Identification and quantitative determination of a carboxylic and a mercapturic acid metabolite of etridiazole in urine of rat and man: potential tools for biological monitoring

Etridiazole, 5-ethoxy-3-trichloromethyl-1, 2,4-thiadiazole, was orally administered to rats and human volunteers. Two metabolites of etridiazole were synthesized: 5-ethoxy-1,2,4-thiadiazole-3-carboxylic acid (ET-CA) and N-acetyl-S-(5-ethoxy- 1,2,4-thiadiazol-3-yl-methyl)-L-cysteine (ET-MA). Selectiv...

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Bibliographic Details
Published in:Archives of toxicology 1991-01, Vol.65 (8), p.625-632
Main Authors: Welie, R.T.H. van, Mensert, R, Duyn, P. van, Vermeulen, N.P.E
Format: Article
Language:English
Subjects:
Acetylcysteine - metabolism
Adult
Animals
biochemical pathways
Biological and medical sciences
biomarkers
Carboxylic Acids - metabolism
Environmental Monitoring - methods
etridiazole
excretion
Fungicides, Industrial - metabolism
Humans
kidneys
liver
Male
Medical sciences
metabolites
oral administration
Pesticides, fertilizers and other agrochemicals toxicology
pharmacokinetics
Rats
Rats, Inbred Strains
Thiadiazoles - metabolism
Thiadiazoles - toxicity
toxicity
Toxicology
urine
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Summary:Etridiazole, 5-ethoxy-3-trichloromethyl-1, 2,4-thiadiazole, was orally administered to rats and human volunteers. Two metabolites of etridiazole were synthesized: 5-ethoxy-1,2,4-thiadiazole-3-carboxylic acid (ET-CA) and N-acetyl-S-(5-ethoxy- 1,2,4-thiadiazol-3-yl-methyl)-L-cysteine (ET-MA). Selective and sensitive analytical procedures to determine etridiazole, the carboxylic acid ET-CA and the mercapturic acid ET-MA in urine were developed. The detection limit of etridiazole, applying GC with nitrogen selective detection (GC-NPD), was 36 microgram/l urine (CV = 15.4%, n = 3). The detection limit of ET-CA, applying GC with sulphur selective detection (GC-FPD). was 100 microgram/l urine (CV = 9.8%, n = 3). In urine of rats orally treated with etridiazole, ET-CA and ET-MA were identified as metabolites of etridiazole, whereas in urine of humans given oral etridiazole, only ET-CA was identified. Unmetabolized etridiazole was excreted for less than 0.1% of the administered dose in rats. ET-CA, however, accounted for 22 +/- 9% of the administered dose of etridiazole in rats and for 13 +/- 6% in humans. ET-MA appeared to be a minor urinary metabolite of etridiazole. ET-CA is proposed as a possible biomarker for the biological monitoring of etridiazole.
ISSN:0340-5761
1432-0738
DOI:10.1007/BF02098027