thiophanate and tetrachloroisophthalonitrile

The objectives of this study were to examine cytotoxic and genotoxic damage in human BJ fibroblasts caused by three pesticides used worldwide by trypan blue dye exclusion assays and to measure the relative level of phosphorylated histone H2A.X by flow cytometry at different concentrations. Captan-based fungicide and methyl thiophanate-based fungicide (100 and 1000 µΜ) showed immediate cytotoxic effects; furthermore, after 24 h, captan-based fungicide, chlorothalonil-based fungicide and methyl thiophanate-based fungicide caused cytotoxic effects in the concentration ranges of 40-100 µM, 30-100 µM and 150-1000 µM, respectively. All fungicides generated DNA damage in the treated cells by activating ATM and H2A.X sensor proteins. The three fungicides tested generated DNA double-stranded breaks and showed cytotoxicity at concentrations 33, 34, and 5 times lower (captan, chlorothalonil and thiophanate-methyl respectively) than those used in the field, as recommended by the manufacturers.

Topics: Captan; DNA Damage; Fibroblasts; Fungicides, Industrial; Humans; Nitriles; Thiophanate

Chlorothalonil and thiophanate-methyl are fungicides widely used in agriculture. The aim of this study was to assess maternal toxicity and embryotoxic potential of exposure to chlorothalonil and thiophanate-methyl during organogenesis period in rats. Pregnant rats were divided into four groups: control and exposed to 400 (CT400), 800 (CT800) and 1200 mg-1kg bw-1 day (CT1200) of commercial formulation constituted of 200 g of thiophanate-methyl kg-1 and 500 g of chlorothalonil kg-1 by gavage, from 6th to 15th gestational day. Maternal toxicity, liver, kidney and placenta histology, reproductive performance, and external, skeletal and visceral malformations of fetuses were evaluated. Maternal liver weight was decreased in CT1200 group and focal necrosis and microvesicular steatosis, inflammatory infiltrate and hepatocytes with pyknotic nucleus were observed in CT800 and CT1200 groups. Reproductive performance was similar among groups. The percentage of fetuses small for pregnancy age was increase in CT400 and CT800 groups. Moreover, incidence of skeletal anomalies was increased in the three groups exposed to fungicides. Chlorothalonil and thiophanate-methyl exposure showed affect the prenatal development and induce maternal toxicity.

Topics: Animals; Female; Fetus; Nitriles; Organogenesis; Pregnancy; Rats; Thiophanate

Mancozeb (MZ), chlorothalonil (CT), and thiophanate methyl (TM) are pesticides commonly used in agriculture due to their efficacy, low acute toxicity to mammals, and short environmental persistence. Although the toxic effects of these pesticides have been previously reported, studies regarding their influence on the immune system are limited. As such, this study focused on the immunomodulatory effect of MZ, CT, and TM pesticides on macrophage cells. RAW 264.7 cells were exposed to a range of concentrations (0.1-100 μg/mL) of these pesticides. CT exposure promoted an increase in reactive oxygen species (ROS) and nitric oxide (NO) levels. The MTT and ds-DNA assay results demonstrated that MZ, CT, and TM exposure induced macrophage proliferation. Moreover, MZ, CT, and TM promoted cell cycle arrest at S phase, strongly suggesting macrophage proliferation. The levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) and caspases (caspase 1, 3, and 8) in macrophages exposed to MZ, CT, and TM pesticides increased, whereas the anti-inflammatory cytokine levels decreased. These results suggest that MZ, CT, and TM exert an immunomodulatory effect on the immune system, inducing macrophage activation and enhancing the inflammatory response.

Topics: Animals; Cytokines; Immunomodulation; Interleukin-1beta; Macrophages; Maneb; Nitric Oxide; Nitriles; Pesticides; Reactive Oxygen Species; Thiophanate; Toxicity Tests; Tumor Necrosis Factor-alpha; Zineb

A new bioassay has been developed combining the simplicity of direct bioautography with the improved chromatographic resolution of 2D-TLC. Mixtures of structurally diverse antifungal agents were tested to establish the validity and utility of this method in the discovery of new natural products with activity against agriculturally important fungal pathogens.

Topics: Acrylates; Aniline Compounds; Antifungal Agents; Ascomycota; Benzimidazoles; Biological Assay; Captan; Carbamates; Chromatography, Thin Layer; Colletotrichum; Dimethyldithiocarbamate; Fungicides, Industrial; Guanidines; Maneb; Methacrylates; Nitriles; Nitrobenzenes; Oxazoles; Piperazines; Plant Diseases; Plants; Pyrimidines; Strobilurins; Thiabendazole; Thiophanate; Triazoles

In the present study we describe the effect of 4 fungicides on the induction of point mutations in strains biA1 methG1 (induction of methionine suppressors) and 118 (induction of arginine resistance) of Aspergillus nidulans. Captan, which was used as a known mutagen, Daconil 2787 and Dithane M-45 were effective in inducing these mutations, whereas the fungicide Cercobin caused no significant increase in the induction frequency of the point mutations selected. Actually, a decrease in the frequency of methionine suppressors was observed in relation to those occurring spontaneously. However, this effect could not be considered antimutagenic because the revertants were more sensitive to the fungicide than the biA1 methG1 strain. Although the induction of methionine suppressors was more convenient because it permits the visualization of several morphological types, the 118 strain system also proved to be effective in detecting point-mutation induction.

Topics: Antifungal Agents; Arginine; Aspergillus nidulans; Captan; Drug Resistance, Microbial; Maneb; Methionine; Mutagenicity Tests; Nitriles; Thiophanate; Zineb