ABF Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152, Planegg, Germany; Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians University Munich, Butenandtstr. 5-13, 81377, Munich, Germany.
ABF Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152, Planegg, Germany.
Int J Hyg Environ Health. 2020 Jun;227:113509. doi: 10.1016/j.ijheh.2020.113509. Epub 2020 Mar 13.
Hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate, better known under its trading name Uvinul A plus® is a UV filter mainly used in sunscreens, but also present in other cosmetic products with a maximum concentration of 10% (w/w) according to the EU directive. In this study we investigated the human metabolism after a single oral and a single dermal dose of Uvinul A plus®, respectively. Samples collected within 72 h of administration were analyzed with a newly developed UHPLC-MS/MS method. Results of the study revealed three major urinary metabolites, namely 2-(4-amino-2-hydroxybenzoyl)benzoic acid (AHB), 2-(4-(ethylamino)-2-hydroxybenzoyl)benzoic acid (EHB) and 2-(4-(diethylamino)-2-hydroxybenzoyl)benzoic acid (DHB), representing 52% of the administered oral dose. The three major metabolites are further converted into four minor metabolites with an additional hydroxyl group in the aniline moiety. Toxicokinetic parameters (amount excreted, t, elimination constant and half-life t) and conversion factors were determined for the three major metabolites. The conversion factors were used to estimate the mean daily exposure to Uvinul A plus® in spot urine samples from 58 volunteers not intentionally exposed to Uvinul A plus® derived from a pilot study. The three major metabolites were quantifiable in 26% of the samples. In 35% of the samples, at least one major metabolite could be quantified. The daily systemic exposure to Uvinul A plus® was estimated to approximately 8.1-9.3 μg/d by applying the combined conversion factor for all three major metabolites. In conclusion, a very low systemic exposure to DHHB was observed with regard to the no observed adverse effect level (NOAEL) as an established threshold for chronic uptake.
2-[4-(二乙氨基)-2-羟基苯甲酰基]苯甲酸己酯，商品名为 Uvinul A plus®，是一种主要用于防晒霜的紫外线滤光剂，但根据欧盟指令，也存在于其他最高浓度为 10%（w/w）的化妆品产品中。在这项研究中，我们分别研究了 Uvinul A plus®单次口服和单次皮肤给药后的人体代谢情况。在给药后 72 小时内采集的样本用新开发的 UHPLC-MS/MS 方法进行分析。研究结果显示，三种主要的尿代谢产物分别为 2-(4-氨基-2-羟基苯甲酰基)苯甲酸（AHB）、2-(4-(乙基氨基)-2-羟基苯甲酰基)苯甲酸（EHB）和 2-(4-(二乙基氨基)-2-羟基苯甲酰基)苯甲酸（DHB），占口服剂量的 52%。这三种主要代谢物进一步转化为苯胺部分增加一个羟基的四个次要代谢物。确定了三种主要代谢物的毒代动力学参数（排泄量、t、消除常数和半衰期 t）和转化率。利用转化率估计了来自一项初步研究的未故意接触 Uvinul A plus®的 58 名志愿者的尿斑样本中 Uvinul A plus®的平均每日暴露量。在 26%的样本中可定量检测到三种主要代谢物。在 35%的样本中，至少可以定量检测到一种主要代谢物。应用所有三种主要代谢物的综合转化率，估计 Uvinul A plus®的每日全身暴露量约为 8.1-9.3μg/d。总之，与作为慢性摄入确立阈值的无观察不良效应水平（NOAEL）相比，观察到 DHHB 的全身暴露量非常低。
