Impurity mediated genotoxicity of glyphosate technical grade active ingredients

Introduction. The study of the potential negative effects of combinations of several pesticide active ingredients is an important and understudied area of toxicological and hygienic research. The initial phase of the genotoxicant action on the genetic structures in cells is the primary DNA damage, the identification of which makes it possible to assess the early stages of the genotoxic effect of xenobiotics and their mixtures. The DNA comet assay is widely used for these purposes. The aim of the research is to assess the primary DNA damage under the combined action of pesticides. Materials and methods. To assess DNA damage the experiments on CD-1 mice of both sexes were performed using alkaline comet analysis. The concentration of active products reacting with thiobarbituric acid (TBA) in the blood serum of white outbred rats was assessed as a marker of lipid peroxidation. Results. It was found that mixtures of 2,4-D-acid + glyphosate and thiram + carbendazim did not cause the formation of breaks and alkali-labile sites in the DNA of mice bone marrow cells. Exposure to the combination of the technical grade active ingredients captan and fludioxonil induced the breaks and alkali-labile sites in the DNA of animal bone marrow cells. The comparison of the genotoxicity assessment results obtained by the comet assay and results of analysis of the TBA-active product concentrations in the rat blood serum suggests that the observed primary DNA damage upon exposure to the captan and fludioxonil combination can be mediated by the induction of lipid peroxidation and subsequent interaction of the resulting products with nucleic acids. Conclusion. The results indicate that some pesticides in combination can damage hereditary material in mammalian cells. Therefore, in order to ensure the safe use of pesticides for public health it is necessary to take into account the data on the genotoxicity not only of individual pesticide technical grade active ingredients but also their combinations.

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Development and Validation of an Analytical Method for Simultaneous Quantitation of Organic Volatile Impurities in Technical-Grade Active Ingredients of Pesticides and Agrochemicals by Headspace Gas Chromatography

Chromatography ◽

10.15583/jpchrom.2015.019 ◽

2015 ◽

Vol 36 (2) ◽

pp. 67-71

Author(s):

Masato KAZUSAKI ◽

Satoshi OKUMURA ◽

Kozo KITA ◽

Makiko MUKUMOTO ◽

Masahiko OKAMOTO

Keyword(s):

Gas Chromatography ◽

Analytical Method ◽

Headspace Gas Chromatography ◽

Active Ingredients ◽

Technical Grade ◽

Headspace Gas ◽

Development And Validation ◽

Volatile Impurities

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APPLICABILITY OF THE AMES TEST AND MICRONUCLEUS TEST IN VIVO FOR THE EVALUATION OF THE EQUIVALENCE OF PESTICIDE TECHNICAL GRADE ACTIVE INGREDIENTS COMPARED TO ORIGINAL ACTIVE SUBSTANCES

Hygiene and Sanitation ◽

10.18821/0016-9900-2019-98-2-219-224 ◽

2019 ◽

Vol 98 (2) ◽

pp. 219-224

Author(s):

Nataliya A. Ilyushina ◽

O. V. Egorova ◽

Yu. A. Revazova

Keyword(s):

Ames Test ◽

Mouse Bone Marrow ◽

Active Ingredients ◽

Genotoxic Effects ◽

Technical Grade ◽

Technical Products ◽

Dose Dependent ◽

Active Substances

Introduction. Analogs of pesticides may differ from the original products in their properties because of the elevated level or the modified composition of the impurities. Therefore, it is necessary to determine the equivalence of such analogs using a number of criteria, including mutagenicity, to ensure their safety. The article compares the results of the research of genotoxic effects of technical grade active ingredients of pesticides in vitro and in vivo conditions to assess the applicability of such methods for equivalence determination of analogs of pesticides to patented products. Material and methods. The genotoxicity of 99 technical grade active ingredients of pesticides (59 names) was studied in vitro (Ames test) and in vivo. Results. In the Ames test mutagenic dose-dependent effects were revealed in the study of technical products of mesotrione, dimethoate, and pendimethalin both in the presence and in the absence of a metabolic activation system.In the in vivo test, a statistically significant dose-dependent increase in the frequency of micronucleated polychromatophilic erythrocytes in mouse bone marrow was detected after administration of six technical products mesotrione, pyrimiphos-methyl, dimethoate, glyphosate (2 products), isoproturon. Furthermore, different levels of genotoxic effects were found with technical materials of the same active ingredient from various productions, probably due to differences in the qualitative and quantitative composition of impurities. Conclusion. The present study indicated that in vitro and in vivo tests do not always demonstrate the same results of the genotoxicity assessment. Therefore, the use of only one bacterial reverse mutation test may not be sufficient to determine the equivalence of technical grade active ingredients of pesticides to the original active substances. To obtain а reliable evidence for the safe use of analogs of pesticides, it is necessary to usе at least two methods on different test objects.

