Occurrence and Significance of Insecticide-Induced Hormesis in Insects

Chapter 8

Downloaded by UNIV OF AUCKLAND on September 18, 2017 | http://pubs.acs.org Publication Date (Web): September 11, 2017 | doi: 10.1021/bk-2017-1249.ch008

Occurrence and Significance of Insecticide-Induced Hormesis in Insects G. Christopher Cutler*,1 and Raul N. C. Guedes2 1Department

of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, P.O. 550, Truro, Nova Scotia, Canada, B2N 5E3 2Department of Entomology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil, 36570-000 *E-mail: [email protected]. Phone: 902-896-2471. Fax: 902-893-1404.

High amounts of stress are harmful to organisms, but in low amounts may stimulate certain biological processes. This biphasic response to a stressor, termed ‘hormesis’, has been seen in many insect taxa following mild exposure to stressors, including insecticides. Insecticide-induced hormesis in arthropods is most often observed as stimulated reproduction, although stimulatory effects on other physiological and behavioral processes have also been reported. Given that insect pests in agricultural settings are often exposed to sub-lethal doses of insecticide, the ramifications of insecticide-induced hormesis for pest outbreaks and insecticide resistance development may be significant. On the other hand, there may be opportunities to use hormetic principles to improve commercial production of insects, or to better understand how beneficial insects like pollinators respond to low doses of insecticide. Keywords: sublethal insecticide exposure; pest outbreaks; preconditioning; insecticide resistance; insect behavior; insect rearing; bees

© 2017 American Chemical Society Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Introduction Insecticides remain important tools in modern crop protection. For example, in the United States an average of more than 90,000 tonnes of insecticidal active ingredient per year were used during the period 1992-2007 (1). This means that insects inhabiting these cropping systems will often be exposed to insecticides. In addition to being exposed to lethal doses of insecticide, exposure to lower doses may lead to any number of sublethal effects on insect physiology and behavior. Traditionally, study of insect response to sublethal doses of insecticide has emphasized inhibitory effects following exposure, such as reduced fecundity, delayed development, decreased longevity, compromised locomotion or learning, and so on (2, 3). However, low-dose pesticide stress can also have modest stimulatory effects on insects. That is, the very chemicals that kill and sub-lethally harm insects at high doses, can at lower doses stimulate certain biological processes. This biphasic dose-response, characterized by high-dose inhibition and low-dose stimulation during or following exposure to a toxicant is termed ‘hormesis’ (4). Hormesis is not a biological phenomenon restricted to insects; it has been observed in a wide range of single-cell and multicellular species, and across multiple levels of biological organization. Hormetic responses are also not limited to chemical stressors such as pesticides, having been widely reported following exposure to low amounts of, for example, temperature stress, ionizing radiation, or heavy metals (4, 5). Such responses are typically depicted as inverted U-shaped curves that reflect increased normal function at certain low doses (e.g., stimulated growth, fecundity), or J-shaped curves that indicate reduced dysfunction at low doses (e.g., reduced carcinogenesis, mutagenesis, disease incidence) (Figure 1). Study of insecticide-induced hormesis – where low doses of insecticide stimulate certain biological processes – and hormesis in general has rapidly increased (6, 7). T.D. Luckey coined the term “hormoligosis” in the 1950s, which he used to describe situations where minute quantities of a stressing agent would stimulate an organism already maintained under stress (e.g., high salt diet, as in Luckey’s study), whereas larger quantities of stressing agent would be harmful to the organism (8, 9). The term has in large part been superseded by “hormesis”, although some entomologists continue to use “hormoligosis” when describing stimulatory responses in insects following insecticide exposure. Irrespective of terminology, it is clear that insect toxicologists are becoming more familiar with the hormesis phenomenon. The data in Table 1 show exponential growth in citations related to hormesis, insects, and pesticides. Table 1 is not exhaustive, as in many instances biological stimulation due to low doses of insecticide is not reported as “hormesis” or “hormoligosis”, and searches based on taxonomic rank of order (e.g., Coloptera, Diptera, etc.) may miss relevant citations that refer only to family or species names. In addition to not being restricted to an particular group of insects, it is also clear that hormesis can be expressed through a number of biological endpoints, life stages, and kinds of insecticidal active ingredients (6).

102 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Figure 1. (A) inverted U-shape (e.g. stimulated growth, fecundity) and (B) J-shaped (e.g. carcinogenesis, mutagenesis, disease incidence) hormetic dose-response curves.


Search Terms

104


Table 1. Citationsa of Hormoligosis and Hormesis with Insect- or Pesticide-Related Terms. Adapted with permission from Cutler 2013b. Copyright (2013) SAGE Publishing. Citations per years indicated pre-1960

1960-69

1970-79

1980-89

1990-99

2000-09

2010-16

Totals

Hormoligosisc

0

3

1

2

11

17

17

51

Hormesis

6

1

1

0

66

238

2290

2602

Hormesis AND Coleoptera

0

0

0

1

1

4

12

18

Hormesis AND Diptera

0

0

0

1

3

27

42

73

Hormesis AND Hemiptera

0

0

0

0

0

4

7

11

Hormesis AND Heteroptera

0

0

0

0

0

6

3

9

Hormesis AND Homoptera

0

0

0

0

2

3

12

17

Hormesis AND Hymenoptera

0

0

0

0

1

1

8

10

Hormesis AND Lepidoptera

0

0

0

0

0

5

22

27

Hormesis AND Insect

0

0

0

2

5

52

93

152

Hormesis AND Insecticide

0

0

0

2

5

21

61

89

Hormesis AND Pesticide

0

0

0

2

11

38

95

146

Hormesis AND Drosophilad

0

0

0

2

3

87

93

185

Totals

6

4

2

12

108

503

2755

3390

From the Thomson Reuters Web of Science database arthropods d Predominantly biomedical research.

