A comprehensive analysis of the animal carcinogenicity data for glyphosate from chronic exposure rodent carcinogenicity studies

Abstract

Since the introduction of glyphosate-tolerant genetically-modified plants, the global use of glyphosate has increased dramatically making it the most widely used pesticide on the planet. There is considerable controversy concerning the carcinogenicity of glyphosate with scientists and regulatory authorities involved in the review of glyphosate having markedly different opinions. One key aspect of these opinions is the degree to which glyphosate causes cancer in laboratory animals after lifetime exposure. In this review, twenty-one chronic exposure animal carcinogenicity studies of glyphosate are identified from regulatory documents and reviews; 13 studies are of sufficient quality and detail to be reanalyzed in this review using trend tests, historical control tests and pooled analyses. The analyses identify 37 significant tumor findings in these studies and demonstrate consistency across studies in the same sex/species/strain for many of these tumors. Considering analyses of the individual studies, the consistency of the data across studies, the pooled analyses, the historical control data, non-neoplastic lesions, mechanistic evidence and the associated scientific literature, the tumor increases seen in this review are categorized as to the strength of the evidence that glyphosate causes these cancers. The strongest evidence shows that glyphosate causes hemangiosarcomas, kidney tumors and malignant lymphomas in male CD-1 mice, hemangiomas and malignant lymphomas in female CD-1 mice, hemangiomas in female Swiss albino mice, kidney adenomas, liver adenomas, skin keratoacanthomas and skin basal cell tumors in male Sprague-Dawley rats, adrenal cortical carcinomas in female Sprague-Dawley rats and hepatocellular adenomas and skin keratocanthomas in male Wistar rats.

Micronucleus Formation Induced by Glyphosate and Glyphosate-Based Herbicides in Human Peripheral White Blood Cells

“…The IARC classification for glyphosate was partly based on strong evidence that glyphosate or GBHs are able to induce genotoxicity, recognized first step in carcinogenesis, in human cells in vitro and in experimental animals ( 3 ). Recently, comprehensive reviews summarizing animal carcinogenicity data and data from multiple in vitro and in vivo genotoxicity assays have further supported the IARC statement ( 18 , 19 ). DNA damage indicated by DNA strand breaks as a marker of genotoxicity was observed as a result of exposure to glyphosate as an active ingredient in various human cell types in vitro ( 20 – 25 ) as well as in mice ( 26 ) and fish ( 23 , 27 , 28 ) in vivo .…”

Comparative toxicogenomics of glyphosate and Roundup herbicides by mammalian stem cell-based genotoxicity assays and molecular profiling in Sprague-Dawley rats

“…Whether glyphosate increases cancer incidence in animal studies is still not certain. A recent collation and re-evaluation of data from laboratory animal model systems, has highlighted evidence of the carcinogenic potential of glyphosate and GBHs (Portier 2020). However, tumor findings in two-year rodent studies were not consistent with poor reproducibility; that is, the same type of cancer was not consistently found in different investigations.…”

A comparison of the persistence, toxicity, and exposure to high-volume natural plant-derived and synthetic pesticides

“…It is possible that the relatively low rate of rodent carcinogenicity has been a factor in elevating this subset of pesticides into the Top 10 positions by poundage of active ingredient used. 63,64…”