The metabolism of fenvalerate in plants: The conjugation of the acid moiety

The metabolism of the pyrethroid insecticide fenvalerate [(RS)-α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate] ( I ), and of its most insecticidal (αS,2S) isomer ( II ), has been examined in cabbage plants grown and treated under laboratory conditions with [¹⁴C]chlorophenyl- and [ring-¹⁴C]benzyllabelled preparations of the two compounds. Both insecticides disappeared from the treated leaves with similar half-lives of approximately 12–14 days; they underwent ester cleavage to a significant extent, together with some hydroxylation at the 2- or 4-position of the phenoxy ring, and hydrolysis of the nitrile group to amide and carboxyl groups. Most of the carboxylic acids and phenols thus produced occurred as glycoside conjugates. In separate experiments, the uptake and metabolism of 2-(4-chlorophenyl)-3-methylbutyric acid ( X ), the acidic half of the molecule, were examined in the laboratory, using abscised leaves of kidney bean, cabbage, cotton, cucumber and tomato plants. The acid X was found to be readily converted, mainly into glucose and 6-O-malonylglucose esters in kidney bean, cabbage and cucumber plants, into glucosylxylose, sophorose and gentiobiose esters in cotton, and into two types of triglucose esters with differing isomerism in tomato. One of the acetyl derivatives of the trisaccharide conjugates was identical with the synthetic deca-acetyl derivative of the [1 → 6]-triglucose ester.     

New conjugated metabolites of 3-phenoxybenzoic acid in plants

The metabolism of 3-phenoxybenzoic acid, a common plant metabolite of deltamethrin, cypermethrin and fenvalerate, has been studied in abscised leaves of cabbage, cotton, cucumber, kidney bean and tomato plants. The [¹⁴C]-acid was readily converted into more polar conjugates by esterification with glucose, 6-O-malonylglucose, gentiobiose, cellobiose, glucosylxylose and two types of triglucose with different isomerism. Other metabolites identified were the glucosyl ether of 3-(4-hydroxyphenoxy)benzoic acid, and a 3-(2-hydroxyphenoxy)benzoic acid derivative with a total of two molar equivalents of glucose linked to the carboxyl and phenolic -OH groups. The conjugation pathways were somewhat plant-specific. The glucosylxylose ester was found only in cotton, and the cellobiose and triglucose esters were found only in tomato. All of the conjugates except the glucose and glucosylxylose esters were plant metabolites that had not been identified previously. Furthermore, this is the first report to show the presence of cellobiose and triglucose conjugates in plants. However, neither of the acetyl derivatives of the [¹⁴C]-triglucoside was identical with the synthetic deca-acetyl derivative of [1→6]-triglucoside.     

Metabolism in rats of 3-phenoxybenzyl alcohol and 3-phenoxybenzoic acid glucoside conjugates formed in plants

Upon single oral administration to rats, the mono-, di- and tri-glucose conjugates of [¹⁴C]-3-phenoxybenzyl alcohol ( I ) or the mono-glucose conjugate of [¹⁴C]-3-phenoxybenzoic acid ( II ) were rapidly hydrolysed and extensively eliminated in the urine mostly as the sulphate conjugate of 3-(4-hydroxyphenoxy)benzoic acid ( X ). The faecal elimination was a minor route, whereas the biliary excretion was about 42% of the dose and the glucuronide conjugates of I , II and X were common major metabolites. The biliary glucuronides were cleaved in the small intestine to the respective aglycones, which were reabsorbed, metabolised further, and excreted in the urine as the sulphate conjugate of X . Although small amounts of the mono-, di-and tri-glucosides were found in the 0.5-h blood and liver samples following oral administration of the tri-glucoside of I , they were not detected in the urine, bile or faeces. Similarly the sulphate conjugate was one of the major urinary metabolites of germ-free rats, dosed with the ¹⁴C-glucosides via the oral or the intraperitoneal route, although they were excreted unchanged in certain amounts in the urine and faeces. The glucose conjugates were cleaved in vitro by gut microflora and in various rat tissues, including blood, liver, small intestine and small intestinal mucosa. The tissue enzymes showed a different substrate specificity in hydrolysis of the glucosides. However, they were not cleaved in gastric juice, bile, pancreatic juice or urine.     