a

b

Cutler 2013 (6)

c

Use of this term has generally, but not exclusively, been confined to insects and

Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Although most work on insecticide-induced hormesis has been done in the laboratory, it is of interest to field entomologists, ecotoxicologists, and pest management practitioners because the dose of insecticide to which insects are exposed in the field will tend to vary greatly due to many biotic and abiotic processes: spray drift, volatilization of spray droplets, density and growth of plant canopies, differential exposure of leaf surfaces, and degradation of the insecticide over time from e.g. microbes and UV radiation, will spatially and temporally change the doses of pesticide to which insect populations are exposed in the field. Though initial insecticide concentrations will usually be lethal to target pests, invariably the aforementioned factors dictate that sublethal concentrations of insecticide will be encountered, and such concentrations could be in the hormetic dose range (Figure 2). It is still early in the study of insecticide-induced hormesis. To date, most work has focussed on documenting evidence of stimulated reproduction and population growth, although an increasing number of studies have examined behavioral effects, and molecular and biochemical mechanisms related to insecticide-induced hormesis (Figure 3). In the following sections we emphasize the practical importance of the phenomenon, while highlighting recent activity and areas of future study we feel will be of interest going forward. Overlap of themes unavoidably occurs in several instances; e.g., discussion of hormetic effects of insecticides on natural enemies or bees may also refer to changes in behavior. Also, in some cases where hormesis is of significance for insects, the stressor may not be an insecticide, and therefore we sometimes discuss hormetic responses stemming from other forms of mild stress, such as heat shock or caloric restriction.

Pest Resurgence and Outbreaks The resurgence of pest species following application of insecticides – whether they be the primary target pest, or secondary pests – has traditionally been attributed to reduced competition from natural enemies of the pest. That is, application of the insecticide reduces populations of both the pest and its natural enemies, but the delayed recovery of the natural enemy population allows the recovering pest population to rapidly resurge (10, 11). Although natural enemy disturbance from insecticides is probably a cause of pest resurgence and outbreaks in many instances, insecticide-induced hormesis is also probably an important driver of this phenomenon. For example, Morse (12) originally observed that some insecticides applied for control of citrus thrips resulted in increased fruit damage, and subsequently showed in the laboratory that specific sublethal doses of these same insecticides or exposure to field-weathered insecticide-treated foliage stimulated thrips reproduction (13). In experiments with brown planthopper, Nilaparvata lugens, Chelliah and Heinrichs (14, 15) found that field resurgences of the pest following application of decamethrin and methyl parathion were most likely due to stimulated reproduction following exposure to insecticides, and not due to effects of the insecticides on predators of N. lugens. 105 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Figure 2. General responses of insects to high and low doses of insecticide that vary across time and space.

Figure 3. Results of search terms with “hormesis” + “insecticide” in the Thomson Reuters Web of Science database (9 July 2016). Several field studies have demonstrated that exposure to certain insecticides can cause outbreaks of aphids. Lowery and Sears (16, 17) reported strong surges in populations of green peach aphid, Myzus persicae, on field potatoes following 106 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


application of azinphosmethyl. Through concurrent laboratory bioassays they showed this was due to direct action of the insecticide on reproduction of aphids rather than from changes in the host potato plants induced by the insecticide. Similarly, field applications of carbaryl against filbert aphid, Myzocallis coryli, in hazelnut orchards resulted in initial population reductions, but populations later resurged to levels that sometimes eclipsed aphid population levels on untreated trees. The effect was not seen with other insecticides that were equally toxic to natural enemies, and laboratory tests showed that aphids directly exposed to low doses of carbaryl had increased reproduction, suggesting exposure to low-dose foliar residues of cabaryl stimulated M. coryli populations. More recently, the potential of insecticides to stimulate M. persicae population growth have been demonstrated in greenhouse studies, where exposure to low concentrations of systemically applied imidacloprid on whole plants for three weeks that spanned multiple generations resulted in a doubling of the aphid population (18, 19). Evidence of insecticide-induced hormesis as mechanism of pest outbreaks is not restricted to insects. As pointed out by Cohen (20), there are many examples of insecticide applications inducing outbreaks of phytophagous mites. Although such outbreaks of pest mites may sometimes be due to effects on natural enemies or plant physiology (21, 22), insecticides can also directly stimulate mite reproduction and population growth (23–25). A demonstration of how insecticide-induced hormesis and not natural enemy disruption probably is the cause of mite outbreaks was provided by Cordeiro et al. (26) On Brazilian coffee farms, applications of deltamethrin against coffee leaf miner, Leucoptera coffeella, are often followed by outbreaks of another pest, the southern red mite, Oligonychus ilicis. Though selectivity favoring O. ilicis over its natural enemies, such as the phytoseiid predator Amblyseius herbicolus, is generally assumed to be the cause of such outbreaks, Cordeiro et al. (26) showed that the predator (A. herbicolus) does not avoid deltamethrin and is three times more tolerant to deltamethrin than its prey. At the same time, field-relevant doses of deltamethrin stimulated population growth of O. ilicis but not A. herbicolus, suggesting that deltamethrin-induced hormesis is a likely cause of the reported red mite outbreaks. Pests like aphids, mites, and leafhoppers reproduce rapidly, and with life cycles that can be as short as 1-3 weeks can have many overlapping generations per year. The occurrence in the field of resurgences and outbreaks due to stimulatory effects of low doses of insecticide suggests that insecticide-induced hormesis does not necessarily reduce the biological fitness of insects. This is not to suggest that fitness trade-offs will not occur, as they most certainly can. Trade-offs can occur within individuals in the form of, for example, increased egg production or pupation following mild insecticide or heavy metal exposure being offset by reduced size, emergence, or survival of individuals (27, 28), or reduced reproduction following stimulated growth of individuals (29). Trade-offs may also occur across generations, such that exposure concentrations that stimulate processes in early generations may be inhibitory in later generations. This was observed by Ayyanath et al. who found that concentrations of insecticides that initially stimulated reproduction or longevity of aphids caused reduced reproduction and longevity in later generations (Figure 4) (18, 30). Nevertheless, insecticide-induced outbreaks do occur and can quantifiably increase the growth 107 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


