Metabolism and toxicological evaluation of the aromatic amide herbicide propanil and its derivatives

Miscellaneous · Sun Jan 01 00:00:00 EST 1989

OSTI ID:6323812

McMillian, D C

Since propanil is structurally similar to other carcinogenic arylamides, the potential chronic toxicity of propanil and its derivatives were examined in short-term assays for genotoxicity. Propanil, 3,4-dichloroaniline, and their N-oxidized derivatives were inactive in the Salmonella typhimurium reversion, Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT), and rat hepatocyte/DNA repair assays. The metabolism of propanil and 3,4-dichloroaniline was subsequently examined in liver microsomes from males Sprague-Dawley rats to identify metabolites that may be involved in the acute toxicity of propanil. The major pathway of propanil metabolism was acylamidase-catalyzed hydrolysis to 3,4-dichloroaniline. Oxidized metabolites were isolated by high performance liquid chromatography, and identified as 2{prime}-hydroxy-propanil and 6-hydroxy-propanil by comparison of their mass and nuclear magnetic resonance spectra to synthetic standards. Experiments were performed to determine if propanil exposure could be monitored by the analysis of hemoglobin binding. Administration of (ring-U-{sup 14}C)propanil to rats increased methemoglobin formation in a dose-dependent manner. Concomitant with methemoglobin formation, dose-dependent covalent binding of radiolabeled propanil to hemoglobin was detected. HPLC analysis indicated that the hemoglobin adducts were sulfinic acid esters, and these data suggest that human exposure to propanil may be monitored by the analysis of propanil metabolites bound to hemoglobin.

• Research Organization: Arkansas Univ., Fayetteville, AR (USA)
• OSTI ID: 6323812
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HERBICIDES
METABOLISM
BIOLOGICAL PATHWAYS
CARBON 14 COMPOUNDS
CHO CELLS
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
GENETIC EFFECTS
HEMOGLOBIN
LIQUID COLUMN CHROMATOGRAPHY
LIVER
METABOLITES
MICROSOMES
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
RATS
SALMONELLA TYPHIMURIUM
TOXICITY
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
GLANDS
GLOBINS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAGNETIC RESONANCE
MAMMALS
MICROORGANISMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PESTICIDES
PIGMENTS
PORPHYRINS
PROTEINS
RECOVERY
REPAIR
RESONANCE
RIBOSOMES
RODENTS
SALMONELLA
SEPARATION PROCESSES
SPECTRA
VERTEBRATES
550501* - Metabolism- Tracer Techniques