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Much of the focus of late has been on the toxicity of the main ingredient in Roundup 'weedkiller,' namely, glyphosate. And rightly so: far from being 'practically non-toxic,' as advertising copy once bragged,[i] the chemical has recently been shown to exhibit toxicity in the parts-per-trillion concentration range, and is being found literally everywhere: in the water, soil, air, rain and our food. But very little research has been performed on its metabolites and so-called 'inactive ingredients' – until now.
A new study, published in Pesticide Biochemistry and Physiology titled, "The effect of metabolites and impurities of glyphosate on human erythrocytes (in vitro)," reveals that the problem with the growing global contamination of the biosphere with agrichemicals used in the farming of genetically modified foods is far worse than most will either admit or acknowledge.
The researchers describe the background context of their study:
"Today, the dissemination of glyphosate in the environment increases, and humans are permanently exposed to its action. Worstcase scenario provides even ten-fold increase of using a glyphosate in the following years . Considering the widespread and frequent use of glyphosate throughout in world, thus the current risk assessment is important because the exposure will concern not only the users of the preparations containing glyphosate, but also those who do not have direct contact with that herbicide."
The researchers used human red blood cells (erythrocytes) to evaluate the effects of "glyphosate, its metabolites: aminomethylphosphonic acid (AMPA); methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine," looking specifically at the following indications of damage:
- Hemolysis (the rupturing of red blood cells)
- Hemoglobin oxidation (oxygen-induced damage to the central metalloprotein within red blood cells)
- Levels of reactive oxygen species (ROS) formation (an indication of oxygen-induced damage)
- Changes in shape of red blood cells
The red blood cells were exposed to different concentrations of glyphosate and its metabolites and impurities at concentration ranges between .01-5 millimolar (mM) for 1, 4 and 24 hours. The authors explain that their choice of ranges "are within the range of the concentrations that are present in the blood of persons not exposed (.01 mM) or may enter human organism only as a result of acute poisoning (0.05–5 mM)." In other words, simply breathing the air, drinking the water, and eating the food in our post-industrial world results in measurable blood levels of .01 mM (i.e. 1.69 parts per million (ppm) or 1.69 mg/L) in the general population.
To put these ranges into further perspective, the US EPA has recently proposed to hike the allowed residue limits of glyphosate in food and feed crops to 100 ppm in teff animal feed and 40 ppm in oilseed crops, essentially telling the American public, "Let Them Eat Roundup Ready Cake."
Also, those working with glyphosate, eating glyphosate-sprayed food, or close to agricultural regions where it is heavily applied, would have far higher levels than .01 mM in their blood. The concentrations, in fact, can accumulate to deadly levels, as evidenced by a recent report proposing that the chemical may be responsible for causing a mysterious global epidemic of deadly kidney disease in farming regions around the world.
The authors also explained their choice of red blood cells for toxicological evaluation: "Damage to erythrocytes is widely used as indicator of toxicity of numerous xenobiotics ,  and . Pesticides, drugs and other toxic compounds are transported by blood of living organisms, thus they enter red blood cells."
The results, which the researchers curiously describe as "negligible," were reported as follows:
"Statistically significant changes in the percent of met-Hb [an indication of damaged hemoglobin] were observed for glyphosate, its metabolites and impurities (Table 2A and Table 2B). Only glyphosate after 1 h incubation did not cause significant changes in this parameter."
The researchers summarized the hemolytic potential of these chemicals as follows:
"In summary, our results indicate that glyphosate, its metabolites and impurities in the concentrations examined induced slightly significant effects on human erythrocytes. The investigated metabolites and impurities caused a slight stronger damage to human erythrocytes than glyphosate."
We find it inappropriate to minimize the significance of these findings. If any adverse change is empirically demonstrated to be linked to any one of these chemicals, the precautionary principle should be employed. Also, in real world exposures red blood cells would not be spared the synergistic toxicity of glyphosate and its metabolites and impurities working in concert to induce damage and destruction. Additionally, the GM food itself containing the transgene Bt, separate from Roundup chemicals, has already been linked to blood disorders, such as hemolysis and leukemia. Therefore, the study did not address this essential problem of combined, synergistic or cumulative toxicity. It did, however, reveal that the toxicity problem associated with glyphosate-formulations like Roundup is far more complex than ascertained by looking at glyphosate as the sole culprit in the over 40 health conditions linked to Roundup herbicide now signaled in the biomedical literature itself.
To their credit, the authors do acknowledge previous research indicating a clearer hemolytic potential of glyphosate formulations taken as a whole:
"It was noted that commercial formulations of glyphosate indicated a higher toxicity than the active substance itself. Earlier research provided by Pieniazek et al.  showed that glyphosate at the concentration of 1500 ppm (corresponding to 9 mM) after 24 h incubation with human erythrocytes induced hemolysis of about 3%. Additionally, Bukowska et al.  reported that Roundup Ultra 360 SL provoked slightly stronger changes in the function of the erythrocytes than its active substance glyphosate, which was probably a result of its additives. Roundup Ultra 360 SL caused slight hemolysis of human erythrocytes, but the differences were statistically significant starting at the concentration of 1500 ppm after 1 h of incubation and at 500 ppm after 24 h of incubation."
The ability of glyphosate and its metabolites to induce oxidative damage was also confirmed:
"Glyphosate, its metabolites and impurities are able to generate ROS in red blood cells. Statistically significant changes started from the concentration of 0.25 mM for almost all compounds studied, except N-methylglyphosate."
The study did not find measurable changes in the shape of the blood cells.
This study has a number of concerning implications, the first being that Roundup and similar glyphosate-based formulations should be understood to have a broad range of risks, beyond the clear danger represented by glyphosate in isolation. If all the components tested in isolation are harmful, the likelihood that they, when combined, exhibit synergistic toxicity should be evaluated in future studies. Until such work is performed, it is clear that exposed populations are living and breathing guinea pigs. The authors themselves point out that, "The European Commission planned to verify the toxicity of glyphosate in 2012, but in the end of 2010 it decided not to perform this verification up to 2015." This, of course, doesn't even take into account that, "There is evidence that metabolites and impurities of the pesticides reveal stronger toxicity than their parent compounds , ,  and ."
The preliminary research here, comprehended through the lens of the precautionary principle, should further catalyze the non-GMO movement to not only push forward in demanding accurate labeling of products containing GM contaminated or inclusive ingredients, but an outright ban on GM agricultural practices which require the wholesale contamination of the biosphere with chemicals and genetic pollution whose persistence will result in inevitable and unavoidable harm to the environment and human life.
[i] Charry T (1997-05-29). "Monsanto recruits the horticulturist of the San Diego Zoo to pitch its popular herbicide". Business Day. New York Times.