rate of insect populations (18, 26, 31, 32), indicating that fitness can remain high or exceed baseline levels, a least temporarily, in spite of any fitness trade-offs that might occur. Although field observations of pest resurgences following insecticide applications were probably the main impetus for initial studies of insect hormoligosis and hormesis, we still lack definitive demonstrations of insecticideinduced hormesis for many pest-crop complexes. More greenhouse and field experiments are required to elucidate the extent to which insecticide-induced hormesis occurs in normal crop production operations, how this plays off other drivers of pest resurgence (such as natural enemy disturbance), and the economic consequences of resulting pest resurgences or outbreaks (6, 7).

Figure 4. Multigenerational (G0, G1, G2, G3) effects of continuous exposure to sublethal concentrations of imidacloprid on the longevity of adult green peach aphid. Reproduced with permission from Reference (18).

Insecticide Resistance Insecticide resistance continues to be a major concern for insect pest management. The Insecticide Resistance Action Committee (IRAC) reports that as of 2015, 14,644 cases of pesticide resistance have been reported in 597 species of arthropods, involving 336 different compounds (33). There are at least three different scenarios that would be of interest and should be explored related to insecticide-induced hormesis and potential implications for insecticide resistance. 108 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


First, if field rates of insecticide fail to kill and suppress an insecticide resistant population, then these sublethal doses might be in the “hormetic zone” for that population. If they are, they might stimulate reproduction and population growth of the resistant population, thereby increasing the frequency of resistance alleles. This was demonstrated by Guedes et al. (31) in experiments with maize weevil, Sitophilus zeamais. They showed that field-relevant concentrations of deltamethrin that were lethal to a susceptible strain of the weevil resulted in significant increases in population growth of a deltamethrin-resistant strain, indicating that field doses of insecticide that do not kill resistant individuals may actually boost their population growth through insecticide-induced hormesis. Second, insecticide-induced hormesis might coincide with induction of detoxification enzymes that render insects less susceptible to insecticides. If increased expression of detoxification enzymes during insecticide-induced hormesis was a heritable epigenetic process, the combination of stimulated population growth via hormesis with detoxification gene induction could augment pest pressure and resistance development (7). This does not suggest that insecticide-induced hormesis per se would cause induction of detoxification enzymes, but that both events could co-occur in time and space to exacerbate pest problems. For example, Rix et al. (19) found that exposure to low doses of imidacloprid significantly increased the instantaneous rate of population growth of M. persicae, and that this same treatment also altered expression of the detoxification genes E4-esterase and cytochrome P450-CYP6CY3 within and across generations. Whether or not such changes in detoxification gene expression functionally translate into reduced susceptibility or resistance to insecticides over generations is unclear. Third, Gressel (34) pointed out that pests which survive exposure to sublethaldoses of pesticide can nonetheless be highly stressed by such exposures, and that stress is a general enhancer of mutation rates. Survivors of sublethal pesticide exposure are thus likely to have more mutations than normal, and some of these mutations might confer pesticide resistance, both for multifactorial and major gene resistance. It is plausible that insects that survive sublethal insecticide stress may respond hormetically (e.g., stimulated reproduction and population growth), while at the same time developing mutations in genes that render the population resistant to the insecticide. So far as we are aware, this hypothesis has not been tested.

Preconditioning Hormesis Preconditioning hormesis occurs where hormetic doses of a stressor stimulate adaptive responses that condition and subsequently protect the organism (or specific tissues) against a second, higher dose of the same or different agents (35). This area of study is rapidly expanding in many areas of biology (35, 36), and preconditioning hormesis in insects exposed to low doses of insecticide has been reported. This is significant for pest insects in that it could present a “double whammy” given that low (hormetic) doses of insecticide could stimulate their reproduction, while also conditioning or priming the pests or their offspring to be better cope with subsequent stressors in the environment. 109 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


For example, the instantaneous rate of increase and total reproductive output of green peach aphids developing for three weeks on potato plants treated systemically with imidacloprid was significantly greater than that on control plants, and this same treatment improved aphid survival when subsequently deprived of food and water (Figure 5); this may have been from observed upregulation of heat shock proteins, which allow organism to survive many biotic and abiotic stresses, including dehydration (19). Interestingly, however, the same preconditioning challenge on imidacloprid-treated plants resulted in aphids that had reduced survival when exposed to an LC20 concentration of spirotetramat, a lipid biosynthesis inhibitor insecticide, suggesting that the success of insecticide-induced preconditioning hormesis depends on the nature of the subsequent stress. In another study, exposure of an insecticide susceptible strain of western flower thrips, Frankliniella occidentalis, to an LC25 concentration of spinosad negatively affected development time, fecundity, and population growth of the parental generation, but for F1 offspring the negative effects of such exposure were reduced (37), suggesting that exposure of the parental generation to the insecticide conditioned offspring to better cope with pending insecticide exposure.

