The metabolism of chlorotoluron in the rat

The metabolic fate of ¹⁴C-labeled chlorotoluron, i.e., 1-(3-chloro-4-methyl[⁴C]-phenyl)-3,3-dimethyl urea, was followed in rats. After a single oral dose the radioactivity was preferably excreted with the urine. Nine of the eleven urinary metabolites isolated, were identified by spectroscopic and derivatization techniques, whereas the structure of the remaining two metabolites was only partially elucidated. N-Demethylation and stepwise oxidation of the ring methyl group to hydroxymethyl and carboxyl derivatives were found as the major metabolic mechanisms. Both mechanisms proceeded simultaneously so that the isolated metabolites showed all combinations of N-demethylation and ring methyl group oxidation in their structures. One of these metabolites was an N-formyl derivative, being probably an intermediate product of demethylation. In the urine of rats fed doses of [¹⁴C]chlorotoluron higher than 50 mg/kg three additional metabolites with different degrees of N-dealkylation were found, the ring methyl group of which was transformed to a methylthio methyl group. The metabolites identified in the faeces were of the same type as those found in the urine. Based on the structures of the metabolites elucidated, a metabolic pathway of chlorotoluron in the rat is presented.     

Metabolism of cisanilide (Cis-2,5-dimethyl-1-pyrrolidinecarboxanilide) by rat liver microsomes

Metabolism of [phenyl-¹⁴C] and [(2,5) pyrrolidine-¹⁴C] cisanilide was investigated in vitro with microsomal preparations from rat liver. Microsomal activity was associated with a mixed-function oxidase system that required O₂ and NADPH and was inhibited by CO. Two major ether-soluble metabolites were isolated. They were identified as primary oxidation products: 2-hydroxy-2,5-dimethyl-1-pyrrolidinecarboxanilide (A) and 4′-hydroxy-2,5-dimethyl-1-pyrrolidinecarboxanilide (B). Minor ether-soluble metabolites were also isolated. Precursor product studies and qualitative thin layer chromatography analysis of [pyrrolidine-¹⁴C] and methylated [phenyl-¹⁴C] hydrolysis products suggested that these metabolites were secondary oxidation products formed from metabolites A or B. One of these metabolites appeared to be the dihydroxy product 2,4′-dihydroxy-2,5-dimethyl-1-pyrrolidinecarboxanilide. Crude microsomal preparations (postmitochondrial supernatant fractions) also formed small quantities (<10%) of polar metabolites. Enzyme hydrolysis with β-glucuronidase (Escherichia coli) indicated that approximately 50% of these metabolites were glucuronides. Similarities and differences in cisanilide oxidation in vivo in plants and in vitro with rat liver microsomal preparations were discussed.     

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.     

Antifungal mode of action of imazalil

Imazalil had no effect on the initial growth of mycelia of Penicillium italicum (for 10 hr) or Aspergillus nidulans (for 2 hr). In P. italicum during this period neither respiration nor cell permeability was affected, but uptake of [³²P]phosphate, [¹⁴C]leucine, or [¹⁴C]uridine was partially inhibited. The initial (5 hr) inhibition of substrate uptake coincided with a 50% reduction in ergosterol content. Within 0.5 hr, incorporation of [¹⁴C]acetate into C-4-desmethyl sterols was strongly inhibited in mycelia of A. nidulans treated with 0.5 μg/ml of imazalil. However, radioactivity in C-4-methyl and dimethyl sterols exceeded that of control cultures. Concentrations of imazalil as low as 0.005 μg/ml caused short-term (1 hr) declines of incorporation into desmethyl sterols and increases into the C-4-methyl and dimethyl sterols. Incorporation into phospholipids, triglycerides, and free fatty acids was not affected. These data suggest that the primary antifungal action of imazalil is inhibition of demethylation in the biosynthesis of ergosterol.     

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).     

