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基于经合组织GL 497中规定的皮肤致敏方法对异噻唑啉酮化合物进行效力分类。

Potency classification of isothiazolinone compounds based on defined approaches of skin sensitization in OECD GL 497.

作者信息

Kim Hyejin, Park Juyoung, Lee Handule, Son Jinseon, Park Yeonjung, Bae Heekyung, Park Sun-Young, Lee Sang Hee, Seo Jungkwan, Shin Sunkyung, Park Kwangsik

机构信息

College of Pharmacy, Dongduk Women's University, Seoul, Republic of Korea.

TO21 Co., Ltd, 350, Seocho-daero, Seocho-gu, Seoul, Republic of Korea.

出版信息

Environ Anal Health Toxicol. 2023 Dec;38(4):e2023026-0. doi: 10.5620/eaht.2023026. Epub 2023 Dec 19.

Abstract

Regulatory decisions for skin sensitization are now based on adverse outcome pathway (AOP) and integrated approaches to testing and assessment (IATA). Based on these, Organisation for Economic Co-operation and Development (OECD) guidelines on defined approaches for skin sensitization were adopted with a fixed data interpretation procedure (DIP). In the guidelines, "Defined Approaches" (DA) on skin sensitization uses the results from multiple information sources of in chemico, in vitro, and in silico data to achieve an equivalent predictive capacity as those of the animal tests. In this review, we evaluated the skin sensitization of eleven isothiazolinone compounds including 4,5-Dichloro-2-octyl-3(2H)-isothiazolone (DCOIT), 2-n-Octyl-4-isothiazolin-3-one (OIT), 2-Methyl-4-isothiazolin-3-one (MIT), 1,2-Benzisothiazolin-3-one (BIT), 1,2-Benzisothiazolin-3-one, 2-butyl (BBIT), 5-Chloro-2-methyl-4-isothiazolin-3-one (CMIT), 2-methyl-4,5-trimethylene-4-isothiazolin-3-one (MTMIT), 2-methyl-1,2-benzothiazol-3-one (MBIT), 2-methyl-1,2-benzothiazole-3-thione (MBIT-S), 1,2-benzisothiazolin-3-one, 2-methyl-, 1,1-dioxide (BBIT-O), and a mixture of CMIT/MIT. Data from direct peptide reactivity assay (DPRA), human cell line activation (h-CLAT) test, and quantitative structure activity relationship (QSAR) Toolbox were evaluated and were applied to the DIP to derive a prediction of hazard identification and a potency classification. Among the evaluated chemicals, six isothiazolinone compounds were classified to be UN GHS 1A, one compound to be UN GHS 1, and four compounds could not be classified due to lack of data. The results of sensitizer chemicals were found to coincide well with those of in vivo test.

摘要

目前,皮肤致敏的监管决策基于不良结局途径(AOP)和测试与评估综合方法(IATA)。基于此,经济合作与发展组织(OECD)通过了关于皮肤致敏定义方法的指南,并采用了固定的数据解释程序(DIP)。在该指南中,皮肤致敏的“定义方法”(DA)利用来自化学、体外和计算机数据等多种信息源的结果,以实现与动物试验相当的预测能力。在本综述中,我们评估了11种异噻唑啉酮化合物的皮肤致敏性,包括4,5-二氯-2-辛基-3(2H)-异噻唑啉酮(DCOIT)、2-正辛基-4-异噻唑啉-3-酮(OIT)、2-甲基-4-异噻唑啉-3-酮(MIT)、1,2-苯并异噻唑啉-3-酮(BIT)、1,2-苯并异噻唑啉-3-酮,2-丁基(BBIT)、5-氯-2-甲基-4-异噻唑啉-3-酮(CMIT)、2-甲基-4,5-三亚甲基-4-异噻唑啉-3-酮(MTMIT)、2-甲基-1,2-苯并噻唑-3-酮(MBIT)、2-甲基-1,2-苯并噻唑-3-硫酮(MBIT-S)、1,2-苯并异噻唑啉-3-酮,2-甲基-,1,1-二氧化物(BBIT-O)以及CMIT/MIT混合物。评估了直接肽反应性测定(DPRA)、人细胞系激活(h-CLAT)试验和定量构效关系(QSAR)工具箱的数据,并将其应用于DIP,以得出危害识别预测和效力分类。在评估的化学品中,6种异噻唑啉酮化合物被分类为联合国全球统一制度1A类,1种化合物为联合国全球统一制度1类,4种化合物因缺乏数据无法分类。致敏化学品的结果与体内试验结果吻合良好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2af/10834078/4978b299a119/eaht-38-4-e2023026f1.jpg

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