Metabolic aspects

The metabolism of propoxur was studied in mammals by Dawson et

al. (1964), Everett and Gronberg (1970), Krishna and Casida (1966),
Waggoner and Olson (1971); in man by Dawson et al. (1964), Hayes
(1971); in insects by Metcalf et al. (1967), Shrivastava (1969); in
plants by Aba el Wahab (1966), Dorough and Casida (1964), Everett and
Gronberg (1968), Gronberg (1970), Kuhr and Casida (1967).
In vitro in animals studies were made by Crosby et al. (1965),
Dorough and Casida (1964) and Oonithan and Casida (1966, 1968).

In rats The metabolites identified in the rat (see below)

include those found in plants, in insects and those derived from
microsomes.
Whereas the oxidative pathways and hydrolytic degradation occur
in the same order of magnitude in mammals, the formation of oxidation
products predominates in plants. In soil, however, hydrolytic
degradation predominates.
Adsorption, distribution and excretion in mammals, including
biotransformation in rats: following oral administration in rats,
propoxur is rapidly ingested to the digestive tract, metabolized in
the body and excreted.
The rats eliminated 85% of the radio-activity after oral
administration of 14C carbonyl labelled, 14C isopropoxy labelled 3H
isopropyl labelled propoxur within 16 hours; 60% of this and amount
was excreted in the urine as conjugates and 20-25% as volatile
compounds in a C02/acetone ratio of 85:15. Only 1-5% of the activity
was found in the faeces in the same period (Everett and Gronberg,
1970).
Evidence was obtained by the same authors that the major routes
of metabolism in rats are depropylation to
2-hydroxyphenyl-N-Methylcarbamate (further indicated as metabolite
A) and subsequent hydrolysis to isopropoxyphenol (metabolite I).
Minor metabolic pathways are ring hydroxylation at the 5 or 6
position (C and E), secondary hydroxylation of the 2-carbon atom of
the isopropoxy group (D and G) and hydroxylation of the N-methyl
group.
From the conjugated compounds in the urine, the following
metabolites were released by hydrolysis of the urine sample with
glucuronidase and/or acid. They were identified by their infra-red and
mass spectra as well as from the 3H/14C ratio yielded of double
labelled propoxur: 2-hydrophenyl-N-methylcarbamate (A),
2-isopropoxyphenyl-N-hydroxy methylearbamate (B) and
2-isopropoxy-5-hydroxyphenyl-N-methylearbamate (C).
The metabolic pathways of propoxur in rats as proposed by Everett

and Gronberg (1970) is shown in the diagram on the following page.

Krishna and Casida (1966) administered 14C carbonyl labelled

propoxur intraperitoneally to rats. After 48 hours only 2.1% of the
administered radio-activity remained in the body; 60% of the activity
was excreted in the urine in the first 29 hours, whereas only 1.2% was
excreted in the faeces. Within 48 hours 31.2% of the administered
radio-activity was expired as CO2.
From these data it may be concluded that the carbamate group was
cleaved from one-third of the injected propoxur dose.
In a similar experiment with 14C isopropyl labelled propoxur,
70-75% of the activity was excreted in the urine, whilst 30%. of the

administered activity was expired as 14CO2; 4% of the activity

remained in the body and only 0.7% was excreted in the faeces.
From this it may be concluded that the isopropyl group is cleaved
from about one-quarter of the injected dose.
Dorough and Casida (1964) incubated rat liver microsomes with
propoxur and obtained 30% conversion to a metabolite from which with
acid Isopropoxyphenol and formaldehyde were yielded. With
cochromatography and infra-red spectroscopy the metabolite was
confirmed with (B).
Oonithan and Casida (1968) studied the metabolic fate of propoxur
in a system containing rat liver microsomes and NADPH2. Two
metabolites were formed, probably (A) and (B).

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