Compatibility of endoparasitoid Hyposoter didymator (Hymenoptera: Ichneumonidae) protected stages with five selected insecticides

Hyposoter didymator (Thunberg) (Hymenoptera: Ichneumonidae) is a koinobiont endoparasitoid that emerges from the parasitization of economically important noctuid pests. H. didymator also is considered one of the most important native biocontrol agents of noctuids in Spain. Side effects of five insecticides with very different modes of action (fipronil, imidacloprid, natural pyrethrins + piperonyl butoxide, pymetrozine, and triflumuron) at the maximum field recommended rate in Spain were evaluated on H. didymator parasitizing Spodoptera littoralis (Boisduval) larvae and pupae of the endoparasitoid. Parasitized larvae were topically treated or ingested treated artificial diet. Parasitoid cocoons were topically treated. Host mortality when parasitized larvae were treated, as well as further development of the parasitoid surviving (e.g., percentage of cocoons spun, adult emergence, hosts attacked, and numbered progeny) were determined. Toxicity after treatment of parasitized larvae differed depending on the mode of exposure and insecticide. Fipronil was always highly toxic; imidacloprid killed all host insects by ingestion, but it was less toxic to both host and parasitoids, when administered topically; natural pyrethrins + piperonyl butoxide and triflumuron showed differing degrees of toxicity, and pymetrozine was harmless. Parasitoid cocoons provided effective protection against all the insecticides, except fipronil.     

Bioassay systems for the pyrethrins; the mode of action of pyrethrum synergists

The components of 'synergistic action' are reviewed in the light of recent work. It has been shown that for sesamin and isobutylundecylenamide at least, synergistic action remains after physical effects are eliminated. The toxicity of the pyrethrins is increased by a factor of three when up to equimolecular proportions of the above synergists are added, further additions having no effect. It is suggested that a surface complex between synergist and insecticide is formed at the peripheral nerve sheath interfaces, resulting in the reorientation of the pyrethrins molecules to give a more efficient discharge of the resting potential at the interface.     

Comparative toxicity of seven insecticides to immature stages of Musca domestica (Diptera: Muscidae) and two of its important biological control agents, Muscidifurax raptor and Spalangia cameroni (Hymenoptera: Pteromalidae)

The toxicity of seven insecticides was evaluated against unparasitized Musca domestica L. pupae and pupae parasitized by Muscidifurax raptor Girault & Sanders or Spalangia cameroni Perkins, two important biological control agents. Only pyrethrins + piperonyl butoxide (Pyrenone) was less toxic to M. raptor compared with house flies. Conversely, all of the insecticides except crotoxyphos were less toxic to S. cameroni compared with house flies. A plateau in the tetrachlorvinphos bioassay line for S. cameroni suggested that this colony had approximately 45% resistant individuals. The selectivity observed between immature stages of house flies and M. raptor or S. cameroni is different from that reported against adult stages of these same species, suggesting that selectivity of an insecticide varies considerably between different life stages.     

Cartap resistance and synergism in populations of Tuta absoluta (Lep., Gelechiidae)

Abstract: Control failures of cartap when used against the tomato leafminer Tuta absoluta (Meyrick) in Brazil and a recent report of cartap resistance in Brazilian populations of this pest species led to the investigation of the possible involvement of detoxification enzymes on this phenomenon using insecticide synergists. The insect populations were collected from seven different sites in the states of Minas Gerais, Rio de Janeiro and São Paulo. These populations were subjected to insecticide-impregnated filter paper assays. The concentration–mortality assays were carried out for cartap alone and in a mixture (1 cartap : 10 synergist) with the synergists diethyl maleate, piperonyl butoxide and triphenylphosphate which, respectively, inhibit the enzymes glutathion-S-transferases, cytochrome P450-dependent monooxygenases and esterases. Resistance to cartap was observed in all populations when compared with the standard susceptible population, with resistance ratios ranging from 2.3- to 21.9-fold. Piperonyl butoxide was the most efficient synergist with cartap synergism ratios ranging from 1.3- to 21.0-fold and nearly completely suppressing the resistance to cartap in all of the populations studied, suggesting a major involvement of cytochrome P450-dependent monooxygenases as a cartap resistance mechanism in these populations of T. absoluta . Diethyl maleate and triphenylphosphate also synergized cartap in nearly every population, and they still provided partial suppression of cartap resistance in the leafminer populations studied. Therefore, glutathion-S-transferases and esterases seem to play a secondary role in cartap resistance in Brazilian populations of T. absoluta .     