Figure 5. Box plots showing effects of subsequent stress (no food/water) on 72-h survival of third-generation green peach aphids from potato plants systemically treated with 0.25 μg imidacloprid L-1. Reproduced with permission from Reference (19). Copyright 2016 Springer. 110 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Though induction of hormesis from insecticide exposure is the emphasis of this chapter, it is important to remember that the principles of preconditioning hormesis – and hormesis in general – in insects are not restricted to insecticides. Studies with Drosophila have shown that, for example, preconditioning with mild heat shock enhances locomotor and synaptic performance during subsequent hyperthermia (38), and that mild endoplasmic reticulum preconditioning stress results in subsequent neuroprotection and triggering of autophagy (natural, regulated disassembly of unnecessary or dysfunctional cellular components) which inhibited caspase (protease enzymes with essential roles in programmed cell death) activation and apoptosis (39). Wang et al. (40) provided evidence from a set of experiments that food deprivation during development of the honey bee (Apis mellifera) resulted in a shift in phenotypes to better cope with nutritional stress. They found that mild starvation of larvae gave rise to adult honey bees that were more resilient toward starvation. Although this was accompanied by reduced ovary size, elevated glycogen stores and juvenile hormone (JH) titers, and decreased sugar sensitivity in those adults, the results suggests mild starvation stress preconditioned the colony to anticipate and cope with poor environmental conditions (40). Further discussion of how preconditioning hormesis may be beneficial for mass culturing of insects is provided below. Another excellent example of the utility of preconditioning hormesis for applied entomology is through rearing of pest insects for use in sterile insect technique (SIT). This technique is founded on the mass rearing and sterilization of particular pest species, with the release of an overwhelming number of those sterile individuals – usually males – into an area containing the pest. Success of SIT requires that sterile males, which are usually produced through gamma irradiation (a stressful event), retain physiological and behavioral fitness so that they are able to compete successfully with wild (fertile) males for mates. To this end, López-Martínez and co-authors carried out a series of experiments to determine if the fitness of Caribbean fruit fly, Anastrepha suspense, destined for irradiation could be improved through anoxic preconditioning. Indeed, challenge with anoxia stress (1 h) prior to irradiation treatments and adult emergence resulted in a hormetic response that conferred increased antioxidant enzyme activity, which resulted in lower lipid and protein oxidative damage, higher adult emergence rates, lower mortality rates, longer lifespan, greater flight ability, and overall enhanced male sexual performance (41–43). These results suggest that preconditioning hormetic treatments, such as those designed to enhance antioxidant activity prior to sterilization can result in more competitive sterile males, thereby improving the efficacy and economy of SIT programs (42).

Stimulatory Effects on Insect Behavior The potential for stress to affect behavior in a biphasic/hormetic manner has been considered across multiple fields. For example, hormetic stress in mice through short-term caloric-restriction can elicit antidepressant-like responses in maze and forced swim tests (44), enhance learning and consolidation processes 111 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


(45), and improve remote contextual fear memory (46). Likewise, several authors have recently explored potentially stimulatory effects of low doses of insecticide on the behavior of insects or other arthropods, including orientation ability, mating behavior, and predatory behavior. Low-dose exposure to toxic insecticide has been shown to stimulate orientation behavior and mating success in pest moths. Rabhi et al. (47) found that low doses of clothianidin induced a biphasic hormetic-like effect on sex pheromone-guided behavior of the black cutworm moth Agrotis ipsilon, a wide-ranging pest that attacks many vegetable and grain crops. Although high and low doses of clothianidin had no effect or inhibited orientation behavior, a LD20 dose of clothianidin improved orientation of male moths. However, this LD20 dose also reduced the survival rate and flight capacity of moths, potentially negating any putative effects of improved flight orientation. Rabhi et al. subsequently showed that this same dose of clothianidin significantly increased antennal lobe sensitivity in male moths, such that 100-fold lower pheromone dose was required to elicit a response in neurons after intoxication compared with control moths (48). Similarly, Lalouette et al. (49) found exposure of cotton leafworm Spodoptera littoralis to a dose equivalent to one-tenth the LD50 of deltamethrin resulted in improved mating success, which was associated with a modified olfactory receptor neuron response to pheromonal stimulation (faster signal termination), and changes to antennal detoxification or stress response. Insecticide-induced hormetic effects on mating behavior have been seen in other insects. Oriental fruit fly, Bactrocera dorsalis, responded biphasically to cyantraniliprole, an anthranilic diamide insecticide; whereas a concentration of 3.27 μg g-1 in adult diet significantly lowered mating competiveness, exposure to diet treated with 1.30 μg g-1 improved the mating frequency and competitiveness of treated males, while resulting in more oviposition in exposed female flies (50). Other work showed that exposure of the neotropical brown stink bug Euschistus heros to low doses of imidacloprid (which is toxic to the insect at high doses) resulted in greater mating frequencies when at least one member of the couple was exposed. Mating duration was shortened when only females were exposed to imidacloprid, and exposed males showed increased walking activity, lower respiration rates, and induced higher fecundity rates when mated to unexposed females, indicating that male E. heros can have increased sexual fitness following insecticidal stress in early adulthood (51). Among non-insect arthropods, when the wolf spider Pardosa pseudoannulata was exposed to high concentrations (25-200 mg L-1) of the neonicotinoid insecticide imidacloprid, inhibitory effects on survival, reproduction, and predatory behavior were observed, but exposure to a low concentration (12.5 mg L-1) of imidacloprid stimulated predation ability (52). Niedobová et al. (53) examined effects of agrochemical surfactants on the foraging behavior of Pardosa agrestis. Although some treatments adversely affected short-term predatory activity, male spiders in one particular surfactant treatment killed significantly more flies than did those in the control group.



