Mutlu Esra, South Natalie, Pierfelice Jessica, Djonabaye Alison, Pauff Mindy, Burback Brian, Waidyanatha Suramya
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
Battelle Memorial Institute, Columbus, OH.
Anal Lett. 2022;55(13):2074-2088. doi: 10.1080/00032719.2022.2044348. Epub 2022 Mar 2.
Phenolic benzotriazoles are used as UV stabilizers in consumer products and have been detected in the environment suggesting potential human exposure. Phenolic benzotriazoles were nominated to the Division of National Toxicology Program for testing based on their potential widespread human exposure and lack of adequate toxicity data. Nine chemicals were selected for toxicological evaluation, representing unsubstituted (2-(2H-benzotriazole-2-yl)phenol, (P-BZT)), monosubstituted (drometrizole; 2-(2H-benzotriazol-2-yl)-4-tert-butylphenol (tBu-BZT); octrizole), disubstituted (2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol (diMeEtPh-BZT), 2-(2H-benzotriazol-2-yl)-4,6-bis(1,1-dimethylpropyl)phenol (ditPe-BZT); 3-(2H-benzotriazol-2-yl)-5-(1,1-dimethylethyl)-4-hydroxybenzenepropanoic acid, octylester (tBuPrOcEst-BZT) and halogenated trisubstituted (bumetrizole; 2-(5-chloro-2H-benzotriazol-2-yl)-4,6-bis(1,1-dimethylethyl)phenol (ditBuCl-BZT)) compounds. Different extraction methods were utilized and methods were developed to analyze phenolic benzotriazoles by quantitating free (unconjugated parent) and total (free and conjugated parent) analyte levels in plasma of rats to aid in interpretation of toxicity data, understanding of absorption, distribution, metabolism, and excretion differences. The calibration standard range was 1-500 ng/mL for free analytes and 1-1000 ng/mL for total analytes. The methods were linear (r ≥ 0.99). The accuracy was determined as relative error (RE) and ranged from -18.2 to +17.8, and precision was determined as relative standard deviation (RSD) and ranged from 0.0 to 20.1% for both free and total plasma calibration standards, respectively. The limit of quantitation was ≤ 5.0 and 10.0 ng/mL and limit of detection was ≤ 1.2 and 2.0 ng/mL, for free and total analytes, respectively. These data demonstrate that the methods are suitable for quantitation of free and total analytes in rat plasma.
酚类苯并三唑在消费品中用作紫外线稳定剂，并且已在环境中被检测到，这表明人类可能会接触到它们。基于酚类苯并三唑潜在的广泛人类接触以及缺乏充分的毒性数据，它们被提名为国家毒理学计划部门进行测试。选择了九种化学品进行毒理学评估，分别代表未取代的（2-(2H-苯并三唑-2-基)苯酚，(P-BZT)）、单取代的（屈美通；2-(2H-苯并三唑-2-基)-4-叔丁基苯酚(tBu-BZT)；辛唑）、双取代的（2-(2H-苯并三唑-2-基)-4,6-双(1-甲基-1-苯乙基)苯酚(diMeEtPh-BZT)，2-(2H-苯并三唑-2-基)-4,6-双(1,1-二甲基丙基)苯酚(ditPe-BZT)；3-(2H-苯并三唑-2-基)-5-(1,1-二甲基乙基)-4-羟基苯丙酸辛酯(tBuPrOcEst-BZT)）以及卤代三取代的（苯甲三唑；2-(5-氯-2H-苯并三唑-2-基)-4,6-双(1,1-二甲基乙基)苯酚(ditBuCl-BZT)）化合物。采用了不同的提取方法，并开发了通过定量大鼠血浆中游离（未结合母体）和总（游离和结合母体）分析物水平来分析酚类苯并三唑的方法，以帮助解释毒性数据，了解吸收、分布、代谢和排泄差异。游离分析物的校准标准范围为1-500 ng/mL，总分析物的校准标准范围为1-1000 ng/mL。这些方法具有线性关系（r≥0.99）。准确度以相对误差（RE）确定，范围为-18.2至+17.8，精密度以相对标准偏差（RSD）确定，游离和总血浆校准标准的精密度分别为0.0至20.1%。游离和总分析物的定量限分别≤5.0和10.0 ng/mL，检测限分别≤1.2和2.0 ng/mL。这些数据表明这些方法适用于定量大鼠血浆中的游离和总分析物。
