Penetration and metabolism of topically applied permethrin and cypermethrin in pyrethroid-tolerant Wiseana cervinata larvae

The penetration, excretion, and metabolism of topically applied [¹⁴C]permethrin and [¹⁴C]cypermethrin have been examined in larvae of the porina moth Wiseana cervinata to determine the factors which affect body levels of unchanged pyrethroids. Metabolism was by hydrolysis and to a lesser extent oxidation and the primary metabolites were quickly conjugated to water-soluble products. Little excretion occurred and body levels of unchanged pyrethroids were dependent on the interaction of penetration and metabolism. cis-Cypermethrin was more resistant to metabolism than trans-cypermethrin and cis- and trans-permethrin. trans-Permethrin most readily penetrated into larvae. The body levels of unchanged permethrin were enhanced by pretreatment of larvae with the metabolic inhibitors carbaryl or piperonyl butoxide. Tolerance of the pasture pest porina to the synthetic pyrethroids is discussed in relation to these findings.     

Antifeeding effect of cypermethrin and permethrin at sub-lethal levels against Pieris brassicae larvae

An antifeeding (feeding deterrent) response by first- and fifth-instar larvae of Pieris brassicae was shown to be significant at sub-lethal levels of cypermethrin and permethrin, using leaf-discs treated with the pyrethroids by dipping. Permethrin was slightly more effective than cypermethrin both as an insecticide and as an antifeedant against fifth-instar larvae, but the reverse order of effectiveness was observed, with a marked difference in mortality, against newly-hatched larvae. When 1-day-old fifth-instar larvae were continuously given leaf discs treated with a solution of the pyrethroid (1 mg litre^?1), up to the time of pupation, both cypermethrin and permethrin induced a significant extension of the larval period, with a reduction in the maximum larval and pupal weights, as well as a reduction in the total leaf-area consumed. However, at higher levels of both pyrethroids, lowering the temperature induced some irritancy, as indicated by regurgitation and frequent uncoordinated wriggling movements of the fifth-instar larvae. The advantages of cypermethrin as a protectant and as an antifeedant over permethrin are discussed.     

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.     

Repellent action of permethrin,cypermethrin and resmethrin against black flies (Simulium spp.) attacking cattle

Permethrin, cypermethrin, and resmethrin were tested under field conditions as repellents to protect cattle from black flies (Simulium spp.). The chemicals were applied topically to the entire body surface of steers. Ethanolic solutions of technical permethrin, at doses of 1, 2, 4 and 6 mg a. i. kg^?1 of body weight, effectively repelled black flies by preventing at least 70% of the flies present from taking a blood meal for up to 8 days, and for at least 11 days at a dose of 12 mg a. i. kg^?1. Aqueous mixtures of a 20% permethrin emulsifiable concentrate (e. c.), at doses of 1, 2 and 6 mg a. i. kg^?1, effectivelyrepelled black flies for 2, 10 and 11 days, respectively. Aready-to-use 5% permethrin dust, at doses of 1, 2, and 4 mg a. i. kg^?1, effectively repelled black flies for 4, 5 and 8 days, respectively. Ethanolic solutions of technical cypermethrin, at doses of 1 and 2 mg a. i. kg^?1, repelled black flies for 3 and 4 days, respectively. Aqueous mixtures of a 40% cypermethrin e. c., at doses of 2 and 4 mg a. i. kg^?1, repelled black flies for at least 5 days. Ethanolic solutions of technical resmethrin, at doses of 2 and 6 mg a. i. kg^?1, repelled black flies for 1 and 2 days, respectively.     

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 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.     

Nerve insensitivity resistance to cypermethrin in larvae of the tobacco budworm Heliothis virescens from USA cotton field populations

Spontaneous neuronal activity was recorded from the peripheral nerves of third-instar larvae of strains of Heliothis virescens (F.) obtained directly from cotton fields in the USA. Following a control period the preparations were exposed to increasing concentrations of cis-cypermethrin in a cumulative dose-response assay. A positive response was defined as an increase of at least five-fold in the rate of neuronal activity over that seen during the control period. Up to 35 individuals of each strain were assayed and the responses used to construct a phenotypic profile categorising the individuals from nerve-susceptible to highly nerve-insensitive. An EC₅₀ for the action of cis-cypermethrin was also obtained. There was a positive, significant correlation between non-synergisable resistance to cypermethrin and nerve insensitivity as defined in the neurophysiological assay. It was shown that nerve insensitivity to cypermethrin increased throughout the cotton-growing season.     

