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W G Taylor

Publications and source records attributed to W G Taylor.

79 records · Page 5Linked to original sources
PubMedDate not supplied

Metabolism of N,N-diethyl-meta-toluamide by rat liver microsomes.

The NADPH- and oxygen-dependent metabolism of N,N-diethyl-m-toluamide (deet insect repellent) has been studied at 37 degrees C in suspensions of liver microsomes from phenobarbital-pretreated male Wistar rats. In pH 8 Tris-HCl buffer and at a substrate concentration of 200 microM, metabolic reactions corresponded to benzylic hydroxylation and N-deethylation, and to combinations of these reactions, leading to N,N-diethyl-m-hydroxymethylbenzamide, N-ethyl-m-toluamide, N-ethyl-m-hydroxymethylbenzamide, and m-toluamide. These compounds and N,N-diethyl-m-formylbenzamide were detected in methyl t-butyl ether extracts by capillary gas chromatography using three fused silica columns of different polarities. The structures of the in vitro metabolites were verified by comparisons with samples of authentic standards using combined gas chromatography-mass spectrometry. A selective derivatization procedure with acetic anhydride and pyridine facilitated the detection of the two alcohols. The major metabolites, N,N-diethyl-m-hydroxymethylbenzamide and N-ethyl-m-toluamide, were quantitatively determined in derivatized extracts with an internal standard of N,N-dipropyl-m-toluamide, a capillary column of DB-1, and a nitrogen-phosphorus detector. The mean enzymatic yield of these two products was 69% in three replicated experiments.

Animals↗
PubMedDate not supplied

Metabolism of N,N-diethyl-m-toluamide (DEET) by liver microsomes from male and female rats. Simultaneous quantitation of DEET and its metabolites by high performance liquid chromatography.

A simple and sensitive HPLC procedure was developed to separate and quantitate N,N-diethyl-m-toluamide (DEET) and its in vitro metabolites using a gradient elution, a reversed phase C18 column, and an internal standard. This procedure was applied to examine the metabolism of this insect repellent in liver microsomes from normal (untreated) male and female Wistar rats. At a pH of 8.6 and at a substrate concentration of 200 microM, the microsomal preparations from males degraded DEET faster than did those from females. The half-life of DEET was 10 min and 15 min, respectively. The benzylic methyl hydroxylated metabolite and the N-deethylated metabolite were determined over 2 hr in fortified microsomal suspensions. Rate constants for appearance of the metabolites showed significantly higher values for males than for females. These observations suggests that a sex difference may be present in the metabolism of DEET.

Animals↗
PubMedDate not supplied

Hydroxylation of 3-acetyl-2-(2,6-dimethyl-5-heptenyl)oxazolidine by rat liver microsomes. Identification of some isomeric metabolites.

The metabolism of nonradiolabeled, stereoisomeric mixtures of 3-acetyl-2-(2,6-dimethyl-5-heptenyl)oxazolidine (I), a new citronelial-based insect repellent, by induced and uninduced rat liver microsomes has been examined in a NADPH-generating system at a substrate concentration of 1.67 mM. By comparison of retention times and mass spectra of the metabolites with the products from oxidation of I with selenium dioxide, the allylic methyl carbons of the isobutenyl group were identified as the major sites of oxidative metabolism, with two samples of I prepared from different sources of (+/-)-citronelial. Both diastereomeric and E-Z isomeric forms of the metabolites were separated by high resolution capillary gas chromatography with Carbowax 20M-terephthalic acid. Diastereomeric mixtures of unmetabolized I, E alcohol (II), Z alcohol (III), and E aldehyde (IV) were detected in postsincubate extracts. From integration of peak areas, the mean ratio of II to III was 70:30 in 47 extracts.

Alcohols↗
PubMedDate not supplied

Metabolism of N,N-diethylbenzamide and N,N-diethyl-alpha,alpha'-13C-benzamide by rat liver microsomes.

The O2 and NADPH-dependent metabolism of N,N-diethylbenzamide (DEB), a topically applied insect repellent, has been investigated in liver microsomal suspensions from phenobarbital-pretreated male Wistar rats. Incubation conditions for the enzymatic production of N-ethylbenzamide (EB) from DEB (0.2 mM) were studied by use of HPLC with UV detection. With the microsomal enzymes suspended in 10 mM phosphate buffer (pH 7.4) and the substrate delivered in acetone (10 microliter), the yield of EB was 81.9 +/- 2.9% in five replicated experiments with NADPH (2 mM) and MgCl2 (4 mM). Conversion of DEB to EB was strongly inhibited by carbon monoxide, a cytochrome P-450 inhibitor. A sample of N,N-diethyl-alpha,alpha'-13C-benzamide was synthesized and was used, in conjunction with high-resolution 13C NMR spectroscopy, to identify the metabolites arising from oxidation of the ethyl group. Using the distortionless enhancement by polarization transfer pulse sequences and a substrate concentration of 0.4 mM, 13C-labeled acetaldehyde and glycolaldehyde, both detected as the hydrates, were found in the microsomal incubates. N-Ethyl-N-(alpha-hydroxyethyl)benzamide, the presumed metabolic progenitor of acetaldehyde, was not detected in these metabolic experiments. A pathway is proposed to account for the metabolic generation of glycolaldehyde by hydroxylation of both carbons of the N-ethyl group.

Animals↗
PubMedDate not supplied

Pharmacokinetic assessment of the dermal absorption of N,N-diethyl-m-toluamide (DEET) in cattle.

Model-independent pharmacokinetic methods based on statistical moments were applied to investigate the plasma disposition characteristics of N,N-diethyl-m-toluamide (DEET insect repellent) after single-dose treatment of experimental cattle by rapid intravenous injection (2.5-2.7 mg/kg) and by dermal application (10 mg/kg) to the back. DEET was determined in jugular blood samples by capillary GC with a nitrogen-selective detector and an internal standard of N,N-dipropyl-m-toluamide. Using weighted least squares linear regression analysis, the assay was validated over the concentration range of 19-1910 ng/ml of plasma. Comparison of areas under the plasma concentration-time curves after intravenous and dermal treatments of four Hereford heifers indicated that 72.9 +/- 8.3% (mean +/- SD) of the dermally applied dose was absorbed into the systemic circulation. The time-to-peak plasma concentrations following dermal treatments was 37.5 +/- 8.7 min. Apparent elimination rate constants were not significantly different between the two routes of administration. Linear pharmacokinetics was demonstrated with four additional cattle by comparing systemic clearance after intravenous infusion to steady-state plasma levels of approximately 0.5 and 2.5 micrograms/ml. The rapid and extensive dermal absorption of DEET observed in this study will probably contribute to a short duration of insect repellent action if ethanol-based sprays are used to protect cattle under field conditions.

Administration, Cutaneous↗