3-phenoxybenzyl Alcohol Research Articles

Catalytic hydrogenation of benzaldehydes over platinum nanoparticles immobilized on magnesium aluminate spinel under mild conditions

Platinum nanoparticles, synthesized via ethanol reduction of hexachloroplatinic acid in the presence of poly-(N-vinyl-2-pyrrolidone), were anchored on magnesium aluminate spinel using a colloidal deposition method. The samples were characterized using the following methods: transmission electron microscopy, powder X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray spectroscopy. The results revealed that platinum nanoparticles, with an average diameter of 2.8 nm, are homogenously dispersed on the surface of the carrier. Under very mild conditions, supported Pt/MgAl2O4 catalysts demonstrated excellent catalytic activity and high selectivity in the hydrogenation reaction of benzaldehydes to benzyl alcohols. The reaction kinetics for the catalytic hydrogenation of 3-phenoxybenzaldehyde to 3-phenoxybenzyl alcohol on a Pt/MgAl2O4 catalyst can be described by equation $$ r = k \times c^{1.44} \times p_{{{\text{H}}_{ 2} }} $$ , and the apparent activation energy is 35.6 kJ mol−1.

Stereoselective Biotransformation of Permethrin to Estrogenic Metabolites in Fish

This study investigated the stereoselective biotransformation and resulting estrogenic activity of the pyrethroid insecticide, permethrin (PM). Results of both in vivo (male Japanese medaka, vitellogenin (VTG) protein in plasma) and in vitro (primary rainbow trout hepatocyte VTG-mRNA expression) assays indicated stereoselective estrogenic activity of PM. 1S-cis-PM was observed to have significantly higher activity (P ≤ 0.05) than the 1R-cis enantiomer in both in vivo and in vitro evaluations. All enantiomers of PM were oxidized to a 4'-hydoxy PM (4OH PM) metabolite and underwent esterase cleavage to 3-phenoxybenzyl alcohol (3-PBOH) and 3-(4'-hydroxyphenoxy)-benzyl alcohol) (3,4'-PBOH). Racemic 4OH PM as well as 3-PBOH, and 3,4'-PBOH possessed significant (P ≤ 0.05) estrogenicity. 1S-trans-PM underwent esterase cleavage more extensively than the corresponding 1R-trans-PM. Inhibition studies with ketoconazole confirmed cytochrome P450-catalyzed hydroxylation as well as esterase cleavage of PM for all stereoisomers. These studies indicated stereoselectivity in the estrogenic activity of PM resulting from stereoselective biotransformation of the parent compound to more estrogenic metabolites.

Synthesis of 3-phenoxyphenylmethoxypropionitrile

New effective synthetic approach to 3-phenoxyphenylmethoxypropionitrile, starting from 3-phenoxybenzyl alcohol and acrylonitrile, was developed. This compound is a 3-phenoxyphenyl-containing product new by structure and can be of interest as semiproduct in the synthesis of biologically active compounds. There is a special interest in the synthesis of molecules, which besides diphenyloxide fragment and nitrile group contain in the side chain functional groups, since combination of different pharmacophores in the structure must lead to expansion of biological activity range of the target compounds [1–4]. The 3-phenoxyphenylmethoxypropionitrile was obtained by the reaction of 3-phenoxybenzyl alcohol with acrylonitrile in anhydrous benzene in the presence of 40% solution of potassium hydroxide along the following scheme:

Toxicokinetics of pyrethroid metabolites in male and female rats

The toxicokinetic characteristics of 3-phenoxybenzyl alcohol (3PBAlc) and 3-phenoxybenzaldehyde (3PBAld; metabolites of pyrethroid [PYR] after 25 mg/kg, single intravenous administration), were investigated in male and female rats. The systemic clearance (Cl) of 3PBAlc in females (0.403 ± 0.040 l/h/kg) was significantly larger than that of males (0.227 ± 0.036 l/h/kg). The plasma concentration-time curve of 3PBAld decreased gradually and then increased again 1 and 2 h after injection, suggesting the effect of enterohepatic circulation. The present study characterized the elimination and distribution of PYR metabolites and suggests that gender-related difference exists in the toxicokinetics of 3PBAlc and 3PBAld in rats.

