Review of genotoxicity studies of glyphosate and glyphosate-based formulations

Abstract

An earlier review of the toxicity of glyphosate and the original Roundupä-branded formulation concluded that neither glyphosate nor the formulation poses a risk for the production of heritable/somatic mutations in humans. The present review of subsequent genotoxicity publications and regulatory studies of glyphosate and glyphosate-based formulations (GBFs) incorporates all of the findings into a weight of evidence for genotoxicity. An overwhelming preponderance of negative results in well-conducted bacterial reversion and in vivo mammalian micronucleus and chromosomal aberration assays indicates that glyphosate and typical GBFs are not genotoxic in these core assays. Negative results for in vitro gene mutation and a majority of negative results for chromosomal effect assays in mammalian cells add to the weight of evidence that glyphosate is not typically genotoxic for these endpoints in mammalian systems. Mixed results were observed for micronucleus assays of GBFs in nonmammalian systems. Reports of positive results for DNA damage endpoints indicate that glyphosate and GBFs tend to elicit DNA damage effects at high or toxic dose levels, but the data suggest that this is due to cytotoxicity rather than DNA interaction with GBF activity perhaps associated with the surfactants present in many GBFs. Glyphosate and typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures.

Genotoxicity Expert Panel review: weight of evidence evaluation of the genotoxicity of glyphosate, glyphosate-based formulations, and aminomethylphosphonic acid

“…Many guidelines recommend that the presence of structural alerts be considered in evaluation of or testing for genotoxicity (Cimino 2006;Eastmond et al 2009;EFSA 2011;ICH 2011). As reported in Kier and Kirkland (2013) analysis of the glyphosate structure by DEREK software identified no structural alerts for chromosomal damage, genotoxicity, mutagenicity, or carcinogenicity. Analysis of structural alerts for genotoxicity inherently includes consideration of potential metabolites.…”

“…However, detailed primary data were extracted and published in reviews such as Kier and Kirkland (2013), although the study reports themselves are unpublished. The Expert Panel concluded that these data along with regulatory studies of GBFs and AMPA summarized in Williams et al (2000) should have been considered by IARC, and should be considered by all stakeholders going forward in evaluating the genetic toxicology of glyphosate and GBFs.…”

“…This was viewed as providing strong support for IARC classifying glyphosate as probably carcinogenic to humans, Group 2A. A number of published and regulatory approval reviews of the carcinogenic and genotoxic potential of glyphosate, AMPA and GBFs were available prior to the development of the IARC Monograph (Health and Welfare Canada 1991;US EPA 1993;WHO 1994;Williams et al 2000;European Commission 2002;Kier & Kirkland 2013;US EPA 2013). The consensus among these reviews was that proper use of glyphosate and GBFs does not pose a genotoxic or carcinogenic hazard/risk with hazard indicating potential for adverse effects and risk indicating potential for adverse effects under actual conditions and amounts of exposure.…”

Re-registration Challenges of Glyphosate in the European Union

“…However, then more recent studies have indicated a range of potential harmful effects, including hepatotoxicity or hepatorenal effects on rats (Benedetti et al, 2004;Larsen et al, 2012), and the number of published studies increased by orders of magnitude e.g., publications related to glyphosate intoxication rose from 44 in 1978-1987to 152 in 1996and to 875 in 2006(Zyoud et al, 2017. Although reviews of genotoxicity studies deemed DNA damage by glyphosate and glyphosate-based formulations secondary to cytotoxic effects (Kier and Kirkland, 2013;Kier, 2015), DNA-damaging effects and genotoxicity of glyphosate and particularly of its formulations (Roundup R , Glyfos R , Glyphogan R , Glyphosate-Biocarb R , etc.) on vertebrates (murine and human cells) (Bolognesi et al, 1997;Koller et al, 2012;Young et al, 2015;Townsend et al, 2017), cytotoxic effects of glyphosate-based herbicides on human embryonic and placental cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009Gasnier et al, , 2010Mesnage et al, 2013a,b), indication of endocrine disrupting effects by showing activity on estrogen receptors in human hormone-dependent breast cancer cells (Thongprakaisang et al, 2013;Mesnage et al, 2017a), inhibition of the biosynthesis of testosterone and estradiol (Romano et al, 2010) and progesterone (Young et al, 2015) or inhibitory effects on aromatase, a key enzyme in steroid hormone biosynthesis (Cassault-Meyer et al, 2014;Defarge et al, 2016), teratogenic effects on vertebrates by inhibiting the retinoic acid signaling pathway (Lajmanovich et al, 2003;Paganelli et al, 2010;Carrasco, 2013), birth defects in rats , and nephrotoxic and hepatotoxic effects of Roundup R have been demonstrated in rats in connection to RR GM maize (originally published in the journal Food and Chemical Toxicology in September 2012, but retracted by the journal in November 2013 following an alleged intervention from the industry stakeholder (Foucart, 2016), and subsequently republished in another jou...…”

Electrochemical degradation and mineralization of glyphosate herbicide

“…The existence of glyphosate in the aquatic environment requires developing methods for its removal from water. Conventional methods often used in water treatment plant, such as physicochemical, biological are sometime ineffective for removing herbicides [1,14]. Existing advanced water treatment techniques include filtration using sand, ultra filtration, reverse osmosis, adsorption by activated charcoal and biological degradation are expensive and require large infrastructure investments and some are specific to particular contaminants [10].…”