IN-VITRO EVALUATION OF THE TOXICITY OF SEVERAL DITHIOCARBAMATES USINGAN ESCHERICHIA-COLI GROWTH-INHIBITION BIOASSAY AND THE ACETYLCHOLINESTERASE INHIBITION TEST

The industrial and sanitary use of dithiocarbamates (DTCs) is on the r ise, and the synthesis of new derivatives has increased the field of t heir application. Both positive and negative pharmacological and toxic ological effects have been documented for DTCs. The development and ap plication of new DTCs must be accompanied by the study of their toxici ty, beginning with the performance of simple and rapid biological scre ening tests. The objective of our study was to apply the IGEC biotest (inhibition of growth of Escherichia coil) and the acetylcholinesteras e (AChE) inhibition test to a group of newly synthesized DTCs with pos sible applications in the area of public health. The substances studie d were (-)-ephedrine-DTC, (+)-pseudoephedrine-DTC, N-ethylbenzyl-DTC, diethyl-DTC, and dimethyl-DTC, and the corresponding amines used in th eir synthesis: (-)-ephedrine, (+)-pseudoephedrine, N-ethylbenzylamine, diethylamine, and dimethylamine. The parameters for the minimal effec tive concentration tested (MEC), median effective concentration (EC50) , and no observed effect concentration (NOEC) of each chemical were de termined using the IGEC biotest. The AChE inhibition test was carried out for all the DTCs as well. Of the synthesized DTCs, (+)-pseudoephed rine-DTC showed the lowest toxicity (NOEC = 30 mu g mL(-1) and EC50 = 301 mu g mL(-1)) and N-ethylbenzyl-DTC showed the highest toxicity (EC 50 = 26 mu g mL(-1)). Although (-)-ephedrine-DTC exhibited a minimal i nhibitory effect on AChE, the results obtained indicate a generalized absence of AChE inhibition for the DTCs. (C) 1998 by John Wiley & Sons , Inc.