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1.
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.  相似文献   

2.
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).  相似文献   

3.
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.  相似文献   

4.
The metabolism of benodanil (2-iodobenzanilide) was studied in rats following an oral dose of 150 mg benodanil kg?1 body weight. The major 24-h urinary metabolite was found to be the 4′-hydroxy derivative, both free (≈ 5%) and as the glucuronide (≈ 4%) and sulphate (≈ 4%) conjugates. Over a 6-day period, about 16% of the administered dose was excreted in the urine and about 80% in the faeces. After dosing with [14C]- benodanil, blood radioactivity levels were highest 30 min after dosing, with small broader peaks at 4 and 7 h, while biliary activity levels rose slowly to a maximum about 10–12 h after the dose, some 16% being excreted in 24 h as the glucuronide conjugate of the 4′-hydroxy derivative.  相似文献   

5.
A single oral dose of [14C]tridemorph was partly, but rapidly absorbed by rats. Most of the radioactivity was excreted with a half-life of about 15 h. During 5 days, 42.6% was excreted in the urine, 46.7% in the faeces, 1.5% in the expired air and 3.4 % was still retained. 24 % was excreted in the 48 h bile. Sequential wholebody autoradiography indicated that much of the radioactivity was confined to the gastrointestinal tract, liver and kidneys. There was no unexpected uptake of radioactivity. Urinary metabolites were more polar than tridemorph and were also detected in the bile and faeces. The major metabolite in 24 h urine, accounting for 22.3% of the dose appeared to be a side-chain hydroxylated derivative. Cleavage of the morpholine ring was limited to about 1.5 % of the dose.  相似文献   

6.
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.  相似文献   

7.
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.  相似文献   

8.
[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).  相似文献   

9.
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.  相似文献   

10.
l-[U-14C]sucrose accumulation by phloem sieve tube members (PSTM) of wheat (Triticum aestivum L. ‘Holley’) and sorghum (Sorghum bicolor L. ‘G522 DR’) was inhibited by the nonpermeant sulfhydryl inhibitor p-chloromercuribenzenesulfonic acid (PCMBS), and this inhibition was reversed by the permeant sulfhydryl protectants dithiothreitol (DTT) and dithioerythritol (DTE). S-Ethyl dipropylthiocarbamate (EPTC) (≤0.1 mM) did not inhibit [14C]sucrose accumulation by wheat or sorghum PSTM. N-N-Diallyl-2-chloroacetamide (CDAA) (1 mM) inhibited [14C]sucrose accumulation by sorghum but not by wheat PSTM. The inhibition of [14C]sucrose accumulation in sorghum PSTM by the membrane permeant CDAA was reversed by DTT. Sorghum growth was inhibited by <1 μM CDAA. Membrane permeant 2-chloroallyl diethyldithiocarbamate (CDEC) (0.1 mM) inhibited [14C]sucrose accumulation by PSTM of sorghum but not wheat. The inhibition of sucrose accumulation in sorghum PSTM by 0.1 mM CDEC was reversed by DDT.  相似文献   

11.
Upon intravenous application of dihydrochlordene dicarboxylic acid-14C to rats, the radioactivity is quickly excreted, and 44% of the excreted radioactivity consists of metabolites. Nine metabolites have been isolated from feces and urine extracts. Three metabolites could be identified by means of authentic samples by thin layer chromatography, gas chromatography, and mass spectrometry: two isomers of dechlorodihydrochlordene-dicarboxylic acid (metabolites I and II, total 22.5%) and dihydrochlordene-dicarboxylic acid-dimethyl-ester (metabolite III, 11.3%).  相似文献   

