Title: Dithiocarbamate toxicity - An appraisal Authors
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: April 10, 2011
Publication Date: September 14, 2011
Citation: Rath, N.C., Rasaputra, K.S., Liyanage, R., Huff, G.R., Huff, W.E. 2011. Dithiocarbamate toxicity - An appraisal. In: Stoytcheva, M. editor. Pesticides in the Modern World - Effects of Pesticides Exposure. InTech. Available from: http://www.intechopen.com/books/pesticides-in-the-modern-world-effects-of-pesticidesexposure/ dithiocarbamate-toxicity-an-appraisal. p. 323-340. Interpretive Summary: Dithiocarbamates (DTC) are widely used as fungicides in agriculture, animal repellants, and some household applications. Excessive exposures to these chemicals produce toxic effects. This review examines the action of some of those pesticides in different systems particularly their effect on poultry-leg bone cartilage which render them lame. The possible modes of action of these chemicals are discussed.
Technical Abstract: Dithiocarbamates are used as agricultural pesticides and general biocides in a variety of applications. However, acute or chronic exposure to these chemicals can produce neurotoxicity, developmental deformities, endocrine disruption, hypersensitivity, and metabolic dysfunctions in animals and humans. Teratogenic effects such as craniofacial and skeletal deformity have been reported for certain dithiocarbamate pesticides such as sodium metam, thiram, and disulfiram. These chemicals also induce a cartilage abnormality called tibial dyschondroplasia (TD) in post hatch poultry which is characterized by the broadening of the growth plate due to the failure of endochondral bone formation. The birds show age dependent effects with younger birds showing more susceptibility to TD inducing effects of thiram. Comparing different dithiocarbamates added to poultry diets and at different concentrations of thiram we have tested their efficacies to induce TD in chickens. The microenvironments of cells and the concentrations of thiram or its metabolites may be responsible for its toxic effects. Our studies show that thiram alters several gene and protein expressions involved in the differentiation and survival of chondrocytes. It also interferes with several other vital processes such as oxido-reductive metabolism involving glutathione. In chicken growth plate, it most probably affects the transition of prehypertrophic chondrocytes to the hypertrophic state precluding bone formation resulting in the accumulation of nonviable cells which broaden the growth plate. Examining the expressions of proteins and peptides in cartilage following in vivo and in vitro treatments, we found the expression of several proteins associated with energy metabolism, signal transduction, and extracellular matrix metabolism significantly impaired which could be the major mechanisms for its toxicity. Besides, these chemicals are known to be chelators of metal ions which have been proposed as one of the modes of their action. The variety actions of these thiocarbamates such as the anti-angiogenic and anti-viral activities along with their moderate toxicity, on adult individuals show potential for their application and exploitation as pharmaceuticals. This review will principally deal with the effects of thiram using poultry as a model based on our previous research and ongoing work in our laboratory.