© 1986 Oxford University Press
research-article |
Urinary N-Acetyl-S-2-hydroxyethyl-L-cysteine in Rats as Biological Indicator of Ethylene Oxide Exposure1
Département de médecine travail et d'hygiene du milieu, Faculté de médecine, Université de Montréal C.P. 6128, Succ.A. Montreal, Québec, Canada H3C3J7
Urinary Ar-Acetyl-5-2-hydroxyethyl-L-cysteine in Rats as Biological Indicator of Ethylene Oxide Exposure. GERIN, M, AND TARDIF, R. (1986). Fundam. Appl. Toxicol. 7, 419-423. There is no simple method known for the biological monitoring of ethylene oxide exposure. N-Acetyl-5-2-hydroxyethyl-L-cysteine (2-hydroxyethylmercapturic acid) excretion was evaluated as a potential indicator of exposure to this gas. Groups of Sprague-Dawley rats were given iv doses of 1, 10, or 100 mg/kg of ethylene oxide dissolved in water. Urines were collected after 12 and 24 hr. In another experiment groups of Sprague-Dawley rats were exposed by inhalation to concentrations of 1, 5, 10, 25, 50, and 200 ppm of ethylene oxide during a 6-hr period and 24-hr urines were collected subsequently. 2-Hydroxyethylmercapturic acid was analyzed in rat urine after enzymatic deacetylation into S-2-hydroxyethyl-L-cysteine, formation of a fluorescent derivative, and separation from other amino acid derivatives by high performance liquid chromatography. No S-2-hydroxyethyl-L-cysteine was observed in any sample when analysis proceeded without the deacetylation step. 2-Hydroxyethylmercapturic acid, however, was present in the urine of all exposed groups. Doses of 1 and 10 mg/kg were excreted at a fairly constant percentage of the dose, ca. 30% from 0 to 12 hr and 5% from 12 to 24 hr, while at 100 mg/kg the equivalent percentages were 16 and 5%, indicating a possible saturation of glutathione conjugation in the first 12 hr. In inhalation experiments, the amount of 2-hydroxyethylmercapturic acid excreted in 24 hr varied linearly with exposure concentration, averaging 0.27 µmol/ppm. The consistency of the excretion of this metabolite over a wide dose span points to 2-hydroxyethylmercapturic acid as a potential biological indicator of exposure to ethylene Oxide.