12.
The metabolism of the carbamate insecticide bendiocarb (2,2-dimethylbenzo-1, 3-dioxol-4-yl methylcarbamate) has been investigated in male and female rats and in a male human volunteer using radiolabelled material. The compound was rapidly and extensively absorbed and completely metabolised following oral administration. In man, absorption was complete, >99% of the dose being excreted in the urine within 22 h. In the rat, > 86% of the radiolabel was excreted in the urine within the first 24 h. Faecal excretion from the rat was minor (3–8% of dose) and a small amount of the compound (1–3%) was metabolised and excreted as [14C]carbon dioxide. The major metabolic pathway in both species involved cleavage of the carbamate ester group to yield the phenol,2,2-dimethylbenzo-1, 3-dioxol-4-ol (I). This metabolite, occurring as sulphate and glucuronide conjugates, accounted for more than 95% of the dose excreted by the human volunteer. In man, small amounts of conjugates of 2, 2-dimethylbenzo-1, 3-dioxol-4-yl N-(hydroxymethyl)carbamate (II) were also found in early samples. In the rat, the metabolism was more complex with the formation of small amounts of conjugates of II and several minor metabolites, thought to be ring-hydroxylated derivatives of bendiocarb and I.  相似文献   

13.
[14C]Endosulfan, α or β isomers separately, was administered to rats as a single oral dose and as a dietary supplement for 14 days. No appreciable differences were observed in the fate of the two isomers. Five days after the single dose, 75% of the dose had been voided in the feces and 13% in the urine. Of the total radiocarbon consumed in the diet after 14 days, 56% had been eliminated in the feces and 8% in the urine. Bile collection studies showed that up to 47% of a single oral dose was eliminated from the liver via this route; enterohepatic circulation was not apparent. Maximum [14C]endosulfan equivalents in body tissue occurred in the kidney and liver, 3 and 1 ppm, respectively, after 14 days of feeding 5 ppm of endosulfan. Apolar metabolites in the excreta and/or tissues were a minor portion of the total residues and consisted of the sulfate, diol, α-hydroxy ether, lactone, and ether derivatives of endosulfan. The sulfate was slightly more toxic to mice than endosulfan, while the other products were less toxic. Neither endosulfan nor its metabolites were active in the Salmonella mutagenicity test. Endosulfan in the diet of rats for 28 days at 50 ppm did not induce liver oxidase enzymes, alter liver or kidney weights, or influence the rate of weight gain of the animals.  相似文献   

14.
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.  相似文献   

15.
Excretion and distribution of single and multiple intraperitoneal doses of [35S]captan and [14C]folpet were similar in normal and 70% hepatectomized male rats. After receiving the single dose of captan, the rats eliminate approximately 76% of the radioactivity in the urine after 72 hr. The elimination in the feces for the same time period was 13%. Normal rats administered single or multiple doses of [14C]folpet excreted nearly 100% of the total dose in the urine within the first 24 hr. Nuclei isolated from the liver of normal and 70% hepatectomized rats receiving multiple doses of [35S]captan contained 0.008–0.009 μg 35S/g of tissue. Appreciable amounts of the radioactivity from [35S]captan were bound by isolated nuclei from the livers of normal and partially hepatectomized rats. After a 1-hr treatment with [36S]captan, the nuclei were fractionated into nuclear sap protein, deoxyribonucleoprotein (including histones), acidic ribonucleoprotein, and “residual” protein fractions. These proteins in normal nuclei bound 10, 14, 39, and 16% of the total label, respectively, with essentially the same results obtained with nuclei from regenerating rat liver. When compared by polyacrylamide gel electrophoresis, acidic nuclear proteins from treated and nontreated normal nuclei were characterized by band diffusion and the presence or absence of Amido Schwartz-staining bands. None of the abovementioned effects on histones from treated nuclei were observed. Captan treatment of isolated nuclei also altered the extraction characteristics of the nuclear protein fractions, presumably because of extensive aggregation of thiol-containing nuclear proteins.  相似文献   

