Metabolism of the cis- and trans-isomers of cypermethrin in mice

Metabolism in mice of the separated cis- and trans-isomers of the pyrethroid insecticide cypermethrin (NRDC 149), (RS)-α-cyano-3-phenoxybenzyl (1RS)-cis, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate, was investigated in each case with preparations that were ¹⁴C-labelled in the benzyl and cyclopropyl moieties. Radioactivity from the trans-isomer was mainly excreted in the urine and that from the cis-isomer in the faeces. Elimination of both isomers was rapid except for a small portion (approximately 2%) of the cis-isomer which was released from the fat with a half-life of approximately 13 days. Metabolism of cypermethrin occurred mainly by ester cleavage and elimination of the cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl- cyclopropanecarboxylic acid moieties as glucuronide conjugates. The α-cyano-3-phenoxybenzyl alcohol released by ester cleavage was mainly converted to 3-phenoxy-benzoic acid which was partly eliminated unchanged, partly conjugated with aminoacids (mainly taurine) and glucuronic acid, and partly oxidised to 3-(4-hydroxyphenoxy) benzoic acid which was excreted as the sulphate conjugate. Metabolites retaining the ester linkage were formed by hydroxylation at various sites in the molecule with more hydroxylation of the cis- than of the trans-isomer occurring.     

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.     

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.     

The metabolism of 3-phenoxybenzyl alcohol,a pyrethroid metabolite,in plants

The metabolism and conjugation of 3-phenoxybenzyl alcohol, a plant metabolite of permethrin and cypermethrin, have been examined in abscised cotton leaves. Mature cotton leaves were treated by petiole uptake of an aqueous solution of [α-¹⁴C]-3-phenoxybenzyl alcohol. Initially there was rapid formation of a compound identified as the glucosyl 3-phenoxybenzyl ether. Subsequently more polar compounds were formed and these were shown to be disaccharide conjugates of the alcohol with glucose and pentose sugars. The alcohol and its mono- and disaccharide conjugates were shown to undergo interconversion in cotton leaves, and evidence was obtained from experiments with [¹⁴C]glucose for the ready exchange of the glucose units on the conjugates with free glucose in the leaves. No larger carbohydrate conjugates of 3-phenoxybenzyl alcohol were detected under the conditions used.     

The metabolism of the pyrethroid insecticide cypermethrin in rats; excreted metabolites

The metabolism of the pyrethroid insecticide cypermethrin has been studied in rats using three forms of ¹⁴C-labelling (benzyl-, cyclopropyl- and cyano-) and separate cis- and trans- isomers. The proportion of the dose absorbed from the intestines (50–70% at 2–3 mg kg^?1) is rapidly metabolised and eliminated. The major reaction is cleavage of the ester bond to afford the constituent cis- and trans- acids which are conjugated with glucuronic acid and eliminated in the urine. The 3-phenoxybenzyl portion of the molecule is probably released as the α-hydroxynitrile, which is converted via the aldehyde into 3-phenoxybenzoic acid. This compound is then largely hydroxylated and eliminated as a sulphate conjugate. The cyanide ion is metabolised via predictable routes, for instance, as thiocyanate. Cypermethrin is hydroxylated to some extent before hydrolysis. Most of this hydroxylation occurs at the methyl group trans to the cyclopropane carboxyl group, and at the 4-position of the phenoxy group. cis- Cypermethrin is slightly more stable than the trans-isomer.     

Further studies of the degradation of the pyrethroid insecticide cypermethrin in soils

Studies of the degradation of the pyrethroid insecticide cypermethrin (NRDC 149) and its cis- and trans-isomers (NRDC 160 and NRDC 159, respectively), have been extended. In soils stored in the laboratory for up to 52 weeks, cypermethrin continued to be degraded by hydrolysis and oxidation. A previously unidentified product has now been identified as the dicarboxylic acid 3-(2, 2-dichlorovinyl)-1-methylcyclopropane-1, 2-dicarboxylic acid. Comparative experiments carried out under indoor and outdoor conditions showed that essentially the same products were formed under these different conditions. However, α-carboxy-3-phenoxybenzyl 3-(2, 2-dichlorovinyl)-2, 2-dimethyl-cyclopropanecarboxylate was one minor product detected only under outdoor conditions. Evidence is presented for the further degradation of bound residues arising in soil from cypermethrin treatments. There was limited uptake of the radiolabel into wheat grown in soil containing radiolabelled bound residues.     