Metabolism of cisanilide (cis-2,5-dimethyl-1-pyrrolidinecarboxanilide) by excised leaves and cell suspension cultures of carrot and cotton

Major methanol-soluble metabolites of cisanilide (cis-2,5-dimethyl-1-pyrrolidinecarboxanilide) were isolated from excised, pulse-treated carrot and cotton leaves. They were identified as O-glucoside conjugates of primary aryl and alkyl oxidation products, 2,5-dimethyl-1-pyrrolidine-4-hydroxycarboxanilide and 2,5-dimethyl-3-hydroxy-1-pyrrolidinecarboxanilide. Comparative studies with carrot and cotton cell cultures showed similar initial pathways of cisanilide metabolism. Time-course studies with [¹⁴C-pyrrolidine]- and [¹⁴C-phenyl]cisanilide showed little, if any, cleavage of the herbicide molecule in either excised leaves or cell cultures. Quantitative differences in the metabolism of cisanilide by cell cultures and excised leaves included; a reduced capacity of cell cultures to form secondary glycoside conjugates and an increased ability of cell cultures to form methanol-insoluble residues.     

Comparative metabolism and disposition of [14C-benzyl] cypermethrin in quail,rat and mouse

The excretion and metabolism of cis + trans-[¹⁴C-benzyl] cypermethrin has been compared in quail, rat and mouse. Radioactivity was rapidly eliminated by quail dosed orally with [¹⁴C]cypermethrin (2 mg kg^?1), as was the case in the rat and the mouse. When the birds were dosed intraperitoneally (IP) with the ¹⁴C-labelled pyrethroid, radioactivity was excreted more slowly than after oral dosing, and almost 20% of the IP dose of ¹⁴C remained in the tissues after 7 days. Both mammalian species excreted [¹⁴C]cypermethrin more rapidly than did the avian species after IP administration, and less than 6% of the dose remained in their tissues after several days. The biotransformation of the pyrethroid was more complex in the avian species (34 metabolites) than in the two mammals (some 10 metabolites in each species). In quail the predominant reactions were ester bond cleavage of cypermethrin together with either aromatic hydroxylation or amino acid conjugation of the 3-phenoxybenzyl moiety. The hydroxylated derivatives were eliminated mainly as sulphates. 3-Phenoxybenzoic acid was conjugated with a variety of amino acids including glycine, taurine, glutamic acid, serine, α-N-acetylornithine and the dipeptide glycylualine. The last two conjugations are unique to avian species. The major metabolite of cypermethrin in the rat was the sulphate conjugate of 3-(¹⁴-hydroxyphenoxy)benzoic acid, whereas in the mouse the major products were 3-phenoxybenzoic acid and its taurine conjugate. Thus, in the mammalian species where hydroxylation was maximal, amino acid conjugation was a minor metabolic route und vice versa. However, in the quail, aromatic hydroxylation and amino acid conjugation of the 3-phenoxybenzyl moiety of cypermethrin were both major reactions. The influence of the rates and sites of metabolism, and of the enzymology of amino acid conjugation, in determining this species difference are discussed. The rapid metabolism of cypermethrin to a variety of polar conjugates that are readily excreted, together with the low brain sensitivity of birds compared with mammals to its neurotoxic effects, explains the low acute toxicity of this pyrethoid to avian species.     

The metabolism of cypermethrin in plants: The conjugation of the cyclopropyl moiety

The metabolism of the pyrethroid insecticide cypermethrin ([S,R,]-α-cyano-3-phenoxybenzyl-(1R,1S,cis,trans)-2,2-dimethyl-3-(2′,2′-dichlorovinyl)cyclopropane carboxylate), I, has been examined in lettuce plants grown and treated twice under outdoor conditions with ¹⁴C-cyclopropyllabeled material. The application rate at each treatment was equivalent to 0.3 kg/ha. At harvest, 21 days after the last application, the plants contained mainly unchanged cypermethrin (33% of the total radiolabel present) and polar materials (54%) which were shown to be conjugates of trans-2(2′,2′-dichlorovinyl)-3,3-dimethylcyclopropane carboxylic acid (II). One of these was identified as the β,d-glucopyranose ester. In separate experiments the uptake and metabolism of the acid (II) in cotton leaves were examined in the laboratory and the acid was shown to be readily converted into a mixture of the β,d-glucopyranose ester, an acidic derivative of this, and disaccharide derivatives including the glucosylarabinose ester and the glycosylxylose ester. Subsequently, cotton leaves were exposed to solutions of these individual conjugates, and interconversions between these metabolites were observed.     

