Ethylene bisdithiocarbamate pesticides Maneb and Mancozeb cause metal overload in human colon cells

• EBDCs Nabam, Zineb, Maneb and Mancozeb trans-chelate copper into colon cells.
• Maneb and Mancozeb exposure causes increases in manganese, zinc, and copper levels.
• Both the metal moiety and organic ligand contribute to toxicity of EBDC fungicides.

Previous studies in our laboratory have shown that ethylene bisdithiocarbamate (EBDC) fungicides Maneb and Mancozeb are equipotent gastrointestinal toxicants that produce cell loss and metal accumulation within HT-29 and Caco2 colon cells. Nabam, MnCl2, CuCl2 and ZnCl2 exposure produced no loss of viability up to 200 μM and increases in metal levels were noted but not to the same extent as Maneb and Mancozeb. EBDC exposure caused increases in copper levels (20–200 μM). Maneb and Mancozeb treatment also caused increases in manganese and zinc concentrations (20–200 μM). Nabam plus MnCl2 and Nabam and MnCl2 plus ZnCl2 caused decreases in viability and increases in metal levels comparable to Maneb and Mancozeb. Decreases in the ratio of reduced glutathione to glutathione disulfide were observed with Maneb and Mancozeb (20–200 μM). Maneb and Mancozeb treatment results in intracellular metal accumulation leading to the oxidative stress. The metal moiety and the organic portion of EBDCs contribute to toxicity.