Introduction

The human race made enormous progress; however, revolutionary achievements are coupled with environmental off-putting factors such as vast use and release of drugs, heavy metals, fertilizers, and pesticides (Stankovic et al. 2014; Ullah et al. 2016a; Vieira et al. 2017; Afridi et al. 2018; Ali and Khan 2018; Khristoforova et al. 2018; Ullah and Li 2018). Pesticides are employed to repel, deter, or kill target organisms such as insects, algae, fungi, and bacteria in agricultural fields, public places such as homes, hospitals, and parks, industries, and public health programs (Ullah et al. 2019). With advancements in the field of pesticides chemistry, the numbers of pesticides are growing continuously. Different types of pesticides are used for targeting different types and/or species of organisms. The use of these pesticides is a major reason of elevating the standard of human life by different ways such as protecting the crops in the fields and stored food, destroying breeding site of different diseases causing insects, controlling harmful microorganisms including bacteria and viruses, and vanishing exasperating flies (Gill et al. 2018; Ullah et al. 2018a).

Different classes of pesticides

Pesticides are synthesized commercially and used under different names, belonging to different types and classes. The different classes of pesticides are employed based on their target organisms such as virucides against viruses, avicides against birds, algicides against algae, fungicides against fungi, nematicides against nematodes, rodenticides against rodents, herbicides against herbs, bactericides against bacteria, and acaricides or insecticides against insects (Regnery et al. 2018; Singh et al. 2018a; Valle et al. 2018). Among different classes of pesticides, insecticides are the most widely employed ones and attribute to about 80% of the use of the total pesticide (Ullah et al. 2018b). There are different registered classes of insecticides including organochlorines, carbamates, organophosphates, formamidines, organotins, organosulfurs, avermectins, neonicotinides, ryanodine, and rotenone, among others (Ullah et al. 2016b, c; Yang et al. 2018). However, one of the late introduced and most widely employed classes of insecticides is synthetic pyrethroids.

Introduction to pyrethroids

Pyrethroids are derived synthetically from pyrethrins, which are extracted from the flower of a plant, Chrysanthemum cinerariaefolium (Ullah 2015). Pyrethrins are insecticidal in nature due to the presence of ketoalcoholic esters of strongly lipophilic pyrethroic and chrysanthemic acids, having the capability of rapidly penetrating into insect bodies and leading to toxicosis. However, being highly sensitive to light natural pyrethrins break down within a few hours and cannot bioaccumulate in a sufficient concentration or amount to kill insects. With the help of modified structures, formulations, and stereochemistry, thousands of synthetic pyrethroids are developed. These modifications include cyano group addition, mixing of optical and geometric isomers, halogenation of the cyclopropane side chain of the pyrethrin molecule, adding different solvents and carriers, and different technical grade formulations (Kaviraj and Gupta 2014). These pyrethroids have a wide range of chemical and biological properties and performance; therefore, suitable pyrethroids are employed in agricultural fields, industries, parks, orchards, and homes (Ullah et al. 2018b).

Biotransformation and environmental fate of synthetic pyrethroids

The routes for the elimination of synthetic pyrethroids in the environmental media include microbial degradation, photodegradation, volatilization, and hydrolysis (Gan et al. 2005). However, in the biological systems, pyrethroids are detoxified by two pathways—esterase-dependent hydrolytic reaction and oxidative reaction mediated by cytochrome P450s. The main factors recognized for nontarget organisms’ susceptibility against synthetic pyrethroids are toxicokinetic factors. Synthetic pyrethroids are degraded through esterase-based hydrolysis followed by cytochrome P450s-based oxidation easily; therefore, they are relatively less toxic to mammals (Gammon et al. 2012). However, pyrethroids are highly toxic to fish because they lack hydrolase and therefore cannot swiftly detoxify synthetic pyrethroids hydrolytically like mammals (Yang et al. 2016). The only metabolic pathway of synthetic pyrethroids in fish is oxidative reaction catalyzed by cytochrome P450s. Different non-specific metabolites of the synthetic pyrethroids have been recognized, such as 3-phenoxybenzoic acid, 3-phenoxybenzaldehyde, 3-phenoxybenzyl alcohol, 3-phenoxybenzoic acid, and 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid. The transformation and degradation of compounds in the environment depend upon their physicochemical properties (Singh et al. 2016). Synthetic pyrethroids have the property of hydrophobicity and are insoluble in water with an n-octanol distribution coefficient 6.6 in water. They are stable and persist in the aquatic sediments and soil (Gammon et al. 2012). Figure 1 shows some toxicological impacts, some metabolites, environmental fate or degradation, and biotransformation of synthetic pyrethroids.