Metabolism of dibutyl-14C-labeled dibutylaminosulfenyl derivative of carbofuran in the cotton plant

The fate of the di-n-butylaminosulfenyl moiety in 2,3-dihydro-2,2-dimethyl-7-benzofuranyl (di-n-butylaminosulfenyl)(methyl)carbamate (DBSC or Marshal) was studied in the cotton plant at 1, 3, 6, and 10 days following foliage treatment with [di-n-butylamino-¹⁴C]DBSC. Dibutylamine and two major radioactive metabolites were obtained following extraction of the plant tissue with a methanol-buffer containing N-ethylmaleimide (NEM), a sulfhydryl scavenger which was added to prevent the cleavage of the NS bond during the workup procedure. The most adundant radioactive material recovered from plants was identified as a product arising from the reaction between NEM and dibutylamine. Extraction of plant tissue with straight methanol-buffer solution or with methol-buffer containing other sulfhydryl scavengers resulted in 57–86% of the applied radioactivity being recovered as dibutylamine in the organosoluble fraction. When [¹⁴C]dibutylamine was applied to cotton leaves, most of the radioactivity, i.e., 96% of the total recovered radioactivity, was found in the organosoluble fraction as dibutylamine. Dibutylamine is the major metabolite of [di-n-butylamino-¹⁴C]DBSC in the cotton plant.     

The uptake,translocation and metabolism of epronaz in selected species

The absorption, translocation and metabolism of the selective pre- or early post- emergence herbicide epronaz (N-ethyl-N-propyl-3-propylsulphonyl-1,2,4-triazole-1-carboxamide) were investigated using selected crop and weed species. The pattern of tolerance to epronaz of both germinating seeds and 10-day-old plants grown in nutrient solution, was found to be soybean (Glycine max L.) > maize (Zea mays L.) > cotton (Gossypium hirsutum L.) > rice (Oryza sativa L.) > barnyard grass [Echinochloa crus-galli (L.) Beauv.]. In all species, absorption and translocation of ¹⁴C from a nutrient solution containing [¹⁴C]epronaz (0.02 μCi ml^?1) increased with time. Autoradiographic and liquid scintillation analysis indicated the presence of radioactivity in the apical regions of all species after 4 h. Interspecies variation in uptake and distribution did not appear to be a major factor explaining selectivity, although the resistance of cotton may be partly due to compartmentalisation of ¹⁴C in the lysigenous glands in stem and leaves. Analysis of extracts from plants treated with [¹⁴C]epronaz indicated the presence of epronaz, its major degradation product [3-propylsulphonyl-l,2,4-triazole (BTS 28 768)] and certain unknown radio-labelled compounds. The major metabolite (Unknown I) was believed to be a conjugate of certain plant components with either epronaz or BTS 28 768. The rate of formation of Unknown I corresponded to the relative resistance and susceptibility to epronaz of soybean, rice and barnyardgrass. The level of the herbicide remained much higher in cotton than in the other species, possibly reflecting compartmentalisation and inactivation of epronaz in the lysigenous glands. For maize, high levels of uptake, exudation and degradation in the nutrient solution were recorded.     

Studies into the differential activity of the hydroxybenzonitrile herbicides: II. Uptake,movement and metabolism in two contrasting species

