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人体单次口服三(2-丁氧基乙基)磷酸酯(TBOEP)的毒代动力学研究。

Toxicokinetic of tris(2-butoxyethyl) phosphate (TBOEP) in humans following single oral administration.

机构信息

Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority, Pfarrstrasse 3, 80538, Munich, Germany.

Department of Toxicology, University of Würzburg, Versbacher Strasse 9, 97078, Würzburg, Germany.

出版信息

Arch Toxicol. 2018 Feb;92(2):651-660. doi: 10.1007/s00204-017-2078-7. Epub 2017 Sep 27.

Abstract

Tris(2-butoxyethyl) phosphate (TBOEP; 20 µg/kg b.w.) was orally administered to three female and three male volunteers. In urine samples collected for 39 h three metabolites of TBOEP were quantitated. bis(2-butoxyethyl) phosphate (BBOEP), tris(2-(3-hydroxy)butoxyethyl) phosphate (OH-TBOEP), bis(2-butoxyethyl)-(2-hydroxyethyl) phosphate (BBOEHEP) were observed in all urine samples within the first 7 h with highest concentration for BBOEHEP. C of OH-TBOEP was in the range of 2-4 h and t was between 1.5 and 6.1 h. Similar results were obtained for BBOEHEP. In contrast BBOEP showed several maxima within 25 h and, therefore, no toxicokinetic data were calculated. As proof of concept 54 urine samples of children staying at day-care centers in Germany were analysed for all 3 biomarkers. Only BBOEP and BBOEHEP were detected in about 80% of the samples with a median of 0.16 µg/l for BBOEP and 0.18 µg/l for BBOEHEP. A recalculation of daily intake (DI) based on BBOEHEP resulted in a clear undercut of the current reference dose of 50 µg/kg per day. As observed in other studies a calculation of the DI based on the dust concentrations and oral uptake of 20 mg of dust for 8 h for young children results in considerably higher DI but would also not exceed the RfD.

摘要

三正(2-丁氧基乙基)磷酸酯(TBOEP;20μg/kg bw)经口给予 3 名女性和 3 名男性志愿者。在收集的 39 小时尿液样本中,定量了 TBOEP 的 3 种代谢物。在所有尿液样本中,在最初 7 小时内观察到双(2-丁氧基乙基)磷酸酯(BBOEP)、三(2-(3-羟基)丁氧基乙基)磷酸酯(OH-TBOEP)和双(2-丁氧基乙基)-(2-羟基乙基)磷酸酯(BBOEHEP),其中 BBOEHEP 的浓度最高。OH-TBOEP 的 C 范围为 2-4 小时,t 为 1.5-6.1 小时。对于 BBOEHEP 也得到了类似的结果。相比之下,BBOEP 在 25 小时内出现了多个最大值,因此没有计算毒代动力学数据。作为概念验证,分析了德国日托中心的 54 名儿童的尿液样本,以检测所有 3 种生物标志物。只有 BBOEP 和 BBOEHEP 在大约 80%的样本中被检测到,BBOEP 的中位数为 0.16μg/l,BBOEHEP 的中位数为 0.18μg/l。基于 BBOEHEP 重新计算每日摄入量(DI),明显低于当前的 50μg/kg 每日参考剂量。与其他研究一样,根据儿童每天 8 小时吸入 20 毫克灰尘的灰尘浓度和口服摄取量计算 DI,结果表明 DI 要高得多,但仍不会超过 RfD。

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