Toxicity and metabolism of methomyl in the European corn borer

The contact and oral toxicity of methomyl (S-methyl N-[(methylcarbamoyl)oxy] thioacetimidate) was similar for two different strains of European corn borer, Ostrinia nubilalis (Hübner). In each case, third- and fourth-instar larvae were equally susceptible, but fifth-instar insects were considerably more difficult to kill. In vivo and in vitro studies revealed that borers from both strains metabolized methomyl via a mixed-function oxidase system to water-soluble products which could not be cleaved by acid or hydrolytic enzymes. By far, the greatest metabolic activity was localized in fat body tissues of last-instar larvae, and although both strains metabolized methomyl at a similar rate, a large difference was found in the rate of metabolism of methomyl oxime.     

The metabolic fate of methomyl in the cabbage looper

Methomyl, S-methyl N-[(methylcarbamoyl)oxy] thioacetimidate, is metabolized primarily to water-soluble products by susceptible, DDT-resistant, and parathion-resistant strains of the cabbage looper, Trichoplusia ni (Hübner). However, the rate of injected methomyl metabolized varies with the strain to give respective half-lives of 60, 44, and 15 min. In each strain, maximum methomyl-metabolizing activity is present in the last larval stage and prepupal forms, particularly in the fat body. Metabolism by fat body homogenates is dependent on oxygen and NADPH and is inhibited by carbon monoxide and methylenedioxyphenyl synergists. The water-soluble metabolites could not be converted to organosoluble materials by acid or enzymatic treatment. Methomyl sulfoxidation products or oxime derivatives do not appear to be terminal metabolites in the cabbage looper.     

Residues of the insecticides phorate and methomyl in mint hay and oil

Since mint oil is used as a flavouring agent for foods and cosmetics, pesticide residues in the oil are undesirable. The residual behaviour of two pesticides, phorate and methomyl, was studied as replacements for chlorinated hydrocarbon pesticides which leave residues in the oil. Phorate applications of 1.1 kg/ha resulted in oil residues of 0.24 mg/kg total phorate in Oregon samples and 1.69 mg/kg in Washington samples. Less than 1% of the residues in the hay distilled with the oil. Mint oil undergoes a 100- to 1000-fold dilution in commercial use with a corresponding reduction of residues in the final product. No residues of methomyl were found in the oil, even with hay residues as high as 5.34 mg/kg. Residues in hay decreased to half of initial levels in 2 to 4 days, independently of use conditions. It was concluded that the proposed use of phorate or methomyl for control of mint pests does not present a residue hazard. Details of the analytical methods used are also presented.     

Determination and confirmation of methomyl residues in soil and water

Gas chromatographic methods for the determination of methomyl residues in soil and water utilising the flame photometric detector are described. Complete extraction of methomyl residues in soil and water was obtained and the analytica.1 results were reproducible. Recovery of 90–96 % of methomyl residues was possible based on 50 g of soil and 1 litre of water. The identity of methomyl residues determined was confirmed by gas chromatography-mass spectrometry.     

Residues of methomyl in strawberries,tomatoes and cucumbers

An accurate and rapid high performance liquid chromatography method was developed to monitor residues of methomyl in plant extracts. The rate of disappearance of foliage-applied methomyl from strawberries, tomatoes and cucumbers was studied. Residues reached levels of 0.55, 0.2 and 0.6 mg kg^?1 seven days after methomyl had been applied to strawberries, tomatoes and cucumbers, respectively. Results also showed that rinsing treated fruits with tap water removed considerable amounts of methomyl. Samples of strawberries, tomatoes and cucumbers were collected from local markets at Ismailia, and checked for methomyl residues. Residues in 12.5% of tomato and 25% of strawberry samples were above 0.2 mg kg^?1.     

Determination of methomyl in rape seeds,oils and meals

Methomyl added to rape seeds, oils or meals was detected by a thin-layer chromatographic-enzyme inhibition technique. The limit of detection in the presence of oil or meal extractive was 20 mg or 0.01 mg/kg. The amounts of methomyl recovered from oils and meals fortified at 0.01 to 20 mg/kg were comparable to the standard. When stored at 4 °C, methomyl in oil or meals, or in chloroform extracts, was stable for at least 10 and 21 days, respectively. No degradation was observed when methomyl was heated in ethanol at 72 °C for 2 h. Methomyl and its oxime were also detected with either iodo- or chloroplatinate reagent after t.l.c. The detection limits were approximately 600 mg for methomyl and 190 for the oxime.     

