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.     

Metabolism of precocene II in the cabbage looper and European corn borer

A comparison of different tissues indicated that fat bodies of both the cabbage looper (Trichoplusia ni Hubner) and the European corn borer (Ostrinia nubilalis Hubner) fifth-instar larvae possessed the greatest in vitro metabolic activity towards the anti-juvenile hormone, precocene II (6,7-dimethoxy-2,2-dimethylchromene). Although the metabolic pathway suggested possible involvement of an epoxide hydratase, addition of epoxide hydratase inhibitors to incubation mixtures containing fat body homogenates of either species did not result in an accumulation of intermediate metabolites. However, all of the compounds tested inhibited metabolism of precocene II by mixed-function oxidase(s) as follows: 1,1,1-trichloropropane-2,3-epoxide, 14%; 1,2,3,4-tetradydronapthalene-1,2-epoxide, 63 to 74%; 2,2-bis[4-(2,3-epoxypropyloxy)phenyl] propane, 39 to 63%; cyclohexane oxide, 23 to 63%; and 1-(4-propargylphenoxy)-2,3-epoxypropane, 85 to 92%.     

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.     

Metabolism of fenitrothion by organophosphorus-resistant and -susceptible house flies, Musca domestica L

The metabolism of fenitrothion was investigated in highly resistant (Akita-f) and susceptible (SRS) strains of the house fly, Musca domestica L. The Akita-f strain was 3500 times more resistant to fenitrothion than the SRS strain. Fenitrothion, topically applied to the flies, was metabolized in vivo far faster in the Akita-f strain than in the SRS strain. In vitro studies revealed that fenitrothion was metabolized by a cytochrome P-450-dependent monooxygenase system and glutathione S-transferases. The former oxidase system metabolized fenitrothion in vitro into fenitrooxon and 3-methyl-4-nitrophenol as major metabolites, and into 3-hydroxymethyl-fenitrothion and 3-hydroxymethyl-fenitrooxon as minor metabolites. Glutathione S-transferases metabolized fenitrothion into desmethylfenitrothion. The cytochrome P-450-dependent monooxygenase system and glutathione S-transferases of the resistant Akita-f strain had 1.4 to 2.2 times and 9.7 times, respectively, as great activities as those of the susceptible SRS strain. These results suggest the importance of glutathione S-transferases in fenitrothion resistance in the Akita-f strain.     

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.     

Effect of hepatic enzyme inducers on the in vivo and in vitro metabolism of dicrotophos,dimethoate, and phosphamidon in mice

Daily 75 mg/kg phenobarbital ip injections for 3 days or 25 ppm dieldrin in the diet of mice for 14 days caused an increase in liver cytochrome P-450 and blood B-esterase. Liver A-esterase was not significantly increased. Under in vitro conditions, phenobarbital and dieldrin induced the oxidative as well as hydrolytic metabolism of dicrotophos, dimethoate, and phosphamidon by liver homogenates or combined microsomes plus 105,000g supernatant fractions. The concentration of dimethoxon was increased more than fourfold by the pretreatments after incubation for 4 hr at 37.5°C with NADPH added. The organophosphorus insecticides used in this study were not metabolized as well by the liver microsomes alone or 105,000g supernatant alone, as by the combination of microsomes and 105,000g supernatant. Under in vivo conditions in mice, phenobarbital and dieldrin treatments increased the urinary recovery of metabolites in the initial 6 hr after [¹⁴C]carbonyl-dimethoate or [¹⁴C]N-ethyl-phosphamidon administration. Analysis of urine showed that the inducers caused a more than sixfold increase in dimethoxon recovered and twofold increase in water-soluble nontoxic metabolites within 6 hr after dimethoate administration. With phosphamidon both inducers increased the rate of metabolism, and the total recovery in aqueous and chloroform fractions was decreased. These results suggest that increased dimethoate toxicity after phenobarbital and dieldrin treatments in whole animals results from stimulation of the activation of dimethoate to dimethoxon, while the increase in hydrolytic products after both pretreatments results in decreased toxicity of the direct acetylcholinesterase inhibitors, dicrotophos and phosphamidon.     

Root exudation of prometryn and its metabolites from Chinese celery (Apium graveolens)

Root exudates from Chinese celery (Apium graveolens) and Chinese cabbage (pak choi, Brassica chinensis) plants treated by prometryn, an herbicide, were qualitatively and quantitatively investigated and compared under hydroponic cultivation. Prometryn and its metabolites released into the nutrient solution were analyzed by ultra-performance liquid chromatograph coupled with orbitrap mass spectrometer to investigate whether this xylem-mobile herbicide is exuded from the roots. The results showed that celery and pak choi had different root exudation profiles. Celery metabolized prometryn to prometryn sulfoxide and released both compounds from the roots. In contrast, pak choi barely metabolized or actively released prometryn from the roots. The concentration of prometryn sulfoxide released from celery after 96 hr was 21 µg/L, which was nearly one-third that of released prometryn. Our results indicate that the root exudation and translocation of xylem-mobile herbicides could be significant in plants and are highly species dependent compared with phloem-mobile herbicides.     

