Dithiocarbamate Toxicity - An Appraisal

Dithiocarbamates (DTC) are organosulfur compounds represented by a general structure (R1R2)N-(C=S)-SX, where R can be substituted by an alkyl, alkylene, aryl, or similar other group, and X usually by a metal ion (Edwards, 1991; Kamrin, 1997; US EPA, 2001). Discovered in the 1930s, the DTC were first introduced as fungicides for commercial applications during World War II (Ware & Whitacre, 2004). Besides their wide use as fungicides for treatment of crops, vegetables, seeds, and ornamental plants, they are also used as accelerators in the rubber industry, animal repellants, and biocides in many household products (Edwards et al., 1991; Kamrin, 1997). Figure 1 shows examples of some common DTC pesticides. Thiram, disulfiram, ziram, and ferbam are analogous dialkyl DTC with differences in their R groups and the later two containing different metal ions between their S atoms. Pyrrolidinedithiocarbamate (PDTC) is a monomeric DTC which contains a five member ring attached to its N atom. It is a metabolic inhibitor used in cell physiological studies (Schreck et al., 1992; Cvek and Dvorak, 2007). In ethylene-bis-dithiocarbamates (EBDTC), the R groups of two DTC molecules form an ethylene bridge. The EBDTC are regarded as polymeric DTC because their metal ions can bind several molecules to form polymeric complexes. Some examples of EBDTC are zineb, maneb, and mancozeb which are used in preharvest agricultural applications. The DTC anions are highly reactive which can conjugate with other molecules containing SH groups and form metal chelates. The multisite interactions of DTC give them advantage to influence the biological activities of different proteins, enzymes, and exert toxic effects. Some of those modes of action of DTC compounds have been exploited for their use in clinical applications (Morrison et al., 2010). However, the extensive use of these chemicals in agriculture has raised concern for their effects as occupational and ecotoxicological hazards. Several reviews on the biological and toxicological effects of DTC summarize many studies in the field (Edwards et al., 1991; US EPA, 2001; Cvek and Dvorak, 2007). The objective of this review is to highlight some of the recent findings on the effects of dialkyl DTC and EBDTC with emphasis on studies of the avian system which has not been a focus of earlier literature.