Uptake, movement, and metabolism of unformulated ioxynil and bromoxynil salts were investigated in Matricaria inodora and Viola arvensis. The morphology of these two species did not give rise to different spray retention and contact angles. After 7 days, uptake of [¹⁴C]ioxynil-Na reached 8.26% of applied ¹⁴C activity in M. inodora and 16.77% of that in V. arvensis compared with 1.54 and 3.83%, respectively, for [¹⁴C]bromoxynil-K. Over 98% of the ¹⁴C activity detected in the plant after 7 days remained in the treated leaves of V. arvensis following [¹⁴C]ioxynil-Na treatment. However, 8.7% of the ¹⁴C activity detected in [¹⁴C]ioxynil-Na-treated M. inodora was recovered from the apex and developing leaves reflecting a greater translocation. [¹⁴C]Bromoxynil-K was more mobile in both species and after 7 days 87.5 and 91.39% were detected in the treated leaves of M. inodora and V. arvensis, respectively. In both species the majority of translocated ¹⁴C activity was recovered from the apex and developing leaves. Up to 20% of the applied [¹⁴C]ioxynil-Na and [¹⁴C]bromoxynil-K was not detected within the treated plant. Extraction of treated plants revealed no detectable metabolic breakdown of ioxynil-Na to halogenated derivatives in either species. However, metabolic breakdown of bromoxynil-K was apparent in V. arvensis. No significant root exudation was detected when [¹⁴C]ioxynil-Na and [¹⁴C]bromoxynil-K were applied to hydroponically grown S. media and V. arvensis. Losses of ¹⁴C activity were due to herbicide volatility or degradation to volatile products on the leaf surface.     

The metabolism of the pyrethroid insecticide (±)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethyl-cyclopropanecarboxylate,WL 41706, in the rat

The metabolism of the pyrethroid insecticide α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate (WL 41706) has been studied in rats using two forms of ¹⁴C-labelling (benzyl- and cyclopropyl-). Excretion of benzyl^?14C was rapid, 57% of the administered dose being eliminated in the urine 48 h after treatment and 40% in the faeces. No significant sex difference was observed. The amount of radioactivity excreted via expired gases was 0.005% of the administered dose and less than 1.5% of the dose remained in the animals 8 days after treatment. The mean percentage recovery of administered dose was 104% for male rats and 97% for female rats. Urinary and faecal metabolites from these rats, and from rats dosed similarly with [cyclopropyl^?14C]-WL 41706 were studied. The rapid metabolism of WL 41706 is due to efficient cleavage of the ester bond by rats in vivo to afford 2,2,3,3-tetramethylcyclopropanecarboxylic acid (partly as glucuronide) and the 3-phenoxybenzyl moiety. Before this cleavage occurs, however, about half of the intake suffers aryl hydroxylation giving the α-cyano-3-(4-hydroxyphenoxy)benzyl ester, part of which is excreted in the bile as a conjugate(s) and part of which is cleaved and eliminated as the O-sulphate of 3-(4-hydroxyphenoxy)benzoic acid and the glucuronide of 2,2,3,3-tetramethylcyclopropanecarboxylic acid. A minor amount of hydroxylation occurs at a trans-methyl group on the cyclopropane acid moiety. The metabolism of WL 41706 by rat liver occurs mainly in the microsomes and mainly via oxidative processes.     

Uptake and distribution of [14C]metalaxyl by detached tobacco leaves

When the petioles of detached tobacco leaves (10–17 cm²) were incubated in aqueous solutions containing [¹⁴C]metalaxyl, uptake of the fungicide was dependent on the temperature and photoperiod. Detached leaves took up 78% more [¹⁴C]metalaxyl at 26°C than at 16°C. The rate of uptake in the light at 21°C was linear, but after an additional 20h in the dark, there was only twice as much fungicide in the leaves. Different sized leaves contained the same amount of fungicide per cm² area. Uptake by detached leaves of the ¹⁴C-labelled anilide lactones ofurace and RE-26940 [2-methoxy-N-(tetrahydro-2-oxo-3-thienyl)acet-2′,6′-xylidide] was similar to that of metalaxyl. At the concentration of metalaxyl (66 ng ml^?1) that controlled blue mould (Peronospora tabacina) on detached tobacco leaves, the amount of fungicide in the leaves was found to be 7.25 ng. Autoradiography showed that the distribution of [14C]metalaxyl in detached leaves after incubation for 23h was uniform, although higher concentrations of the label were present in the smaller veins of the leaves.     

