Pyrethroid metabolism: microsomal oxidase metabolites of (S)-bioallethrin and the six natural pyrethrins

Abstract

Metabolism of the chrysanthemates (S)-bioallethrin, cinerin I, jasmolin I, and pyrethrin I by NADPHdependent oxidases of mouse liver microsomes yields 13-18 metabolites in each case oxidized a t the methyl, methylene, and alkenyl substituents to form alcohols, aldehydes, carboxylic acids, epoxides, and dihydrodiols. Rat microsomes are more specific than mouse microsomes in hydroxylating the @)-methyl substituent of the 2-methylpropenyl moiety compared with other molecular sites. Metabolites in the urine of allethrin-treated rats include compounds modified in both the 2-methylpropenyl and allyl moieties as free carboxylic acids and glucuronides. The pyrethrates cinerin 11, jasmolin 11, and pyrethrin I1 undergo microsomal hydrolysis of the methoxycarbonyl group and oxidation of the butenyl, pentenyl, and pentadienyl substituents to alcohols, epoxides, and dihydrodiols. Metabolites of these chrysanthemates and pyrethrates are tentatively identified by chemical ionization mass spectrometry following treatment with diazomethane or diazoethane and bis(trimethylsily1)acetamide and separation by high-resolution gas chromatography with hydrogen as the carrier gas.The six natural pyrethrins in pyrethrum extract and their synthetic analogue (SI-bioallethrin (i.e., the rethrins) are important insecticides for control of household and stored products pests (Casida, 1973). The metabolic fates (S)-bioallethrin (A): R, = CH,, R, = H pyrethrin chrysanthemate (I) pyrethrate (11) cinerins (C) CI: R, = CH,, CII: R, = CO,CH,, --R, CH,-R, = CH, R, = CH,CH, R, = CH=CH, jasmolins (J) JI: R, = CH,, JII: R, = CO,CH,, pyrethrins (P) PI: R, = CH,, PII: R, = CO,CH,, R, = CH,CH, R, = CH=CH, of A and PI, partially defined in microsomal oxidase systems and in rats, involve multiple sites of oxidation with little or no cyclopropanecarboxylate hydrolysis (Casida et al., 1971;Elliott et al., 1972). Comparable information is not available on the other pyrethrum constituents except for their relative ease of oxidation in microsomal oxidase systems (Soderlund and Casida, 1977a). With molecules as complex as the rethrins it is difficult to predict the effects of relatively small structural modifications (e.g., R, = CH,, CO,CH,; R2 = H, CH,, CH,CH,, CH=CH,) on their rates and sites of biodegradation. In further evaluating the comparative fate of the rethrins, it is important to use analytical methods applicable to all of the relevant compounds. The pyrethrum constitPresent address:uents and A are conveniently analyzed by high-resolution gas chromatography (HRGC) with an electron-capture detector (ECD) or HRGC-chemical ionization (CI) mass spectrometry (MS). These methods are applied here to the rethrin metabolites, after appropriate derivatizations. This study compares the metabolic fate of A and the six natural pyrethrins in mouse and rat liver microsomal oxidase systems and of A in rats.

Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

“…36912-77-3). The last two metabolites were found by Class et al (1990) in urine to partly exist as conjugates. Metabolites were tentatively identified by chemical ionization mass spectrometry, following treatment with diazomethane or diazoethane and trimethylsilylacetamide and high-resolution GC.…”

Simultaneous determination of pyrethroid and pyrethrin metabolites in human urine by gas chromatography–high resolution mass spectrometry

“…Immunoassay methods are on the one hand comparable cheap and easy to perform, but on the other hand they do not achieve the sensitivity and specificity of analytical methods. For the determination of the internal pyrethrum, allethrin, resmethrin, phenothrin and tetramethrin burden, trans-chrysanthemumdicarboxylic acid (CDCA) turned out to be the relevant biomarker in the urine [10,23]. Regarding the detection of trans-CDCA in human urine there are only two publications available [10,17].…”

Control of Dark-winged Fungus Gnats (Lycoriella ingenua) using Mist Fogger with Natural Pyrethrum (Tanacetum cinerariifolium)

“…In Rhesus monkeys, however, administration of pyrethrins into the body (100% bioavailability) by avoiding the digestive canal (parenteral studies) showed that 22.5% of the chemical was excreted in the urine seven days after administration (Wester et al, 1992). The compound has been found to rapidly degrade in the stomach by hydrolysis of the ester bond to harmless metabolites (Class et al, 1990). The metabolic fate of pyrethrins in rats has been partially defined in microsomal oxidase system (Casida et al, 1971;Elliott et al, 1972).…”

“…The metabolic fate of pyrethrins in rats has been partially defined in microsomal oxidase system (Casida et al, 1971;Elliott et al, 1972). The sites of metabolic attack on the pyrethrins and the metabolites (Figure 1 and 2) were determined by Class et al (1990).…”