灭多威和吡虫啉对棉苗缩合单宁含量的影响

为明确常用杀虫剂对棉花抗虫性的影响,研究了灭多威和吡虫啉营养液处理对棉苗中抗虫次生物质缩合单宁含量的影响。结果表明,25mg/L灭多威处理3叶期棉苗后第6、9、12和15天,50mg/L灭多威处理棉苗后第6天和第15天,棉叶中缩合单宁含量均显著增加,其中25mg/L灭多威处理棉苗15天,棉叶中缩合单宁的含量较对照增加74%。50mg/L吡虫啉处理棉苗后第2天,棉叶中缩合单宁含量与对照相比增加了45%,而吡虫啉的其它处理浓度和处理时间未对棉苗缩合单宁含量产生显著影响。杀虫剂对棉苗缩合单宁含量的影响与杀虫剂本身的性质密切相关,其中灭多威对棉苗缩合单宁含量影响较大,而吡虫啉影响则较小。此外,杀虫剂对棉苗缩合单宁含量的影响还具有一定的剂量效应与时间效应。     

The metabolism of mebenil in rats,rabbits and guinea-pigs

The metabolism of mebenil (o-toluanilide) was studied in rats, rabbits and guinea-pigs. The major metabolite in all three species was 4′-hydroxy-o-toluanilide, both free and as glucuronide and sulphate conjugates. Traces of aniline were also excreted, showing that the amide bond was hydrolysed in vivo.     

The role of ferrous ions in the rapid degradation of oxamyl,methomyl and aldicarb in anaerobic soils

The carbamoyloxime pesticides methomyl, oxamyl and aldicarb, together with the oxidation products of aldicarb, are known to break down much more rapidly in certain anaerobic subsoils than in the aerobic topsoils from the same site. Ferrous ions have now been shown to be involved in this reaction. Oxamyl was degraded in aqueous solutions at 30°C containing 250 μg ml^?1 Fe²⁺ with a half-life of about 10 h, independent of pH in the range of 5.65–7.66; the observed products of this reaction were N,N-dimethyl-l-cyanoformamide and methanethiol. These same products, rather than the oximino hydrolysis product observed from degradation in aerobic soils, were rapidly and quantitatively formed from oxamyl in suspensions of anaerobic reduced subsoils (Fe²⁺ concentration 27–41 μg ml^?1 soil water), but oxamyl was rather stable in water-saturated Vredepeel subsoil (Fe²⁺ concentration 0.65 μg ml^?1) in which the redox potential was much higher. Methomyl behaved similarly. The rates of reaction in the suspensions of anaerobic subsoils were greater than expected from the concentrations of Fe²⁺ in the soil water, but most of the Fe²⁺ present in soil was bound to the soil particles by cation exchange and this bound Fe²⁺ may have participated. Breakdown of aldicarb was accelerated both in solutions of Fe²⁺ and in the suspensions of anaerobic reduced subsoils, though the rate enhancement was less than observed with methomyl and oxamyl; 2-methyl-2-methylthiopropionitrile and 2-methyl-2-methylthiopropionaldehyde were the observed products from aldicarb in anaerobic soil but only the former was produced in Fe²⁺ solutions; the corresponding nitriles and aldehydes were also yielded by aldicarb sulphoxide and aldicarb sulphone in the anaerobic, reduced subsoils.     

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.     

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).     

The effects of dicofol on induction of hepatic microsomal metabolism in rats

In a comparative study, the induction effects of dicofol, technical Kelthane, and DDT on hepatic microsomal and cytosolic enzyme activities in rats were compared with those effects produced by phenobarbital (PhB) and β-naphthoflavone (BNF). Male rats (ca. 250 g) were injected (ip) for 4 consecutive days with 1.0 ml of vehicle containing either dicofol (1.5, 15.0, 29.5, or 59.0 mM, Kelthane (dicofol content equal to 29.5 or 59.0 mM), DDT (59.0 mM), or BNF (36.7 mM). Liver weights, microsomal protein, and cytochrome P-450 concentrations and microsomal and cytosolic enzyme specific activities were measured. Dicofol produced dose-related increases in all of the parameters measured except liver weight and cytosolic epoxide hydrolase activity. At a concentration of 59.0 mM, dicofol increased the concentrations of microsomal protein (1.7-fold) and cytochrome P-450 (2.9-fold), and the specific activities of cytochrome c reductase (1.6-fold), ethoxycoumarin O-deethylase (2.3-fold), aminopyrine N-demethylase (3.0-fold), microsomal epoxide hydrolase (2.6-fold), and glutathione S-transferase (2.9-fold). The induction potency of dicofol was equivalent to Kelthane, DDT, and PhB at equimolar (59.0 mM) concentrations of chemical.     