Metabolic resistance mechanisms of the housefly (Musca domestica) resistant to pyraclofos

In vivo and in vitro metabolism of pyraclofos labeled with ¹⁴C on benzene ring was studied in the pyraclofos-resistant and -susceptible female houseflies. In vivo metabolism studies, the metabolic rate of pyraclofos was the same in both strains. Pyraclofos primarily undergoes metabolic detoxification by cleavage of P-S-alkyl bond, and cleavage of the P-O-aryl bond followed by CHP [1-(4-chlorophenyl)-4-hydroxypyrazole]]-glucose conjugation. Cleavage of P-O-aryl bond and CHP-glucose conjugation is more predominant in the resistant strain whereas the cleavage of P-S-propyl bond resulting in EHP-CHP [O-1-(4-chlorophenyl)pyrazol-4-yl ethyl hydrogen phosphate] is more preferred in the susceptible strain. CHP production by P-O-aryl bond cleavage was controlled by P450 monooxygenase and esterase. UDP-glucosyltransferase appeared to play an important role in the pyraclofos metabolism of the resistant strain. Production of CHP-glucose conjugate was largely reduced by piperonyl butoxide and S,S,S-tributylphosphorotrithioate in both strains. EHP-CHP production seemed to be controlled by P450 monooxygenase and stimulated by UDP-glucose.     

Acifluorfen metabolism in soybean: Diphenylether bond cleavage and the formation of homoglutathione, cysteine, and glucose conjugates

Metabolism of the substituted diphenylether herbicide, acifluorfen [sodium 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate], was studied in excised leaf tissues of soybean [Glycine max (L.) Merr. ‘Evans’]. Studies with [chlorophenyl-¹⁴C]- and [nitrophenyl-¹⁴C]acifluorfen showed that the diphenylether bond was rapidly cleaved. From 85 to 95% of the absorbed [¹⁴C]acifluorfen was metabolized in less than 24 hr. Major polar metabolites were isolated and purified by solvent partitioning, adsorption, thin layer, and high-performance liquid chromatography. The major [chlorophenyl-¹⁴C]-labeled metabolite was identified as a malonyl-β- -glucoside (I) of 2-chloro-4-trifluoromethylphenol. Major [nitrophenyl-¹⁴C]-labeled metabolites were identified as a homoglutathione conjugate [S-(3-carboxy-4-nitrophenyl) γ-glutamyl-cysteinyl-β-alanine] (II), and a cysteine conjugate [S-(3-carboxy-4-nitrophenyl)cysteine] (III).     

Metabolism of trifluralin,profluralin, and fluchloralin by rat liver microsomes

Three structurally related [¹⁴C]dinitroaniline herbicides, trifluralin, profluralin, and fluchloralin, were extensively metabolized in vitro by both normal and phenobarbital-induced rat liver microsomes. Identification of the metabolites in the ethyl acetate extracts indicated that aliphatic hydroxylation, N-dealkylation, reduction of a nitro group, and cyclization were the predominant metabolic routes for these herbicides in vitro. Of particular interest was the formation of a benzimidazole metabolite.     

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.     

Herbicide perfluidone (1,1,1-trifluoro-N-[2-methyl-4-(phenylsulfonyl)phenyl]methanesulfonamide): Its metabolism in rats and chickens

Rats and chickens were each given a single oral dose (10 or 100 mg/kg body wt) of 1,1,1-trifluoro-N-[2-methyl-4-(phenylsulfonyl)phenyl-¹⁴C(U)]methanesulfonamide ([¹⁴C]perfluidone). Depending on the size of the dose, from 8.4 to 36.2% of the [¹⁴C] was eliminated in the urine and from 36.4 to 85.4% was eliminated in the feces within 48 hr after dosing. Less than 1% of the [¹⁴C] given to laying hens as [¹⁴C]perfluidone was present in the eggs produced during the first 96 hr after dosing. The percentage of the administered [¹⁴C] that remained in these animals (body with G.I. tract and contents removed) varied from 0.34 (96 hr after dosing) to 1.68% (48 hr after dosing). ¹⁴C-labeled compunds in the urine and feces from the rats and chickens were purified by solvent extraction, column chromatography, and gas-liquid chromatography, and then identified by infrared and mass spectrometry. The parent compound was the major ¹⁴C-labeled component in the urine and feces of both animals. 1,1,1-Trifluoro-N-[2-methyl-4-(3-hydroxyphenylsulfonyl)phenyl]methanesulfonamide was present in the feces of both animals. The proposed structures of other metabolites were 1,1,1-trifluoro-N-hydroxy-N-[2-methyl-4-(phenylsulfonyl)phenyl]methanesulfonamide (rat urine) and 1,1,1-trifluoro-N-{2-methyl-4-[(methylsulfonyl)-phenylsulfonyl]phenyl}methanesulfonamide (chicken urine).     

Metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] inhibition of gibberellin precursor biosynthesis

[2-¹⁴C]Mevalonic acid incorporation into gibberellic acid precursors was measured in cell-free extracts from sorghum [Sorghum bicolor (L.) Moench var. G-522 DR] coleoptiles. ¹⁴C incorporation into ent-kaur-16-ene was inhibited ca. 90% by 10^?7 to 10^?4M metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide]. [¹⁴C]Geranylgeraniol (GG) content increased. [¹⁴C]Farnesol content was not altered and [¹⁴C]geraniol content decreased. Total ¹⁴C incorporation was decreased by metolachlor. In the safener [α-(cyanomethoximino)benacetonitrile]-treated sorghum seed coleoptile cell-free system, total ¹⁴C incorporation increased, [¹⁴C]kaurene and relative kaurence content increased 4× up to 10⁵M metolachlor, and [¹⁴C]farnesol, and [¹⁴C]GG contents increased while relative farnesol and relative GG contents were not influenced by metolachlor. Thus, the inhibition of kaurene synthesis by metolachlor was reversed by the safener. Since the biosynthetic processes are mevalonic acid → geraniol → farnesol → GG → copalylol → kaurene, these data corroborate a proposed gibberellic acid biosynthesis inhibition between GG and kaurene as well as a partial blockage between mevalonic acid and geraniol. Thus, a portion of metolachlor-induced growth inhibitions of sorghum could be explicable on the basis of gibberellic acid biosynthesis inhibitions.     

Mercapturic acid formation in the metabolism of propachlor,CDAA, and fluorodifen in the rat

When [¹⁴C]F₃-fluorodifen (2,4′-dinitro-4-trifluoromethyl diphenylether), carbonyl-[¹⁴C]CDAA (N,N-diallyl-2-chloroacetamide), and carbonyl-¹⁴C-propachlor (2-chloro-N-isopropylacetanilide) were fed to rats, 57 to 86% of the ¹⁴C was excreted via the urine within 48 hr. Although very little radioactivity was excreted in the feces of CDAA-treated rats, 15–22% of the ¹⁴C was excreted in the feces of propachlor- of fluorodifentreated rats and an average of 8% of the ¹⁴C remained in these rats 48 hr after treatment. Oxidation of the ¹⁴C label to [¹⁴C]O₂ was not a major process in the metabolism of these herbicides. The only major radioactive metabolite present in the 24-h urine of fluorodifen-treated rats, 2-nitro-4-trifluoromethylphenyl mercapturic acid, accounted for 41% of the administered dose of ¹⁴C. In the metabolism of CDAA, the corresponding mercapturic acid accounted for 76% of the dose; it was the only major metabolite present in the 24-h urine. In contrast, three major metabolites were detected in the 24-h urine of propachlortreated rats, and the mercapturic acid accounted for only 20% of the dose. The mercapturic acid of each herbicide was identified by mass spectrometry.     

Gastric absorption of a pesticide (1-naphthyl N-methylcarbamate) in the fasted rat

The gastric absorption of [1-naphthyl-1-¹⁴C]N-methylcarbamate (radiolabeled carbaryl) administered intragastrically (7.5 μmoles/kg body wt) to fasted, anesthetized female rats was investigated by measurement of ¹⁴C absorption and by identification of the radiolabeled constituents in the portal blood. At 22 and 67 min after dosing, 52.6 ± 14.1% (n = 3) and 81.7 ± 15.7% (n = 3), respectively, of the ¹⁴C was absorbed from the stomachs (ligated pylori) of rats with intact portal circulation. In another experiment, 69.1 ± 25.9% (n = 3) of the ¹⁴C was absorbed from the rat stomachs (ligated pylorus and esophagus) during 66.0 ± 1.0 min of total portal blood collection (via an in vivo perfusion technique). The radiolabeled material in the collected portal blood accounted for 97.2 ± 1.9% (n = 3) of the ¹⁴C absorbed from rat stomachs. On the basis of thin-layer chromatography, gas chromatography, and infrared spectroscopy, 89.3% of the radiolabeled material in the collected portal blood was [1-naphthyl-1-¹⁴C]N-methylcarbamate.     