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.     

Mode of entry of oxime carbamates into insects

The outcome of our earlier work suggested that the transport of contact insecticides into insects does not involve the haemolymph, but that the chemical probably reaches the internal organs by migrating in and/or over integumental tissue. This applies to various insects having quite different integumental organisation, and to various groups of insecticides differing widely in physical and chemical characteristics. The present work has shown that carbamates (1-alkylthioacetaldoxime carbamates) with high water solubility are no exception. The permeability of the body wall of the housefly for the methyl homologue (methomyl) which is the most water-soluble of the series, although relatively high, is not high enough to account for the toxicity of the compound if it followed the haemolymph route. Methomyl when injected with water instead of an organic solvent was also found to be less toxic than the equivalent amount topically applied. Lateral migration in the integument could be demonstrated with all the carbamates tested and dissimilarities in rates were apparent. Methomyl migrated the most rapidly and the cyanomethylene homologue the most slowly. Differences in mobility may be partly responsible for inequality in toxic effect, but it is thought that metabolic detoxication is of over-riding importance.     

N-Dealkylation of atrazine and simazine in Senecio vulgaris biotypes: A major degradation pathway

Separate populations of Senecio vulgaris were found that evolved partial tolerance to s-triazine herbicides and others that were totally resistant (plastid resistance). In plants from the susceptible, tolerant, and resistant populations, about one half of applied [¹⁴C]atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) was rapidly N-dealkylated to the des-ethyl and des-isopropyl products. These products were relatively inactive in inhibiting photosystem II and did not compete with atrazine. After 6 days, less than 25% of the applied [¹⁴C]atrazine was metabolized to water-soluble degradation products but they were not 2-hydroxy derivatives. Less than 2% of the applied atrazine was incorporated into methanol-insoluble residues. The results on metabolism do not explain the tolerance of Senecio to atrazine. However, our results show that N-dealkylation of the s-triazines is more active than previously reported.     

Degradation of fluometuron by Rhizoctonia solani

Degradation studies of fluometuron [Cotoran, 1,1-dimethyl-3-(α,α,α-trifluoro-m-tolyl)urea] by Rhizoctonia solani have been conducted to elucidate further the pathway of degradation. Analysis by thin-layer chromatography and autoradiography demonstrated that R. solani degraded 88% of fluometuron (¹⁴CF_3^?) into seven nonpolar metabolites after 35 days of incubation. Trace amounts of polar, water-soluble products were detected, but no ¹⁴CO₂ or radioactive volatile products were detected. Two of the major metabolites were identified by thin-layer chromatography and ultraviolet spectroscopy as 1-methyl-3-(α,α,α-trifluorotolyl)urea and (3-trifluoromethylphenyl)urea, which indicated a stepwise demethylation of fluometuron. The remaining five metabolites have not been identified and have not been previously reported in the literature. Time course experiments and metabolite degradative studies indicated that the sequence of degradation involved a multibranched pathway which did not include CO₂ evolution. The proposed pathway does not include the conversion of fluometuron to the aniline derivative as has been reported for other urea herbicides. All of the data from this study indicate the incomplete degradation of fluometuron which suggests a cometabolic degradative pathway.     

Insect pyrethroid-hydrolyzing esterases

Esterases in acetone powder preparations of milkweed bugs, cockroaches, houseflies, cabbage loopers, mealworms, and mouse liver hydrolyze the (+)-trans- and (+)-cis-isomers of resmethrin and tetramethrin but they do not hydrolyze S-bioallethrin. Homogenate fractions are less suitable than acetone powders for assaying the insect esterases due to interfering reactions or inhibitors. The milkweed bug, looper and mouse liver esterases cleave the trans-isomers more rapidly than the cis-isomers of resmethrin and tetramethrin but this isomer specificity is less prominent or not present with the other esterase sources. Pyrethroid-hydrolyzing esterases are much less active in insect than in mouse liver preparations. 1-Naphthyl N-propylcabamate is a more potent inhibitor than S,S,S-tributyl phosphorotrithioate for the insect esterases whereas the latter compound is more effective in inhibiting the mouse esterases. Both of these chemicals are noncompetitive inhibitors in each case suggesting that they carbamoylate and phosphorylate the detoxifying enzymes. Esterase inhibitors acting in the nmolar range may be useful synergists in species where pyrethroid detoxification by esterases limits the insecticidal action.     

