To be or not to be a carcinogen; delving into the glyphosate classification controversy

The International Agency for Research on Cancer (IARC) placed the most widely used herbicide glyphosate (GLY) into the category 2A (probably carcinogenic to humans), a classification questioned by experts from academia and industry. This article critically appraised the epidemiological and experimental data that led the IARC working group (WG) to consider GLY a probable human carcinogen and the ensuing controversy. An association of GLY with non-Hodgkin lymphoma was suggested by some observational studies. A non-causal explanation for this weak association, however, cannot be excluded. Contrary to WG’s view, long-term rodent assays yielded no convincing evidence that GLY is carcinogenic. The mechanistic evidence remains elusive as well. Bacterial reverse mutation tests (including tester strains sensitive to oxidative mutagens) were clearly negative, and so were rodent genotoxicity assays by oral route. Tests with mammalian cells in vitro yielded conflicting results at high (cytotoxic) concentrations of GLY-based formulations. Conflicting results were also obtained when high doses of GLY-based herbicides were administered to rodents by the intraperitoneal route. Such high doses are unlikely to be attained in realistic scenarios of exposure. Finally, the IARC classification is based on a conjectural hazard, and rational public health interventions must be based on estimated risks.

国际癌症研究机构（IARC）将全球使用最广泛的除草剂草甘膦（glyphosate，GLY）归类为2A类致癌物（即对人类很可能具有致癌性），该分类遭到了学术界与工业界专家的质疑。本文批判性评述了促使IARC工作组（WG）将草甘膦认定为很可能对人类具有致癌性的流行病学与实验数据，以及由此引发的争议。部分观察性研究提示草甘膦与非霍奇金淋巴瘤存在关联，但无法排除该弱关联的非因果性解释。与工作组的观点相悖，长期啮齿动物实验并未提供草甘膦具有致癌性的令人信服的证据。相关机制证据同样尚不明确。细菌回复突变试验（包括对氧化诱变剂敏感的测试菌株）结果明确为阴性，经口染毒的啮齿动物遗传毒性实验结果亦如此。体外哺乳动物细胞实验在使用高浓度（达到细胞毒性水平）草甘膦制剂时，得到了相互矛盾的结果；当以腹腔注射方式给啮齿动物施用高剂量草甘膦除草剂时，同样得到了相互矛盾的实验结果。而在实际暴露场景中，不太可能达到此类高剂量。最后，IARC的该分类基于推测性危害，而合理的公共卫生干预措施应基于实际估算的风险。