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Pesticides can affect the health of individual organisms and the function of the entire ecosystem. Therefore, thorough assessment of the risks associated with the use of pesticides is a high-priority task. An enzyme inhibition-based assay is used in this study as a convenient and quick tool to study the effects of pesticides at the molecular level. The contribution of formulants to toxicological properties of the pesticide formulations has been studied by analyzing effects of 7 active ingredients of pesticides (AIas) and 10 commercial formulations based on them (AIfs) on the function of a wide range of enzyme assay systems differing in complexity (single-, coupled, and three-enzyme assay systems). Results have been compared with the effects of AIas and AIfs on bioluminescence of the luminous bacterium Photobacterium phosphoreum. Mostly, AIfs produce a considerably stronger inhibitory effect on the activity of enzyme assay systems and bioluminescence of the luminous bacterium than AIas, which confirms the contribution of formulants to toxicological properties of the pesticide formulation. Results of the current study demonstrate that "inert" ingredients are not ecotoxicologically safe and can considerably augment the inhibitory effect of pesticide formulations; therefore, their use should be controlled more strictly. Circular dichroism and fluorescence spectra of the enzymes used for assays do not show any changes in the protein structure in the presence of commercial pesticide formulations during the assay procedure. This finding suggests that pesticides produce the inhibitory effect on enzymes through other mechanisms. [ABSTRACT FROM AUTHOR]

Toxicological investigations of pesticides largely focus on the declared active ingredient, which constitutes only between a few percent to around 50% of the total formulation. The complete formulations are unknown. For each declared active ingredient, there are dozens or hundreds of formulations. We demonstrate that petroleum has always been and is still always in pesticides. Gas chromatography and mass spectrometry (GC-MS) were applied for 24 pesticides. The measured compounds were the 16-priority polycyclic aromatic hydrocarbons (PAHs). The ratio of the PAHs to the threshold of toxicity was from 2.16 to 8288 times. The levels and distribution of PAHs per pesticide were different. Petroleum residues appear to be a waste product. The declared active component is taken alone for toxicity calculations, such as the acceptable daily intake (ADI). The PAHs with 2–3 cycles are more represented in pesticides than those with 4–6 cycles, which underlines that the petroleum residues appear to come mainly from crude unburned material. The ADI should be divided by 1000 if it is considered that petroleum residues amplify the toxicity by 1000. The admixture of PAHs in pesticides can be highly carcinogenic or toxic in the long term, even more than the declared active ingredient itself. [ABSTRACT FROM AUTHOR]

Pesticides are commonly used in agriculture to enhance crop production and control pests. Therefore, pesticide residues can persist in the environment and agricultural crops. Although modern formulations are relatively safe to non-target species, numerous theoretical and experimental data demonstrate that pesticide residues can produce long-term negative effects on the health of humans and animals and stability of ecosystems. Of particular interest are molecular mechanisms that mediate the start of a cascade of adverse effects. This is a review of the latest literature data on the effects and consequences of contamination of agricultural crops by pesticide residues. In addition, we address the issue of implicit risks associated with pesticide formulations. The effects of pesticides are considered in the context of the Adverse Outcome Pathway concept.

Toxicological investigations of pesticides largely focus on the declared active ingredient, which constitutes only between a few percent to around 50% of the total formulation. The complete formulations are unknown. For each declared active ingredient, there are dozens or hundreds of formulations. We demonstrate that petroleum has always been and is still always in pesticides. Gas chromatography and mass spectrometry (GC-MS) were applied for 24 pesticides. The measured compounds were the 16-priority polycyclic aromatic hydrocarbons (PAHs). The ratio of the PAHs to the threshold of toxicity was from 2.16 to 8288 times. The levels and distribution of PAHs per pesticide were different. Petroleum residues appear to be a waste product. The declared active component is taken alone for toxicity calculations, such as the acceptable daily intake (ADI). The PAHs with 2–3 cycles are more represented in pesticides than those with 4–6 cycles, which underlines that the petroleum residues appear to come mainly from crude unburned material. The ADI should be divided by 1000 if it is considered that petroleum residues amplify the toxicity by 1000. The admixture of PAHs in pesticides can be highly carcinogenic or toxic in the long term, even more than the declared active ingredient itself.

Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, and other products contained in formulations, named formulants, which have been declared as inerts and diluents by the manufacturers. These formulants have, in fact, been demonstrated to be much more toxic than G, in particular to placental and embryonic human cells. In this work, we thus compared the effect of G and a GT+ formulation named R, using placental perfusion ex vivo. R, but not G alone, was demonstrated to alter the placental permeability of a known small model molecule, antipyrine. Similar results were observed for the fetal venous flow rate. The transfer of G alone increases with time, but is significantly decreased in presence of its formulants. The perfusion of R provokes a destruction of fetal vessels, as demonstrated by immunohistochemistry. Formulants obviously alter the fetal-placental circulation and placental integrity according to time of exposure. Therefore, G does not appear to be the main toxic agent of R. Formulants, although undeclared, include polyoxyethanolamines, PAHs, or heavy metals, and may be responsible for this toxicity. These compounds are also present in other pesticides. The progressive blood flow reduction due to the toxic compounds of formulations may diminish the nutrient supply to the fetus, alter the development, and may enhance the poisoning effects. Although these are preliminary results, they could at least partially explain some adverse pregnancy outcomes in mothers exposed to pesticides or other environmental pollutants. The debate on glyphosate alone is proven insufficient for the understanding of the toxicity.

Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, and other products contained in formulations, named formulants, which have been declared as inerts and diluents by the manufacturers. These formulants have, in fact, been demonstrated to be much more toxic than G, in particular to placental and embryonic human cells. In this work, we thus compared the effect of G and a GT+ formulation named R, using placental perfusion ex vivo. R, but not G alone, was demonstrated to alter the placental permeability of a known small model molecule, antipyrine. Similar results were observed for the fetal venous flow rate. The transfer of G alone increases with time, but is significantly decreased in presence of its formulants. The perfusion of R provokes a destruction of fetal vessels, as demonstrated by immunohistochemistry. Formulants obviously alter the fetal-placental circulation and placental integrity according to time of exposure. Therefore, G does not appear to be the main toxic agent of R. Formulants, although undeclared, include polyoxyethanolamines, PAHs, or heavy metals, and may be responsible for this toxicity. These compounds are also present in other pesticides. The progressive blood flow reduction due to the toxic compounds of formulations may diminish the nutrient supply to the fetus, alter the development, and may enhance the poisoning effects. Although these are preliminary results, they could at least partially explain some adverse pregnancy outcomes in mothers exposed to pesticides or other environmental pollutants. The debate on glyphosate alone is proven insufficient for the understanding of the toxicity. [ABSTRACT FROM AUTHOR]

Pesticides are commonly used in agriculture to enhance crop production and control pests. Therefore, pesticide residues can persist in the environment and agricultural crops. Although modern formulations are relatively safe to non-target species, numerous theoretical and experimental data demonstrate that pesticide residues can produce long-term negative effects on the health of humans and animals and stability of ecosystems. Of particular interest are molecular mechanisms that mediate the start of a cascade of adverse effects. This is a review of the latest literature data on the effects and consequences of contamination of agricultural crops by pesticide residues. In addition, we address the issue of implicit risks associated with pesticide formulations. The effects of pesticides are considered in the context of the Adverse Outcome Pathway concept., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)