Hormesis in “Beneficial” Insects Most work on insecticide-induced hormesis has focused on pest insects (6, 7). However, given that the term “pest” is anthropocentric, insecticide-induced hormesis is just as likely to occur in “beneficial” insects. Culture and sale of beneficial insects for scientific inquiry, biological control, pollination, textiles (e.g. silk), and food for pets, livestock, poultry, fish, or humans is worth billions of dollars globally. Given the burgeoning interest in applying hormetic principles to benefit human health (54), it seems we should also examine opportunities to harness potential benefits of hormesis when rearing or maintaining beneficial insects. Contamination that results in competition, parasitism, predation, or disease is one of the most serious problems in mass production of insects. Insect pathogens are perhaps the most pervasive and difficult problem to contend with, and efforts to supress their impacts can be costly and labour intensive (55). Exploitation of hormetic responses may be beneficial during insect rearing to help reduce susceptibility to pathogens. For example, Galleria melonella is an important insect model in many lines of research, and is also reared as food for captive animals in terraria. G. melonella, like many insects, is susceptible to infection by the fungus Beauveria bassiana, but Wojda et al. (56) found that exposure of G. melonella larvae to mild heat shock (38 °C for 30 min), before infection of the fungus, extended the insect’s lifespan, which the authors suggested was due to higher expression of antimicrobial peptides and higher antifungal and lysozyme activities in the heat-shocked animals. It was subsequently shown that G. melonella larvae exposed to heat shock or heat-killed pathogens were more resistant to infection by entomopathogenic bacteria like Bacillus thuringiensis and Photorhabdus luminescens, with corresponding increases in amounts of anti-microbial peptides, and increased transcription of genes encoding antimicrobial peptides (57–59). This priming response to mild stress (preconditioning hormesis) seems to be conserved across insect taxa (60), and thus could be explored with many insects that are commonly cultured. In addition to improving the hardiness of insects in culture, there might be applications for hormetic stress to increase reproductive outputs of insect cultures. Several laboratory studies have shown that exposure to low doses of insecticide can boost reproduction or oviposition of natural enemies, such as the Heteroptera predators Podisus distinctus (32) (Figure 6) and Supputius cincticeps (61), the lacewing Chrysopa californica (62), the ladybird beetles Harmonia axyridis (63) and Coleomegilla maculate (64), and the parasitoid Bracon hebetor (65). Insecticide-induced hormesis might also benefit natural enemy behavior. For example, exposure of Leptopilina heterotoma, a parasitoid of Drosophila, to a LC20 concentration of chlorpyrifos significantly increased oviposition probing (with or without conditioning of a stimulatory banana odor) 1 h after conditioning. After 24 h, the stimulation produced by chlorpyrifos was no longer significant, but nonetheless remained higher than that of non-conditioned female wasps, suggesting that sublethal insecticide exposure could increase parasitoid efficiency without compromising odor memory (66). In other experiments with L. heterotoma, LC20 concentrations of chlorpyrifos and deltamethrin significantly 113 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


increased the arrestment of parasitoids by kairomones, which increased their residence time on the kairomone infested area, a behavioral change that could be advantageous for parasitoids by increasing their host-finding (67). Stimulatory effects of low-dose insecticide exposure on bee learning are described below.

Figure 6. Effect of sublethal doses of permethrin on the mean (+/- standard error) net reproductive rate of the predatory bug Podisus distinctus. Adapted with permission from reference (32). Adapted with permission from Reference (32). Copyright 2009 Oxford University Press.

Although it would probably be difficult to achieve practical applications or repeatability in most field situations, there is also some evidence that insecticide-induced hormesis can affect natural enemy behavior in the field. Mills et al. (68) examined effects of different pesticides used in orchard pest management on eight different natural enemies. Though inhibitory effects of insecticides were found, exposure to some of the insecticides resulted in significant increases in performance among survivors. For example, life table analysis found that Deraeocoris brevis juveniles exposed to chlorantraniliprole and cyantraniliprole gave more adult females relative to controls, and Hippodamia convergens adults exposed to spinetoram and copper+mancozeb had increased daily fecundity. To date, experiments showing hormetic responses in beneficial insects seem to have been limited to observations within a single generation. Whereas some single and multi-generational studies with pest species suggests insects can have hormetic 114 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

responses to mild stress without fitness consequences, others studies show that there can be fitness costs associated with hormesis in insects (see above). Thus, it is not yet clear if and how hormetically induced changes in vigor or reproduction can be satisfactorily maintained in beneficial insects across multiple generations, or if such stimulations are temporary and costly for the population. This will be an important line of inquiry for the discipline going forward.