Photodegradation of the pyrethroid insecticide fenpropathrin in water,on soil and on plant foliage

The photodegradation of fenpropathrin [(RS)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate] ( I ), in water, on soil and on plant foliage, was investigated using ¹⁴C-preparations labelled separately at the cyano group, cyclopropyl-C₁ or in the benzyl ring. On exposure to sunlight, I was photodecomposed with initial half-lives of >6 weeks in distilled water, 6.0 weeks in humic acid aqueous solution, 2.7 weeks in river water, 1.6 weeks in sea water and 0.5 of a day in 2% aqueous acetone. A triplet photosensitiser, acetone, together with naturally occurring substances in river and sea water, including humic acid, enhanced the photodegradation of I . On three kinds of soil, I was rapidly photodegraded with initial half-lives of 1–5 days, whereas it was fairly photostable on a mandarin orange leaf. The photoreactions involved were: decarboxylation, hydration of the cyano group to carboxamide, cleavage of the ester or the diphenyl ether linkage, hydrolysis of the carboxamide group to carboxyl, and hydroxylation at either or both of the gem dimethyl groups. The predominant reactions in water were decarboxylation, ester bond cleavage and photo-induced evolution of [¹⁴C] carbon dioxide from the [¹⁴C] cyano label; on soil, hydration or ester bond cleavage predominated. The hydration was also of importance in river and sea water. Decarboxylation did not occur on soil and plant foliage.     

Metabolic studies of 14C-labeled propham and chlorpropham in the female rat

The tissue distribution and excretion of ¹⁴C-labeled propham and chlorpropham were investigated in the adult female rat after a single oral dosage. The average 3-day urinary excretions of radioactivity were 55.9%, 82.6%, 79.5%, and 85.4% of an oral dose of chain [¹⁴C] chlorpropham, ring [¹⁴C] chlorpropham, chain [¹⁴C] propham, and ring [¹⁴C] propham, respectively. With chain [¹⁴C] chlorpropham 35.4 ± 7.5% of the administered radioactivity appeared in the respired air, whereas only 5.0 ± 0.8% was found in CO₂ from chain [¹⁴C] propham. There was no significant difference in the rate of excretion or the route of elimination among rats receiving different oral dosages, ranging from less than 4 mg/kg to 200 mg/kg. The radioactivity was distributed in all tissues with highest concentration found in the kidney. The average biological half-life of ¹⁴C from chlorpropham and propham in most organs was short, ranging between 3 and 8 hr; however, in brain, fat, and muscle, the half-life was about twice the value for other organs.Both compounds were metabolized by hydrolytic and oxidative mechanisms and the resulting metabolites were excreted either as free forms or as conjugates.Subcellular distribution of ¹⁴C in the rat liver and kidney after an oral administration of chlorpropham and propham was investigated. The percentage distribution of ¹⁴C in the particulate and soluble fractions was dependent on the elapsed time after dosing.     

Animal metabolism of propham (isopropyl carbanilate): The fate of residues in alfalfa when consumed by the rat and sheep

Alfalfa was root-treated with [¹⁴C]propham (isopropyl carbanilate[¹⁴C-phenyl(U)]) for 7 days and then harvested and freeze-dried. Rats and sheep were orally given either ¹⁴C-labeled alfalfa roots ([¹⁴C]root) or ¹⁴C-labeled alfalfa shoots ([¹⁴C]shoot). When the [¹⁴C]root was given, 6.5–11.0% of the ¹⁴C was excreted in the urine and 84.6–89.4% was excreted in the feces within 96 h after treatment. Less than 3% of the ¹⁴C remained in the carcass (total body—gastrointestinal tract and contents) 96 h after treatment. When [¹⁴C]shoot was given, 53.2–55.2% of the ¹⁴C was excreted in the urine, 32.1–43.4% was excreted in the feces, and the carcass contained 0.2–1.1% of the ¹⁴C 96 h after treatment. When the insoluble fraction (not extracted by a mixture of CHCl₃, CH₃OH, and H₂O) of both alfalfa roots and shoots was fed to rats, more than 86% of the ¹⁴C was excreted in the feces and less than 3% remained in the carcass 96 h after treatment. The major radiolabeled metabolites in the urine of the sheep fed ¹⁴C shoot were purified by chromatography and identified as the sulfate ester and the glucuronic acid conjugates of isopropyl 4-hydroxycarbanilate. Metabolites in the urine of the sheep treated with [¹⁴C]root were tentatively identified as conjugated forms of isopropyl 4-hydroxycarbanilate, isopropyl 2-hydroxycarbanilate, and 4-hydroxyaniline. The combined urine of rats dosed with [¹⁴C]shoot and [¹⁴C]root contained metabolites tentatively identified as conjugated forms of isopropyl 4-hydroxycarbanilate, isopropyl 2-hydroxycarbanilate, and 4-hydroxyaniline.     