16.
N,N-Diallyl-2-chloroacetamide (CDAA) (0.25 ppmw; I μM) inhibited growth of 14-day-old sorghum (Sorghum bicolor (L) Moench. cv Funks G 522DR) when the herbicide was incorporated into sand. Kaurene oxidation was inhibited in a cell-free enzyme preparation from 4-day-old unruptured, etiolated coleoptiles. CDAA (1 μM) inhibited incorporation of [14C]mevalonic acid into kauren-19-oic acid (50%), with resultant increases in concentration of precursors. Thus, inhibition of gibberellin precursor biosynthesis was demonstrated, and this activity would explain many of the morphogenic and biochemical responses of grasses to CDAA.  相似文献   

17.
A rat, given a single oral dose of [14C] cymoxanil, 1-(2-cyano-2-methoxyimino-[2-14C]-acetyl)-3-ethylurea, eliminated 91% of the radioactivity within 72 h. The urine contained 71%, the faeces 11%, and the expired air about 7% of the radiolabel; no 14C residue was found in the internal organs. Greater than 70% of the radioactivity in the urine was identified. The major metabolite was characterised as glycine, both free and conjugated, as hippuric acid and phenylaceturic acid [N-(phenylacetyl)-glycine], and probably in the form of polypeptides of low molecular weight. The other metabolites identified included 2-cyano-2-methoxyiminoacetic acid, 2-cyano-2-hydroxyiminoacetic acid and 1-ethylimidazolidine-2, 4, 5-trione. The minor metabolites included succinic acid and 2-oxoglutaric acid which indicated reincorporation of metabolic 14C. Cymoxanil, as such, was not detected in the urine.  相似文献   

18.
Orally administered [1-14C]ethyl paraoxon, O,O-diethyl-O-p-nitrophenyl phosphate, is readily absorbed from the gastrointestinal tract of male albino rats. Radioactivity is essentially eliminated in 72 hr by excretion into urine and feces and by expiration as 14CO2. Compounds with radioactivity in the urine are tentatively identified as diethyl phosphoric acid, desethyl paraoxon, ethanol, metabolites conjugated with amino acids, and paraoxon; the first compound is the predominant radioactive metabolite. Intraperitoneally injected phenobarbital, DDT, dieldrin, and endrin are inducers of microsomal enzymes that degrade paraoxon. The aryl phosphate-cleaving activity in vitro is not dependent on the addition of NADPH. O-Dealkylation of paraoxon is catalyzed by microsomal enzymes that require NADPH and oxygen and are inhibited by carbon monoxide. Microsomal enzymes from rats pretreated with enzyme inducers give an increased rate of O-dealkylation of paraoxon. Reduced glutathione has little or no effect on paraoxon degradation by either microsomal or soluble enzymes. Actinomycin D inhibits O-dealkylation of paraoxon in vivo, as indicated by reduction of 14CO2 formation, and in vitro, as indicated by decreased activity of microsomal O-dealkylase. The role of microsomal mixed-function oxidases and NADPH-dependent O-dealkylase in the metabolism of organophosphorus insecticides is discussed.  相似文献   

19.
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.  相似文献   

20.
As preliminary probes to determine the mode of delayed toxic action of O,O,S-trimethyl phosphorothioate (I) in the rat, the effect of I on rat tissue and organs, and on blood, urine, and pharmacokinetic parameters was investigated. Following oral administration, 30 to 200 mg/kg I caused liver necrosis as a major pathological effect. Morphological changes were also observed in the heart, adrenal, tissues of the small intestine, and kidney. Most animals treated with I developed bronchopneumonia after 3 days. Blood samples taken from rats poisoned with 60 mg/kg I showed severe hemoconcentration; however, serum Na+, Cl?, albumin, and total carbonate/bicarbonate varied only slightly. Na+ and Cl? concentrations in the urine showed a steady decline with time following poisoning but K+ levels remained relatively constant. Pharmacokinetic studies showed that 14C levels in the blood following intraperitoneal or intravenous administration of 60 mg/kg [CH3O14C]I were not affected when the animals were cotreated with 5% of the antagonist O,O,O-trimethyl phosphorothioate. However, lower levels of 14C were found in antagonized animals following oral administration.  相似文献   

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