Insecticide-Induced Hormesis in Bees Given mounting concerns of declines of managed and wild pollinator populations, study of potential effects of insecticides on pollinators has increased rapidly; a Thomson Reuters Web of Science search (12 July 2016) of the terms “bee” and “insecticide” generates 771 hits since the year 1950, but 479 of these articles have been published since 2010. The occurrence and significance of insecticide-induced hormesis in bees has recently been discussed (69), but some authors who detect insecticide-induced hormesis in bees are clearly still not familiar with the phenomenon. For example, Moffat et al. (70) found that chronic exposure to field-relevant concentrations of the neonicotinoid insecticide clothianidin had no significant effects on any measure of bumblebee colony health (no. live bees, no. brood cells, change in nest mass, proportion of females) except queen production, where clothianidin-treated colonies produced 266% more queens than control colonies (P = 0.005). Unfortunately, the authors paid little attention to this result and make no reference to hormesis. Given that pesticide-induced hormesis occurs across so many diverse taxa of insects, it is not surprising that insecticide-induced hormesis in bees will occur (69). Fortunately, more researchers are becoming aware of this and are reporting their findings in the literature. For example, bumble bees (Bombus terrestris) exposed to low, sublethal doses of clothianidin in the laboratory had slightly, but not significantly, faster learning compared to other treatments (71). This result is similar to findings with nicotine and caffeine, which though lethally toxic to honey bees (Apis mellifera) (72), were also shown to improve learning and memory when administered at low doses (73, 74), as was a combination of imidacloprid and the miticide coumaphos (75). Stimulating effects of low-dose insecticide exposure have even been seen in field studies with bees. For example, B. terrestris workers from colonies chronically exposed to 10 ppb thiamethoxam had increased visitation to Lotus corniculatus flowers, spent less time learning to forage, and collected more pollen than control bees (76). Similarly, chronic exposure to 2.4 ppb thiamethoxam (a field-realistic exposure concentration) resulted in B. terrestris workers visiting a higher number of apple flowers than bees from control colonies (77), even though thiamethoxam and other neonicotinoid insecticides (e.g. imidacloprid, clothianidin) are highly toxic to bees under certain experimental conditions (78, 79). Others have shown that exposure to sublethal doses of nicotine, thiamethoxam, and biopesticide can improve survival of honey bees and bumble bees (80–82). 115 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

These results suggest that bees are not passive organisms when it comes to pesticides exposure. Rather, like all organisms, they have evolved to adapt to stress, and such adaptations may result in hormetic (stimulatory) responses. Increased awareness of insecticide-induced hormesis in bees will hopefully lead to new mechanistic and evolutionary insights into how bees adapt to chemical stress, and how different doses of insecticide interact with target sites in bees, with potential implications for pollinator risk assessment (69).


Conclusions The occurrence of insecticide-induced hormesis is now well supported experimentally, both in the laboratory and in the field. The potential significance of the phenomenon for pest outbreaks is clear, but more study is required to clarify the most likely pest-crop-insecticide scenarios for its development, as well as its consequences for pest management. In addition, hormesis might have applications for mass culture of insects, and may produce new perspectives during characterization of risk of pesticides to bees and other beneficial insects. Although there has been progress into basic molecular, biochemical, and physiological underpinnings of insecticide-induced hormesis (19, 30, 40, 51, 83, 84), there is need for far more work in this area. This will give insight into mechanisms responsible for specific events, while also increasing our overall understanding of the phenomenon.

Acknowledgments The authors acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC), the National Council of Scientific and Technological Development (CNPq), the CAPES Foundation (Brazilian Ministry of Education), and the Minas Gerais State Foundation of Research Aid (FAPEMIG) for financial support of their research on insecticide-induced hormesis.

References 1.

2. 3. 4. 5. 6. 7. 8. 9.

FAO. FAOSTAT - Food and Agricultural Organization of the United Nations Statistical Division. http://faostat3.fao.org/home/E (last accessed 22 Sep 2016). Desneux, N.; Decourtye, A.; Delpuech, J. M. Annu. Rev. Entomol. 2007, 52, 81–106. Guedes, R. N. C.; Smagghe, G.; Stark, J. D.; Desneux, N. Annu. Rev. Entomol. 2016, 61, 43–62. Calabrese, E. J.; Baldwin, L. A. Nature 2003, 421, 691–692. Calabrese, E. J. Environ. Pollut. 2005, 138, 379–411. Cutler, G. C. Dose-Response 2013, 11, 154–177. Guedes, R. N. C.; Cutler, G. C. Pest Manage. Sci. 2014, 70, 690–697. Luckey, T. D. Nature 1963, 198, 263–265. Luckey, T. D. J. Econ. Entomol. 1968, 61, 7–12. 116 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


