Miller R R, Hermann E A, Young J T, Calhoun L L, Kastl P E
Toxicol Appl Pharmacol. 1984 Sep 30;75(3):521-30. doi: 10.1016/0041-008x(84)90188-1.
Male Fischer 344 rats were given a single po dose of approximately 8.7 mmol/kg of [1-14C]propylene glycol monomethyl ether acetate (PGMEA) or exposed to 3000 ppm [1-14C]PGMEA for 6 hr. After dosing, expired air, excreta, and tissues were analyzed for 14C activity, and metabolites in urine were isolated and identified. Approximately 64% of the administered 14C activity was eliminated as 14CO2 and about 24% was excreted in urine within 48 hr after a single po dose of radiolabeled PGMEA. Similarly, 53% was eliminated as 14CO2 and 26% was excreted in urine within 48 hr after the inhalation exposure. Propylene glycol, propylene glycol monomethyl ether (PGME), and the sulfate and glucuronide conjugates of PGME were identified as urinary metabolites after po dosing, as well as after inhalation exposure to PGMEA. The urinary metabolite profile and disposition of [14C]PGMEA were nearly identical to results previously obtained with propylene glycol monomethyl ether (PGME), indicating that PGMEA is rapidly and extensively hydrolyzed to PGME in vivo. A short-term vapor inhalation toxicity study in which male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 300, 1000, or 3000 ppm PGMEA confirmed that there were no substantial differences in the systemic effects of PGMEA as compared to PGME. However, histopathologic examination did reveal changes in the olfactory portions of the nasal mucosa of rats and mice exposed to PGMEA, which may be related to acetic acid resulting from hydrolysis of PGMEA in the nasal epithelium.
给雄性Fischer 344大鼠经口单剂量给予约8.7 mmol/kg的[1-14C]丙二醇单甲醚乙酸酯（PGMEA），或使其暴露于3000 ppm的[1-14C]PGMEA中6小时。给药后，分析呼出气体、排泄物和组织中的14C活性，并分离和鉴定尿液中的代谢物。经口单剂量给予放射性标记的PGMEA后，在48小时内，约64%的给药14C活性以14CO2的形式被消除，约24%经尿液排出。同样，吸入暴露后，53%以14CO2的形式被消除，26%在48小时内经尿液排出。经口给药以及吸入暴露于PGMEA后，丙二醇、丙二醇单甲醚（PGME）以及PGME的硫酸盐和葡糖醛酸共轭物被鉴定为尿液代谢物。[14C]PGMEA的尿液代谢物谱和处置情况与先前用丙二醇单甲醚（PGME）获得的结果几乎相同，表明PGMEA在体内迅速且广泛地水解为PGME。一项短期蒸气吸入毒性研究中，雄性和雌性Fischer 344大鼠以及B6C3F1小鼠暴露于0、300、1000或3000 ppm的PGMEA，结果证实与PGME相比，PGMEA的全身效应没有实质性差异。然而，组织病理学检查确实发现暴露于PGMEA的大鼠和小鼠鼻黏膜嗅觉部分有变化，这可能与PGMEA在鼻上皮中水解产生的乙酸有关。