Analysis of Photochemically Induced Cotton Bound Residues of Deltamethrin by an Immunoassay Technique

A sensitive and selective indirect competitive ELISA was developed for the detection of deltamethrin bound residues on cotton texture. Cross-reactivity studies with the main deltamethrin photodegradation products showed high specificity of deltamethrin polyclonal antibody to the parent compound. No cross-reactivity was measured with deltamethrin photodegradtion products derived from the alcohol moiety (3-phenoxybenzaldhyde, phenoxybenzyl alcohol, cyanohydrin, and 3-phenoxybenzoic acid), and lesser amounts were observed with the acid moiety (deltamethric acid). The dot-blot immunoassay was performed on cotton fabric discs spiked with deltamethrin and irradiated to assess the suitability of this system to detect bound residue. The dot-blot immunoassay results revealed that the bound form of deltamethrin has binding affinity with deltamethrin antibody similar to the parent compound. In addition, the test system was used to detect bound and free residues of deltamethrin on cotton samples exposed to three cycles of simulated sunlight and water wash. The results obtained suggest that the competitive ELISA format can be used as a tool for monitoring free and bound residues of deltamethrin impregnated on cotton targets.

The pyrethroid metabolites 3-phenoxybenzoic acid and 3-phenoxybenzyl alcohol do not exhibit estrogenic activity in the MCF-7 human breast carcinoma cell line or Sprague–Dawley rats

Synthetic pyrethroids are one of the most frequently and widely used class of insecticides, primarily because they have a higher insect to mammalian toxicity ratio than organochlorines or organophosphates. The basic structure of pyrethroids can be characterized as an acid joined to an alcohol by an ester bond. Pyrethroid degradation occurs through either oxidation at one or more sites located in the alcohol or acid moieties or hydrolysis at the central ester bond, the latter reaction being important for mammalian metabolism of most pyrethroids. The primary alcohol liberated from the ester cleavage is hydroxylated to 3-phenoxybenzyl alcohol, which for most pyrethroids is then oxidized to 3-phenoxybenzoic acid. These products may then be conjugated with amino acids, sulfates, sugars, or sugar acids. In vitro studies have suggested that some of the pyrethroids may have estrogenic activity. Interestingly, the chemical structure of specific pyrethroid metabolites indicates that they may be more likely to interact with the estrogen receptor than the parent compounds. Two of the pyrethroid metabolites, 3-phenoxybenzoic acid (3PBA) and 3-phenoxybenzyl alcohol (3PBalc) have been reported to have endocrine activity using a yeast based assay. 3PBAlc exhibited estrogenic activity with reported EC 50s of 6.67 × 10 −6 and 2 × 10 −5 while 3PBAcid exhibited anti-estrogenic activity with a calculated IC 50 of 6.5 × 10 −5. To determine if the metabolites were able to cause the same effects in a mammalian system, the estrogen-dependent cell line, MCF-7, was utilized. Cells were treated with 1.0, 10.0 or 100.0 μM concentrations of each metabolite and cytotoxicity was assessed. The two lowest concentrations of both metabolites did not induce cell death and even appeared to increase proliferation over that of the control cells. However, when cellular proliferation was measured using a Coulter counter neither metabolite stimulated proliferation (1.0 nM, 10.0 nM, or 10.0 μM) or induced an estrogen receptor α/ERE-controlled luciferase reporter in the MCF-7 cells. Following the in vitro screenings, the metabolites were then evaluated for estrogenic activity in vivo using the uterotrophic assay in Sprague–Dawley rats. Animals were orally gavaged (10.0, 5.0, and 1.0 mg/kg) once daily for 3 days. Neither metabolite had any effect on uterine wet weight, body weight, or organ weight. Lastly, in order to determine if either metabolite was able to alter the onset of puberty, immature female rats were orally gavaged (10.0, 5.0, and 1.0 mg/kg) once a day with the metabolites beginning 1 day post-weaning until the onset of puberty as evidenced by vaginal opening (VO). Again, neither metabolite had any effect on the onset of VO.