10. Ripper, W. E. Annu. Rev. Entomol. 1956, 1, 403–438. 11. Hardin, M. R.; Benrey, B.; Coll, M.; Lamp, W. O.; Roderick, G. K.; Barbosa, P. Crop Prot. 1995, 14, 3–18. 12. Morse, J. G. Hum. Exp. Toxicol. 1998, 17, 266–269. 13. Morse, J. G.; Zareh, N. J. Econ. Entomol. 1991, 84, 1169–1174. 14. Chelliah, S.; Heinrichs, E. A. Environ. Entomol. 1980, 9, 773–777. 15. Chelliah, S.; Fabellar, L. T.; Heinrichs, E. A. Environ. Entomol. 1980, 9, 778–780. 16. Lowery, D. T.; Sears, M. K. J. Econ. Entomol. 1986, 79, 1530–1533. 17. Lowery, D. T.; Sears, M. K. J. Econ. Entomol. 1986, 79, 1534–1538. 18. Ayyanath, M. M.; Cutler, G. C.; Scott-Dupree, C. D.; Sibley, P. K. PLoS One 2013, 8, e74532. 19. Rix, R. R.; Ayyanath, M. M.; Cutler, G. C. J. Pest Sci. 2015, 89, 581–589. 20. Cohen, E. Pestic. Biochem. Physiol. 2006, 85, 21–27. 21. Saini, R. S.; Cutkomp, L. K. J. Econ. Entomol. 1966, 59, 249–253. 22. Rodriguez, J. G.; Chen, H. H.; Smith, W. T. J. Econ. Entomol. 1960, 53, 487–490. 23. Zeng, C.-X.; Wang, J.-J. J. Insect Sci. 2010 10, 20. Available online: insectscience.org/10.20. 24. Dittrich, V.; Streibert, P.; Bathe, P. A. Environ. Entomol. 1974, 3, 534–540. 25. James, D. G.; Price, T. S. J. Econ. Entomol. 2002, 95, 729–32. 26. Cordeiro, E. M. G.; de Moura, I. L. T.; Fadini, M. A. M.; Guedes, R. N. C. Chemosphere 2013, 93, 1111–1116. 27. Fujiwara, Y.; Takahashi, T.; Yoshioka, T.; Nakasuji, F. Appl. Entomol. Zool. 2002, 37, 103–109. 28. Nascarella, M. A.; Stoffolano, J. G.; Stanek, E. J.; Kostecki, P. T.; Calabrese, E. J. Environ. Pollut. 2003, 124, 257–262. 29. Sial, A. A.; Brunner, J. F. J. Econ. Entomol. 2010, 103, 340–347. 30. Ayyanath, M. M.; Scott-Dupree, C. D.; Cutler, G. C. Chemosphere 2015, 128, 245–251. 31. Guedes, N. M. P.; Tolledo, J.; Correa, A. S.; Guedes, R. N. C. J. Appl. Entomol. 2010, 134, 142–148. 32. Guedes, R. N. C. J. Econ. Entomol. 2009, 102, 170–176. 33. IRAC. Arthropod Pesticide Resistance Database (APRD) Update. Insecticide Ressitance Action Committee, 50th IRAC International Meeting, Dublin, April 5−8th, 2016. http://www.irac-online.org/teams/resistancedatabase/ (last accessed 22 Sep 2016). 34. Gressel, J. Pest Manage. Sci. 2011, 67, 253–257. 35. Calabrese, E. J. Pharmacol. Res. 2016, 110, 242–264. 36. Calabrese, E. J. Pharmacol. Res. 2016, 110, 265–275. 37. Gong, Y. H.; Xu, B. Y.; Zhang, Y. J.; Gao, X. W.; Wu, Q. J. Ecotoxicology 2015, 24, 1141–1151. 38. Xiao, C. F.; Mileva-Seitz, V.; Seroude, L.; Robertson, R. M. Dev. Neurobiol. 2007, 67, 438–455. 39. Fouillet, A.; Levet, C.; Virgone, A.; Robin, M.; Dourlen, P.; Rieusset, J.; Belaidi, E.; Ovize, M.; Touret, M.; Nataf, S.; Mollereau, B. Autophagy 2012, 8, 915–926. 117 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