The bioaccumulation and biotransformation of cis,trans-cypermethrin in the rat

The disposition of the pyrethroid insecticide cypermethrin, (RS)-a-cyano-3-phenoxybenzyl (1RS)-cis, trans-3-(2,2-dichlorovinly)-2, 2-dimethylcyclopropane-carboxylate, has been studied in male and female rats following a single toxic oral dose (200mg kg⁻¹) of two radiolabelled forms ([¹⁴C-benzyl] and [¹⁴C-cyclopropyl]) of the insecticide. The bioaccumulation and elimination of ¹⁴C-benzyl-labelled cypermethrin, following repeated administration at a sub-toxic dose (2mg kg⁻¹), has also been studied in male and female rats. Although, at the toxic dose, radioactivity from the two radiolabelled forms was rapidly eliminated in urine and faeces, the increased excretion in the faeces, over that for low doses, was evidence that absorption was incomplete. The major pathways of metabolism involved cleavage of the ester bond, with subsequent hydroxylation and glucuronidation of the cyclopropyl acid moieties, together with hydroxylation and sulphation of the 3-phenoxybenzyl moiety. The absence of sex- or dose-dependent changes was reflected by the constant proportions of these metabolites found in the urine. Constant levels of radioactivity in tissues were achieved rapidly, generally within the first week of repeated administration. Elimination was rapid on the cessation of dosing, although less rapid from the fat and skin. The material in the fat was mainly the cis-isomers of cypermethrin, which were eliminated with a mean half-life of 18.2 days, compared with 3.4 days for the trans-isomers.     

Distribution of the radioactivity in sugar beet plants treated with [14C]aldicarb

Sugar beet plants were grown in the field, after in-furrow application of [¹⁴C]aldicarb (3 kg of aldicarb ha^?1) at planting. Some plants (the growing plants) were harvested 99 days after sowing and the rest (the ripe plants) 196 days after sowing. The percentages of the weights of [¹⁴C]aldicarb equivalents (the total aldicarb plus aldicarb sulphoxide and sulphone, plus all the other metabolites of [¹⁴C]aldicarb which contain ¹⁴C, expressed as aldicarb equivalents) incorporated into the beet plants, relative to the weight applied to the soil, were 2.8 and 1.8, respectively for the growing and ripe plants. The concentrations of [¹⁴C]aldicarb equivalents (mg kg^?1 fresh weight) in the growing and ripe plants, respectively were: blades of the external leaves, 3.16 and 0.93; blades of the internal leaves, 0.63 and 0.68; petioles of the external leaves, 0.51 and 0.26; petioles of the internal leaves, 0.15 and 0.05; crowns, 0.14 and 0.15; roots, 0.16 and 0.13. The proportions of the extractable aldicarb plus aldicarb sulphoxide and aldicarb sulphone determined by gas-liquid chromatography (expressed as aldicarb equivalents) relative to [¹⁴C]aldicarb equivalents, in the external and internal leaf blades of the growing beets, were 56 and 60%, respectively; these values declined to 25 and 19%, respectively in the ripe plants. The proportion was 21 % or less in all other parts of the growing and ripe plants.     

Structure—activity relationships in pyrethroid esters derived from substituted 2-phenoxy-3-methylbutanoic acids

Non-cyclopropane pyrethroid esters of different substituted 2-phenoxy-3-methylbutanoic acids have been synthesised using the three alcohols—3-phenoxybenzyl alcohol, α-cyano-3-phenoxybenzyl alcohol and 3, 4-methylene-dioxybenzyl alcohol. Among the 35 esters synthesised and tested against Culex quinquefasciatus Say, the Bancroftian filariasis vector, for both larvicidal and adulticidal activities, α-cyano-3-phenoxybenzyl 2-(4-fluorophenoxy)-3-methylbu-tanoate, with an LC₅₀ value of 2.5 × 10^?3 mg litre^?1 for larvicidal activity, and α-cyano-3-phenoxybenzyl-2-(4-chlorophenoxy)-3-methylbutanoate, with an LD₅₀ value of 30 times; 10^?4 ug insect^?1 for adulticidal activity, were found to be as effective as fenvalerate, a well-known non-cyclopropane pyrethroid ester. Structure-activity studies showed that the insecticidal activity is dependent on the nature and position of the substituent in the phenyl ring of the acid moiety and also on the type of alcohol moiety.     