Syntheses and Synergistic Activity of Some Pyrethrum Synergists from Dillapiole

In a search for alternative pyrethrum synergists, dillapiole, one of the chief constituents of Indian dill (Anethum sowa Roxb.) seed oil has been converted into a number of derivatives. Syntheses of 16 such compounds, their spectrometric characterization and factors of synergism towards Pyrethrins against Tribolium castaneum Herbst. are being reported. Some of these compounds showed superior activity to piperonyl butoxide, the most commonly used pyrethrum synergist.     

Parathion and methyl parathion toxicity and metabolism in piperonyl butoxide and diethyl maleate pretreated mice

Pretreatment of male mice with piperonyl butoxide, 400 mg/kg 1 h before challenge with insecticides, resulted in a 40-fold antagonism of the acute i.p. toxicity of methyl parathion but potentiated the toxicity of parathion two-fold. Piperonyl butoxide had no effect on the toxicity of the oxygen analogs of these insecticides, methyl paraoxon and paraoxon. Diethyl maleate (1 ml/kg) depleted liver glutathione by 80% after one hour, potentiated the toxicity of both methyl parathion and methyl paraoxon, and partially counteracted the protective effect of piperonyl butoxide on methyl parathion toxicity. Piperonyl butoxide delayed the onset of brain cholinesterase inhibition by parathion. Studies of the metabolism of the insecticides by liver homogenates in vitro demonstrated that piperonyl butoxide inhibited both the oxidative formation of the oxygen analogs (activation) and oxidative cleavage to p-nitrophenol and dialkylphosphorothioic acid (detoxification). While parathion metabolism was mostly oxidative, methyl parathion metabolism appeared to be predominantly via glutathione-dependent enzymes. Studies of in vitro distribution of the insecticides demonstrated that piperonyl butoxide pretreatment resulted in elevated tissue concentrations of parathion and methyl parathion; however, the rate constant for elimination from plasma for both insecticides was unaffected by piperonyl butoxide. The overall rate of metabolism of methyl parathion in vivo was approximately twice that of parathion. These results suggest that during piperonyl butoxide inhibition of oxidative activation and cleavage, methyl parathion detoxification continues through uninhibited glutathione-dependent pathways of metabolism. The net result is a reduction in the acute toxicity of methyl parathion. Lack of an effective alternate pathway of detoxification may explain the delayed but greater toxicity of parathion in piperonyl butoxide pretreated mice.     

A substrate-specific cytochrome P450 monooxygenase, CYP6AB11, from the polyphagous navel orangeworm (Amyelois transitella)

The navel orangeworm Amyelois transitella (Walker) (Lepidoptera: Pyralidae) is a serious pest of many tree crops in California orchards, including almonds, pistachios, walnuts and figs. To understand the molecular mechanisms underlying detoxification of phytochemicals, insecticides and mycotoxins by this species, full-length CYP6AB11 cDNA was isolated from larval midguts using RACE PCR. Phylogenetic analysis of this insect cytochrome P450 monooxygenase established its evolutionary relationship to a P450 that selectively metabolizes imperatorin (a linear furanocoumarin) and myristicin (a natural methylenedioxyphenyl compound) in another lepidopteran species. Metabolic assays conducted with baculovirus-expressed P450 protein, P450 reductase and cytochrome b₅ on 16 compounds, including phytochemicals, mycotoxins, and synthetic pesticides, indicated that CYP6AB11 efficiently metabolizes imperatorin (0.88 pmol/min/pmol P450) and slowly metabolizes piperonyl butoxide (0.11 pmol/min/pmol P450). LC-MS analysis indicated that the imperatorin metabolite is an epoxide generated by oxidation of the double bond in its extended isoprenyl side chain. Predictive structures for CYP6AB11 suggested that its catalytic site contains a doughnut-like constriction over the heme that excludes aromatic rings on substrates and allows only their extended side chains to access the catalytic site. CYP6AB11 can also metabolize the principal insecticide synergist piperonyl butoxide (PBO), a synthetic methylenedioxyphenyl compound, albeit slowly, which raises the possibility that resistance may evolve in this species after exposure to synergists under field conditions.     