Fig. 1
figure 1

Synthetic pyrethroids (SPs) exposure leads to different toxicological impacts in the exposed organisms such as the induction of oxidative stress followed by oxidative damage, neurotoxicity, hematological toxicity, biochemical toxicity, and developmental toxicity. Some metabolites of synthetic pyrethroids have been identified, and their exposure led to different immunotoxicity, endocrine disruption, and reproductive toxicity. Pyrethroids get degraded by microbial degradation, photodegradation, hydrolysis, and volatilization. Moreover, pyrethroids are biotransformed easily by mammals through hydrolytic (esterase) and oxidative (cytochrome P450s) reactions. Therefore, pyrethroids are less toxic to them. However, fish lack hydrolase and metabolize synthetic pyrethroids through oxidative (cytochrome P450s) reaction only. Therefore, they are highly toxic to fish and other aquatic organisms

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Bioavailability of synthetic pyrethroids in the aquatic environment

Synthetic pyrethroids lead to aquatic bodies through runoffs from the sprayed agricultural fields, parking lots, industries, and public health programs through spray drift to some extent; however, the main source of bioavailability in the water bodies is flowing therethrough rainstorm events. The magnitude and frequency of synthetic pyrethroids use and their precipitation patterns are observed to be critical factors governing synthetic pyrethroids transport to water bodies (Oros and Werner 2005). Moreover, the breakdown rates of the pyrethroids such as persistence on the soil surface, temperature, and canopy cover in association with their precipitation events may play a specific role in the determination of concentrations of synthetic pyrethroids in the runoffs (Palmquist et al. 2012). The concrete drainage system may transport a higher concentration of aqueous-phase pyrethroids in the urban and suburban areas as compared to earthen ditches channeled from agricultural particulate-rich runoffs (Weston and Lydy 2010).

Synthetic pyrethroids in the environment

Owing to the widespread applications of synthetic pyrethroids, these are reported from various parts of the world. Table 1 shows the reported concentrations of different synthetic pyrethroids from the soil, and land organisms or their products, whereas Table 2 shows the reported concentration of different synthetic pyrethroids from sediments, water, fish, and other aquatic organisms from different countries across the globe. The range is given for individual synthetic pyrethroids, such that any of them observed in minimum and maximum concentrations. Synthetic pyrethroids are divided into two types, type I and type II. Type I pyrethroids are non-cyano pyrethroids, while type II pyrethroids contain the α-cyano group. Figure 2 shows the chemical structure of widely employed esters of synthetic pyrethroids of different generations from both type I and type II groups, whereas Fig. 3 shows the chemical structure and formulae of different esters of natural pyrethrin isolated from C. cinerariaefolium. Type II pyrethroids are considered to be more severely neuro-intoxicating as compared to type I, solely due to the presence of an α-cyano group (Soderlund et al. 2002). Table 3 shows the acute toxic concentrations of type II synthetic pyrethroids against different fish species. Synthetic pyrethroids are widely used across the globe due to their low toxicity to mammals and birds. However, synthetic pyrethroids are known to pose marked hostile effects on aquatic organisms, more specifically on fish (Assis et al. 2009). Keeping in view the toxic effects of synthetic pyrethroids on fish, different biomarkers are used to delineate their toxic impacts as well as envisaging biomarkers for future research.

