In vitro toxicity of several dithiocarbamates and structure-activity relationships.
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.
Segovia
N
N
Department of Preventive Medicine and Public Health, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain.
Crovetto
G
G
Lardelli
P
P
Espigares
M
M
D001681:Biological Assay; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D015394:Molecular Structure; D008970:Molecular Weight; D021281:Quantitative Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*
D002614:Chelating Agents; D013859:Thiocarbamates