Ethoxylated adjuvants found in glyphosate-based herbicides were up to 10.000 times more toxic than the so-called active AP glyphosate and are better candidates for secondary side effects. Our previous investigation showed unexpected APs for human cell toxicity in the adjuvants of glyphosate-based herbicides. Only the AP and one metabolite are used as markers, but this does not exclude the presence of adjuvants, which are cell penetrants. This allows the calculation of the acceptable daily intake (ADI)-the level of exposure that is claimed to be safe for humans over the long term-and justifies the presence of residues of these pesticides at “admissible” levels in the environment and organisms. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle (AP), which is the only one tested in the longest toxicological regulatory tests performed on mammals. Pesticides are used throughout the world as mixtures called formulations. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. 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. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. 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. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. 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 tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). 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.
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