Table 1 Concentrations of pyrethroids from the soil, cash crops, and land/terrestrial organisms and/or their products across the globe
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Table 2 Concentrations of pyrethroids in sediments, water, fish, and other aquatic organisms across different countries around the globe
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Fig. 2
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Synthetic pyrethroids (SPs) induced neurotoxicity (mechanism and subtle consequences) and chemical structures of different SPs [type I (without α-cyano group) including allethrin (first generation), permethrin (second generation), resmethrin (third generation), and bifenthrin (fourth generation), while type II (with α-cyano group) including fenvalerate (third generation), cyhalothrin (fourth generation), cypermethrin (fourth generation), and deltamethrin (fourth generation)]

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Fig. 3
figure 3

The isolated pyrethrins from Chrysanthemum cinerariaefolium flowers with their chemical structures and formulae—the shown pyrethrins are esters of natural pyrethrum. Mechanism of action of synthetic pyrethroids (SPs): (1) SPs exposure results in the production of excessive reactive oxygen species (ROS) that leads to detrimental effects on lipids, proteins, and DNA, (2) SPs interrupt ligand-gated channel and allow inflow of sodium in a higher concentration which leads to multiple nerve impulses and ultimately to inhibition of acetylcholinesterase and accumulation of acetylcholine, which stimulate other nerves, (3) SPs affect voltage-gated calcium channel and consequently (4) increase calcium concentration in the cytosol that consequently lead to cytotoxicity, (5) SPs inhibit receptor of γ-aminobutyric acid that consequently inhibits GABA receptor and ultimately leads to excitability and convulsion, (6) SPs disturb ATP formation/synthesis directly as well as glucose regulation is disturbed in response to cortisol regulation, (7) SPs exposure leads to the retention of acetylcholine in the synaptic gap (due to closing of synaptic cleft) which increases acetylcholine level, and (8) SPs lead to genotoxicity either by oxidative stress induction or due to accumulation of calcium in a higher concentration in the cytosol

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Table 3 Acute toxic concentrations (LC50) of different type II synthetic pyrethroids against different fish species
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Biomarkers of pyrethroid toxicity in fish

Biomarkers are indicators of the response of exposure to any toxicant, chemical, pollutant, or any other foreign particle. Biomarkers can be evaluated at a molecular or cellular level to community or ecosystem level. These biomarkers can substantially reveal the toxic effects of the toxicant on the exposed organism, such as toxicities on their neurology resulting in altered behavior, histopathological, morphological, anatomical, physiological, hematological, and biochemical profiles. Table 4 presents various toxic effects of pyrethroids to biomarkers in different fish species.

Table 4 Toxic effects of pyrethroids on fish as revealed by different biomarkers
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Pyrethroid-induced oxidative stress or damage in fish

Oxidative stress is widely employed as a sensitive biomarker in ecotoxicological assessments in order to understand the underlying hostile effects. The oxidative stress is evaluated in terms of reactive oxygen species (ROS) or free radicals’ production, increased lipid peroxidation, and altered activities of the antioxidant enzymes in response. ROS production leads to oxidative damage at the cellular level to DNA, lipids, and protein (Ullah et al. 2018a). To cope with the oxidative damage and to defend the cell against free radicals, different stress proteins such as heat-shock proteins, glucose-regulating proteins, and antioxidant enzymes including catalase, peroxidases, superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase are produced. However, when the production of the free radicals exceeds the potential of the defense system of the exposed organisms, it leads to different levels of oxidative damage such as DNA damage (Ullah et al. 2017). Research revealed that synthetic pyrethroids-induced oxidative stress leads to the different type of instant toxicities as well as toxicities and weak immunity at later stages in fish. In response to the oxidative stress, the fish adapt defensive mechanism by changing their antioxidant enzymatic activities such as increasing their activities to cope with the free radicals.