The metabolism of the herbicide flamprop-methyl in rats and some comparative data for dogs,mice and rabbits

[¹⁴C]Flamprop-methyl administered orally to rats (3-4 mg kg^?1 body weight) was excreted mostly via the faeces (78.7 and 61.6% in males and females, respectively). Elimination was rapid and 90% of the dose of ¹⁴C was excreted in faeces and urine 0-48 h after dosing. The distribution of ¹⁴C between faeces and urine was different in males and females. No expired [¹⁴C]carbon dioxide was detected and less than 2% of the dose remained in the animals 4 days after dosing. The predominant metabolic pathway was hydrolysis of the ester bond to afford the carboxylic acid which was excreted unchanged and as its glucuronide conjugate. Aromatic hydroxylation occurred at the para- and meta-positions of the N-benzoyl ring. N-(3)-Chloro- 4-fluorophenyl-N-(3,4-dihydroxybenzoyl)-DL -alaninate was also formed. This hydroxylated form of flamprop-methyl was partially O-methylated at the 3-hydroxy group. Flamprop-methyl was also metabolised and eliminated rapidly by dogs, mice and rabbits. The last of these three species afforded very little aromatic hydroxylation and also differed from the others in that the metabolites were eliminated mostly in the urine. Aromatic hydroxylation lay in the order: male rat = female rat > dog= mouse>rabbit (female).     

Metabolism of methfuroxam (2,4,5-trimethyl-N-phenyl-3-furancarboxamide) in the rat and isolated rat hepatocytes

Isolated rat hepatocytes were incubated for 4 hr with [phenyl-U-¹⁴C]2,4,5-trimethyl-N-phenyl-3-furancarboxamide ([¹⁴C]methfuroxam). ¹⁴C-Labeled metabolites were isolated by solvent extraction, column chromatography, and high-pressure liquid chromatography, and were then characterized by analysis of infrared and mass spectra. Metabolism of [¹⁴C]methfuroxam by isolated hepatocytes included: (1) hydroxylation of the 2-, 4-, and 5-methyl groups on the furan ring; (2) hydroxylation at the para position of the benzene ring; (3) combinations of 1 and 2; (4) the addition of a sulfur-containing adjunct to the methylfuran moiety; and (5) conjugation of 1–4. Rats given a single intragastric dose of [¹⁴C]methfuroxam excreted 56% of the ¹⁴C in the urine and 42% in the feces within 54 hr. Metabolism of [¹⁴C]methfuroxam by the intact rats included: (1) hydroxylation of the methylfuran moiety; (2) hydroxylation of the benzene ring; (3) the addition of S-methyl, methyl sulfoxide, and other sulfur-containing groups to methfuroxam; (4) combinations of 1–3; and (5) conjugation of 1–4.     

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.     

The conjugation and accumulation of metabolites of cypermethrin by earthworms

When earthworms are maintained in soil containing [¹⁴C]cypermethrin they accumulate radioactive residues. These residues are not eliminated when the worms are transferred to untreated soil. The accumulated radioactive residue is a complex mixture of conjugates of two metabolites of cypermethrin (3-phenoxybenzoic acid and (1RS)-cis, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid). One major constituent of this mixture of conjugates has been identified as N¹, N¹²-di-(3-phenoxybenzoyl)spermine. Feeding studies with quail and rats have established that the residues accumulated by the earthworms are not further bioaccumulated by earthworm predators.     

Excretion and residues of the pyrethroid insecticide cypermethrin in lactating cows

Two radiolabelled forms of racemic [¹⁴C]cypermethrin (¹⁴C at the benzylic carbon or at C-1 of the cyclopropane ring) were separately administered twice daily to lactating cows in portions of the feed. The amounts dosed were equivalent to 0.2, 5 and 10 μg of cypermethrin per g of feed. The radioactivity eliminated in the milk indicated that the ingestion and elimination of radioactivity were in balance at about day 4 after the start of dosing. Urine and faeces were equally the major routes of elimination, and only a fraction of a percent of the dose appeared in the milk. The residue in the milk was unchanged cypermethrin and was found at a concentration that was proportional to the dose. At the high cypermethrin intake of 10 μg g^?1 of diet, the residue in the milk was 0.03 μg g^?1. Concentrations of residues in the tissues, measured after 7, 20 or 21 days of treatment, were low and in the order: liver>kidney>renal fat>subcutaneous fat>blood>muscle>brain. The major residue in the liver and kidney of a cow that received 10 μg of cypermethrin per g of diet was N-(3-phenoxybenzoyl)glutamic acid. Other conjugates of 3-phenoxybenzoic acid and of 3-(4-hydroxyphenoxy)benzoic acid (unidentified, with the exception of the glycine conjugate) were also present. The residue in fat (about 0.1 μg g^?1 from an intake of 10 μg g^?1 of feed) consisted mainly of cypermethrin.     

Degradation of the pyrethroid cypermethrin NRDC 149 (±)-α-cyano-3-phenoxybenzyl (±)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate and the respective cis-(NRDC 160) and trans- (NRDC 159) isomers in soils

The degradation of the pyrethroid insecticide cypermethrin and the geometric isomers NRDC 160 (cis-) and NRDC 159 (trans-) in three soils has been studied under laboratory conditions. Samples of the insecticides labelled separately with ¹⁴C in the cyclopropyl and benzyl rings were used. The rate of degradation was most rapid on sandy clay and sandy loam soils, 50% of the NRDC 160 and NRDC 159 applied to both soils being decomposed in 4 weeks and 2 weeks respectively. The major degradative route in all soils was hydrolysis of the ester linkage leading to the formation of 3-phenoxybenzoic acid and 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid; soil treated with the cis-isomer (NRDC 160) was found to contain both cis- and trans-isomer forms of the cyclopropanecarboxylic acid. Further degradation of these carboxylic acids was evident since ¹⁴CO₂ was released from cyclopropyl- and benzyllabelled cypermethrin in amounts equivalent to 24 and 38% of the applied radioactivity over a 22 week period. A minor degradative route was ring-hydroxylation of the insecticide to give an α-cyano-3-(4-hydroxyphenoxy)benzyl ester followed by hydrolysis of the ester bond. Under waterlogged conditions the rate of hydrolysis of cypermethrin on sandy loam soil was slower than under aerobic conditions and 3-phenoxybenzoic acid accumulated in the anaerobic soil.     

