| toxicity summary | IDENTIFICATION AND USE: Acetone is a colorless volatile liquid. It is a solvent for fats, oils, waxes, resins, rubber, plastics, lacquers, varnishes, rubber cements. It is a versatile reagent in organic synthesis. Acetone is used in manufacturing of coatings, plastics, pharmaceuticals and cosmetics. It is also used in production of other solvents and intermediates including: methyl isobutyl ketone, mesityl oxide, acetic acid , diacetone alcohol, bisphenol A, methyl methacrylate, explosives, rayon, photographic films, isoprene. Acetone is not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Acetone has been identified as being used in hydraulic fracturing as a corrosion inhibitor. HUMAN EXPOSURE AND TOXICITY: Acetone is relatively less toxic than many other industrial solvents; however, at high concentrations, acetone vapor can cause CNS depression, cardiorespiratory failure and death. In children 2 to 3 mL/kg is considered to be toxic. Acute exposures of humans to atmospheric concentrations have been reported to produce either no gross toxic effects or minor transient effects, such as eye irritation. More severe transient effects were reported for workers exposed to acetone vapor concentrations for about 4 hr. Acute exposures to acetone have also been reported to alter performances in neurobehavioral tests in humans. Females were reported to suffer menstrual irregularities. Acetone also occurs as a metabolic component in blood, urine and human breath. Acetone is one of three ketone bodies that occur naturally throughout the body. It can be formed endogenously in the mammalian body from fatty acid oxidation. Fasting, diabetes mellitus and strenuous exercise increase endogenous generation of acetone. Under normal conditions, the production of ketone bodies occurs almost entirely within the liver and to a smaller extent in the lung and kidney. Products are excreted in the blood and transported to all tissues and organs of the body where they can be used as a source of energy. ANIMAL STUDIES: Oral LD50 values in adult rats are in the range of 5800-7138 mg/kg. Mice were given 2,500, 5,000, 10,000, 20,000, or 50,000 ppm acetone and 1,250, 2,500, 5,000, 10,000, or 20,000 ppm acetone via drinking water for 13 weeks. Absolute liver weight and liver weight to body weight ratios were significantly increased and absolute spleen weight and spleen weight to body weight ratios were significantly decreased in the females . In other experiments, rats were assessed for liver oxidative balance and lipid content after treatments with acetone in water for 28 days. Compared with controls, acetone-treated rats had increased hepatic GSH, hepatic vitamin E, glycemia, cholesterolemia, and hepatic fat, which is similar to the features of non-alcoholic steatohepatitis. Acetone is not considered to be genotoxic or mutagenic. In a study of pregnant rats and mice exposed to acetone vapor during days 6-19 of gestation, slight developmental toxicity was observed. Reports of other reproductive effects of acetone include observations of testicular effects and changes of sperm quality in rats. Acetone has been used extensively as a solvent vehicle in skin carcinogenicity studies and is not considered carcinogenic when applied to the skin. The avoidance and escape behavior of female rats exposed to 3000, 6000, 12,000, or 16,000 ppm of acetone vapors for 10 days for 4 hr/day were studied. The 3000 ppm exposures had no effect on all exposure days, the 6000 ppm exposure initially inhibited the conditioned avoidance response but not the unconditioned escape response, and the two highest exposures inhibited both responses. Normal responses were obtained after three days of exposure to 6000 and 12,000 ppm, indicating that adaptive changes develop upon repeated exposure. ECOTOXICITY STUDIES: Acetone was tested with mallard eggs. Fertile eggs were immersed in 0, 10 or 100% acetone for 30 seconds at room temperature on days 3 or 8 of incubation. There were no significant effects with 10% acetone; however, 100% acetone caused a significant decrease in survival, embryonic weight and embryonic length for both exposure groups. It is unknown whether the mortality was due to the toxicity of acetone or to its solvent capabilities.Since acetone is highly water soluble, it is readily taken up by the blood and widely distributed to body tissues. Acetone may interfere with the composition of the membranes, altering their permeability to ions. Systemically, acetone is moderately toxic to the liver and produces hematological effects. The renal toxicity may be due to the metabolite, formate, which is known to be nephrotoxic and is excreted by the kidneys. One of the major effects of acetone is the potentiation of the toxicity of other chemicals. Pretreatment with acetone has been shown to potentiate the hepatotoxicity and nephrotoxicity of carbon tetrachloride and chloroform by inducing particular forms of cytochrome P-450, especially cytochrome P-45OIIE1, and associated enzyme activities. |