In vitro metabolism of EPN and EPNO in susceptible and resistant strains of house flies

EPN is twice as toxic as EPNO to house flies from both the Diazinon-resistant strain and the susceptible strain. EPN and EPNO are also eight times more toxic to the susceptible than the resistant strain. This is due to the ability of the resistant strain to metabolize these compounds to a greater extent. Metabolism by the glutathione S-transferases present in the 100,000g supernatant is more extensive than that by the NADPH-dependent microsomal mixed-function oxidases. The glutathione S-transferases are the major route of metabolism for EPN and appear to be the principal mechanism conferring resistance. EPN was metabolized by the microsomal fraction via oxidative desulfuration to the oxygen analog, EPNO, and by oxidative dearylation to p-nitrophenol. EPNO was metabolized by the same system to p-nitrophenol and desethyl EPNO as well as to an unknown metabolite. The soluble fraction metabolized EPN to p-nitrophenol, S-(p-nitrophenyl)glutathione, O-ethyl phenylphosphonothioic acid, and S-(O-ethyl phenylphosphonothionyl)glutathione. The identification of the latter conjugate demonstrates a new type of metabolite of organophosphorus compounds. EPNO was metabolized by the soluble fraction to p-nitrophenol and S-(p-nitrophenyl)glutathione.     

Resistance in the highly DDT-resistant 91-R strain of Drosophila melanogaster involves decreased penetration,increased metabolism,and direct excretion

Resistance to 4,4′-dichlorodiphenyltrichloroethane (DDT) in the 91-R strain of Drosophila melanogaster is extremely high compared to the susceptible Canton-S strain (>1500 times). In addition to enhanced oxidative detoxification, the 91-R strain also has a reduced rate of DDT penetration, increased levels of reductive and conjugative metabolism, and substantially more excretion than the Canton-S strain. Contact penetration of DDT was ∼30% less with 91-R flies, which also had significantly more cuticular hydrocarbons and a thicker, more laminated cuticle compared to Canton-S flies, possibly resulting in penetration differences. DDT was metabolized ∼1.6-fold more extensively by 91-R than Canton-S flies, resulting in dichlorodiphenyldichloroethane (DDD), two unidentified metabolites and polar conjugates being formed in significantly greater amounts. 91-R flies also excreted ∼4-fold more DDT and metabolites than Canton-S flies. Verapamil pretreatment reduced the LD₅₀ value for 91-R flies topically dosed with DDT by a factor of 10-fold, indicating that the increased excretion may involve, in part, ATP-binding cassette (ABC) transporters. In summary, DDT resistance in 91-R is polyfactorial and includes reduced penetration, increased detoxification and direct excretion.     

The mechanism of bentazon selectivity

Absorption, translocation and metabolism of [¹⁴C]3-isopropyl-2,1,3-benzothiadiazin-4-one-2,2-dioxide (bentazon) by several plant species were investigated to determine the mechanism of bentazon selectivity.Marked selective phytotoxicities were observed between resistant rice (Oryza sativa L.) and susceptible Cyperus serotinus Rottb. when treated with bentazon. Absorption and transolcation of bentazon did not differ greatly between highly resistant rice and susceptible C. serotinus. However, a marked difference in bentazon metabolism occurred between the two species. In rice about 80% of the absorbed bentazon was metabolized within 24 h, and after 7 days about 85% was converted to a major water-soluble metabolite and unchanged bentazon was only 5%. In C. serotinus 50–75% of the radioactivity was unchanged bentazon after 7 days.Large amounts of water-soluble metabolites were detected in root-treated resistant plants such as barnyardgrass (Echinochloa crus-galli Beauv.), soybean (Glycine max Merr.) and corn (Zea mays L.), but only small amounts were present in such susceptible plants as Sagittaria pygmaea Miq. and Eleocharis kuroguwai Ohwi. Therefore, the mechanism of bentazon selectivity appears to be a difference between resistant and susceptible species in their ability to metabolize and detoxify bentazon.The major metabolite in rice was identified as 6-(3-isopropyl-2,1,3-benzothiadiazin-4-one-2,2-dioxide)-O-β-glucopyranoside, determined by GC-MS, NMR, IR and gas chromatography after hydrolysis with sulfuric acid or β-glucosidase.     

