Ballantyne Bryan, Jensen Charles B, Weaver Elizabeth V
Applied Toxicology Group, Union Carbide Corporation, 39 Old Ridgebury Road, Danbury, CT 06817, USA.
J Appl Toxicol. 2003 Sep-Oct;23(5):301-14. doi: 10.1002/jat.920.
Ethylene glycol monohexyl ether (EGHE; CAS no. 112-54-4) is a liquid industrial chemical with a potential for skin contact. The toxicokinetics of EGHE was investigated in Fischer 344 rats and New Zealand White rabbits by intravenous (i.v.) and 48-h occluded epicutaneous dosing. Given i.v. to male rats (2.5-25 mg kg(-1)) [(14)C]EGHE demonstrated fi rst-order kinetics. Carbon-14 was eliminated mainly in urine (68-74%) as metabolites, with no free EGHE. The plasma free EGHE concentration declined rapidly post-dosing and was not detectable by 8 h. Similar results were obtained for [(14)C]EGHE given i.v. to male rabbits in the dosage range 1-10 mg kg(-1), except that the metabolism of EGHE was more rapid, with no free EGHE being detectable in plasma by 1 h post-dosing. After cutaneous dosing of male and female rats with 25 mg kg(-1), there was rapid percutaneous absorption, with >95% of the radiochemical dose being recovered. Percutaneous bioavailability was >75%. Carbon-14 was excreted in urine (21-33%) to a lesser extent than by the i.v. route, and (14)CO(2) and volatiles accounted for 15-18%. Carbon-14 recovery was low from tissues and organs (0.39-0.46%), with no preferential accumulation. Extensive metabolism was indicated by the rapid decline in plasma free EGHE, with none being detectable by 48 h. Free EGHE was not present in urine, and urinary radioactivity was associated with up to seven metabolites. After cutaneous dosing of male and female rabbits (10 mg kg(-1)) ca. 75% of the dose was recovered, most (14)C being in urine (58-60%). Urine radioactivity was associated with up to nine metabolite peaks, but no free EGHE. The toxicokinetic findings indicate a significant percutaneous absorption of EGHE across both rat and rabbit skin, which is rapidly and extensively metabolized, with renal excretion being the principal route of elimination of metabolites. A 9-day repeated skin contact study in the male and female New Zealand White rabbit, using a dosage range of 44-444 mg kg(-1) day(-1), did not show any evidence for percutaneous systemic toxicity.
乙二醇单己醚（EGHE；化学物质登记号：112 - 54 - 4）是一种液态工业化学品，有可能与皮肤接触。通过静脉注射（i.v.）给药以及48小时封闭性经皮给药，在Fischer 344大鼠和新西兰白兔中研究了EGHE的毒代动力学。给雄性大鼠静脉注射[(14)C]EGHE（剂量为2.5 - 25 mg kg(-1)）显示为一级动力学。碳 - 14主要以代谢物形式经尿液排出（68 - 74%），无游离EGHE。给药后血浆中游离EGHE浓度迅速下降，8小时后检测不到。给雄性兔子静脉注射剂量范围为1 - 10 mg kg(-1)的[(14)C]EGHE也得到了类似结果，只是EGHE的代谢更快，给药后1小时血浆中就检测不到游离EGHE。给雄性和雌性大鼠经皮给予25 mg kg(-1)剂量后，经皮吸收迅速，放射性化学剂量的回收率>95%。经皮生物利用度>75%。碳 - 14经尿液排泄的比例（21 - 33%）低于静脉注射途径，(14)CO(2)和挥发性物质占15 - 18%。组织和器官中的碳 - 14回收率较低（0.39 - 0.46%），无优先蓄积现象。血浆中游离EGHE迅速下降表明有广泛的代谢，48小时后检测不到游离EGHE。尿液中不存在游离EGHE，尿放射性与多达七种代谢物有关。给雄性和雌性兔子经皮给予10 mg kg(-1)剂量后，约75%的剂量被回收，大部分(14)C存在于尿液中（58 - 60%）。尿放射性与多达九个代谢物峰有关，但无游离EGHE。毒代动力学研究结果表明，EGHE可经大鼠和兔子皮肤显著经皮吸收，吸收后迅速且广泛地代谢，肾脏排泄是代谢物消除的主要途径。在雄性和雌性新西兰白兔中进行的一项为期9天的重复皮肤接触研究，使用的剂量范围为44 - 444 mg kg(-1) 天(-1)，未显示经皮全身毒性的任何证据。
