Ahmed A E, Jacob S, Au W W
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0605.
Fundam Appl Toxicol. 1994 Feb;22(2):266-76. doi: 10.1006/faat.1994.1030.
Glycol ethers such as ethylene glycol monomethyl ether (EGME) are common solvents used in many industrial products. A large number of individuals are exposed to EGME through different exposure routes. We investigated the differential distribution of EGME following various routes of administration using whole body autoradiographic (WBA) techniques. Male B6C3F1 mice were treated with tracer iv or oral doses of [2-14C]EGME (4.05 micrograms EGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24 hr following treatment. In both groups of animals the highest levels of radioactivity were detected in the liver, urinary bladder, bone marrow, kidney, and epididymis, at 1- and 24-hr time periods. Computer-assisted quantitation of WBA indicated that there was markedly higher deposition of [2-14C]EGME and/or its metabolites in various tissues of the orally treated animals than in animals treated intravenously. Our studies also suggest that [2-14C]EGME is rapidly distributed either from blood or stomach to various tissues. Preferential deposition of radioactivity in the peripheral tissues of the bone, with a progressive inward accumulation in the bone marrow, was observed. Selective permeability of EGME and/or its metabolites was indicated by the higher uptake by the epididymis than that by testis. The high levels of radioactivity in biosynthetically active tissues, e.g., the liver, bone marrow, and gastric mucosa, is an indication of persistent interaction of the compound with cellular components of these tissues. These interactions may lead to EGME toxicity.
乙二醇醚类,如乙二醇单甲醚(EGME),是许多工业产品中常用的溶剂。大量个体通过不同的接触途径接触到EGME。我们使用全身放射自显影(WBA)技术研究了EGME经各种给药途径后的差异分布。雄性B6C3F1小鼠接受示踪剂静脉注射或口服剂量的[2-¹⁴C]EGME(4.05微克EGME/千克,相当于0.8毫居里/千克),并在给药后1小时和24小时处死。在这两组动物中,在1小时和24小时时,肝脏、膀胱、骨髓、肾脏和附睾中检测到的放射性水平最高。WBA的计算机辅助定量分析表明,口服给药动物的各种组织中[2-¹⁴C]EGME和/或其代谢产物的沉积明显高于静脉注射给药的动物。我们的研究还表明,[2-¹⁴C]EGME可迅速从血液或胃分布到各种组织。观察到放射性优先沉积在骨骼的外周组织中,并在骨髓中逐渐向内积累。附睾对EGME和/或其代谢产物的摄取高于睾丸,表明其具有选择性通透性。生物合成活跃组织,如肝脏、骨髓和胃黏膜中放射性水平较高,表明该化合物与这些组织的细胞成分持续相互作用。这些相互作用可能导致EGME毒性。