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).
Profile of Nonprotein Thiols, Lipid Peroxidation and D-Aminolevulinate Dehydratase Activity in Mouse Kidney and Liver in Response To Acute Exposure To Mercuric Chloride and Sodium Selenite