Toxicology and metabolism of chloromethiuron in Boophilus microplus larvae

The toxicity of the acaricide chloromethiuron, 3-(4-chloro-o-tolyl)-1,1-dimethyl- (thiourea), and of nine related compounds to Boophilus microplus larvae was determined by a spray-tower method. Four of these compounds were toxic but only chloromethiuron and its N-demethyl derivative were of practical importance. Metabolism of [¹⁴C]chloromethiuron, in the formamidine-susceptible but organo-phosphorus-resistant Mt. Alford strain, was compared with that in a chlordimeform-selected Mt. Alford strain, which in laboratory tests was two to three times resistant to chloromethiuron, chlordimeform and amitraz. The latter strain produced smaller quantities of the toxic N-demethyl derivative than the Mt. Alford strain; this was the only resistance mechanism determined. Rates of degradation of chloromethiuron were the same in both strains. Piperonyl butoxide strongly antagonised the toxicity of chloromethiuron by 18 to 33 times and depressed the production of the N-demethyl derivative in both strains (0.3 times that of the control), while degradation rates of chloromethiuron itself were halved by piperonyl butoxide in both strains. These results indicated that the parent material was not toxic until oxidised to the N-demethyl derivative. As, in addition, some symptoms of chloromethiuron toxicosis in larvae were similar to those caused by formamidine acaricides, a common mode of lethal action is suggested.     

Simultaneous recording of neurophysiological effects and toxicological symptoms of cypermethrin poisoning in intact larvae of Spodoptera littoralis boisd

A method is described for simultaneous recording of in-vivo nerve activity and toxicological symptoms from 6th-instar larvae of Spodoptera littoralis poisoned with insecticide. Topically applied doses (9 ng-180 μg insect^?1) of cypermethrin induced hyperactivity, repetitive activity and bursting in the ventral nerve cord; these activities were associated with different stages of poisoning in the whole animal and are consistent with pharmacokinetic studies. Nerve activity continued long after the larvae appeared to be dead (i.e. up to 5-6 days), although microscopic examination of these larvae revealed that they were still capable of small movements. At the lower doses (up to the LD₉₅) time to death was inversely proportional to dose. Death of the organism may be related to the number of neurones which are affected by the insecticide.     

Neurophysiological studies of the effects of permethrin upon pyrethroid resistant (kdr) and susceptible strains of dipteran larvae

Permethrin at concentrations as high as 10^?6 had no detectable effect upon neuromuscular transmission at 20-21°C in the body-wall muscles of susceptible larvae of Lucilia sericata and susceptible and resistant (kdr) strains of larvae of Musca domestica. At the higher concentrations of 5 × 10^?6M, muscle cells in all strains and species of larva were slowly depolarised, resulting in failure of neuromuscular transmission when the level of depolarisation corresponded with the peak height of the postsynaptic potentials. Multiple postsynaptic potentials were sometimes obtained in response to a single electrical stimulus to the motor axon. Neither of these effects is considered to result from interference with release of the neurotransmitter or its binding to the postsynaptic receptors. Spontaneous activity in sensory nerve fibres from susceptible larvae was increased followed by intermittent bursting and block at concentrations of permethrin as low as 10^?9M at 20-21°C and 10^?10 at 26°C. Resistant larvae of M. domestica were 1000 times less sensitive, needing concentrations of permethrin as high as 10^?6M at 20-21°C and 10^?7M at 26°C to affect sensory discharge. The results are discussed in relationship to the cause of knockdown by pyrethroid insecticides and to possible changes in the nervous system which may be brought about by the kdr resistance factor.     

Influence of application methods on the degradation of permethrin in laboratory,soil aerobic metabolism studies

The effects of application rate, volume, solvent and soil moisture content on the kinetics of mineralization and degradation, of [¹⁴C] permethrin have been studied in a sandy loam soil under standard laboratory conditions. During the incubation period, up to 32 days, the temperature and moisture level of the soil were controlled. Apart from the effects of application rate, which have been widely reported, application volume had the most significant effect on mineralization rate and T_1/2. [¹⁴C]Permethrin, at a level of a 1 mg kg^?1 in the soil, applied in 100 μl of methanol, resulted in the evolution of 14% of the applied radiochemical as [¹⁴C] carbon dioxide over 30 days. The same level applied in 1000 μl mineralized at a faster rate, with 30% [¹⁴C]carbon dioxide evolved over 30 days. The test chemical applied to soil in methanol mineralized at a significantly faster rate than a similar concentration applied in ethanol. There was no significant difference when comparing applications made using acetonitrile with those using methanol or ethanol. The addition of formulation ingredients resulted in little or no variation in mineralisation rate compared to an equivalent application volume of methanol/water.     

Absorption,translocation and metabolism of the herbicide naproanilide in tobacco

Naproanilide [2-(2-naphthyloxy)propionanilide] has a high activity against dicotyledonous weeds in rice fields, but is very safe to rice. This study was designed to clarify the absorption and translocation of radiolabelled naproanilide in tobacco plants and the metabolism in tobacco callus. The results indicated that naproanilide is translocated easily to the upper part of tobacco plants. Distribution of radioactivity in tobacco plants at the 7th day was shown to be 0.88, 0.24 and 0.03%, and at the 14th day 1.71, 1.86 and 2.32% of the total activities of [¹⁴C]naproanilide in root, stem and leaf, respectively. When compared to earlier results obtained with rice, the translocation rate in tobacco is much higher and might therefore contribute a possible mechanism of herbicidal selectivity. Metabolites including NOP [2-(2-naphthyloxy)propionic acid], NOPM [methyl 2-(2-naphthyloxy)propionate], 2-naphthol, 2,3-naphthalenediol, 2,6-naphthalenediol, 2,7-naphthalenediol and 2-hydroxy-1,4-naphthoquinone were identified in tobacco callus by co-chromatography.     