Exposure to different synthetic pyrethroids induced oxidative stress in different species of fish, for example, cypermethrin induced oxidative stress in different tissues of Tor putitora (Ullah et al. 2014), Labeo rohita (Ullah 2015), and Oncorhynchus mykiss (Kutluyer et al. 2015), cyhalothrin induced oxidative stress in different tissues of Cyprinus carpio (Clasen et al. 2018) and Prochilodus lineatus (Vieira and dos Reis Martinez 2018), and deltamethrin induced oxidative stress in different tissues of Cyprinus carpio (Ensibi et al. 2013), Sparus aurata (Guardiola et al. 2014), Oreochromis niloticus (Abdel-Daim et al. 2015), Danio rerio (Parlak 2018), and Hypophthalmichthys molitrix (Ullah et al. 2019).

Neurotoxicity

Pyrethroids exert toxic effects on the nervous system of the fish by affecting their sodium channels. They attached to these gated channels and delay the inactivation of the Na+ channels, which ultimately led to neuronal excitability (Ullah et al. 2019). However, recent research revealed that synthetic pyrethroids also affect the other voltage-gated channels such as calcium and chloride channels, and receptor of γ-aminobutyric acid as their secondary targets (Soderlund 2012). Disturbance to these channels leads to different neurobehavioral changes. Moreover, the neurotoxic effects lead to complex consequences such as affected energy metabolism, neuromuscular functions, neural transduction, and homeostasis. Figure 2 shows the neurotoxic effects of synthetic pyrethroids, their mechanisms, and subtle consequences. The neurotoxic effects can be in the form of disturbed voltage-gated channels, behavioral inconsistencies or alterations, and inhibition of acetylcholinesterase activity.

Behavioral inconsistencies and alterations

Research revealed that exposure to synthetic pyrethroids resulted in different behavioral inconsistencies in fish, such as sluggish movement, disturbed swimming or swimming pattern, inability to maintain their position, reduced feeding, interrupted school behavior, hypo- or hyperexcitability, dangling or irregular or erratic swimming, increased opercula movements, rapid jerky movements, loss of equilibrium, frequently surfacing, adapting vertical position, sinking to bottom, hypo- or hyperactiveness, jumping, loss of balance, motionlessness, and disturbed migratory pattern in different fish species such as Tor putitora (Ullah et al. 2014), Labeo rohita (Ullah 2015), and Clarias batrachus (Kumar et al. 2011b). The acetylcholinesterase is active at both the neural and neuromotor junctions of the muscle tissues; therefore, the neuromuscular inhibition of acetylcholinesterase leads to blocked neural transmission and increased acetylcholine at the nerve endings, which consequently lead to different behavioral inconsistencies. Therefore, these alterations are often associated with the inhibition of acetylcholinesterase activity in the brain or muscles of the fish and/or increment in the level of acetylcholine.

Inhibition of acetylcholinesterase activity

A number of research studies revealed that synthetic pyrethroids induce neurotoxic effects by inhibiting the activity of acetylcholinesterase or incrementing the level of acetylcholine in the brain of various fish tissues. The inhibition of acetylcholinesterase results in nerve impulses and makes them permeable to sodium. Synthetic pyrethroids delay the closing of sodium channels, allowing sodium inflow in a heavy concentration, which consequently leads to multiple never impulses, which in turn release a neurotransmitter, acetylcholine, leading to their higher accumulation in the nerve synapses and ultimately decreased cholinergic transmission and other neurotoxic effects. In fish, these effects are increased operculum movement, convulsions, and surfacing (Singh et al. 2018b). Deltamethrin exposure resulted in inhibition of the acetylcholinesterase in the brain of silver carp resulting in erratic swimming, vertical position adaptation, hyperactivity, and equilibrium loss as well as in the muscle tissues that resulted in the desensitization of the receptors of nicotine acetylcholine and subsequently resulted in muscular weakness and changed swimming pattern (Ullah et al. 2019).

