The authors hypothesised that oxidative stress was resulting from the activation of NMDA receptors and voltage-dependent calcium channels. Martini et al (2016) described a ROSincrease in 3T3-L1 fibroblasts (a cell line derived from mouse adipose tissue) after exposure to a glyphosate-based formulation.
in a change in the structure or function of the gene. The damage can be mutagenic (heritable) or non-mutagenic. Mutagenic means causing a change in the genetic structure, usually through base-pair substitution (change in amino acid sequence), deletion, or addition of gene fragments, or some other mechanism which include disruptions or breaks in chromosomes A large number of publications consistently that result in the gain, loss, or rearrangements presented evidence that glyphosate-based of chromosomal segments (clastogenicity). It formulations can cause oxidative stress in also includes “sister chromatid exchanges”, fish including at environmentally relevant interchanges and re-attachments of strands in concentrations (de Menezes et al 2011; the chromosome during DNA replication, and Guilherme et al 2010, 2012a; Lushchak et induction (increase) in the frequency of microal 2009; Modesto & Martinez 2010a, 2010b; nuclei (small fragments formed when chromoMurussi et al 2016; Ortiz-Ordeñez et al 2011; somes break). Besides causing inheritable damSamanta et al 2014; Sinhorin et al 2014). age (germ cell mutagenicity) one of the main Navarro & Martinez (2014) showed that POEA, a health implications of genotoxicity in somatic surfactant used in some of the glyphosate-based cells is the induction of cancer. formulations, can cause oxidative stress in fish at concentrations as low as 150 µg/L. However, The US EPA (2006) reported that glyphosate it can be excluded that the effects seen after was non-mutagenic in the bacteria Salmonella exposure to glyphosate-based formulations is typhimurium, Chinese hamster ovary cells, and solely caused by surfactants, because when rat bone marrow. FAO (2000) also reported it to comparing the effects of glyphosate and a be non-mutagenic in human lymphocytes (white glyphosate-based formulation in brown trout at blood cells) and mouse bone marrow. Both water concentrations of 0, 0.01, 0.5 and 10 mg/L these determinations are based on test results using global transcriptomic profiling. Webster & reported by Monsanto (FAO 2000). Likewise, in Santos (2015) provided evidence that glyphosate the recent assessments performed on behalf of (active ingredient) as well as a formulation was the EFSA (RMS Germany 2015b) and the ECHA inducing transcriptional changes indicative of (BAuA 2016), the BfR using a weight of evidence oxidative stress. For more information on these approach came to the overall conclusion “that studies, and studies showing oxidative stress in glyphosate does not induce mutations in vivo and tadpoles, refer to the section on Aquatic toxicity. that no hazard classification for mutagenicity is warranted” (RMS Germany 2015b, p.49). Similar Taken together, a plethora of papers to the US EPA and the FAO, the BfR relied heavily demonstrated the induction of oxidative stress on the regulatory studies submitted by industry, by glyphosate as well as glyphosate-based i.e. the “Glyphosate Task Force”, a consortium formulations in in vitro and in vivo tests with of 25 glyphosate-producing corporations. On mammals and fish. For amphibians this effect the other hand, the BfR cautioned that “for the was investigated with glyphosate-based different glyphosate-based formulations, no firm formulations only. In spite of all this, the BfR conclusions can be drawn with regard to a need refused to recognise the importance of this for classification” and it “strongly recommends evidence. After denying the well-documented further genotoxicity studies in compliance with induction of malignant lymphoma by glyphosate OECD test guidelines in general and for the in male mice (see above), the BfR reasoned that representative formulation” (RMS Germany “from the sole observation of oxidative stress 2015b, p. iv). One would assume that there is a and the existence of a plausible mechanism for reason for this. induction of oxidative stress through uncoupling of mitochondrial oxidative phosphorylation In general, a huge discrepancy exists between alone, genotoxic or carcinogenic activity in industry studies and results published in the humans cannot be deduced for glyphosate and scientific literature. Only 2 of the 36 industry glyphosate-based formulations (RMS Germany studies reported in the RAR exhibited genotoxic 2015b p. iv). effects (RMS Germany 2015a). On the other hand, 62 of the 87 tests published in the peerreviewed scientific literature demonstrated Genotoxicity / mutagenicity genotoxic effects of glyphosate or glyphosateA pesticide is genotoxic if it causes damage to based formulations. While some of the a gene that could result in cell death, or result publications from the scientific literature had
25