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.     

Metabolism of permethrin isomers in American cockroach adults,house fly adults,and cabbage looper larvae

Forty-two insect metabolites of [1RS,trans]-and [1RS,cis]-permethrin are tentatively identified in studies with Periplaneta americana adults, Musca domestica adults, and Trichoplusia ni larvae involving administration of ¹⁴C preparations labeled in either the alcohol or acid moieties. The less-insecticidal trans isomer is generally metabolized more rapidly than the more-insecticidal cis isomer, particularly in cabbage looper larvae, and metabolites retaining the ester linkage appear in larger amount with cis-permethrin. Although the dichlorovinyl group effectively blocks oxidation in the acid side chain, the permethrin isomers are metabolized by hydrolysis and hydroxylation at the geminal-dimethyl group (either trans- or cis-methyl substituent) and the phenoxybenzyl group (predominantly at the 4′-position in all species but also at the 6-position in house flies). The alcoholic and phenolic metabolites are excreted as glucosides, and the carboxylic acids are excreted as glucosides and amino conjugates (glycine, glutamic acid, glutamine, and serine) with considerable species variation in the preferred conjugating moiety.     

Monooxygenase mediated pyrethroid detoxification in sea lice (Lepeophtheirus salmonis)

The role of monooxygenases in detoxification of the pyrethroids cypermethrin and deltamethrin was examined. Four strains of sea lice (Lepeophtheirus salmonis Krøyer) with normal or moderately reduced sensitivity towards the pyrethroids were tested in bioassays by exposure to the pyrethroid alone and in combination with an oxygenase inhibitor, piperonyl butoxide (PBO). The normal (baseline) sensitivity was considered as the sensitivity range for the two most sensitive strains. Pre‐treatment with PBO elevated the sensitivity (P < 0.01) compared with groups exposed to the pyrethroid only. A positive, but not statistically significant, correlation between the activity of haem peroxidases and the pyrethroid concentration immobilizing 50% of the parasites was demonstrated (ρ = 0.500 for deltamethrin and ρ = 0.310 for cypermethrin). The results indicate that cytochrome P450 monooxygenases are involved in detoxification of pyrethroids in sea lice. ¹⁴C‐Deltamethrin was absorbed in a lesser amount in a group of sea lice exposed to a mixture of the compound and PBO than in a group exposed to ¹⁴C‐deltamethrin alone. A significant difference could be demonstrated both immediately after exposure (P < 0.01) and 24 h after exposure (P < 0.05). No significant differences were found between groups pre‐treated with PBO and groups exposed to ¹⁴C‐deltamethrin only. ¹⁴C‐Deltamethrin was taken up mainly through the cuticle, especially the cuticle on the extremities of the ventral surface, and subsequently distributed throughout the body of the parasite. Copyright © 2005 Society of Chemical Industry     

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.     

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.     

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.     

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.     

The metabolism of p,p′-DDT by the feral pigeon (Columba livia)

Male feral pigeons were dosed with ring-labeled $\text{[}{}^{14}\text{C}\text{]p,p′-}\text{DDT}$ and the tissues and droppings analyzed for total ¹⁴C, extractable ¹⁴C, and metabolites. Only 16% of an intraperitoneal dose of 1.5–2.2 mg kg^?1 was voided in the droppings over 28 days; the rate of loss reached a maximum on the 14th day and then fell quickly away. The rate of removal of ¹⁴C in droppings was low in comparison to that found in the rat and the Japanese quail. When pigeons were dosed with 32–38 mg kg^?1 DDT per bird, and killed after 77 days, 5.4% of the dose was eliminated in droppings and 87% was recovered in the body. The tissues and droppings from this experiment were analyzed for DDT and its metabolites. Of the ¹⁴C remaining in tissues 88% was accounted for as the apolar compounds DDE, DDT, and DDD. Approximately half of the ¹⁴C in droppings was present as DDE, DDT, and DDD, whereas 27–35% was apparently in conjugated form, extractable from aqueous solutions by ethyl acetate after prolonged acid hydrolysis. Two polar metabolites were isolated from the acid-released material. One was p,p′-DDA; the other was extractable from aqueous solution at pH 8 and was tentatively identified as a monohydroxy derivative of p,p′-DDT. DDE accounted for 93% of the ¹⁴C present as metabolites in tissues and droppings, clearly indicating the importance of this intermediate in this study. The metabolism of DDT in the feral pigeon is discussed in relation to its metabolism by other species.