40. Wang, Y.; Kaftanoglu, O.; Brent, C. S.; Page, R. E.; Amdam, G. V. J. Exp. Biol. 2016, 219, 949–959. 41. Lopez-Martinez, G.; Carpenter, J. E.; Hight, S. D.; Hahn, D. A. J. Econ. Entomol. 2014, 107, 185–197. 42. Lopez-Martinez, G.; Hahn, D. A. J. Exp. Biol. 2012, 215, 2150–2161. 43. Lopez-Martinez, G.; Hahn, D. A. PLoS One 2014, 9, e88128. 44. Lutter, M.; Sakata, I.; Osborne-Lawrence, S.; Rovinsky, S. A.; Anderson, J. G.; Jung, S.; Birnbaum, S.; Yanagisawa, M.; Elmquist, J. K.; Nestler, E. J.; Zigman, J. M. Nat. Neurosci. 2008, 11, 752–53. 45. Fontán-Lozano, Á.; Sáez-Cassanelli, J. L.; Inda, M. C.; de los SantosArteaga, M.; Sierra-Domínguez, S. A.; López-Lluch, G.; Delgado-García, J. M.; Carrión, Á. M. J. Neurosci. 2007, 27, 10185–10195. 46. Hornsby, A. K. E.; Redhead, Y. T.; Rees, D. J.; Ratcliff, M. S. G.; Reichenbach, A.; Wells, T.; Francis, L.; Amstalden, K.; Andrews, Z. B.; Davies, J. S. Psychoneuroendocrinology 2016, 63, 198–207. 47. Rabhi, K. K.; Esancy, K.; Voisin, A.; Crespin, L.; Le Corre, J.; TricoireLeignel, H.; Anton, S.; Gadenne, C. PLoS One 2014, 9, e114411. 48. Rabhi, K. K.; Deisig, N.; Demondion, E.; Le Corre, J.; Robert, G.; TricoireLeignel, H.; Lucas, P.; Gadenne, C.; Anton, S. Proc. R. Soc. London, Ser. B 2016, 283 DOI:10.1098/rspb.2015.2987. 49. Dewer, Y.; Pottier, M. A.; Lalouette, L.; Maria, A.; Dacher, M.; Belzunces, L. P.; Kairo, G.; Renault, D.; Maibeche, M.; Siaussat, D. Environ. Sci. Pollut. Res. Int. 2016, 23, 3086–3096. 50. Zhang, R. M.; Jang, E. B.; He, S. Y.; Chen, J. H. Pest Manage. Sci. 2015, 71, 250–256. 51. Haddi, K.; Mendes, M. V.; Barcellos, M. S.; Lino-Neto, J.; Freitas, H. L.; Guedes, R. N. C.; Oliveira, E. E. PLoS One 2016, 11, e0156616. 52. Chen, X. Q.; Xiao, Y.; Wu, L. B.; Chen, Y. F.; Peng, Y. Bull. Environ. Contam. Toxicol. 2012, 88, 654–658. 53. Niedobová, J.; Hula, V.; Michalko, R. Environ. Pollut. 2016, 213, 84–89. 54. Mattson, M. P.; Calabrese, E. J. Hormesis - A Revolution in Biology, Toxicology and Medicine; Springer: New York, 2010. 55. Etzel, L. K.; Legner, E. F. Culture and colonization. In Handbook of biological control: Principles and applications of biological control; Bellows, T. S., Fisher, T. W., Caltagirone, L. E., Dahlsten, D. L., Gordh, G., Huffaker, C. B., Eds.; Academic Press: San Diego, 1999; pp 125−197. 56. Wojda, I.; Kowalski, P.; Jakubowicz, T. J. Insect Physiol. 2009, 55, 525–531. 57. Taszlow, P.; Wojda, I. Arch. Insect Biochem. Physiol. 2015, 88, 123–143. 58. Wojda, I.; Taszłow, P. J. Insect Physiol. 2013, 59, 894–905. 59. Wu, G. Q.; Xu, L.; Yi, Y. H. Immunol. Lett. 2016, 174, 45–52. 60. Masri, L.; Cremer, S. Trends Immunol. 2014, 35, 471–482. 61. Zanuncio, T. V.; Serrao, J. E.; Zanuncio, J. C.; Guedes, R. N. C. Crop Prot. 2003, 22, 941–947. 62. Fleschner, C. A.; Scriven, G. T. J. Econ. Entomol. 1957, 50, 221–222. 63. Xiao, D.; Zhao, J.; Guo, X.; Li, S.; Zhang, F.; Wang, S. J. Appl. Entomol. 2016, 140, 598–608. 64. Atallah, Y. H.; Newson, L. L. J. Econ. Entomol. 1966, 59, 1181–1187. 118 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


65. Grosch, D. S.; Vacovic, L. R. J. Econ. Entomol. 1967, 60, 1177–1179. 66. Rafalimanana, H.; Kaiser, L.; Delpuech, J. M. Pest Manage. Sci. 2002, 58, 321–328. 67. Delpuech, J. M.; Bardon, C.; Bouletreau, M. Arch. Environ. Contam Toxicol. 2005, 49, 186–191. 68. Mills, N. J.; Beers, E. H.; Shearer, P. W.; Unruh, T. R.; Amarasekare, K. G. Biol. Control 2016, 102, 17–25. 69. Cutler, G. C.; Rix, R. R. Pest Manage. Sci. 2015, 71, 1368–1370. 70. Moffat, C.; Buckland, S. T.; Samson, A. J.; McArthur, R.; Chamosa Pino, V.; Bollan, K. A.; Huang, J. T.; Connolly, C. N. Sci. Rep. 2016, 6, 24764. 71. Piiroinen, S.; Botias, C.; Nicholls, E.; Goulson, D. PeerJ 2016, 4, e1808. 72. Detzel, A.; Wink, M. Chemoecology 1993, 4, 8–18. 73. Thany, S. H.; Gauthier, M. Brain Res. 2005, 1039, 216–219. 74. Wright, G. A.; Baker, D. D.; Palmer, M. J.; Stabler, D.; Mustard, J. A.; Power, E. F.; Borland, A. M.; Stevenson, P. C. Science 2013, 339, 1202–1204. 75. Williamson, S. M.; Baker, D. D.; Wright, G. A. Invert. Neurosci. 2013, 13, 63–70. 76. Stanley, D. A.; Raine, N. E. Funct. Ecol. 2016, 30, 1132–1139. 77. Stanley, D. A.; Garratt, M. P. D.; Wickens, J. B.; Wickens, V. J.; Potts, S. G.; Raine, N. E. Nature 2015, 528, 548–550. 78. Mommaerts, V.; Reynders, S.; Boulet, J.; Besard, L.; Sterk, G.; Smagghe, G. Ecotoxicology 2010, 19, 207–215. 79. Blacquiere, T.; Smagghe, G.; van Gestel, C. A. M.; Mommaerts, V. Ecotoxicology 2012, 21, 973–992. 80. Démares, F. J.; Crous, K. L.; Pirk, C. W. W.; Nicolson, S. W.; Human, H. PLoS One 2016, 11, e0156584. 81. Kohler, A.; Pirk, C. W. W.; Nicolson, S. W. J. Insect Physiol. 2012, 58, 286–292. 82. Ramanaidu, K.; Cutler, G. C. Pest Manage. Sci. 2013, 69, 949–954. 83. Ayyanath, M. M.; Cutler, G. C.; Scott-Dupree, C. D.; Prithiviraj, B.; Kandasamy, S.; Prithiviraj, K. Dose-Response 2014, 12, 480–497. 84. Yu, Y.; Shen, G.; Zhu, H.; Lu, Y. Pestic. Biochem. Physiol. 2010, 98, 238–242.


Occurrence and Significance of Insecticide-Induced Hormesis in Insects

Recommend Documents