Ineffectiveness of over-the-counter total-release foggers against the bed bug (Heteroptera: Cimicidae)

Field-collected bed bugs (Cimex lectularius L.) showed little, if any, adverse effects after 2-h direct exposure to the aerosolized pyrethroid(s) from three over-the-counter total-release foggers ('bug bombs' or 'foggers'); Hotshot Bedbug and Flea Fogger, Spectracide Bug Stop Indoor Fogger, and Eliminator Indoor Fogger. One field-collected population, EPM, was an exception in that there was significant mortality at 5-7 d when bugs out in the open had been exposed to the Spectracide Fogger; mortality was low when these bugs had access to an optional harborage, a situation observed for all field-collected populations when exposed to the three foggers. Even the Harlan strain, the long-term laboratory population that is susceptible to pyrethroids and that served as an internal control in these experiments, was unaffected if the bugs were covered by a thin cloth layer that provided harborage. In residences and other settings, the majority of bed bugs hide in protected sites where they will not be directly contracted by the insecticide mist from foggers. This study provides the first scientific data supporting the position that total-release foggers should not be recommended for control of bed bugs, because 1) many field-collected bed bugs are resistant to pyrethroids, and they are not affected by brief exposure to low concentrations of pyrethrins and/or pyrethroids provided by foggers; and 2) there is minimal, if any, insecticide penetration into typical bed bug harborage sites. This study provides strong evidence that Hotshot Bedbug and Flea Fogger, Spectracide Bug Stop Indoor Fogger, and Eliminator Indoor Fogger were ineffective as bed bug control agents.     

Effects of the synergists piperonyl butoxide and S,S,S-tributyl phosphorotrithioate on propoxur pharmacokinetics in Blattella germanica (Blattodea: Blattellidae).

Effects of the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) on propoxur pharmacokinetics were examined in the German cockroach, Blattella germanica (L.). Treatment of adult male German cockroaches with the cytochrome P450 monooxygenase inhibitor, PBO, or the esterase inhibitor, DEF, increased propoxur toxicity by 2- and 6.8-fold, respectively, implicating hydrolysis as a major detoxification route of propoxur in the German cockroach. However, significant hydrolytic metabolism could not be demonstrated conclusively in vitro resulting in a conflict between in situ bioassay data and in vitro metabolic studies. In vitro propoxur metabolism with NADPH-fortified microsomes produced at least nine metabolites. Formation of metabolites was NADPH-dependent; no quantifiable metabolism was detected with cytosolic fractions. However, microsomal fractions lacking an NADPH source did produce a low, but detectable, quantity of metabolites (1.6 pmol). PBO inhibited NADPH-dependent propoxur metabolism in a dose-dependent fashion, implicating cytochrome P450 monooxygenases as the enzyme system responsible for the metabolism. Interestingly, DEF also inhibited the NADPH-dependent metabolism of propoxur, albeit to a lower extent. Treatment with PBO or DEF also caused a significant reduction in the cuticular penetration rate of propoxur. The data demonstrate that unanticipated effects are possible with synergists and that caution must be exercised when interpreting synergist results.     

Susceptibility of pest Nezara viridula (Heteroptera: Pentatomidae) and parasitoid Trichopoda pennipes (Diptera: Tachinidae) to selected insecticides

Susceptibility of the southern green stink bug, Nezara viridula (L.) (Heteroptera: Pentatomidae), and its endoparasitoid Trichopoda pennipes (F.) (Diptera: Tachinidae) to acetamiprid, cyfluthrin, dicrotophos, indoxacarb, oxamyl, and thiamethoxam was compared in residual and oral toxicity tests. In the residual toxicity test, cyfluthrin, dicrotophos, and oxamyl were highly toxic to N. viridula. Thiamethoxam was moderately toxic to these insects. Each of the four insecticides was highly toxic to T. pennipes after prolonged tarsal contact with dried residues of these chemicals. In the oral toxicity test, where N. viridula fed on food covered with insecticide residues, none of the insecticides were toxic to adults of this stink bug, but acetamiprid, dicrotophos, and thiamethoxam were moderately toxic to the nymphs. In the oral toxicity test, where N. viridula fed on a gel-food containing insecticides, cyfluthrin, dicrotophos, oxamyl, and thiamethoxam were highly toxic to this stink bug. In an oral toxicity test using contaminated sugar water, all of the insecticides were highly toxic to T. pennipes. Because insecticides were as toxic, or more toxic, to T. pennipes than to N. viridula, it is extremely important to conserve this parasitoid by applying these insecticides for control of southern green stink bugs only when the pest reaches economic threshold.     

