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首页> 外文会议>Joint annual meeting of the International Society of Exposure Science and the International Society for Environmental Epidemiology >Human toxicokinetic profiles after the dermal exposure to methyl-, ethyl-, and propyl paraben in human
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Human toxicokinetic profiles after the dermal exposure to methyl-, ethyl-, and propyl paraben in human

机译：皮肤暴露于对羟基苯甲酸甲酯，对羟基苯甲酸乙酯，对羟基苯甲酸乙酯和对羟基苯甲酸丙酯后的人体毒性动力学

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Parabens are commonly used preservatives in cosmetics, but there have been concerns on the association between their exposure and adverse outcomes. Although humans are exposed to various parabens through food intake and dermal exposure, the information on the relative contribution to internal dose via each exposure pathway are limited. This study investigated urinary excretion of methyl- (MtP), ethyl- (EtP), and propyl paraben (PrP) after topical application in human volunteers and compares with the results from oral exposure study to find out the contributions. We determined the pharmacokinetic characteristics of MtP, EtP, and PrP in humans following a single dermal application of 6.5 g of cream containing deuterium labeled MtP, EtP, and PrP (approx. 1% each). Blood and urine were collected at several intervals over the course of 48 hours to measure levels of the parabens and their metabolites in five male volunteers. The unconjugated parent compounds (free parabens), glucuronide and sulfate conjugates were measured using HPLC-MS/MS. The fraction of dermally exposed dose excreted into urine (Fue) based on the applied amounts were ranged from 0.13 ～ 0.15 % for free parabens, 1.38 ～ 1.88 % for total parabens (sum of free and conjugated parabens). Meanwhile, the Fue calculated from orally administered PrP experiment in our previous study (male, n - 7) were lower than those in free PrP (0.04 %) and much higher than those in total PrP (8.5%) compared to the data from dermal exposure. Depending on the exposure pathways of parabens, the quantitative difference on excretion rates were observed. Especially, the difference of conjugated metabolites by exposure pathways was obviously larger than the other metabolite. The present study can be utilized to predict the contribution of parabens to the human body by exposure pathways. Eventually, it can provide important information on making strategies to reduce paraben exposures.
机译：对羟基苯甲酸酯是化妆品中常用的防腐剂，但人们一直担心它们的暴露与不良后果之间的关系。尽管人类通过食物摄入和皮肤接触而接触到各种对羟基苯甲酸酯，但有关通过每种接触途径对内部剂量的相对贡献的信息仍然有限。本研究调查了在人类志愿者中局部应用后甲基（MtP），乙基（EtP）和对羟基苯甲酸丙酯（PrP）的尿排泄情况，并将其与口服暴露研究的结果进行比较以找出其贡献。在单次皮肤应用6.5 g含氘标记的MtP，EtP和PrP的乳膏（各约1％）后，我们确定了MtP，EtP和PrP在人体内的药代动力学特性。在48小时的过程中，每隔几个时间采集一次血液和尿液，以测量五位男性志愿者中对羟基苯甲酸酯及其代谢产物的水平。使用HPLC-MS / MS测量未结合的母体化合物（游离的对羟基苯甲酸酯），葡糖醛酸苷和硫酸盐结合物。基于施用量，经皮肤排泄到尿液中的剂量（Fue）的比例为游离对羟基苯甲酸酯的0.13〜0.15％，总对羟基苯甲酸酯（游离和结合对羟基苯甲酸酯的总和）为1.38〜1.88％。同时，通过口服PrP实验计算出的Fue（男性，n-7）低于游离PrP（0.04％），远高于总PrP（8.5％）。接触。根据对羟基苯甲酸酯的暴露途径，观察到排泄率的数量差异。特别是，暴露途径对共轭代谢产物的差异明显大于其他代谢产物。本研究可用于通过暴露途径预测对羟基苯甲酸酯对人体的贡献。最终，它可以提供有关制定减少对羟基苯甲酸酯暴露量的策略的重要信息。

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