Two critical parameters in the evaluation of the toxicological hazards of the use of carbamate pesticides are: (1) a rapid, sensitive, and precise analytical method of identification of the carbamate and its metabolites; and (2) their metabolism. A method in this study was developed whereby various carbamates and their metabolites could be chromatographed in the gaseous phase. Also, a comparative in vitro study of 15,000 g liver supernatants from human, rat, and dog was performed. Additional tissues investigated for metabolic activity toward the carbamates, Zectran and Mesurol, were kidney (from the dog only) and various blood fractions (red blood cells, serum and whole blood). The various homogenates from the liver and kidney were ether-extracted after incubation. The ether extract was processed and spotted on silica gel G thin-layer chromatographic plates and developed bidimensionally to resolve metabolites. Radioautographic analysis was used to identify the radioactive areas. After incubation the blood was treated in a similar manner as the liver and kidney homogenates.
It was found that, in vitro, the liver was the major site of metabolism, and that the oxidative enzymes mediated by the NADPH mixed oxidase system were the major participants in the metabolism of Zectran and Mesurol. These enzymes utilized primarily non-hydrolytic pathways in the processes of degradation. The main metabolite produced with Zectran was 4-methylamino-3,5-xylyl N methylcarbamate (MA). Minor metabolites produced were 4-dimethylamino-3,5-xylyl N hydroxy methylcarbamate (NOHME), 4-methylformamido-3,5-xylyl-N methylcarbamate and 4-formamido-3,5-xylyl N methylcarbamate. The rat and the dog produced eight times as much NOHME as the human. 4-methylsulfinyl-3,5-xylyl N methylcarbamate (sulfoxide) · and 4-methylthio-3,5-xylyl N-methylcarbamate (NOHME) were the major metabolites produced with Mesurol. The human and the rat produced four times· as much NOHME as the dog. These examples demonstrate the wide interspecies variation prevalent in Zectran and Mesurol metabolism.
These data indicate that N-dealkylation is the major route of metabolism for Zectran in all three species. Minor pathways included hydroxylation of the carbamate moiety N-methyl groups. Sulfoxidation and hydroxylation were the major routes of metabolism with Mesurol in all three species.
The kidney and blood possessed very low hydrolytic and nonhydrolytic metabolic activity.
Master of Science (MS)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Carbamates; Pesticides -- toxicity
Loma Linda University Libraries
This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Wheeler, Larry A., "A Comparative In Vitro Metabolic Study of Certain Pesticidal Phenyl N-Methyl-Carbamates" (1970). Loma Linda University Electronic Theses, Dissertations & Projects. 837.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives