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

Abstract

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.

A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment

“…Four additional studies in rats, described by Greim et al (2015) not evaluated by IARC, similarly did not show pancreatic islet cell tumors. Based on this information the Expert Panel concludes that there is no evidence that glyphosate induces islet cell tumors in the pancreas.…”

“…The carcinogenicity Expert Panel reviewed all listed cancer bioassays reviewed by Greim et al (2015) and IARC (2015). The recommended method for evaluating the results of an extensive database of toxicology and carcinogenicity bioassays, as exist for glyphosate, involves the application of a WoE approach (US EPA 1986c;ECHA 2010).…”

“…For example, chemically induced rat hepatocellular carcinogenesis is a multiple stage process characterized by progressive Greim et al (2015). functional, morphological, and molecular changes that indicate or precede the full establishment of neoplasia, such as enzyme induction, hepatocyte hypertrophy, degeneration and necrosis, hepatocyte proliferation, altered hepatocellular foci, etc.…”

A regulatory perspective on the potential carcinogenicity of glyphosate

“…In 2015 a review was published on fourteen cancer studies conducted over the last several decades in rats and mice [36]. The general conclusion that came out of this review is that no solid evidence could be synthesized from these studies to indicate that glyphosate causes cancer.…”

Evaluating the potential carcinogenic hazard of glyphosate

“…Four review papers, commissioned by Monsanto Company, addressing various aspects of the toxicity of glyphosate and glyphosate-based formulations, were submitted to Critical Reviews in Toxicology, subjected to rigorous external review, revised and published in CRT prior to the IARC meeting (Kimmel et al 2013;Kier & Kirkland 2013;Kier 2015;Greim et al 2015). Those papers were frequently accessed on-line and, most importantly, copies were provided to IARC prior to the meeting of the IARC review panel in Lyon, France in March 2015.…”