4-取代酚诱导化学性白斑的机制及研究进展

doi:10.3969/j.issn.2097-2806.2024.03.011

摘要/Abstract

摘要：

4-取代酚是一类广泛应用于制药、农药、染料、食品添加剂以及化妆品中的有机化合物。4-取代酚在化妆品中的应用主要是由于其与酪氨酸的结构上的相似性，使其具有独特的抑制酪氨酸酶活性以及抑制皮肤中黑色素形成的效果，因此包括熊果苷、白藜芦醇等化学物质在内，已有多种4-取代酚作为美白成分用于化妆品中。但包括杜鹃醇在内的4-取代酚同时也具有一定安全风险，大量研究表明许多4-取代酚具有黑素细胞毒性，且不同的取代基也会对黑素细胞毒性的诱导途径、毒性强弱等产生不同的影响，使用不当可能会诱发白癜风（Vitiligo）和白斑病（Leukoderma）的产生，对消费者的健康造成损害。本文综述了4-取代酚及杜鹃醇的美白及黑素细胞毒性机制，以及不同国家发生白斑病的案例，以期为开发更安全的有美白效果的化学物质提供参考。

关键词: 4-取代酚, 杜鹃醇, 化学性白斑, 机制

Abstract:

4-substituted phenols are a class of organic compounds widely used in pharmaceuticals, pesticides, dyes, food additives and cosmetics. The application of 4-substituted phenols in cosmetics is mainly due to its structural similarity with tyrosine, which makes it have a unique effect of inhibiting tyrosinase activity and inhibiting melanin formation in the skin. Therefore, including chemical substances such as arbutin and resveratrol, there are many 4-substituted phenols used as whitening ingredients in cosmetics. However, 4-substituted phenols including hydroquinone also have certain safety risks. A large number of studies have shown that many 4-substituted phenols have melanocyte toxicity, and different substituents will also induce different pathways and toxicities of melanocyte toxicity. The improper use of them may induce the occurrence of vitiligo and leukoderma, causing harm to the consumers’ health. This article reviews the whitening and melanocyte toxicity mechanisms of 4-substituted phenols and hydroquinone, as well as the cases of leukoderma in different countries, in order to provide reference for the development of safer whitening chemicals.

Key words: 4-substituted phenol, rhododendrol, chemical leukoderma, mechanism

中图分类号:

TQ658

张婉萍, 彭祺, 张冬梅, 郑时莲, 蒋汶, 顾理浩. 4-取代酚诱导化学性白斑的机制及研究进展[J]. 日用化学工业（中英文）, 2024, 54(3): 320-328.

Wanping Zhang, Qi Peng, Dongmei Zhang, Shilian Zheng, Wen Jiang, Lihao Gu. Mechanism and research progress of chemical leukoderma induced by 4-substituted phenols[J]. China Surfactant Detergent & Cosmetics, 2024, 54(3): 320-328.

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类别	物质名称	CAS
苯酚衍生物	4-苄氧基苯酚	103-16-2
	1,4-苯二酚（氢醌）	123-31-9
	4-甲氧基苯酚	150-76-5
	4-乙氧基苯酚	622-62-8
	4-叔丁基苯酚	98-54-4
	4-叔戊基苯酚	80-46-6
	4-苯基苯酚	92-69-3
	4-辛基苯酚	1806-26-4
	4-壬基苯酚	104-40-5
	丁基羟基甲苯	128-37-0
	丁基羟基茴香醚	25013-16-5
	4-甲基苯酚	106-44-5
	4-（4-羟苯基）-2-丁醇（杜鹃醇）	501-96-2
	4-（4-羟基苯基）-2-丁酮（覆盆子酮）	5471-51-2
儿茶酚衍生物	4-叔丁基儿茶酚	98-29-3
	4-甲基儿茶酚	452-86-8
	4-异丙基儿茶酚	2138-43-4
	儿茶酚（邻苯二酚）	120-80-9
巯基化合物	半胱胺	60-23-1
	N-（2-巯基乙基）-二甲胺盐酸盐	13242-44-9
	磺酸	—
	胱胺二盐酸盐	56-17-7
	3-氨基丙硫醇盐酸盐	7211-54-3
光学制剂	毒扁豆碱	57-47-6
	氟磷酸二异丙酯	55-91-4
	塞替派	52-24-4
	呋喃硝基鸟苷	—
系统性疾病药物	氯喹	54-05-7
系统性疾病药物	氟非那嗪	69-23-8
其他	汞制剂	—
	桂皮醛	14371-10-9
	砷	7440-38-2
	苯甲醇	100-51-6
	过氧化苯甲酰	94-36-0
	皮质类固醇	—
	壬二酸	123-99-9
	苯基缩水甘油醚	122-60-1
	聚氯乙烯塑料	25702-80-1
	酸性红 73	5413-75-2
	罗丹明B	81-88-9
	亮红R	5858-77-5
	卡莫司汀	154-93-8
	丙烯酸酯类	—
	镍	7440-02-0
	氟尿嘧啶	51-21-8
	维甲酸	302-79-4
	2, 4-二硝基氯苯	97-00-7
	方酸二正丁酯	2892-62-8
	对苯二胺	106-50-3

阶段	症状
阶段Ⅰ	只在接触化学产品的部位有症状
阶段Ⅱ	化学性白斑通过接触部位以外的淋巴管进行的局部传播
阶段ⅢA	化学性白斑通过血行传播在接触部位以外的远处传播
阶段ⅢB	化学性白斑通过血行扩散超过接触部位，并累及全身器官
阶段ⅢC	除皮肤接触外，全身引入（注射、吸入或摄入）引起化学白斑，不一定累及全身器官
阶段Ⅳ	白癜风样斑块的远距离传播，甚至在严格禁止接触有害化学物质1年后仍然如此

已经报道的RD诱导白斑病的机制	参考文献
RD诱导黑素细胞的细胞毒性，且依赖于酪氨酸酶	[29,30]
在较高浓度的酪氨酸酶中，RD会代谢成RD-醌和RD儿茶酚等其他氧化产物	[31?-33]
RD诱导的黑素细胞的细胞毒性与内质网应激和细胞凋亡有关	[22,34? -36]
ROS，特别是·OH是在酪氨酸酶的RD氧化过程中产生的，并可能通过氧化性DNA损伤诱导细胞毒性	[23,24,38,39,44,45]
ROS的产生可能与RD代谢物与谷胱甘肽和半胱氨酸的结合有关	[32,33,37]
UVB暴露可能通过诱导内质网应激增加RD诱导的黑素细胞毒性	[34]
RD在小鼠皮肤中部分代谢为RK，ADH可能参与了RD的氧化	[46]

化学物质名称	CAS号	机制	参考文献	化学物质名称	CAS号	机制	参考文献
4-苯氧基苯酚	831-82-3	i	[50]	4-苄氧基苯酚	103-16-2	i	[50,54,58,60]
4-己氧基苯酚	18979-55-0	i	[50]	4-苄基苯酚	101-53-1	i	[50,59]
4-甲基苯酚	106-44-5	i	[50]	4-甲氧基苯酚	150-76-5	i	[50,59,61]
4-苯基苯酚	92-69-3	i	[50]	4-叔戊基苯酚	80-46-6	i	[50,61]
1,4-苯二酚（氢醌）	123-31-9	ii	[50, 53, 55]	4-辛基苯酚	1806-26-4	—	[62]
4-乙氧基苯酚	622-62-8	—	[56]	4-壬基苯酚	104-40-5	—	[62]
4-叔丁基苯酚	98-54-4	iii	[57, 58]