Mechanisms of resistance to spinosad in the western flower thrip, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae)

Cross‐resistance, resistance mechanisms, and mode of inheritance of spinosad resistance were studied in the western flower thrip, Frankliniella occidentalis (Pergande). Spinosad (naturalyte insecticide) showed low cross‐resistance to prothiophos (organophosphorus insecticide) and chlorphenapyr (respiratory inhibitor) showed some cross‐resistance to thiocyclam (nereistoxin). The synergists PBO (piperonyl butoxide), DEM (diethyl maleate), and DEF (s, s, s‐tributyl phosphorotrithioate) did not show any synergism on the toxicity of spinosad in the resistant strain (ICS), indicating that metabolic‐mediated detoxification was not responsible for the spinosad resistance, suggesting that spinosad may reduce sensitivity of the target site: the nicotinic acetylcholine receptor and GABA receptor. Following reciprocal crosses, dose‐response lines and dominance ratios indicated that spinosad resistance was incompletely dominant and there were no maternal effects. The results of backcross showed that spinosad resistance did not fit a single‐gene hypothesis, suggesting that resistance was influenced by several genes.     

Comparative study of insecticide susceptibility and activities of detoxification enzymes in larvae and adults of cotton bollworm,Heliothis armigera

Susceptibility of moths and larvae of cotton bollworm to ten different insecticides by topical application and their effect on enzymes involved in insecticide detoxification were determined. The moths were more susceptible than larvae to the insecticides tested, with the exception of pyrethroids and sulprofos. Combination of several insecticides with the synergists piperonyl butoxide (PB) and S,S,S-tributylphosphorotrithioate (TBPT) showed that lower level of carbamate and organophosphate toxicity in larvae, as compared to moths, was the result of higher detoxification enzyme activities. Studies of the post-treatment fate of ¹⁴C-labeled malathion and ³H-trans-permethrin indicated that both the cuticular penetration, internal accumulation, and excretion of applied toxicants and their metabolites occurred more rapidly in larvae than in moths. The activities in vitro of esterases, glutathione S-transferases, and monooxygenases were determined but there were no correlations with either toxicity of insecticides or synergistic effect for combination of insecticides with PB and TBPT in moths. © 1996 Wiley-Liss, Inc.     

In vitro glucosylation of 1-naphthol by insects

Glucosylation in insects was investigated using tobacco hornworms (Manduca sexta) as the primary test insect and 1-naphthol-¹⁴C as the substrate. Of 6 common co-factors tested, only UDPG was utilized by the conjugating enzyme system. Neither the hornworm nor housefly enzymes could form the glucuronic acid derivative of 1-naphthol using UDPGA. Centrifugal fractionation of the hornworm homogenates showed that the glucosyltransferase activity was in the 105,000 g soluble fraction. In the housefly, the enzyme activity was associated with the 15,000 g pellet and to a lesser extent with the 105,000 g pellet. In vitro inhibition of the glucosyltransferase by sulphoxide, piperonyl butoxide, and other insecticide synergists was demonstrated.     

Insecticide toxicity, synergism and resistance in the German cockroach (Dictyoptera: Blattellidae)

The toxicity of synergism of and resistance to insecticides in four strains of German cockroach, Blattella germanica (L.), were investigated. Toxicity of nine insecticides by topical application to the susceptible strain varied greater than 2,000-fold, with deltamethrin (LD50 = 0.004 micrograms per cockroach) and malathion (LD50 = 8.4 micrograms per cockroach) being the most and least toxic, respectively. Resistance to pyrethrins (9.5-fold) in the Kenly strain was unaffected by the synergists piperonyl butoxide (PBO) or S,S,S-tributylphosphorotrithioate (DEF), suggesting that the metabolism is not involved in this case. Malathion resistance in the Rutgers strain was suppressible with PBO, implicating oxidative metabolism as a resistance mechanism. The Ectiban-R strain was resistant to all the pyrethroids tested, and cypermethrin resistance was not suppressible with PBO or DEF. These findings support results of previous studies that indicated this train has a kdr-like mechanism. Bendiocarb resistance in both the Kenly and Rutgers strains was partially suppressed by either PBO or DEF, suggesting that oxidative and hydrolytic metabolism are involved in the resistance. Trends between the effects of the synergists on the susceptible versus resistant strains are discussed.     