Developmental toxicity

Synthetic pyrethroids are reported to exhibit greater acute toxic effects on the developing stages of animals as compared to adult stages (Yang et al. 2018). However, fish is highly sensitive and more susceptible to synthetic pyrethroids during their early life stages as compared to their adult stage (Yang et al. 2014). Synthetic pyrethroids also have the capability of affecting the development and growth of various animals (DeMicco et al. 2010). There is a continuously growing body of evidence, revealing the developmental toxicity of different pyrethroids on nontarget organisms, more specifically against fish, for example, exposure to bifenthrin accelerated hatching and impaired the normal morphology of Danio rerio, same as by cypermethrin, by inducing craniofacial abnormalities, pericardial edema, body curvatures, yolk edema, and crooked body (DeMicco et al. 2010; Jin et al. 2009; Shi et al. 2011). Similarly, joint exposure of Danio rerio to cypermethrin and permethrin led to different toxicities at larval stage (Yang et al. 2014), bifenthrin disturbed the dopaminergic signaling at the juvenile stage of Oncorhynchus mykiss (Crago and Schlenk 2015), cypermethrin induced different developmental deformities and altered the enzymatic activities in the developmental stages of Labeo rohita (Dawar et al. 2016), and deltamethrin induced oxidative stress leading to apoptosis and different morphological alterations in Danio rerio (Parlak 2018).

Hematological toxicity

Hematology is often assessed as a useful biomarker in eco-, aquatic, pesticides, and fisheries toxicology. Synthetic pyrethroids exposure results in different hematotoxic effects because after entering into the fish body, blood and blood-producing hematopoietic tissues are continuously exposed to the destructive effects of the respective pyrethroid. Exposure of Tor putitora to the acute concentration of cypermethrin led to an increase in white blood cells and a decrease in red blood cells (Ullah et al. 2015). Similarly, a number of studies reported different types of toxic effects on the hematological profile including white blood cells such as lymphocytes, thrombocytes, granulocytes, and monocytes, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin concentration, and mean corpuscular hemoglobin of different fish species after exposure to different synthetic pyrethroids such as Cyprinus carpio (Velisek et al. 2009a), Catla catla (Vani et al. 2012), Rhamdia quelen (Montanha et al. 2014), and Alburnus tarichi (Özok et al. 2018) in response to cypermethrin, Catla catla (Vani et al. 2011) and Salmo trutta fario (Karatas 2016) in response to deltamethrin, and Prochilodus lineatus in response to λ-cyhalothrin (Vieira and dos Reis Martinez 2018). The alterations in the hematological parameters including red blood cells might be attributed to the inhibition of hemosynthesis or erythropoiesis, destruction of blood cells such as red blood cells (anemia), decreased genesis of the red blood cells due to hypoxia, less hemoglobin or no hemoglobin, hematopoietic system’s failure, and osmoregulatory dysfunction, whereas white blood cells may be altered due to the stimulated defense mechanism or immune system of the fish, as a compensatory response to the circulating lymphocytes by the lymphoid tissues, and tissue damage (Ullah et al. 2019).

Biochemical toxicity

Biochemical parameters are often employed as handy biomarkers to appraise the toxic effects of different exogenous compounds, toxicants, and chemicals including pesticides, heavy metals, and pharmaceutical drugs on fish. Different generations of synthetic pyrethroids have been tested against different fish species, and almost all of them resulted in varying levels of biochemical toxicity, for example, deltamethrin induced different biochemical toxicities in Hypophthalmichthys molitrix including a marked reduction in the total protein contents in the liver, gills, muscles, blood, and brain tissues, marked increase in blood glucose concentration, and significant alterations in the concentration of potassium, sodium, chloride, total bilirubin, albumin, urea, inorganic phosphate, and cholesterol in serum (Ullah et al. 2019). Similarly, the activities of metabolic enzymes including aspartate aminotransferases, alanine aminotransferases, lactate dehydrogenases, and glutamate dehydrogenases, and concentration of whole-body cortisol were significantly increased.