Effect of permethrin insecticide on rat polymorphonuclear neutrophils

Polymorphonuclear neutrophils are professional phagocytes whose efficacy depends on a multicomponent NADPH oxidase for generating superoxide anions and bacterial killing. They can be primed and activated by different agents that can impair oxidative burst and phagocytosis with opposite effects: reduced capability to destroy bacteria or hyperactivation that induces the generation of large quantities of toxic reactive oxygen species, which can damage surrounding tissue and participate in inflammation. The present study was designed to evaluate the effect of sub-chronic (60 days) permethrin treatment (1/10 DL 50) on rat polymorphonuclear neutrophils respiratory burst. The results show that permethrin treatment increases superoxide anion production (33 times) and the activity of hydrogen peroxide–myeloperoxidase system (67 times). In vitro experiments suggest that this effect can be related to permethrin priming and to physico-chemical changes at the plasma membrane level of neutrophils. The antioxidant supplementation with Vitamin E and coenzyme Q 10 can protect against the abnormal respiratory burst in rat treated with permethrin. The in vitro studies show that neutrophil apoptosis begins soon after 1 h of incubation with permethrin (0.725% of total cells) or its metabolites (3-phenoxybenzyl alcohol, 3-phenoxybenzaldehyde and 3-phenoxybenzoic acid 1.36, 2.26 and 1.3 of total cells, respectively) and that the level of apoptotic cells is very low. In conclusion, immunotoxicity of permethrin measured in rats could prompt future studies on the consequences of chronic insecticide exposure.

Application of Separated Leaf Cell Suspension to Xenobiotic Metabolism in Plant

Metabolic profiles of (14)C-labeled primary metabolites from several pesticides, 4-cyanophenol (1), 3-phenoxybenzoic acid (2), 3-phenoxybenzyl alcohol (3), 3,5-dichloroaniline (4), and (1RS)-trans-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylic acid (5), were examined by using enzymatically separated leaf cell suspension from seedlings of cabbage ( Brassica oleracea ) and tomato ( Lycopersicon esculentum ). After 1 day of incubation, the metabolites were extensively transformed in cabbage, whereas they were scarcely metabolized in tomato. The major metabolic pathways were the phase II reactions leading to a number of conjugates such as glucoside/malonylglucoside of 1-5, malate of 2, and glutamate of 4. The oxidation of 1 and 2 was observed as a minor reaction to produce 4-hydroxybezoic acid and 3-(4-hydroxyphenoxy)benzoic acid. The chemical identities of the secondary metabolites were determined by various spectrometric analyses (LC-MS, LC-MS/MS, and NMR) and/or HPLC cochromatography with the synthetic reference standards. As a result, this separated leaf cell suspension system was found to well reproduce the in vivo plant metabolism.

Assignment of absolute configurations of permethrin and its synthon 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid by electronic circular dichroism, optical rotation, and X-ray crystallography