Toxicity of several insecticide formulations against adult German cockroaches (Dictyoptera: Blattellidae)

Toxicity of bendiocarb, chlorpyrifos, cyfluthrin, cypermethrin, fenvalerate, hydramethylnon, malathion, propetamphos, propoxur, and pyrethrins against the adult German cockroaches, Blattella germanica (L.), was investigated. At LD50, cyfluthrin was the most toxic insecticide to adult males (0.53 microgram/g), adult females (1.2 micrograms/g), and gravid females (0.85 microgram/g). Malathion was the least toxic insecticide to adult males (464.83 micrograms/g), adult females (335.83 micrograms/g), and gravid females (275.90 micrograms/g). Males and gravid females were generally more sensitive than nongravid females to the insecticides that we tested. In tests with malathion, however, males were more tolerant. The order of toxicity of the insecticide classes varied among the stages of adult German cockroaches. The order of toxicity for males and nongravid females was pyrethroids greater than pyrethrins = organophosphates (except malathion) greater than carbamates = amidinohydrazone. The order of toxicity for gravid females was pyrethroids greater than pyrethrins = organophosphates (except malathion) greater than carbamates greater than amidinohydrazone. These differences in toxicity suggest that sex differences should be considered when determining insecticide toxicity for German cockroaches.     

Mechanisms of resistance to DDT and pyrethroids in Patagonian populations of Simulium blackflies

Mixed populations of the pest blackflies Simulium bonaerense Coscarón & Wygodzinsky, S. wolffhuegeli (Enderlein) and S. nigristrigatum Wygodzinsky & Coscarón (Diptera: Simuliidae) are highly resistant to DDT and pyrethroids in the Neuquén Valley, a fruit-growing area of northern Patagonia, Argentina. As these insecticides have not been used for blackfly control, resistance is attributed to exposure to agricultural insecticides. Pre-treatment with the synergist piperonyl butoxide (PBO) reduced both DDT and fenvalerate resistance, indicating that resistance was partly due to monooxygenase inhibition. Pre-treatment with the synergist tribufos to inhibit esterases slightly increased fenvalerate toxicity in the resistant population. Even so, biochemical studies indicated almost three-fold higher esterase activity in the resistant population, compared to the susceptible. Starch gel electrophoresis confirmed higher frequency and staining intensity of esterase electromorphs in the resistant population. Incomplete synergism against metabolic resistance indicates additional involvement of a non-metabolic resistance mechanism, such as target site insensitivity, assumed to be kdr-like in this case. Glutathione S-transferase activities were low and inconsistent, indicating no role in Simulium resistance. Knowing these spectra of insecticide activity and resistance mechanisms facilitates the choice of more effective products for Simulium control and permits better coordination with agrochemical operations.     

Impact of an insecticide resistance strategy for house fly (Diptera: Muscidae) control in intensive animal units in the United Kingdom

A strategy for house fly (Musca domestica L.) control in intensive animal units in the United Kingdom was proposed by the Pesticide Safety Directorate (PSD) of the Ministry of Agriculture, Fisheries and Food in 1993. An advice leaflet was circulated to farmers, and label recommendations for insecticides used to control house flies were altered to prevent their long-term and frequent use. A study was carried out between 1996 and 1998 to gather data on insecticide use and resistance in house fly populations and compared with results from a study carried out in 1990-1992 to assess the impact of the 1993 label recommendations. As in the 1990-1992 study, resistance to methomyl, azamethiphos and pyrethrins + piperonyl butoxide was assessed. Larvicide tests with cyromazine, which had recently been released in the United Kingdom, were also included in this study. Most of the farmers claimed to have received and read the PSD insecticide advice leaflet, and half claimed to have altered insecticide treatments as a result. Comparing results for insecticides used before and after 1993, the proportion of farmers claiming to have used each of the insecticides had decreased. However, there had been no amelioration in resistance to synergised pyrethrins, and the number of house fly populations with reduced response to the insecticide baits had increased between 1990-1992 and 1996-1998. All the house fly populations tested were fully susceptible to cyromazine. There is an urgent need, therefore, to devise new strategies and particularly to minimize the risk of selecting for resistance to cyromazine.     

Effect of synergists on the oral and topical toxicity of azamethiphos to organophosphate-resistant houseflies (Diptera: Muscidae).