A number of well-documented studies revealed that different esters of synthetic pyrethroids induced different toxic impacts on the biochemical indices of various fish species, for example, permethrin altered the vitellogenin protein’s concentration in the liver of Oryzias latipes (Nillos et al. 2010), fenvalerate increased blood glucose level, serum creatinine, and triglyceride and reduced total protein, globulin, and albumin in the serum of Labeo rohita (Prusty et al. 2011), cypermethrin decreased total proteins in the muscles, gills, brain, and liver and increased blood glucose in Tor putitora (Ullah et al. 2014), and deltamethrin increased alkaline phosphatase and decreased acid phosphatase in the liver and kidney of Labeo rohita (Suvetha et al. 2015). A number of such other changes have been reported for different fish species exposed to various synthetic pyrethroids such as cypermethrin-exposed Rhamdia quelen (Montanha et al. 2014) and Brycon amazonicus (de Moraes et al. 2018) and λ-cyhalothrin-exposed Prochilodus lineatus (Vieira and dos Reis Martinez 2018).

Reproductive and endocrine disruptive toxicity

The reproductive toxic effects and endocrine disrupting potential of synthetic pyrethroids are widely studied. They are known as endocrine disruptors, for example, they interfere with the receptors of steroid hormone, and exhibit anti-mineralocorticoid, anti-glucocorticoid, and anti-estrogenic effects (Zhang et al. 2016, 2018). Bifenthrin disrupted the development of testis, inhibited the sperm maturation, delayed spermatocyte development, and reduced testosterone and 17β-estradiol in Sebastiscus marmoratus (Li et al. 2017), decreased gonadosomatic index and increased ovarian follicle diameter and 17β-estradiol in the plasma of Oncorhynchus mykiss (Forsgren et al. 2013), and significantly decreased the reproductive output of Menidia beryllina (Brander et al. 2016). Similarly, several studies documented different toxic effects of different pyrethroids on reproduction and endocrine disruption in different fish species, such as altering the dopaminergic and estrogenic pathways in Danio rerio (Bertotto et al. 2018), changing the spermatozoa quality in Oncorhynchus mykiss (Kutluyer et al. 2016), denaturing the structure of the ovaries in Heteropneustes fossilis (Monir et al. 2016), and up-regulating the vitellogenin gene expression in Oncorhynchus mykiss (Crago and Schlenk 2015), Pimephales promelas (Beggel et al. 2011), and Dario rerio (Jin et al. 2009).

Histomorphological and anatomical toxicity

Histopathological assessment in response to exogenous toxicants, environmental stressors, and abrupt deleterious environmental change is a powerful, useful, and key biomarker in ecotoxicological studies. It emerged as a key parameter in chemical risk assessment and safety studies using fish as a model organism because it is rapid and can be applied to a number of fish tissues such as kidneys, intestines, brain, gills, and liver. Moreover, it is a more sensitive biomarker than a single biochemical response because the histological changes reveal a transition of bio-organization from individual-level biochemical effect at a lower level to population-level effect at a higher level (Ullah et al. 2018a). For histopathological investigation, different important tissues of the fish are employed based on their significance and objective of the study. Gills are studied because of their involvement in different major functions including excretion, respiration, osmoregulation, acid–base balance, being primary contact organ to ambient water having the toxicants, and continuously exposed to the exogenous chemicals. Liver histopathology is often studied in aquatic toxicology because of being the detoxification center. The histopathological alterations in the intestine reveal typical stress induction in fish. Similarly, the histomorphological changes in the brain of fish can display a different level of severity, more specifically in response to synthetic pyrethroids because of their lipophilicity and efficient accumulative and absorptive capability of the fish brain.

A number of well-documented research studies demonstrated synthetic pyrethroids induced histomorphological alterations in different tissues of the exposed species of fish, for example, deltamethrin mediated different histopathological changes in the liver such as congestion, sinusoidal dilation, vacuolation, inflammatory cell accumulation, hemosiderosis, and cellular shrinkage, in the gills such as secondary lamellae folding, epithelium disruption, epithelium fusion, calcium accumulation, secondary lamellae detachment, secondary lamellae degeneration, and secondary lamellae fusion, in the brain such as spongiosis, neuronal degeneration, discoloration, and infiltration, and in the intestine such as disruption of mucosal cells, goblet cells increase, necrosis, and mucosal cells shredding of Hypophthalmichthys molitrix (Ullah et al. 2019). Similarly, a number of other histomorphological changes are observed in different tissues of different fish species in response to different synthetic pyrethroids, such as cypermethrin-exposed Tor putitora (Ullah et al. 2015) and Pangasianodon hypophthalmus (Monir et al. 2015), deltamethrin-exposed Oreochromis niloticus (Kan et al. 2012), Aphanius dispar (Al-Ghanbousi et al. 2012), Cyprinus carpio (Stará et al. 2015), Danio rerio (Parlak 2018), and Colossoma macropomum (Cunha et al. 2018), and bifenthrin-exposed Oncorhynchus mykiss (Velisek et al. 2009b).