The availability of single stereoisomers of biologically/toxicologically relevant chiral compounds such as the pyrethroid-type insecticide permethrin (PM) and the reliable determination of their absolute configurations are of central importance for the detailed investigation and correct assignment of stereoselective effects. In this context, single stereoisomers of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (DCCA), a precursor, metabolite, and environmental degradation product of PM, were isolated from a mixture of all four stereoisomers in enantiomeric excesses of >99% via a two-step chromatographic process combining a diastereoselective reversed-phase separation in the first step with a direct enantiomer separation in the second step. Esterification of DCCA stereoisomers with 3-phenoxybenzyl alcohol yielded PM. Electronic circular dichroism (ECD) spectra of DCCA and PM stereoisomers were measured in non-polar (cyclohexane containing 5% v/v 1,2-dichloroethane) and non-protic polar (acetonitrile) solvents. Cotton effects suitable to distinguish the four stereoisomers of each DCCA and PM were obtained. Absolute configurations of DCCA were determined by confrontation of calculated (time-dependent density-functional theory using B3LYP hybrid functional) and experimental ECD and optical rotation (OR) data. Fully convergent results between ECD and X-ray diffractometry (analysis of DCCA isomers co-crystallized with O-9-(2,6-diisopropylphenylcarbamoyl)quinine), which was employed as a reference method, were obtained. The importance of considering dimer formation of DCCA in solution for the computational delineation of absolute configurations was demonstrated by (1 R,3 R)- cis-DCCA for which the Δ G Boltzmann averaged calculated monomeric form delivered the opposite sign of OR compared to the dimeric form and the value determined experimentally in dichloromethane. For (1 S,3 R)- trans-DCCA both monomer and dimer delivered the identical sign of OR and this was in agreement with the experimental measurement. In contrast to OR, the calculated ECD spectra of these two DCCA stereoisomers were less sensitive toward intermolecular association.

Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides.

A phenylalanine residue (Phe1519) in the sixth transmembrane segment of domain III (IIIS6) of the cockroach BgNa(v) sodium channel is required for the binding and action of pyrethroids. However, whether or not other residues in IIIS6 participate in the action of pyrethroids remains to be determined. In the present study, we conducted a systematic analysis of 20 residues in IIIS6 of the BgNa(v) channel using alanine-scanning mutagenesis. Our results show that alanine substitutions of four residues, Ile1514, Gly1516, Phe1518 and Asn1522, altered sodium channel sensitivity to pyrethroid insecticides. Whereas the G1516A, F1518A and N1522A substitutions diminished sodium channel sensitivity to all seven pyrethroids examined, including four type I (lacking the alpha-cyano group at the phenoxybenzyl alcohol) and three type II (containing the alpha-cyano group) pyrethroids, the I1514A substitution enhanced sodium channel sensitivity to four type I and type II pyrethroids that contain the phenoxybenzyl alcohol only. We also show that alanine/lysine substitutions of Leu1521 and Ser1517 affected the action of BTX (batrachotoxin), but not pyrethroids. In the Kv1.2-based homology model of the open sodium channel, side chains of Ile1514, Phe1518 and Asn1522 are exposed towards helix IIS5 and linker IIS4-IIS5, which contain previously identified pyrethroid-interacting residues, whereas Ser1517 and Leu1521 face the inner pore where the BTX receptor is located. Thus the present study provides further evidence for structural models in which pyrethroids bind to the lipid-exposed interface formed by helices IIIS6, IIS5 and linker helix IIS4-IIS5, whereas BTX binds to the pore-exposed side of the IIIS6 helix.

Development of Sensitive Immunoassays for the Detection of the Glucuronide Conjugate of 3-Phenoxybenzyl Alcohol, a Putative Human Urinary Biomarker for Pyrethroid Exposure

Pyrethroids are widely used in agriculture as insecticides. This study describes a sensitive enzyme-linked immunosorbent assay for the detection of the glucuronide conjugate of 3-phenoxybenzyl alcohol, a putative pyrethroid metabolite that may be used as a biomarker of exposure to pyrethroids. Four antisera were elicited against two different immunizing haptens. Antisera were characterized in combination with several coating haptens. The lowest IC50 value (0.5 ng/mL) was obtained with antiserum 1891 and 3-phenoxybenzoic acid-BSA conjugate as the coating antigen. Antiserum 1891 was highly selective for the target compound with an overall cross-reactivity of <0.3% to structurally related compounds. The assay sensitivity was negligibly affected by pH 4-9. A 5-fold improvement in IC50 was observed using a 10-fold concentrated phosphate-fuffered saline as the assay buffer. Compared to assays conducted in normal phosphate-fuffered saline, the maximal absorbance was almost identical. A good correlation (r 2 = 0.99 and 0.97 for urine samples A and B, respectively) was observed between spiked levels and the levels detected by the immunoassay.