Dermal and oral toxicities of azamethiphos were determined in two organophosphate-resistant and one susceptible strain of houseflies, Musca domestica L. The 594vb strain was 1,967-fold more resistant to azamethiphos when compared with the susceptible Chemical Specialties Manufacturers Association (CSMA) strain by dermal application. When the compound was administered orally to the 594vb strain, we observed only a 15-fold resistance. In contrast, the Yachiyo strain, which show 1,500-fold resistance to diazinon and which has known multiple mechanisms for organophosphate resistance, showed only 6-fold resistance to azamethiphos by topical application and 4-fold resistance by oral administration. Azamethiphos administered dermally and orally was equally toxic to the CSMA and Yachiyo strains. However, when azamethiphos was administered to the 594vb strain, the insecticide was 71 times more toxic orally than by the dermal route. This result indicated involvement of a cuticular penetration factor in the resistance mechanism. The effect on azamethiphos toxicity of piperonyl butoxide (PB), an inhibitor of the monooxygenases, and tributylphosphorotrithioate (DEF), an esterase inhibitor, was investigated in the three strains. Pretreatment of the flies with PB, DEF, or PB+DEF before topical application of azamethiphos resulted in a significant decrease in LD50s in all the strains. The degree of synergism, however, varied depending upon the strains and the synergists. Similar results were obtained when azamethiphos was administered orally following pretreatment of the flies with PB+DEF. We attribute the high level of azamethiphos resistance in the 594vb strain partly to increased degradation by oxidative and hydrolytic enzymes. The hydrolytic enzymes are more important, but other factors including reduced cuticular penetration and insensitive acetylcholinesterase may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)     

臭虫的再猖獗、生物学及防治研究进展

由于DDT等现代杀虫剂的问世,臭虫在20世纪40-50年代以后在全球大部分地区尤其是发达国家和地区销声匿迹,但近10多年来臭虫在部分国家和地区重新出现.本文对其再猖獗原因、生物学和行为、饲养、抗药性、监测与防治策略进行了综述,旨在引起国人的重视,对今后臭虫的监测和防治起到抛砖引玉的作用.本文分析了近15年有关温带臭虫Cimex lectulariusL.和热带臭虫C.hemipterus(F.)的研究文献.臭虫再猖獗被认为是因为它对目前使用的杀虫剂例如拟除虫菊酯类等产生抗性以及频繁的地区及国际交往等因素造成的.简单、经济和大规模臭虫种群饲养方法——人工膜饲喂法的研发为我们开展臭虫生物学和生态学研究提供了便利.控制和根除臭虫目前仍较困难,采用害虫综合治理(integrated pest management,IPM)策略,包括臭虫知识宣传、主动监测、非化学防治方法(例如:经常洗涤床上用品、蒸汽熏蒸、热处理、使用床垫罩、在家具腿下放置臭虫拦截装置)、有选择使用杀虫剂以及定期监测及反复防治等措施,可达到很好的防控效果.在我国部分地区,臭虫发生也呈上升趋势,工人宿舍和火车车厢是常见的臭虫为害环境.有必要对我国臭虫发生现状及其抗药性进行调查与监测.还应借鉴国际先进技术,研制出我国适用的、有效的监测工具和防治方法,并根据我国具体国情制定出切实可行的防治标准.同时积极开展臭虫科普宣传,做到早发现、早防治,防止臭虫再猖獗和扩散.     

Effects of a naturally occurring and a synthetic synergist on toxicity of three insecticides and a phytochemical to navel orangeworm (Lepidoptera: Pyralidae)

The navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), is the most destructive lepidopteran pest of almonds [Prunus dulcis (Mill.) D.A.Webb] and pistachios (Pistacia vera L.) in California and is a serious problem in figs (Ficus carica L.) and walnuts (Juglans spp.). In addition to direct damage, larval feeding leaves nuts vulnerable to infection by Aspergillus spp., fungi that produce toxic aflatoxins. A potentially safe and sustainable approach for managing navel orangeworm in orchards may be to use natural essential oil synergists to interfere with this insect's ability to detoxify insecticides and phytochemicals. We tested the effects of a naturally occurring plant-derived chemical, myristicin, and a synthetic inhibitor of cytochrome P450 monooxygenases (P450s), piperonyl butoxide, on the toxicity of three insecticides (alpha-cypermethrin, tau-fluvalinate, and methoxyfenozide [Intrepid]) and a phytochemical (xanthotoxin) to A. transitella. Piperonyl butoxide significantly synergized alpha-cypermethrin and tau-fluvalinate, whereas myristicin synergized only alpha-cypermethrin. Piperonyl butoxide synergized the toxicity of xanthotoxin as early as 72 h after exposure, whereas myristicin synergized xanthotoxin after 120 h. In view of these findings and the limited availability of environmentally safe synthetic insecticides for sustainable management, particularly in organic orchards, myristicin is a potential field treatment in combination with insecticides to reduce both navel orangeworm survival and aflatoxin contamination of nuts. In addition, this study demonstrates that in A. transitella the insect growth regulator methoxyfenozide is not detoxified by P450s.