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 (AP), which is usually tested alone. This is true even in the longest toxicological regulatory tests performed on mammals. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293 and JEG3). 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. 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. The human placental JEG3 cells appeared to be the most sensitive. Despite its relatively benign reputation, Roundup was by far the most toxic among the herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were several hundred times more toxic than their active principle. 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. The study of combinatorial effects of several APs together may be of only secondary importance if the toxicity of the combinations of each AP with its adjuvants is neglected or unknown. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.