The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats

The in vitro metabolism of permethrin and its hydrolysis products in rats was investigated. Cis- and trans-permethrin were mainly hydrolyzed by liver microsomes, and also by small-intestinal microsomes of rats. trans-Permethrin was much more effectively hydrolyzed than the cis-isomer. When NADPH was added to the incubation mixture of the liver microsomes, three metabolites, 3-phenoxybenzyl alcohol (PBAlc), 3-phenoxybenzaldehyde (PBAld) and 3-phenoxybenzoic acid (PBAcid), were formed. However, only PBAlc was formed by rat liver microsomes in the absence of cofactors. The microsomal activities of rat liver and small intestine were inhibited by bis- p-nitrophenyl phosphate, an inhibitor of carboxylesterase (CES). ES-3 and ES-10, isoforms of the CES 1 family, exhibited significant hydrolytic activities toward trans-permethrin. When PBAlc was incubated with rat liver microsomes in the presence of NADPH, PBAld and PBAcid were formed. The NADPH-linked oxidizing activity was inhibited by SKF 525-A. Rat recombinant cytochrome P450, CYP 2C6 and 3A1, exhibited significant oxidase activities with NADPH. When PBAld was incubated with the microsomes in the presence of NADPH, PBAcid was formed. CYP 1A2, 2B1, 2C6, 2D1 and 3A1 exhibited significant oxidase activities in this reaction. Thus, permethrin was hydrolyzed by CES, and PBAlc formed was oxidized to PBAld and PBAcid by the cytochrome P450 system in rats.

Enantiomeric Differences in Permethrin Degradation Pathways in Soil and Sediment

Chirality occurs widely in synthetic pyrethroids. Studies have shown significant differences in both aquatic toxicity and degradation rates between enantiomers from the same diastereomer of selected pyrethroids. To better understand chiral selectivity in biodegradation of pyrethroids, 14C-labeled permethrin was used to characterize enantiomeric differences in the formation of transformation intermediates in two soils and a sediment. Individual enantiomers of permethrin were spiked into soil and sediment samples, and transformation products were identified with known standards. Enantioselectivity was observed in most treatments when the dissipation of the parent enantiomers, the amount of intermediates and bound residues formed, and mineralization rates were compared between the enantiomers. The results show that all enantiomers of permethrin hydrolyzed rapidly and that the hydrolysis products were quickly further transformed. The direct hydrolysis products, cyclopropanic acid (Cl2CA), 3-phenoxybenzyl alcohol (PBalc), and 3-phenoxybenzoic acid (PBacid), were recovered at small percentages, ranging from 1 to 14% for Cl2CA and from 0.2 to 6% for PBalc and PBacid. The R-enantiomer of both cis- and trans-permethrin was mineralized more quickly than the S-enantiomer after hydrolysis. The degradation products from cis-permethrin were more persistent than those from trans-permethrin. As some transformation intermediates of permethrin may have greater acute and chronic toxicity than the parent compound, enantioselectivity in the formation of degradation intermediates may lead to different overall toxicities and merit further investigation. This study suggests that for chiral compounds, enantioselectivity may be reflected not only in the dissipation of the parent enantiomers but also in the kinetics of formation of intermediate transformation products.

