... The current study was aimed at quantitating the extent of metabolism of inspired ethyl acetate in the upper respiratory tract (URT) of the F344 rat and Syrian hamster. Ethyl acetate deposition was measured in the surgically isolated URT of these species under constant velocity unidirectional flow conditions. The degree of metabolism was estimated by mathematic modeling based on a simple venous-equilibration approach and by direct comparison of deposition efficiencies in naive and carboxylesterase-inhibited animals. Ethyl acetate deposition efficiencies averaged between 10 and 35% in the rat URT and 36 and 72% in the hamster. Carboxylesterase inhibition decreased deposition in both species. Both the modeling efforts and the direct comparisons between naive and inhibited animals indicated that significant amounts of the deposited ethyl acetate were metabolized in the URT of both species with the extent of metabolism being more pronounced in the hamster. Specifically, 40-65% of the deposited ethyl acetate was metabolized in the URT of the rat compared to 63-90% in the hamster. This first-pass metabolism (i) increased URT deposition efficiencies; (ii) led to production of high metabolite levels in URT tissues; and (iii) decreased the amount of parent ethyl acetate available for absorption into the bloodstream in the URT.
Because of the abundance of nonspecific esterases, one might expect the common solvent ethyl acetate (EtAc) to be hydrolyzed to ethyl alcohol (EtOH) in vivo. It would then be possible to demonstrate EtOH accumulation following exposure to EtAc vapor. Preliminary studies showed that rat blood incubated at 37 °C does hydrolyze EtAc to EtOH, with a half-time of approximately 65 min. Analyses were done by gas chromatography. To study this reaction in vivo, rats were anesthetized with pentobarbital, and cannulae were inserted into the femoral arteries. EtAc was injected ip as a 25% () solution in corn oil (1.6 g/kg) and blood samples were drawn periodically. Hydrolysis was very rapid in vivo, with a half-time estimated at 5-10 min. Inhalation studies were then carried out by exposing anesthetized rats to several concentrations of EtAc vapor via an endotracheal tube. When EtAc concentrations were increased above 2000 ppm, EtAc absorption exceeded EtOH oxidation, leading to an accumulation of EtOH in the blood. Although blood EtOH concentrations increased steadily to over 0.10 g/100 mL in 5 hr, EtAc remained consistently below 0.01 g/100 mL and did not change throughout the course of the experiment, again indicating rapid hydrolysis. The data indicate that EtOH will accumulate during exposure to EtAc if the ambient concentration of EtAc is sufficiently high.
Metabolic studies in the rat have revealed an approximate 2000 ppm no-effect level. At higher levels, the rate of hydrolysis of ethyl acetate appeared to exceed ethanol oxidation, leading to its accumulation in the vascular system. Also, when it was injected intraperitoneally at 1.6 g/kg, hydrolysis to acetic acid and ethanol occurred rapidly. Intraperitoneal injections of 1 mL/kg to male rats for 8 days increased the blood pyruvic and lactic acid content considerably and also elevated the glycolytic enzymatic activity.
IDENTIFICATION AND USE: Ethyl Acetate is a colorless liquid with a smell similar to glue or nail polish that is used as an industrial solvent. Ethyl Acetate is used as a solvent for chemical reactions. Because of its odor it is often used in cosmetics and its smell is associated with nail polishes. Additionally, it is used in confectionery, perfumes, and fruits because it evaporates at a fast rate, leaving but the scent of the perfume on the skin. Ethyl acetate is an effective poison for use in insect collector as its vapors are a respiratory tract irritant whose vapors can kill the insect quickly without destroying it, leaving it intact for study. HUMAN EXPOSURE AND TOXICITY: Short-term exposure to high levels of ethyl acetate results first in irritation of the eyes, nose and throat, followed by headache, nausea, vomiting, sleepiness, and unconsciousness. High concentrations can cause CNS depression and congestion of the liver and kidneys. Chronic poisoning has been described as producing anemia, leucocytosis (transient increase in the white blood cell count), and cloudy swelling, and fatty degeneration. Runners were evaluated after complaining of wheezing coughing, rhinitis, or shortness of breath after practicing in a facility under construction. Investigation revealed levels of ethyl acetate and toluene low enough to meet federal guidelines but apparently sufficient to cause symptoms in the athletes. Its carcinogenic properties are not known. Workers who in earlier years had been exposed to ethyl acetate concentrations of 300 mL/cu m and who were exposed at the time of the investigation to 16 mL/cu m were found to have normal sperm quality. ANIMAL STUDIES: In animals it has a narcotic effect at concentrations of over 5000 ppm. Repeated exposures of rabbits to 4450 ppm for 1 hr daily for 40 days resulted in anemia with leukocytosis, and damage to liver and kidneys. Male rats exposed to a high dose (3600 mg/kg/day) of ethyl acetate by gavage showed significant toxic effects, which resulted in depressed body and organ weights, and depressed food consumption. Female rats exposed to the high dose showed slight but non-significant depression of above parameters compared with controls. Exposure of rats to 750 and 1500 ppm ethyl acetate via inhalation for 6 hr per day, 5 days per week for 13 weeks, diminished behavioral responses to unexpected auditory stimuli during the exposure session and appeared to have an acute sedative effect. There were no signs of acute intoxication 30 min after exposure sessions ended. Rats exposed to 750 and 1500 ppm had reduced body weight, body weight gain, feed consumption, and feed efficiency, which fully or partially recovered within 4 weeks. Reductions in body weight gain and feed efficiency were observed in male rats exposed to 350 ppm. The principal behavioral effect of subchronic exposure was reduced motor activity in the 1500 ppm females, an effect that was not present after the 4-week recovery period. All other functional observation battery and motor activity parameters were unaffected, and no pathology was observed in nervous system tissues. In conclusion, there was no evidence that subchronic exposure up to 1500 ppm ethyl acetate produced any enduring neurotoxic effects in rats. Ethyl acetate is strong inducer of aneuploidy in the yeast Saccaromyces cerevisiae, but was negative for mutagenicity in Salmonella typhimurium assays. The solvent yielded negative result in the micronucleus assay in Chinese hamsters in vivo. In vivo hydrolysis of ethyl acetate to acetic acid and ethanol occurred rapidly. ECOTOXICITY STUDIES: Exposure of the common indian catfish (Heteropneustes fossilus) to 170 ppm of ethyl acetate for 3, 6, 12, 48, and 96 hr induced marked changes in carbohydrate metabolism. Hepatic glycogen levels declined significantly at 3, 48, and 96 hr, but there was no marked alteration in muscle glycogen content at any of the exposure periods. Hyperglycemia occurred at all time intervals. Blood pyruvate levels were elevated at 3, 6, 48, and 96 hr. Hyperlacticemia resulted at 3 and 96 hr, but hypolacticemia occurred at 6 and 12 hr. Impairment of carbohydrate metabolism might be responsible for the toxic action of ethyl acetate.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
暴露途径
该物质可以通过吸入其蒸气被身体吸收。
The substance can be absorbed into the body by inhalation of its vapour.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
暴露途径
吸入，摄入，皮肤和/或眼睛接触
inhalation, ingestion, skin and/or eye contact
来源:The National Institute for Occupational Safety and Health (NIOSH)