Metabolism of EPTC in germinating corn: Sulfone as the true carbamoylating agent

Corn (Zea mays L. single cross hybrid Mv 620) was germinated in a petri dish with addition of carbonyl[¹⁴C]EPTC (S-ethyl-N,N-dipropylthiocarbamate). The shoots and roots of 4-day-old seedlings were crushed and extracted in 80% methanol. On the chromatogram of the extract three radioactive peaks were found. The main peak was identified as S-(N,N-dipropylcarbamoyl)-glutathione. For the comparison of carbamoylating ability [¹⁴C]EPTC, [¹⁴C]EPTC-sulfoxide, and [¹⁴C]EPTC-sulfone were incubated with glutathione. Only EPTC-sulfone reacted in the 10-day incubation time. In aquatic solutions EPTC and EPTC-sulfoxide proved to be stable during the 10 days compared to EPTC-sulfone which quickly degraded, S-(N,N-Dipropylcarbamoyl)-glutathione was converted to S-(N,N-dipropylcarbamoyl)-cysteine in corn shoot homogenate. [¹⁴C]EPTC, [¹⁴C]EPTC-sulfoxide and [¹⁴C]EPTC-sulfone were added to corn shoot homogeneates and each of the three mixtures were analyzed by chromatography after 1 day incubation. EPTC was partly oxidized to EPTC-sulfoxide. EPTC-sulfoxide did not change and EPTC-sulfone produced similar metabolites as had been found in the germination experiment.     

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.     

Analogy in the mode of action of fluotrimazole and clotrimazole in Ustilago avenae

Fluotrimazole [BUE 0620; 1-(3-trifluoromethyltriphenyl) 1,2,4-triazole] (20 μg/ml of nutrient solution) and clotrimazole [Bay b 5097; bisphenyl(2-chlorophenyl)-1-imidazolyl methane] (5 μg/ml) did not inhibit dry weight increase and only slightly reduced multiplication of sporidia of Ustilago avenae during the first doubling period (about 4 hr). After 8 hr, both fluotrimazole and clotrimazole more strongly inhibited sporidia multiplication than dry weight increase. As a consequence of treatment with both fungicides the usually single-celled sporidia appear swollen, multicellular, and branched. Both chemicals at a concentration range of 5–100 μg/ml did not affect oxidation of glucose. The effect of fluotrimazole and clotrimazole on protein, DNA, and RNA synthesis was similar to that on dry weight. Following a 6-hr incubation period total lipid synthesis was quantitatively unaffected by both chemicals. As the analysis of major fatty acids of total lipids revealed fluotrimazole substantially induced the synthesis of 20:4 carbon fatty acids, while in clotrimazole-treated sporidia the pattern of fatty acids did not differ from that of control sporidia. Fluotrimazole and clotrimazole produced a higher quantity of free fatty acids in sporidia of U. avenae. Gas-liquid chromatographic analysis of sterol fractions in treated and control sporidia (6 hr) indicated that both fluotrimazole and clotrimazole seriously inhibited ergosterol biosynthesis and concomitantly caused an accumulation of immediate ergosterol precursors which represent C-4-methyl and 4,4-dimethyl sterols. Incorporation of [¹⁴C]acetate for 2 hr into various lipid fractions of sporidia of U. avenae also revealed that radioactivity in C-4-desmethyl sterols in both fluotrimazole- and clotrimazole-treated sporidia was drastically reduced, while the radioactivity of C-4-methyl and 4,4-dimethyl sterols distinctly increased. The data suggest that fluotrimazole and clotrimazole are specific inhibitors of the oxidative demethylation of the C-14-methyl group during ergosterol biosynthesis in U. avenae.     

