Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies

Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

草甘膦（Glyphosate）是氨基酸甘氨酸的除草衍生物，于20世纪70年代被引入农业应用。草甘膦可靶向并阻断植物体内的莽草酸途径（shikimate pathway）——该途径是植物合成芳香族氨基酸所必需的，而动物体内并不存在这一代谢通路。在近四十年的商业化应用后，经过包括毒理学评价、文献综述以及大量人体健康风险评估在内的多项监管审批，学界已形成明确且一致的结论：草甘膦的毒理学关注度较低，且其使用与人类癌症之间不存在任何关联风险。本论文即探讨上述结论的依据所在。
多数用于支撑监管评价的毒理学研究均带有商业属性，且属于保密资料。鉴于该化合物受到广泛关注，研究团队获取了提交至监管机构的致癌性数据，先对各项研究进行概述，随后对肿瘤发生率数据开展证据权重分析。本研究对14项致癌性研究（9项大鼠研究、5项小鼠研究）的个体可靠性进行评估，并筛选出部分肿瘤类型，用于跨数据库的进一步分析。研究报告中的原始肿瘤发生率数据已收录于在线补充材料中。
未发现草甘膦暴露与致癌效应存在关联的证据。由于缺乏合理的作用机制，且已发表的流行病学研究均未证明草甘膦与任何病因类型的癌症之间存在明确、具有统计学显著性、无偏倚且未受混杂因素影响的关联，再加上极具说服力的证据权重，共同支撑了以下结论：草甘膦不会对人类产生致癌性风险。