Trans-disciplinary diagnosis for an in-depth reform of regulatory expertise in the field of environmental toxicology and security.

Repeated health and environmental scandals, the loss of biodiversity and the recent burst of chronic diseases constantly remind us the inability of public authorities and risk assessment agencies to protect health and the environment. After reviewing the main shortcomings of our evaluation system of chemicals and new technologies, supported by some concrete examples, we develop a number of proposals to reform both the risk assessment agencies and the evaluation processes. We especially propose the establishment of an independent structure, a High Authority of Expertise, supervising, either at European level or at national level, all the evaluation agencies, and ensuring the transparency, the methodology and the deontology of the expertise. In addition to modifying the evaluation protocols, both in their nature and in their content, especially in order to adapt them to current pollutants such as endocrine disruptors, we propose a reform of the expertise processes based on transparency, contradiction, and greater democracy, including close collaboration between the institutional and scientific parties on the one hand and the whole civil society on the other. All the proposals we make are inspired by the desire to prevent, through appropriate mechanisms, the human, health, ecological, but also economic consequences of contemporary technological choices.

Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels.

Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests.

The quality of diets in rodent feeding trials is crucial. We describe the contamination with environmental pollutants of 13 laboratory rodent diets from 5 continents. Measurements were performed using accredited methodologies. All diets were contaminated with pesticides (1-6 out of 262 measured), heavy metals (2-3 out of 4, mostly lead and cadmium), PCDD/Fs (1-13 out of 17) and PCBs (5-15 out of 18). Out of 22 GMOs tested for, Roundup-tolerant GMOs were the most frequently detected, constituting up to 48% of the diet. The main pesticide detected was Roundup, with residues of glyphosate and AMPA in 9 of the 13 diets, up to 370 ppb. The levels correlated with the amount of Roundup-tolerant GMOs. Toxic effects of these pollutants on liver, neurodevelopment, and reproduction are documented. The sum of the hazard quotients of the pollutants in the diets (an estimator of risk with a threshold of 1) varied from 15.8 to 40.5. Thus the chronic consumption of these diets can be considered at risk. Efforts toward safer diets will improve the reliability of toxicity tests in biomedical research and regulatory toxicology.

Major pesticides are more toxic to human cells than their declared active principles.

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.

Conflicts of interests, confidentiality and censorship in health risk assessment: the example of an herbicide and a GMO.

We have studied the long-term toxicity of a Roundup-tolerant GM maize (NK603) and a whole Roundup pesticide formulation at environmentally relevant levels from 0.1 ppb. Our study was first published in Food and Chemical Toxicology (FCT) on 19 September, 2012. The first wave of criticisms arrived within a week, mostly from plant biologists without experience in toxicology. We answered all these criticisms. The debate then encompassed scientific arguments and a wave of ad hominem and potentially libellous comments appeared in different journals by authors having serious yet undisclosed conflicts of interests. At the same time, FCT acquired as its new assistant editor for biotechnology a former employee of Monsanto after he sent a letter to FCT to complain about our study. This is in particular why FCT asked for a post-hoc analysis of our raw data. On 19 November, 2013, the editor-in-chief requested the retraction of our study while recognizing that the data were not incorrect and that there was no misconduct and no fraud or intentional misinterpretation in our complete raw data - an unusual or even unprecedented action in scientific publishing. The editor argued that no conclusions could be drawn because we studied 10 rats per group over 2 years, because they were Sprague Dawley rats, and because the data were inconclusive on cancer. Yet this was known at the time of submission of our study. Our study was however never attended to be a carcinogenicity study. We never used the word 'cancer' in our paper. The present opinion is a summary of the debate resulting in this retraction, as it is a historic example of conflicts of interest in the scientific assessments of products commercialized worldwide. We also show that the decision to retract cannot be rationalized on any discernible scientific or ethical grounds. Censorship of research into health risks undermines the value and the credibility of science; thus, we republish our paper.