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Guidance Document for the Assessment of the Equivalence of Technical Grade Active Ingredients for Identical Microbial Strains and Isolates

10.1787/489def79-en ◽

2018 ◽

Author(s):

Keyword(s):

Guidance Document ◽

Active Ingredients ◽

Technical Grade ◽

Microbial Strains

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Systemic assessment of pesticide genotoxicity

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.09.67-69 ◽

2020 ◽

pp. 67-69

Author(s):

Н.А. Илюшина

Keyword(s):

Bone Marrow ◽

Active Ingredient ◽

General Mechanism ◽

Expert Evaluation ◽

Erythroid Cells ◽

Active Ingredients ◽

Technical Grade ◽

Inhibiting Action ◽

Genotoxicity Tests ◽

Pesticide Genotoxicity

Изучена генотоксичность более 200 технических продуктов (ТП) пестицидов. Разработан алгоритм оценки эквивалентности ТП оригинальным действующим веществам (ДВ) по критерию «мутагенность». Обоснована необходимость изучения генотоксической активности комбинаций ДВ пестицидов. Установлены ограничения тестов на генотоксичность, обусловленные токсичностью пестицидов разных химических классов. Выявлена зависимость ингибирующего эритропоэз действия триазоловых пестицидов от структуры ДВ. Изучено влияние и предложен общий механизм действия карбендазима на процессы кариокинеза, экструзии ядер и цитокинеза в эритроидных клетках костного мозга млекопитающих. Разработаны критерии экспертной оценки мутагенности пестицидов. The genotoxicity of more than 200 technical grade active ingredients (TGAI) of pesticides has been studied. An algorithm for evaluating the equivalence of TGAIs to the original active ingredients upon the criterion of “mutagenicity” has been developed. The necessity of studying the genotoxic activity of the combinations of pesticide active ingredients was substantiated. Limitations of the genotoxicity tests due to toxicity of pesticides of different chemical classes have been established. The dependence of the erythropoiesis-inhibiting action of triazole pesticides on the structure of the active ingredient was revealed. The effects and the general mechanism of the carbendazim action on the processes of karyokinesis, extrusion of nuclei and cytokinesis in mammalian bone marrow erythroid cells were studied. The criteria for expert evaluation of pesticide mutagenicity have been developed.

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A Comparison of Acute Toxicity Endpoints for Adult Honey Bees with Technical Grade Active Ingredients and Typical End-use Products as Test Substance

Journal of Economic Entomology ◽

10.1093/jee/toz305 ◽

2019 ◽

Vol 113 (2) ◽

pp. 1015-1017

Author(s):

Susan E Spruill ◽

Bridget F O'Neill ◽

Silvia Hinarejos ◽

Ana R Cabrera

Keyword(s):

Acute Toxicity ◽

Active Ingredient ◽

Honey Bees ◽

Model Organism ◽

Toxicity Tests ◽

Oral Exposure ◽

Test Substance ◽

Active Ingredients ◽

Technical Grade ◽

End Use

Abstract The honey bee, Apis mellifera L. (Hymenoptera: Apidae), is a model organism for pollinators in risk assessment frameworks globally. The acute toxicity tests with adult honey bees for contact and oral exposure are part of the requirements for pesticide registration and are typically conducted with the active ingredient. A question often asked is if the typical end-use product (TEP) is more toxic than the technical grade active ingredient (TGAI) to honey bees. We explored this question by mining publicly available databases from regulatory agencies worldwide, where testing with the TEP is required. The objective of this study was to determine whether TEPs are comparable in toxicity to the TGAI. The dataset was analyzed via a 3 × 3 contingency table with toxicity categories, as the data cannot be computed for regression analysis. Of the 151 active ingredients with reported endpoints for contact exposure, 28 were classified as either moderately or highly toxic, 123 were classified as practically nontoxic, and 3 were inconclusive. Only two (1.3%) were reclassified from nontoxic to moderately toxic as the TEP. Of the 141 active ingredients with reported endpoints for oral exposure, 23 were classified as moderately or highly toxic, 113 were classified as practically nontoxic, and 5 were inconclusive. Only five (3.6%) were reclassified from nontoxic to moderately toxic as the TEP. Fewer than 5% of the total TEPs evaluated (contact and oral) were shown to be more toxic than the TGAI, suggesting that the risk assessments of TGAIs would be sufficiently protective to pollinators at the screening laboratory level.

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