Alachlor influence on sorghum growth and gibberellin precursor synthesis

Growth (14 days) of sorghum (Sorghum bicolor L. cv G522 DR) from seed planted in sand into which alachlor [2-chloro-2′,6′-diethyl-N-(methoxymethyl)acetanilide] was uniformly incorporated (0, 0.07, 0.14, 0.28, 0.56, 1.12, 2.24, or 4.48 kg/ha) was reduced by 0.14 kg/ha and severely inhibited (88%) by 0.56 kg/ha while cellular water cotent was not greatly influenced by 0.56 kg/ha. When added into the nutrient solution bathing the roots of 96-hr sorghum seedlings, alachlor (0, 0.0156, 0.0312, 0.0625, 0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, or 128 ppmw) was not lethal to 14-day-old sorghum at rates up to 32 ppmw (92% survival); however, shoot and root lengths were reduced 43 and 58%, respectively. Alachlor inhibition of sorghum growth appears to be closely associated with inhibition of cell enlargement; the coleoptile is the most susceptible stage of sorghum growth to alachlor. This situation closely resembles growth where gibberellic acid (GA) synthesis is inhibited. [2-¹⁴C]Mevalonic acid ([2-¹⁴C]MVA) incorporation into terpenoid GA precursors was evaluated using a cell-free enzyme system from etiolated sorghum coleoptiles. Alachlor did not inhibit total ¹⁴C incorporation but incorporation of ¹⁴C into kaurenol and sterols was decreased ca 80 and 75%, respectively, by 10^?6M alachlor. Analyses for [¹⁴C]geranylgeraniol (GG), [¹⁴C]farnesol, and [¹⁴C]geraniol contents showed accumulation of [¹⁴C]farnesol and [¹⁴C]GG, and decreased [¹⁴C]geraniol. When seeds to which CGA-43089 [α-(cyanomethoximino)-benzacetonitrile] was applied 8 weeks prior to planting were substituted for untreated seeds, incorporation of [2-¹⁴C]MVA into [¹⁴C]kaurenol was increased by alachlor while [¹⁴C]GG and [¹⁴C]farnesol accumulated and [¹⁴C]geraniol was absent at 10^?6M alachlor. Additionally, sterol content increased in “safened” systems but was still decreased by alachlor. These data demonstrate multiple sites of alachlor activity in the GA and terpenoid biosynthetic pathway.     

Metabolism of chlorsulfuron by plants: Biological basis for selectivity of a new herbicide for cereals

A major factor responsible for the selectivity of chlorsulfuron [2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]benzenesulfonamide] (formerly DPX-4189), as a postemergence herbicide for small grains is the ability of the crop plants to metabolize the herbicide. Chlorsulfuron is the active ingredient in Du Pont “Glean” weed killer. Tolerant plants such as wheat, oats, and barley rapidly metabolize chlorsulfuron to a polar, inactive product. This metabolite has been characterized as the O-glycoside of chlorsulfuron in which the phenyl ring has undergone hydroxylation followed by conjugation with a carbohydrate moiety. Sensitive broadleaf plants show little or no metabolism of chlorsulfuron.     

The metabolism of the nonionic surfactant 14C-labeled α[p-1,1,3,3-tetramethylbutyl)phenyl]-ω-hydroxyhexa(oxyethylene) in the goat

A goat given a single dose of ¹⁴C-labeled α-[p-(1,1,3,3-tetramethylbutyl)phenyl]-ω-hydroxyhexa(oxyethylene) ([¹⁴C]TOP-6EOH) eliminated 18% of the ¹⁴C in the urine and 77% in the feces within 96 hr after dosing. Another goat (surgically modified for total bile collection) given a single dose of [¹⁴C]TOP-6EOH eliminated 81% of the ¹⁴C in the bile, 17% in the urine, and only 6% in the feces. When ¹⁴C-bile from the animal in the second study was perfused into the small intestine of a third goat, 72% of the ¹⁴C was eliminated in the feces, 20% in the bile, and 6% in the urine within 96 hr. Eighteen different types of metabolites accounting for most of the ¹⁴C in the bile and urine were isolated, derivatized, and then characterized by mass spectral analysis. The [¹⁴C]TOP-6EOH was metabolized by: (i) oxidation of the alkyl group to give alcohols and acids, (ii) oxidation of the terminal ethylene oxide moiety to an acid, (iii) cleavage of the polyoxyethylene side chain, (iv) combinations of i–iii, and (v) conjugation of the products of i–iv.     

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.