Degradation of the pyrethroid insecticide WL 41706, (±)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate,in soils

The degradation of the insecticide WL 41706, (±)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate, (I), in two soils from Spain and one from the UK has been studied in the laboratory. Samples of (I) labelled separately with ¹⁴C in the benzyl ring (uniform labelling) and at C₍₁₎ of the cyclopropyl ring were used. The insecticide underwent degradation by hydrolysis at the cyano group to form the amide and carboxylic acid analogues. However, the major degradative route was hydrolysis at the ester linkage leading initially to the formation of 3-phenoxy-benzoic acid and 2,2,3,3-tetramethylcyclopropanecarboxylic acid. When a sandy clay soil was treated with [benzyl^?14C]-WL 41706 under balance conditions, ¹⁴CO₂ was evolved at a steady rate and 16 % of the applied radiolabel was detected as ¹⁴CO₂ over a 26 week period. The rate of degradation of I was most rapid on a moist sandy clay (loss of 50 % initial quantity in 4 weeks) but it was considerably slower on dry sandy clay and moist clay soils (> 16 weeks). Under flooded, anaerobic conditions the rate of hydrolysis of the insecticide was slower than under aerobic conditions and the 3-phenoxybenzoic acid and 2,2,3,3-tetramethylcyclopropanecarboxylic acid were found to accumulate over the 24 weeks of the experiment.     

In vitro metabolism of pentachloronitrobenzene to pentachloromethylthiobenzene by onion: Characterization of glutathione S-transferase,cysteine C-S lyase,and S-adenosylmethionine methyl transferase activities

Pentachloromethylthiobenzene (PCTA) was synthesized in vitro from pentachloronitrobenzene (PCNB) at pH 7.9 by an enzyme system from onion root that required dithiothreitol, glutathione, and S-adenosylmethionine. The soluble enzyme system was isolated from onion root by ammonium sulfate fractionation and differential centrifugation. The system contained glutathione S-transferase activity with PCNB, C-S lyase activity with S-(pentachlorophenyl)cysteine, S-adenosylmethionine methyl transferase activity with pentachlorothiophenol (PCTP), and presumably several peptidase activities. All activities were stable when the crude enzyme system was stored at ?25°C. Evidence for the following sequence of reactions in PCTA synthesis was presented: PCNB→¹S-(pentachlorophenyl)glutathione→²S-(pentachlorophenyl)-γ-glutamylcysteine→³S-(pentachlorophenyl)cysteine→⁴ PCTP→⁵ PCTA. The first reaction was studied with [¹⁴C]PCNB. Reactions 2–4 were studied with S-([¹⁴C]pentachlorophenyl)glutathione, S-([¹⁴C]pentachlorophenyl)cysteine, and peptide inhibitors. Reaction 5 was studied with [¹⁴C]PCTP, S-[¹⁴C]adenosylmethionine, and inhibitors. The possible use of the enzyme system in the characterization of other glutathione conjugates was discussed.     

The elimination of (N-[[(4-chlorophenyl)amino]carbonyl]-2,6-difluorobenzamide) by the boll weevil

Boll weevils, Anthonomus grandis Boheman, were either dipped in or injected with a solution of [¹⁴C]diflubenzuron (N-[[(4-chlorophenyl)amino]carbonyl]-2,6-difluorobenzamide) or fed on cotton squares that had been treated with the chemical to determine its turnover time and metabolic fate. No significant differences were observed between male and female weevils in their ability to eliminate [¹⁴C]diflubenzuron. Only minor differences were observed when immersion and injection treatments were compared. When weevils were treated with 66.3 ng of [¹⁴C]deflubenzuron per weevil by injection, the insects contained 13 to 15% of the radiolabel after 6 days and 4 to 6% after 13 days. The remainder of the radiolabel was in the frass. When weevils fed for 66 hr on cotton squares that had been treated with a wettable [¹⁴C]diflubenzuron preparation (Dimilin W-25), the insects averaged 120 ng of diflubenzuron per weevil. Forty-four hours after removing insects from the treated squares, 50% of the radiolabel had been excreted. In all cases, the radiolabel found in the frass or in the weevil was unchanged diflubenzuron. There were no data to indicate that the boll weevil could metabolize appreciable amounts of diflubenzuron.