Phototransformation of Alphacypermethrin as Thin Film on Glass and Soil Surface*

Photodegradation of alphacypermethrin ((RS)-α cyano-3-phenoxy benzyl (1RS) cis-3-(2,2,dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate) was studied as a thin film on glass surface and on black and red soil surfaces. A number of photoproducts from glass surfaces have been isolated, characterized and identified by gas chromatography-mass spectroscopy (GC-MS). However, only two of them viz. 3-phenoxy benzyl alcohol and [2,2-dichlorovinyl-3(2,2,dimethyl) cyclopropane carboxylate] could be identified from both the soil. Rate of photodegradation on glass and soil surface under UV and sunlight followed first order kinetics with significant correlation coefficients. The rate of photodegradation was greater on black than on red soil. *A part of Ph.D. thesis of the first author in the Department of Chemistry submitted to the Bundelkhand University, Jhansi, U.P., India.

Estrogenicity of pyrethroid insecticidemetabolites

There is concern that insecticides are able to mimic the action of 17beta-estradiol by interaction with the human estrogen receptor. Pyrethroids are commonly used insecticides and several have been assessed for potential endocrine disrupting activity by various methods. It has been noted that some metabolites of pyrethroids, in particular, permethrin and cypermethrin, have chemical structures that are more likely to interact with the cellular estrogen receptor than the parent pyrethroid. For this study permethrin and cypermethrin metabolites 3-(4-hydroxy-3-phenoxy)benzyl alcohol, 3-(4-hydroxy-3-phenoxy)benzoic acid, and N-3-(phenoxybenzoyl)glycine were synthesised, and together with the commercially available 3-phenoxybenzyl alcohol, 3-phenoxybenzaldehyde, and 3-phenoxybenzoic acid, were studied in a recombinant yeast assay expressing human estrogen receptors (YES). Three metabolites, 3-phenoxybenzyl alcohol, 3-(4-hydroxy-3-phenoxy)benzyl alcohol, and 3-phenoxybenzaldehyde, showed estrogenic activity of approximately 10(5) less than that of 17beta-estradiol. No activity was observed in the yeast assay for 3-phenoxybenzoic acid, 3-(4-hydroxy-3-phenoxy)benzoic acid, and N-3-(phenoxybenzoyl)glycine. The results from this study show that pyrethroid metabolites are capable of interacting with the human estrogen receptor, and so might present a risk to human health and environmental well being. The impact would be expected to be small, but still add to the overall environmental xenoestrogen load.

New lipophilic phthalimido- and 3-phenoxybenzyl sulfonates: Inhibition of antigen 85C mycolyltransferase activity and cytotoxicity

Four new sulfonates were prepared as potential inhibitors of antigen 85C, a mycolyl transferase involved in the biosynthesis of the mycobacterial cell wall being designed on the basis of the proposed catalytic mechanism and antigen 85C crystal structure. The inhibitors contained a sulfonate moiety, 3-phenoxybenzyl alcohol or N-(hydroxyethyl)phthalimide as trehalose mimetics, and an alkyl chain of different length mimicking either the mycolate (α-chain or the mycolic acid (β-branch. One compound displayed promising activity in a mycolyltransferase inhibition assay (compound 2b, IC50 = 4.3 μM). The two compounds containing a phthalimide moiety (compounds 3a and 3b) showed significant and selective cytotoxicity against the breast cancer cell line MDA-MB231.

Relative contribution of detoxifying enzymes to pyrethroid resistance in a resistant strain of Helicoverpa armigera

