Centre for Occupational and Environmental Health, Division of Population Health, University of Manchester, Manchester M13 9PL, UK.
Int J Environ Res Public Health. 2022 Feb 24;19(5):2632. doi: 10.3390/ijerph19052632.
In January 2021, the European Union ended the license of Mancozeb, the bestselling ethylenedithiocarbamate (EBDC) fungicide, because of some properties typical of human carcinogens. This decision contrasts the IARC classification of EBDC fungicides (Group 3, not classifiable as to human carcinogenicity). A systematic review of the scientific literature was conducted to explore the current evidence.
Human and experimental studies of cancer and exposure to EBDC fungicides (Mancozeb, Maneb, Zineb, and others) and ethylene thiourea (ETU), their major metabolite, published in English as of December 2021, were retrieved using PubMed, the list of references of the relevant reports, and grey literature.
The epidemiological evidence of EBDC carcinogenicity is inadequate, with two studies each suggesting an association with melanoma and brain cancer and inconsistent findings for thyroid cancer. Experimental animal studies point at thyroid cancer in rats and liver cancer in mice, while multiple organs were affected following the long-term oral administration of Mancozeb. The mechanism of thyroid carcinogenesis in rats has also been shown to occur in humans. Genotoxic effects have been reported.
The results of this systematic review suggest inadequate evidence for the carcinogenicity of EBDC fungicides from human studies and sufficient evidence from animal studies, with positive results on three out of ten key characteristics of carcinogens applying to humans as well. An IARC re-evaluation of the human carcinogenicity of EBDC fungicides is warranted.
2021 年 1 月，欧盟因某些具有人类致癌剂典型特征的特性而终止了代森锰锌（Mancozeb）的许可证，代森锰锌是最畅销的乙撑双二硫代氨基甲酸酯（EBDC）杀菌剂。这一决定与 IARC 对 EBDC 杀菌剂（第 3 组，不能归类为人类致癌性）的分类形成对比。对科学文献进行了系统回顾，以探讨当前的证据。
检索了截至 2021 年 12 月在英文期刊上发表的关于人类癌症和接触 EBDC 杀菌剂（代森锰锌、代森锰、代森锌等）及其主要代谢物乙撑硫脲（ETU）的人类和实验研究，使用了 PubMed、相关报告的参考文献列表和灰色文献。
EBDC 致癌性的流行病学证据不足，有两项研究分别提示与黑色素瘤和脑癌有关，甲状腺癌的发现不一致。实验动物研究表明，大鼠存在甲状腺癌，小鼠存在肝癌，而长期口服代森锰锌会影响多个器官。大鼠甲状腺癌的发生机制也已在人类中得到证实。已有报道称其具有遗传毒性。
本系统评价的结果表明，人类研究中 EBDC 杀菌剂致癌性的证据不足，而动物研究中证据充分，适用于人类的致癌物十大关键特征中有三个特征呈阳性结果。有必要对 EBDC 杀菌剂的人类致癌性进行 IARC 重新评估。
