The health effects of a Roundup-tolerant genetically modified maize (from 11% in the diet), cultivated with or without Roundup, and Roundup alone (from 0.1 ppb in water), were studied 2 years in rats. In females, all treated groups died 2-3 times more than controls, and more rapidly. This difference was visible in 3 male groups fed GMOs. All results were hormone and sex dependent, and the pathological profiles were comparable. Females developed large mammary tumors almost always more often than and before controls, the pituitary was the second most disabled organ; the sex hormonal balance was modified by GMO and Roundup treatments. In treated males, liver congestions and necrosis were 2.5-5.5 times higher. This pathology was confirmed by optic and transmission electron microscopy. Marked and severe kidney nephropathies were also generally 1.3-2.3 greater. Males presented 4 times more large palpable tumors than controls which occurred up to 600 days earlier. Biochemistry data confirmed very significant kidney chronic deficiencies; for all treatments and both sexes, 76% of the altered parameters were kidney related. These results can be explained by the non linear endocrine-disrupting effects of Roundup, but also by the overexpression of the transgene in the GMO and its metabolic consequences.

Commercial formulations of pesticides are invariably not single ingredients. Instead they are cocktails of chemicals, composed of a designated pesticidal “active principle” and “other ingredients,” with the latter collectively also known as “adjuvants.” These include surfactants, antifoaming agents, dyes, etc. Some adjuvants are added to influence the absorption and stability of the active principle and thus promote its pesticidal action. Currently, the health risk assessment of pesticides in the European Union and in the United States focuses almost exclusively on the stated active principle. Nonetheless, adjuvants can also be toxic in their own right with numerous negative health effects having been reported in humans and on the environment. Despite the known toxicity of adjuvants, they are regulated differently from active principles, with their toxic effects being generally ignored. Adjuvants are not subject to an acceptable daily intake, and they are not included in the health risk assessment of dietary exposures to pesticide residues. Here, we illustrate this gap in risk assessment by reference to glyphosate, the most used pesticide active ingredient. We also investigate the case of neonicotinoid insecticides, which are strongly suspected to be involved in bee and bumblebee colony collapse disorder. Authors of studies sometimes use the name of the active principle (for example glyphosate) when they are testing a commercial formulation containing multiple (active principle plus adjuvant) ingredients. This results in confusion in the scientific literature and within regulatory circles and leads to a misrepresentation of the safety profile of commercial pesticides. Urgent action is needed to lift the veil on the presence of adjuvants in food and human bodily fluids, as well as in the environment (such as in air, water, and soil) and to characterize their toxicological properties. This must be accompanied by regulatory precautionary measures to protect the environment and general human population from some toxic adjuvants that are currently missing from risk assessments.

Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.

Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely ignored in pesticide safety evaluations. We identified the surfactants in a cross-section of GBH formulations and compared their acute toxic effects. The first generation of polyethoxylated amine (POEA) surfactants (POE-tallowamine) in Roundup are markedly more toxic than glyphosate and heightened concerns of risks to human health, especially among heavily-exposed applicators. Beginning in the mid-1990s, first-generation POEAs were progressively replaced by other POEA surfactants, ethoxylated etheramines, which exhibited lower non-target toxic effects. Lingering concern over surfactant toxicity was mitigated at least in part within the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants are ∼100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As GBH composition is legally classified as confidential commercial information, confusion concerning the identity and concentrations of co-formulants is common and descriptions of test substances in published studies are often erroneous or incomplete. In order to resolve this confusion, laws requiring disclosure of the chemical composition of pesticide products could be enacted. Research to understand health implications from ingesting these substances is required.

The health effects of a Roundup-tolerant NK603 genetically modified (GM) maize(from 11% in the diet), cultivated with or without Roundup application and Roundupalone (from 0.1 ppb of the full pesticide containing glyphosate and adjuvants) indrinking water, were evaluated for 2 years in rats. This study constitutes afollow-up investigation of a 90-day feeding study conducted by Monsanto in orderto obtain commercial release of this GMO, employing the same rat strain andanalyzing biochemical parameters on the same number of animals per group as ourinvestigation. Our research represents the first chronic study on thesesubstances, in which all observations including tumors are reportedchronologically. Thus, it was not designed as a carcinogenicity study. We reportthe major findings with 34 organs observed and 56 parameters analyzed at 11 timepoints for most organs. Biochemical analyses confirmed very significant chronic kidney deficiencies, forall treatments and both sexes; 76% of the altered parameters were kidney-related.In treated males, liver congestions and necrosis were 2.5 to 5.5 times higher.Marked and severe nephropathies were also generally 1.3 to 2.3 times greater. Infemales, all treatment groups showed a two- to threefold increase in mortality,and deaths were earlier. This difference was also evident in three male groups fedwith GM maize. All results were hormone- and sex-dependent, and the pathologicalprofiles were comparable. Females developed large mammary tumors more frequentlyand before controls; the pituitary was the second most disabled organ; the sexhormonal balance was modified by consumption of GM maize and Roundup treatments.Males presented up to four times more large palpable tumors starting 600 daysearlier than in the control group, in which only one tumor was noted. Theseresults may be explained by not only the non-linear endocrine-disrupting effectsof Roundup but also by the overexpression of the EPSPS transgene or othermutational effects in the GM maize and their metabolic consequences. Our findings imply that long-term (2 year) feeding trials need to be conducted tothoroughly evaluate the safety of GM foods and pesticides in their full commercialformulations.