Genotoxicity of dithiocarbamates and their metabolites

Franekić, Jasna; Bratulić, N.; Pavlica, Mirjana; Papeš, Dražena

doi:10.1016/0165-7992(94)90003-5

Cited by 45 publications

(19 citation statements)

References 19 publications

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“…propineb, zineb, maneb, mancozeb, ziram, thiram), leading to analytical methods designed to detect the presence of these potentially hazardous chemicals and their degradation products in different media. 2 -5 Other current uses of DTCs are as antiviral agents, 6 antidotes for preventing the effects of phytotoxic agents, 7 bactericides and antimicrobial agents, 8 antitumour drugs 9 and prophylactic or therapeutic agents for metal toxicity. 10 -19 Although DTCs are suitable for the removal of metals from organisms, they also are able to alter redistribution, resulting in increased toxicity.…”

Section: Introductionmentioning

confidence: 99%

In vitro toxicity of several dithiocarbamates and structure–activity relationships

Segovia

Crovetto

Lardelli

et al. 2002

J of Applied Toxicology

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Dithiocarbamates (DTCs) are chemicals featuring a great chelating capacity. The toxicological study of DTCs is very important in view of their relatively simple synthesis and wide array of sanitary and industrial applications. In this study, the toxicity of some of the more recently synthesized DTCs is determined using an extremely simple bioassay, described in previous studies, based on the inhibition of growth of Escherichia coli (IGEC). The lowest-observed-effect concentration (LOEC), the median effective concentration (EC(50)) and no-observed-effect concentration (NOEC) of the following sodium dithiocarbamates was determined: N-benzyl-N-methyldithiocarbamate x 2H(2)O, N-benzyl-N-isopropyldithiocarbamate x 3H(2)O, N-benzyl-N-ethyldithiocarbamate x 2H(2)O, N-butyl-N-methyldithiocarbamate x 2H(2)O, N,N-dibenzyldithiocarbamate x 2H(2)O and N-benzyl-2-phenethyldithiocarbamate x 4H(2)O. Our results showed N,N-dibenzyl-DTC to be the least toxic of the tested substances, with an EC(50) value of 1,269.9 micro g ml(-1), whereas N-butyl-N-methyl-DTC and N-benzyl-N-methyl-DTC, with respective EC(50) values of 14.9 micro g ml(-1) and 23.5 micro g ml(-1), were the most toxic. Regression analysis showed, through exponential models, that the degree of toxicity of this group of substances correlated with the molecular weight of the compound, the molecular weight of the smallest chemical radical linked to the dithiocarbamate group and the number of benzene rings present in the molecule. The consideration of these models allows us to establish that in general terms the toxicity of DTCs decreases exponentially with a greater molecular weight and the number of benzene rings.

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Section: Introductionmentioning

confidence: 99%

In vitro toxicity of several dithiocarbamates and structure–activity relationships

Segovia

Crovetto

Lardelli

et al. 2002

J of Applied Toxicology

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“…The available reported data do not allow a proper evaluation of the carcinogenicity of zineb. Plate incorporation assays with Salmonella typhimurium demonstrated a direct nonmutagenic effect of the pesticide, whereas mitotic chromosome malsegregation, gene conversion and point mutation assays with Saccharomyces cerevisiae and Bacillus subtilis gave positive results (Shiau et al, 1980;Franekic et al, 1994;Della Croce et al, 1996). Zineb exerted a high dose-related cytotoxicity in BALB/c 3T3 mouse cells in vitro, but only in the absence of an exogenous metabolizing system (Perocco et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Effect of the dithiocarbamate pesticide zineb and its commercial formulation azzurro. I. Genotoxic evaluation on cultured human lymphocytes exposed in vitro

Soloneski¹

2001

Mutagenesis

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The in vitro cytogenetic effects exerted by the dithiocarbamate fungicide zineb and one of its commercial formulations currently used in Argentina, azzurro, were studied in whole blood human lymphocyte cultures. The genotoxicity of the fungicides was measured by analysis of the frequency of chromosomal aberrations and sister chromatid exchanges (SCEs) and cell cycle progression assays. Both zineb and azzurro activities were tested within the range 0.1-100.0 µg/ml immediately after in vitro lymphocyte stimulation. Only concentrations of 50.0 and 100.0 µg/ml zineb and azzurro induced a significant increase in SCE frequency over control values. Furthermore, this genotoxicity appears to be correlated with its cytotoxicity, measured as cell cycle kinetics, since both a significant delay in cell cycle progression and a significant reduction in proliferative rate index were only observed in those cultures treated with these fungicide concentrations. For both chemicals, a progressive dose-related inhibition of the mitotic activity of cultures was observed when increasing the fungicide concentration. Moreover, only the mitotic activity statistically differed from control values when doses of zineb or azzurro <10 µg/ml were employed. For both fungicides the mitotic index reached the minimal value at doses of 100 µg/ml. Both products induced a significant dose-dependent increase in the number of abnormal cells, chromatid-type and chromosome-type aberrations as well as in the total number of aberrations in the 0.1-100.0 µg/ml dose range. Based on these results, the evaluation of zineb as a controversial genotoxic/nongenotoxic compound for human health should be reconsidered. Instead, we demonstrate that the fungicide induces large DNA alterations and should be considered as a clastogenic mutagen.

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“…In another report, the same research group has reported that the fungicide ziram is mutagenic in the wing, eye and female germ-line mosaic assays, and in sex linked recessive lethal test in Drosophila melanogaster (Tripathy et al, 1989). In a more recent study, Franekic et al (1994) reported that ziram, zineb and thiaram are mutagenic in a battery of bacterial test systems. The thiocarbamate pesticide malinate and vernolate have been reported to cause chromosomal changes like SCE and chromosomal aberrations in vitro and increased frequency of polychromatic erythrocytes in mouse bone marrow cells (Pinter et al, 1989).…”

Section: Genotoxic Effects Of Pesticides In Living Organismsmentioning

confidence: 94%