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.     

Absorption,metabolism and excretion of the fungicide triforine in the rat

Eighty per cent of orally administered triforine is absorbed by the rat. Maximum blood levels are reached 4 h after administration. After complete metabolic conversion has occurred, the fungicide absorbed is excreted mainly in the urine as a metabolite, N-[2,2,2-trichloro-1-(piperazin-1-yl)ethyl]formamide. Elimination is complete with most of the compound being excreted during the first 24 h following administration.     

Absorption, translocation and metabolism of metamitron in Chenopodium album

BACKGROUND: In recent years, common lambsquarters (Chenopodium album L.) populations from sugar beet fields in different European countries have responded as resistant to the as‐triazinone metamitron. The populations have been found to have the same D1 point mutation as known for atrazine‐resistant biotypes (Ser₂₆₄ to Gly). However, pot experiments revealed that metamitron resistance is not as clear‐cut as observed with triazine resistance in the past. The objectives of this study were to clarify the absorption, translocation and metabolic fate of metamitron in C. album. RESULTS: Root absorption and foliar absorption experiments showed minor differences in absorption, translocation and metabolism of metamitron between the susceptible and resistant C. album populations. A rapid metabolism in the C. album populations was observed when metamitron was absorbed by the roots. The primary products of metamitron metabolism were identified as deamino‐metamitron and metamitron‐N‐glucoside. PABA, known to inhibit the deamination of metribuzin, did not alter the metabolism of metamitron, and nor did the cytochrome P450 inhibitor PBO. However, inhibition of metamitron metabolism in the presence of the cytochrome P450 inhibitor ABT was demonstrated. CONCLUSION: Metamitron metabolism in C. album may act as a basic tolerance mechanism, which can be important in circumstances favouring this degradation pathway. Copyright © 2011 Society of Chemical Industry     

Effect of partial plant resistance in brassicas on tolerance of diamondback moth (Plutella xylostella) larvae to cypermethrin

Brassica cultivars with varying degrees of partial plant resistance were fed to larvae (up to 4th instar) of the diamondback moth (DBM), Plutella xylostella, and were bioassayed by topical application of cypermethrin to investigate the interaction of plant resistance with insecticide. Larvae reared on the least preferred brassica, Minicole, showed a significantly higher LD₅₀ value than those on the most preferred brassica, Chinese cabbage. Bioassay of 4th instar DBM larvae fed on artificial diet containing pure compounds of glucosinolates revealed a negative interaction between their susceptibility to cypermethin and certain glucosinolates (in particular sinigrin), suggesting that such compounds induced the production of insecticide-detoxifying enzymes.     

Inhibition of carbaryl metabolism by nitrogen in three species of cockroach and one species of locust

The in vivo release of ¹⁴CO₂ arising from decarbamoylation of [¹⁴C]-carbaryl (1-naphthyl methyl-[¹⁴C]-carbamate) injected into male and female Periplaneta americana, Leucophaea maderae, Gromphadorhina portentosa and Schistocerca gregaria was measured up to 50 nmol carbaryl/g body weight. The amount of ¹⁴CO₂ released was proportional to the dose of [¹⁴C]-carbaryl injected and was similar for both sexes of each species. The KD₅₀ values for carbaryl for each species did not correlate with their ability to decarbamoylate carbaryl. The degradation of carbaryl by this pathway is not therefore the limiting factor in determining the overall toxic effect of carbaryl in the four species studied. Decarbamoylation is inhibited by nitrogen in all four species. In P. americana the inhibition is virtually complete, in L. maderae, G. portentosa and S. gregaria the inhibition is 84%, 74% and 51% respectively. The results suggest the involvement of two enzymes, one of which is oxygen dependent. Decarbamoylation studies in air suggest the involvement of two enzymes with differing K_M values. The involvement of aliesterases and mixed function oxidases in the decarbamoylation pathway(s) have not been established so far with this series of experiments.     

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 6,7-dihydroisodrin by microsomes and southern armyworm larvae

Dihydroisodrin is hydroxylated to 6-exo-hydroxy-6,7-dihydroisodrin in southern armyworm gut and vertebrate liver microsomal preparations. The sedimentation characteristics of the hydroxylase, its requirement for NADPH and oxygen, and its inhibition by carbon monoxide and 4,5,6,7-tetrachloro-1,3-benzodioxole indicate that the enzyme system may be classed as a typical microsomal oxidase. The enzyme system is susceptible to substrate inhibition, but in other respects it is similar to microsomal aldrin epoxidase and p-chloro-N-methylaniline demethylase.