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Catz and Friend (1990) reported the steady state transdermal flux rate for ethyl acetate through human cadaver and rat skin. The rate for human skin was 0.5 mg/cm2/hr with a lag time of 24 hours, compared to rat skin of 12mg/cm2/hr and a lag time of 8 hours.  A QSAR model predicts a figure of 0.19mg/cm2/hr for human skin.

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Respiratory uptake of ethyl acetate in human volunteers exposed for four-hours to 0.344 – 0.501 mg/L was 63.2% in men and 56.7% in women (Nomiyama, 1974). Ethyl acetate was no longer detectable in expired air from these subjects one hour after cessation of exposure. In another study urinary excretion of ethyl acetate in male volunteers dropped below levels of detection within 2 hours after cessation of four-hour exposures to 1.45 mg/L (Vangala, 1991). Ethanol concentrations in alveolar air during exposure reached 0.008 mg/L in these subjects. These studies indicate that ethyl acetate is readily absorbed and rapidly biotransformed to ethanol.

Ethyl acetate is the acetate ester of ethanol and in vivo hydrolysis by endogenous esterases, present in many mammalian tissues, yields equimolar amounts of acetate (which enters the acetate pool) and ethanol. Significant esterase activity is present in the skin, lungs, and gastrointestinal tract. Therefore, exposure via dermal, inhalation, and water or dietary administration of ethyl acetate is expected to result in the rapid appearance of ethanol in the systemic circulation. Deisinger and English (1998) have developed toxicokinetic data for ethyl acetate, utilizing data from intravenous injection studies in rats. Ethyl acetate is rapidly hydrolyzed to ethanol with an in vivo elimination half-life in blood of 33-37 seconds. Rapid metabolism of ethyl acetate to ethanol has also been reported in rats following intraperitoneal injection or inhalation exposure (Gallaher, 1975). Inhalation exposures at concentrations greater than 2000 ppm (approx. 7.32 mg/L) were required to show any accumulation of ethanol in the blood and levels of 10,000 ppm (approx. 36.6 mg/L) provided blood ethyl acetate levels of less than 10 mg/L, and blood ethanol levels of the order 150 mg/L. There is evidence in this study that ethyl acetate undergoes hydrolysis very rapidly in vivo and that esterases are not saturated at levels as high as 10,000 ppm (approx. 36.6 mg/L). Indeed, ester hydrolysis of ethyl acetate proceeds more rapidly than ethanol metabolism. At exposure below 2000 ppm (approx. 7.32 mg/L), ethanol metabolism removes the ethanol produced by ethyl acetate hydrolysis.

Morris, 1990 reported that the upper respiratory tract itself, of rats and hamsters, has substantial ability to hydrolyze inhaled ethyl acetate (40 – 65% of deposited material in rats; 63 – 90 % in hamsters), thereby reducing the availability for absorption into the blood.

Resultant ethanol is metabolized by alcohol dehydrogenase (ADH), catalase and microsomal ethanol oxidising (MEOS) systems (Crabb, 1987). The catalase route is a major pathway in rodents.  In humans, ADH is the principal enzyme involved in hepatic metabolism of ethanol to acetaldehyde, especially at the concentrations associated with inhalation exposure. Acetaldehyde is normally cleared rapidly by conversion first in to acetate and then into acetyl-CoA (the biochemically active form of acetate) in the mitochondria. Acetyl-CoA can be oxidised completely to carbon dioxide or can serve as the starting point for the biosyntheses of fatty acids and lipids (Gurr, 1996).