Acetaldehyde

Endpoint summary

Additional information

Absorption

Acetaldehyde is absorbed through the lung and gastrointestinal tract. Although there are no adequate quantitative studies on dermal absorption of acetaldehyde, it is shown from studies on toxicity of acetaldehyde described later that absorption through the skin is possible (IPCS, 1995).

Distribution

In the nasal inhalation study of acetaldehyde in eight volunteers at the concentrations ranging from 100 to 800 mg/m3, 45% to 70% of the exposed amount of acetaldehyde was retained in the respiratory tracts (Egle, 1970). In a inhalation study (1-hr) in SD rats, acetaldehyde was distributed in the blood, liver, kidney, spleen, heart, myocardium and skeletal muscle. The concentration in the liver was relatively low due to the rapid metabolism of acetaldehyde (Hobara et al., 1985; Watanabe et al., 1986). The possibility that acetaldehyde can enter the fetal circulatory system through the placenta is suggested. Pregnant ICR mice were given intraperitoneally a dose of 200 mg/kg on gestation day 10, and acetaldehyde was detected in the fetuses 2 hours after the administration. After intraperitoneal administration of ethanol at 79 mg/kg, acetaldehyde at a low level of concentration or near the limit of detection was detected in the fetuses 12 hours after the administration (Blakley and Scott, 1984b). After an oral administration of ethanol at a dose of 4,500 mg/kg in male and female Wistar rats, it was confirmed that produced acetaldehyde was distributed in the blood and brain interstitial fluid (Westcott et al., 1980). Most of acetaldehyde in the blood of volunteers after alcohol ingestion was distributed in

erythrocytes. The concentration of acetaldehyde in the erythrocyte was approximately 10-fold higher than that in the plasma, indicating high transition of acetaldehyde to hemocytes (Baraona et al., 1987).

Metabolization

Acetaldehyde is metabolized to acetic acid by nicotinamide adenine dinucleotide (NAD)-dependent aldehyde dehydrogenase (ALDH), which exists in the liver and nasal mucosa, and finally degraded to carbon dioxide and water. (Brien and Loomis, 1983)

Regarding ALDH, there are two types of ALDH in mitochondrial and cytosolic forms. Kinetic characteristics of enzymatic reaction of liver mitochondrial ALDH are similar among human, rat and Syrian hamster, while, the Km value of human cytosolic ALDH1 was approximately 180 M but those of rat and Syrian hamster were 15 and 12 M, respectively (Klyosov et al., 1996). In human liver,

mitochondrial ALDH alone oxidizes acetaldehyde at physiological concentrations, but in rodent liver, both mitochondrial and cytosolic ALDHs have a role in acetaldehyde metabolism (IARC, 1999). Approximately 40% of Oriental population is inactive in mitochondrial ALDH2, which is associated with alcohol intolerance (Yoshida et al., 1984). In humans, inhaled acetaldehyde is retained in the respiratory tract at a high rate, and, therefore, acetaldehyde metabolism is mainly associated with thiol compounds (cysteine and glutathione) and subsequently hemimercaptal and thiazolidine intermediates are produced. Thioether and disulfide are

excreted in the urine, however, most of them are metabolized to acetic acid by ALDH2, and finally degraded to carbon dioxide and water (Brien and Loomis, 1983; Cederbaum and Rubin, 1976; Hemminki, 1982; Nicholls et al., 1992; Sprince et al., 1974).

It is shown that acetaldehyde (purity: 99%) that is incubated with ribonucleosides and deoxyribonucleosides forms adducts with cytosine or purine nucleoside, and one of acetaldehyde guanosine adducts is N2-ethylguanosine (Hemminki and Suni, 1984).

Excretion

In an intravenous administration of acetaldehyde solution (0.5% to 5%) in rabbits, metabolites were excreted at a rate of 7 to 10 mg/min (Hald and Larsen, 1949). In an intraperitoneal administration of acetaldehyde at a single dose of 6.2 mmol (273 mg) in rats, sulfur-containing metabolites in urine was significantly increased (approximately 100%) (Hemminki, 1982). In an oral administration of acetaldehyde at a dose of 600 mg/kg in dogs, no excretion of unmetabolized acetaldehyde was comfirmed in urine (Booze and Oehme, 1986).

[cited from Chemicals Evaluation and Research Institute (CERI), Japan, Hazard assessment on Acetaldehyde 2007, http://www.cerij.or.jp/ceri_en/hazard_assessment_report/yugai_indx_en.htm]