of cases of peripheral neuropathy that occurred in factory workers employed in a fabric-printing plant in 1973, chronic inhalation experiments have been conducted using the printing-ink solvents methyl n-butyl ketone (MBK) and methyl iso-butyl ketone (MIBK). After four months of intermittent respiratory exposure to 1,300 parts per million (ppm) MBK, all six rats tested developed severe symmetric weakness in the hindlimbs. Morphological studies showed massive focal axonal enlargements containing abnormally large numbers of neurofilaments and dying-back axonal degeneration in peripheral and central nerve fibers. Six rats similarly exposed for five months to 1,500 ppm of MIBK showed minimal distal axonal change, but remained neurologically intact. The principal conclusion of this study is that MBK is a neurotoxin in rats.