Host-based life cycle traits and detoxification enzymes of major looper pests (Lepidoptera: Geometridae) of tea from Darjeeling Terai,India

Three polyphagous looper caterpillars, Buzura suppressaria Guenée, Hyposidra talaca Walker and Hyposidra infixaria Walker, have established themselves as severe pests of tea [Camellia sinensis (L.) Kuntze] in the plantations of sub Himalayan West Bengal (Terai region). Schima wallichii (DC.) Korth. is a naturally occurring alternative host of all these looper species. To gain an insight into looper and host plant relationships, the present work contemplates studies on host preference, host-based life cycle traits and levels of detoxification enzymes, such as general esterases (GEs) and glutathione S-transferases (GSTs). From the study, host-induction of feeding preference was evident in all the three looper species. Hyposidra spp. exhibited similar post-embryonic development periods both on tea and S. wallichii, whereas B. suppressaria reared on tea needed a longer development period than on S. wallichii. Tea-reared caterpillars of Hyposidra spp. were significantly heavier, having higher quantities of GEs and GSTs than S. wallichii-reared ones. B. suppressaria, however, exhibited similar body weights on tea and S. wallichii. While GST level was higher in tea-reared B. suppressaria, its GE quantity was higher on S. wallichii. Although tea was found to be a more suitable host for Hyposidra spp., the host S. wallichii proved marginally better than tea for supporting B. suppressaria. However, all the three looper species could utilize the foliage of tea and S. wallichii successfully. So S. wallichii trees can act as a sylvan reservoir of the looper species, prompting their possible invasion of tea plantations and thus making management of looper pests in tea more difficult.     

Interaction of acetic acid and phenylacetaldehyde as attractants for trapping pest species of moths (Lepidoptera: Noctuidae)

BACKGROUND: Phenylacetaldehyde is a flower volatile and attractant for many nectar‐seeking moths. Acetic acid is a microbial fermentation product that is present in insect sweet baits. It is weakly attractive to some moths and other insects, but can be additive or synergistic with other compounds to make more powerful insect lures. RESULTS: Acetic acid and phenylacetaldehyde presented together in traps made a stronger lure than either chemical alone for moths of the alfalfa looper Autographa californica (Speyer) and the armyworm Spodoptera albula (Walker). However, this combination of chemicals reduced captures of the cabbage looper moth Trichoplusia ni (Hübner), the silver Y moth Autographa gamma (L.), MacDunnoughia confusa (Stephens) and the soybean looper moth Chrysodeixis includens (Walker) by comparison with phenylacetaldehyde alone. CONCLUSION: These results indicate both positive and negative interactions of acetic acid, a sugar fermentation odor cue, and phenylacetaldehyde, a floral scent cue, in eliciting orientation responses of moths. This research provides a new two‐component lure for the alfalfa looper A. californica and for the armyworm S. albula for potential use in pest management. Copyright © 2012 Society of Chemical Industry     

Pesticide interactions: Effects of organophosphorus pesticides on the metabolism,toxicity, and persistence of selected pyrethroid insecticides

The organophosphorus pesticides profenofos, sulprofos, O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN), and S,S,S,-tributyl phosphorotrithioate (DEF) administered intraperitoneally to mice at 0.5 to 5 mg/kg strongly inhibit the liver microsomal esterase(s) hydrolyzing trans-permethrin. Profenofos, EPN, and DEF at 25 mg/kg increase the intraperitoneal toxicity of fenvalerate > 25-fold and of malathion > 100-fold. Topically applied profenofos, sulprofos, and DEF significantly synergize the toxicity of cis-cypermethrin to cabbage looper larvae and house fly adults but these phosphorus compounds are much less effective in synergizing the toxicity of trans-permethrin. The magnitude of synergism appears to depend on the species, organophosphorus compound, and pyrethroid involved. Profenofos, sulprofos, and EPN do not significantly alter the persistence of trans-permethrin on bean foliage.     

Biotransformations of photoheptachlor in the rat: II. Analysis and origin of major metabolites

The metabolites isolated and purified from the excreta of the rats treated with [¹⁴C]photoheptachlor were analyzed by gc-mass spectrometry. Molecular structure of two of the major metabolites indicated that they were produced by hydroxylations at two different CCl bonds of photoheptachlor. One of these metabolites was conjugated with glucuronic acid, the other with an unknown compound. Hepatic origin of the products was shown by concordance of the in vitro and in vivo study. Most of the radioactivity in fat, skin, liver, kidney, and muscle tissues of male and female rats was organosoluble containing photoheptachlor and its nonpolar metabolites.     

Metabolic conversion of methyl benzimidazol-2-yl carbamate (MBC) in Aspergillus nidulans

Methyl benzimidazol-2-yl carbamate was metabolized by Aspergillus nidulans mycelium to two metabolites, one of which was identified as methyl 5-hydroxybenzimidazol-2-yl carbamate. This compound was further converted to a second metabolite which was not identified. Conversion rate was highest when the culture medium was depleted of nutrients. Especially in aged concentrated mycelial suspensions conversion was rapid and complete. Since strains differing in MBC sensitivity metabolized MBC at equal rates, conversion of MBC to the nonfungitoxic metabolites has no bearing on the mechanism of resistance to this compound.