Abstract: The relative contribution of oxidases and esterases to pyrethroid resistance was studied in a YS‐FP strain of Helicoverpa armigera from China. The YS‐FP strain was derived from a field‐collected strain (YS) by 16 generations of selection with a mixture of fenvalerate and phoxim. Compared with the YS strain, the YS‐FP strain showed 1850‐ to &gt;7140‐fold resistance to four ester‐bonded phenoxybenzyl alcohol pyrethroids (fenvalerate, deltamethrin, cypermethrin and cyhalothrin), &gt;205‐fold resistance to a non‐ester phenoxybenzyl alcohol pyrethroid (etofenprox) and only 19‐fold resistance to an ester‐bonded methylated biphenyl alcohol pyrethroid (bifenthrin). The oxidase inhibitor piperonyl butoxide eliminated most the of resistance to fenvalerate, deltamethrin, cypermethrin, cyhalothrin and etofenprox, whereas the esterase inhibitor S,S,S‐tributylphosphorothioate had a small synergistic effect for fenvalerate and cyhalothrin only. This suggests that the resistance to these pyrethroids in the YS‐FP strain was mainly because of enhanced oxidative detoxification. The monooxygenase activities of the midguts of sixth‐instar larvae of the YS‐FP strain to substrates p‐nitroanisole, ethoxycoumarin and methoxycoumarin were 3.7‐, 4.7‐ and 10‐fold, respectively, compared with that of the YS strain. Glutathione S‐transferase activity and esterase activity were not significantly altered in the YS‐FP strain. This confirms that enhanced oxidative detoxification was a major mechanism contributing to pyrethroid resistance in the YS‐FP strain.

Determination of Pyrethrin and Pyrethroid Pesticides in Urine and Water Matrixes by Liquid Chromatography with Diode Array Detection

The following pyrethrin and pyrethroid pesticides were determined in urine and water matrixes by liquid chromatography with diode array detection (LC-DAD): pyrethrin I, pyrethrin II, tetramethrin, baythroid, bifenthrin, fenvalerate, phenothrin, allethrin, resmethrin, cis-permethrin, and trans-permethrin. In addition, 3-phenoxybenzyl alcohol, a metabolite of various pyrethroids, was also successfully determined by the analytical method. The matrix extraction was simple, inexpensive, and fast, using only sodium chloride and acetonitrile. The acetonitrile extract was filtered and analyzed by LC-DAD. The method detection limits for the pyrethrin pesticides in 5 mL urine were determined to range from 0.002 to 0.04 microg/mL, depending on the individual pyrethrin. Recoveries from spiked tap water ranged from 77 to 96%; recoveries from urine ranged from 80 to 117%. This method is especially well-suited to clinical investigations, in which rapid analysis of forensic samples is often required.

Synthesis of Ethophenprox.

AbstractFor Abstract see ChemInform Abstract in Full Text.

In vitro human metabolism of permethrin: the role of human alcohol and aldehyde dehydrogenases

Permethrin is a pyrethroid insecticide widely used in agriculture and public health. It has been suggested that permethrin may interact with other chemicals used during military deployments and, as a result, be a potential cause of Gulf War Related Illness. To determine the causal relationship between permethrin and human health effects, the basic enzymatic pathway of permethrin metabolism in humans should be understood. In the present study we report that trans-permethrin is metabolized in human liver fractions, producing phenoxybenzyl alcohol (PBOH) and phenoxybenzoic acid (PBCOOH). We identified human alcohol (ADH) and aldehyde dehydrogenases (ALDH) as the enzymes involved in the oxidation of phenoxybenzyl alcohol, the permethrin hydrolysis product, to phenoxybenzoic acid by way of phenoxybenzaldehyde (PBCHO). Cis-permethrin was not significantly metabolized in human liver fractions. Cytochrome P450 isoforms were not involved either in the hydrolysis of trans-permethrin or in the oxidation of PBOH to PBCOOH. Purified ADH isozymes oxidized PBOH to PBCHO and PBOH was a preferred substrate to ethyl alcohol. Purified ALDH was responsible for PBCHO oxidation to PBCOOH with similar substrate affinity to a previously known substrate, benzyl alcohol. Based on these observations, it appears that PBOH is oxidized to PBCHO by ADH and subsequently to PBCOOH by ALDH, although PBCHO does not accumulate during microsomal incubation. In order to analyze permethrin and its metabolites, previous HPLC-UV methods had to be re-validated and modified. The resulting refined HPLC-UV method is described in detail.