Evaluation of the dermal bioavailability of aqueous xylene in F344 rats and human volunteers.
Evaluation of the dermal bioavailability of aqueous xylene in F344 rats and human volunteers.
复制标题
评估 F344 大鼠和人类志愿者中含水二甲苯的皮肤生物利用度。
DOI：
10.1080/15287390306407
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Woodstock,Angela
中科院分区：
文献类型：
--
作者：
Thrall,Karla;Woodstock,Angela
二甲苯是一种透明、无色的液体，用作印刷、橡胶和皮革工业的溶剂，通常用于油漆稀释剂、油漆、清漆和粘合剂中。虽然人类最可能通过吸入接触二甲苯，但井水和地表水中也存在二甲苯。因此，评估皮肤对二甲苯摄取总量的贡献对于了解人体暴露是有用的。为了评估这些暴露的意义，使用实时呼气分析和基于生理的药代动力学（PBPK）建模相结合的方法评估了F344只雄性大鼠和人类志愿者对邻二甲苯的皮肤吸收。动物皮肤接触邻二甲苯。在开始接触后，个体动物被放置在一个玻璃排气室中，并对其呼气进行监测。参与这项研究的人类志愿者将双腿放在一个不锈钢水疗浴缸中，浴缸中初始浓度约为500微克/升的邻二甲苯。在暴露于跟踪吸收和随后的实时消除化合物之前，期间和之后，对每个志愿者呼出的气体进行持续分析。在动物和人类研究中，使用PBPK模型来估计皮肤渗透系数（kp），以描述每组呼出的数据。研究发现，大鼠皮肤对水性邻二甲苯的渗透性大约是人类皮肤的12倍。估计人类和大鼠的邻二甲苯K p值分别为0.005 ~ 0.001 cm/h和0.058 ~ 0.009 cm/h。
Xylene is a clear, colorless liquid used as a solvent in the printing, rubber, and leather industries and is commonly found in paint thinners, paints, varnishes, and adhesives. Although humans are most likely to be exposed to xylene via inhalation, xylene is also found in well and surface water. Therefore, an assessment of the dermal contribution to total xylene uptake is useful for understanding human exposures. To evaluate the significance of these exposures, the dermal absorption of o-xylene was assessed in F344 male rats and human volunteers using a combination of real-time exhaled breath analysis and physiologically based pharmacokinetic (PBPK) modeling. Animals were exposed to o-xylene dermally. Immediately following the initiation of exposure, individual animals were placed in a glass off-gassing chamber and exhaled breath was monitored. Human volunteers participating in the study placed both legs into a stainless steel hydrotherapy tub containing an initial concentration of approximately 500 w g/L o-xylene. Exhaled breath was continually analyzed from each volunteer before, during, and after exposure to track absorption and subsequent elimination of the compound in real time. In both animal and human studies, a PBPK model was used to estimate the dermal permeability coefficient (K p ) to describe each set of exhaled breath data. Rat skin was found to be approximately 12 times more permeable to aqueous o-xylene than human skin. The estimated human and rat aqueous o-xylene K p values were 0.005 - 0.001 cm/h and 0.058 - 0.009 cm/h, respectively.