A comparison of permethrin and methomyl insecticides for the control of a multiresistant strain of houseflies (Musca domestica)

A methomyl sugar bait formulation and permethrin residual spray were compared for the control of a multi-insecticide resistant strain of housefly in a UK pig farm. The methomyl was applied as a granular scatter bait at the manufacturer's recommended rate of 25 mg m^?2 active ingredient (a.i.) to the treated floor area. Permethrin was applied at 32, 64 and 128 mg m^?2 a.i. to structural surfaces. The highest deposit rate of permethrin used was four times that recommended by the manufacturer for the control of flying insects. The methomyl bait gave effective control but the permethrin spray failed at all deposit rates tested. The use of permethrin increased resistance to this compound at the KD50 level from x 13 to x 560 within 10 weeks and significantly increased the proportion of flies resistant to natural pyrethrins synergised with piperonyl butoxide (P<0.01).     

灭多威对果蝇胚胎S2和人肝癌HepG2细胞的遗传毒性研究

灭多威对环境中非靶标生物的毒性作用广受关注。选用果蝇胚胎S2细胞和人肝癌HepG2细胞为研究对象,采用噻唑蓝(MTT)细胞活力测定、单细胞彗星电泳和磷酸化组蛋白(γH2AX)免疫荧光印迹等方法研究了灭多威的细胞毒性。结果表明:随着灭多威浓度的升高,S2和HepG2细胞活力均呈逐渐下降趋势;两种细胞均出现显著的彗星现象,且彗星尾长增加,尾部面积增大;γH2AX阳性细胞百分率逐渐增大。表明果蝇S2和人HepG2细胞DNA受损程度随着灭多威剂量的增大而加重,灭多威可诱导细胞DNA双链断裂,最终导致细胞凋亡。灭多威具有潜在的基因毒性,长时间接触会损害人类健康。     

The structural rearrangement of iprodione in ethanolic solution

Iprodione, in ethanolic solution, was found to undergo structural rearrangement over a period of days to give a solid product which was shown by mass spectrometry to be an isomer. Mechanistic considerations led to a proposed structure, which was verified by synthesis of an authentic specimen by an unambiguous route. The biological implications of these findings are discussed.     

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.     

The metabolism of benodanil in the rat

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.     

The metabolism of tefluthrin in the goat

A goat was dosed orally with [¹⁴C]tefluthrin, twice daily for 4 days, at a rate equivalent to 10.9 mg kg^?1 in its diet. Within 16 h of the final dose, 70.1% of the dose had been excreted (urine 41.4%, faeces 28.7%). Extensive metabolism occurred in the goat by ester cleavage and oxidation at a variety of positions on the molecule. Low radioactive residues were detected in the milk (0.076 mg kg^?1), fat (0.076 mg kg^?1) and muscle (0.016 mg kg^?1), with tefluthrin as the largest individual component of the residue (milk 66.5%, fat 76.7%, muscle 34.2%). Higher residues were present in the kidney (0.3 mg kg^?1) and liver (1.0 mg kg^?1) and only a small percentage of this residue was due to tefluthrin (kidney 3.4%, liver 6.1%). The remainder of the residue in the kidney and liver was a complex mixture of metabolites. Most of the kidney metabolites were identified, but a high proportion of the liver residue was due to six unidentified polar compounds.     

Toxicity and metabolism of carbaryl in the European corn borer

Larvae from two strains of the European corn borer, Ostrinia nubilalis (Hübner), were compared for differences in their tolerance and metabolism of carbaryl (1-naphthyl N-methylcarbamate). The Geneva strain was about twice as susceptible to carbaryl, but both Valley and Geneva borers converted carbaryl to oxidative metabolites at similar rates in vivo and in vitro. Maximum carbaryl-metabolizing activity was present in last-instar larvae, particularly in the fat body and gut tissues. However, the specific activity of gut homogenates was highest in the Geneva strain and the specific activity of fat body was highest in the Valley strain. Other differences in the mixed-function oxidase systems of gut and fat body were also found. The major metabolite in vivo and in vitro was hydroxymethyl carbaryl.