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大鼠体内对苯二甲酸二(2-乙基己基)酯的水解、吸收及代谢

Hydrolysis, absorption and metabolism of di(2-ethylhexyl) terephthalate in the rat.

作者信息

Barber E D, Fox J A, Giordano C J

机构信息

Eastman Kodak Co., Corporate Health and Environment Laboratories, Rochester, NY 14652-3615.

出版信息

Xenobiotica. 1994 May;24(5):441-50. doi: 10.3109/00498259409043247.

DOI:10.3109/00498259409043247
PMID:8079503
Abstract
  1. The hydrolysis of di(2-ethylhexyl) terephthalate (DEHT) and di(2-ethylhexyl) phthalate (DEHP) were studied using rat gut homogenate fractions in vitro. Both isomers were hydrolysed by the intestinal fraction; however, DEHP was hydrolysed to 2-ethylhexanol (2-EH) and mono(2-ethylhexyl) phthalate (MEHP) in about equal proportions, whereas DEHT was hydrolysed to 2-EH and terephthalic acid (TPA). The half-lives for disappearance of the diesters were determined to be 12.6 min for DEHP and 53.3 min for DEHT. 2. The absorption and metabolism of DEHT were studied by administering [hexyl-2-14C]DEHT (in corn oil) by oral gavage at a dose level of 100 mg/kg to 10 adult male Sprague-Dawley rats. Urine, faeces and expired air were collected for 144 h and analysed for the presence of radioactivity, and faeces and urine were analysed for unlabelled metabolites. 3. Radioactivity was eliminated in faeces (56.5 +/- 12.1% of dose) primarily as unchanged DEHT, small amounts of MEHT and polar metabolites; excreted in urine (31.9 +/- 10.9% of dose) principally as MEHT and metabolic products of 2-EH; and expired as 14CO2 (3.6 +/- 0.9% of dose). Less than 2% of the administered radioactivity was found in the carcass. Small amounts of 14C were found in the tissues with the highest amounts found in liver and fat. 4. Metabolites identified in urine included terephthalic acid (equivalent to 51% of dose), oxidized metabolites of 2-EH and MEHT, and glucuronic and sulphuric acid conjugates (equivalent to about 10% of dose).(ABSTRACT TRUNCATED AT 250 WORDS)
摘要
  1. 采用大鼠肠道匀浆组分在体外研究了对苯二甲酸二(2-乙基己基)酯(DEHT)和邻苯二甲酸二(2-乙基己基)酯(DEHP)的水解情况。两种异构体均被肠道组分水解;然而,DEHP水解生成2-乙基己醇(2-EH)和邻苯二甲酸单(2-乙基己基)酯(MEHP)的比例大致相等,而DEHT水解生成2-EH和对苯二甲酸(TPA)。二酯消失的半衰期经测定,DEHP为12.6分钟,DEHT为53.3分钟。2. 通过以100mg/kg的剂量水平经口灌胃给予[己基-2-¹⁴C]DEHT(溶于玉米油),对10只成年雄性斯普拉格-道利大鼠研究了DEHT的吸收和代谢情况。收集尿液、粪便和呼出气体144小时,并分析其中放射性的存在情况,同时分析粪便和尿液中的未标记代谢物。3. 放射性主要以未变化的DEHT、少量的MEHT和极性代谢物的形式在粪便中消除(占剂量的56.5±12.1%);主要以MEHT和2-EH的代谢产物的形式经尿液排泄(占剂量的31.9±10.9%);并以¹⁴CO₂的形式呼出(占剂量的3.6±0.9%)。在 carcass中发现的给药放射性不到2%。在组织中发现少量¹⁴C,其中肝脏和脂肪中的含量最高。4. 在尿液中鉴定出的代谢物包括对苯二甲酸(相当于剂量的51%)、2-EH和MEHT的氧化代谢物以及葡萄糖醛酸和硫酸共轭物(相当于约剂量的10%)。(摘要截断于250字)

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