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Phototoxic risk assessment of dermally-applied chemicals with structural variety based on photoreactivity and skin deposition.
Regulatory Toxicology and Pharmacology ( IF 3.0 ) Pub Date : 2020-02-21 , DOI: 10.1016/j.yrtph.2020.104619
Yoshiki Seto 1 , Hiroto Ohtake 1 , Hideyuki Sato 1 , Satomi Onoue 1
Affiliation  

Combined use of photochemical and pharmacokinetic (PK) data for phototoxic risk assessment was previously proposed, and the system provided reliable phototoxic risk predictions of chemicals in same chemical series. This study aimed to verify the feasibility of the screening system for phototoxic risk assessment on dermally-applied chemicals with wide structural diversity, as a first attempt. Photochemical properties of test chemicals, 2-acetonaphthalene, 4'-methylbenzylidene camphor, 6-methylcoumarin, methyl N-methylanthranilate, and sulisobenzone, were evaluated in terms of UV absorption and reactive oxygen species (ROS) generation, and PK profiles of the test chemicals in rat skin were characterized after dermal co-application. All test chemicals showed strong UVA/B absorption with molar extinction coefficients of over 3000 M-1⋅cm-1, and irradiated 2-acetonaphthalene, 6-methylcoumarin, and methyl N-methylanthranilate exhibited significant ROS generation. Dermally-applied 2-acetonaphthalene and 4'-methylbenzylidene camphor indicated high and long-lasting skin deposition compared with the other test chemicals. Based on the photochemical and PK data, 2-acetonaphthalene was predicted to have potent phototoxic risk. The predicted phototoxic risk of the test chemicals by integration of obtained data was mostly consistent with their in vivo phototoxicity observed in rat skin. The screening strategy employing photochemical and PK data would have high prediction capacity and wide applicability for photosafety evaluation of chemicals.

中文翻译:

基于光反应性和皮肤沉积的结构多样的真皮应用化学品的光毒性风险评估。

先前曾提出将光化学和药代动力学(PK)数据结合用于光毒性风险评估,并且该系统提供了同一化学系列中化学品的可靠光毒性风险预测。这项研究旨在验证筛选系统对具有广泛结构多样性的经皮肤施用的化学物质进行光毒性风险评估的可行性,这是首次尝试。根据紫外线吸收和活性氧(ROS)的产生以及测试的PK曲线评估了测试化学品2-乙酰萘,4'-甲基亚苄基樟脑,6-甲基香豆素,N-甲基邻氨基苯甲酸甲酯和磺基异戊二烯的光化学性质皮肤共施用后,对大鼠皮肤中的化学物质进行了表征。所有测试化学品均表现出较强的UVA / B吸收能力,摩尔消光系数超过3000 M-1·cm-1,辐照的2-乙酰萘,6-甲基香豆素和N-甲基邻氨基苯甲酸甲酯显示出明显的ROS生成。与其他测试化学品相比,皮肤上施用的2-乙酰萘和4'-甲基亚苄基樟脑表明皮肤沉积高而持久。根据光化学和PK数据,预计2-乙酰萘具有潜在的光毒性风险。通过整合获得的数据,预计测试化学物质的光毒性风险与在大鼠皮肤中观察到的体内光毒性基本一致。采用光化学和PK数据的筛选策略将具有较高的预测能力和广泛的适用于化学品的光安全性评估。与其他测试化学品相比,皮肤上施用的2-乙酰萘和4'-甲基亚苄基樟脑表明皮肤沉积高而持久。根据光化学和PK数据,预计2-乙酰萘具有潜在的光毒性风险。通过整合获得的数据,预计测试化学物质的光毒性风险与在大鼠皮肤中观察到的体内光毒性基本一致。采用光化学和PK数据的筛选策略将具有较高的预测能力和广泛的适用于化学品的光安全性评估。与其他测试化学品相比,皮肤上施用的2-乙酰萘和4'-甲基亚苄基樟脑表明皮肤沉积高而持久。根据光化学和PK数据,预计2-乙酰萘具有潜在的光毒性风险。通过整合获得的数据,预计测试化学物质的光毒性风险与在大鼠皮肤中观察到的体内光毒性基本一致。采用光化学和PK数据的筛选策略将具有较高的预测能力和广泛的适用于化学品的光安全性评估。通过整合获得的数据,预计测试化学物质的光毒性风险与在大鼠皮肤中观察到的体内光毒性基本一致。采用光化学和PK数据的筛选策略将具有较高的预测能力和广泛的适用于化学品的光安全性评估。通过整合获得的数据,预计测试化学物质的光毒性风险与在大鼠皮肤中观察到的体内光毒性基本一致。采用光化学和PK数据的筛选策略将具有较高的预测能力和广泛的适用于化学品的光安全性评估。
更新日期:2020-02-21
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