Kennedy C H, Bechtold W E, Chang I Y, Henderson R F
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Fundam Appl Toxicol. 1993 Nov;21(4):486-91. doi: 10.1006/faat.1993.1124.
Glycol ethers such as 2-ethoxyethanol (EE) are widely used as solvents because they are miscible in aqueous and organic solutions. Toxic effects of EE in rodents include teratogenicity, fetotoxicity, hematotoxicity, and testicular atrophy. The purpose of this study was to determine the effect of dose on the absorption, metabolism, and excretion of 2-ethoxy [U-14C]ethanol by F344/N rats after inhalation exposure. Rats were exposed to either 5 ppm EE for 5 hr 40 min or 46 ppm EE for 6 hr. The uptake and metabolism of EE were linear in the concentration range studied. Significant percentages of the retained doses were exhaled during (22%) and after exposure (16%) as 14CO2. Forty-six percent of the retained dose was excreted in the urine. Approximately 10% of the retained dose was detected in the carcass 66 hr after exposure. The major urinary metabolite was ethoxyacetic acid (EAA), the toxic metabolite of EE. The amount of EAA excreted was linearly related to exposure concentration. Ethylene glycol and N-ethoxyacetyl glycinate were identified as minor metabolites excreted in the urine. The results of this study suggest that the toxicity of inhaled EE should be directly proportional to the exposure concentration up to 46 ppm if the toxicity of EE is due to EAA.
乙二醇醚，如2-乙氧基乙醇（EE），因其可与水溶液和有机溶液混溶而被广泛用作溶剂。EE对啮齿动物的毒性作用包括致畸性、胚胎毒性、血液毒性和睾丸萎缩。本研究的目的是确定吸入暴露后，剂量对F344/N大鼠吸收、代谢和排泄2-乙氧基[U-14C]乙醇的影响。大鼠暴露于5 ppm的EE中5小时40分钟或46 ppm的EE中6小时。在所研究的浓度范围内，EE的摄取和代谢呈线性关系。在暴露期间（22%）和暴露后（16%），有相当比例的滞留剂量以14CO2的形式呼出。46%的滞留剂量经尿液排泄。暴露66小时后，在 carcass中检测到约10%的滞留剂量。主要的尿液代谢产物是乙氧基乙酸（EAA），即EE的有毒代谢产物。EAA的排泄量与暴露浓度呈线性相关。乙二醇和N-乙氧基乙酰甘氨酸被鉴定为尿液中排泄的次要代谢产物。本研究结果表明，如果EE的毒性是由EAA引起的，那么吸入EE的毒性在高达46 ppm的暴露浓度下应与暴露浓度成正比。
