zineb and zinc-chloride

The effects of the fungicides Maneb, Mancozeb, and Zineb were investigated in transformed colon cells, HT-29, Caco2 and non-transformed cells, CCD-18Co. Significant decreases in viability were observed with Maneb and Mancozeb in HT-29 and CCD-18Co (80-260μM), and Caco2 cells (40-180μM). No significant decreases in viability were observed in all cell types up to 800μM with Zineb. MnCl(2) and ZnCl(2) exposure produced no loss of viability in all cell types up to 400μM. Light microscopy confirmed viability analysis. Lipid peroxidation was observed with Maneb and Mancozeb in cell types tested (60-200μM). Caspase 3/7, 8, and 9 activities were observed with Maneb and Mancozeb in cell types tested (40-200μM). Maneb and Mancozeb treated HT-29 and Caco2 cells demonstrated increases in manganese and zinc concentrations (20-200μM). The lack of toxicity observed with Zineb, MnCl(2), and ZnCl(2) suggests that both the metal moiety and the organic portion of these fungicides together contribute to toxicity.

Topics: Caco-2 Cells; Caspases; Cell Line; Cell Survival; Chlorides; Fungicides, Industrial; HT29 Cells; Humans; Lipid Peroxidation; Maneb; Manganese; Manganese Compounds; Zinc; Zinc Compounds; Zineb

After repeated-dose toxicity studies with the fungicide propineb, reversible effects on muscle functions were found. Therefore, mechanistic investigations should contribute to clarification of its mode of action in relation to disulfiram and diethyldithiocarbamate neurotoxicity or direct effects on muscle cells. In principle, besides the dithiocarbamate effects, two different mechanisms have been discussed for this fungicide. One mechanism is the degradation to carbon disulfide (CS(2)) and propylenthiourea (PTU) and the other are direct effects of zinc. Primary neuronal cell cultures of the rat are a well established model to identify neurotoxic compounds like n-hexane or acrylamide. In this cell culture model, endpoints such as viability, energy supply, glucose consumption and cytoskeleton elements were determined. Additionally, skeletal muscle cells were used for comparison. Propineb and its metabolite PTU were investigated in comparison to CS(2), disulfiram and diethyldithiocarbamate. The toxicity of zinc was tested using zinc chloride (ZnCl(2)). It was clearly shown that propineb exerted strong effects on the cytoskeleton of neuronal and non-neuronal cell cultures (astrocytes, muscle cells). This was similar to ZnCl(2,) but not to CS(2). With CS(2) and disulfiram effects on the energy supply were more prominent. In conclusion, the toxicity of propineb is not comparable to disulfiram, diethyldithiocarbamate or CS(2) neurotoxicity. In regard to these findings, a direct reversible effect of propineb on skeletal muscle cells seems to be more likely.

Topics: Animals; Carbon Disulfide; Cell Survival; Cells, Cultured; Cerebral Cortex; Chlorides; Cytoskeleton; Disulfiram; Ditiocarb; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Fungicides, Industrial; Glucose; Muscle, Skeletal; Neurons; Rats; Thiourea; Zinc Compounds; Zineb