Molecular toxicity

There is a growing body of emerging evidence, depicting the molecular toxicological impacts of synthetic pyrethroids on fish. Synthetic pyrethroids-induced DNA damage is well studied in different fish species, for example, cypermethrin induced genotoxicity in Channa punctatus (Ansari et al. 2011) and DNA damage in the gills of Prochilodus lineatus (Poletta et al. 2013) and in the erythrocyte of Labeo rohita (Ullah 2015) and λ-cyhalothrin induced DNA damage in the blood erythrocyte Prochilodus lineatus (Vieira and dos Reis Martinez 2018). Synthetic pyrethroids-mediated micronuclei induction is also well studied, for example, λ-cyhalothrin exposure led to nuclear abnormalities and induced micronuclei formation in Gambusia affinis (Gökalp Muranli and Güner 2011) and deltamethrin induced micronuclei formation in the erythrocyte of Oreochromis niloticus (Kan et al. 2012). There is also enough evidence regarding synthetic pyrethroids-mediated alterations in gene/mRNA expression, for example, permethrin altered VTG-mRNA expression in the hepatocytes of Oncorhynchus mykiss (Nillos et al. 2010). Moreover, research revealed that synthetic pyrethroids up-regulate or down-regulate several transcripts or genes, for example, bifenthrin down-regulated several estrogen-associated transcripts in Menidia beryllina (Brander et al. 2016).

Mechanism of action of synthetic pyrethroids

Synthetic pyrethroids adapt different mechanisms of toxicity; however, the primary mechanism is neurotoxicity or intoxicating the nervous system of the fish. Figure 2 shows a summary of neurotoxicity induction in response to synthetic pyrethroids and the leading subtle consequences. The schematic presentation of the mechanism of action of synthetic pyrethroids is provided in Fig. 3. Synthetic pyrethroids such as cypermethrin form cyanohydrin, which is decomposed into aldehydes and cyanides and subsequently results in the production of reactive oxygen species (Ullah et al. 2018b). Reactive oxygen species induce lipid peroxidation, increase oxidative stress leading to oxidative damage, and increase the concentration of calcium in the cytosol which in turn leads to cytotoxicity and genotoxicity in fish (Ullah 2015). Synthetic pyrethroids layer on the nerve cells and hinder the sodium channels during repolarization, which lead to an unconstrained depolarization and disturbed transmission of the driving forces. The adverse impacts of the synthetic pyrethroids are mainly attributed to their neurotoxic effects linked with the pathological retention of acetylcholine in the synaptic gaps and inhibition of acetylcholinesterase, giving rise to multiple nerve impulses and consequently leading to decreased cholinergic transmission. Moreover, exposure to synthetic pyrethroids results in trans-activated p53 leading to induction of MiR-200 and consequently resulting in apoptosis. Similarly, synthetic pyrethroids change the mitochondrial proteome, leading to mitochondrial dysfunction and subsequently leading to apoptosis, whereas the induced oxidative stress ultimately results in nigrostriatal dopaminergic neurodegeneration (Ullah et al. 2018b).

Control and prevention of synthetic pyrethroids

In order to minimize the use of synthetic pyrethroids, an adaptation of proper strategies and practicing proper management should be ensured. Synthetic pesticides should be phased out gradually and continuously till completely phased out. In order to reduce potential risks, ecological farming should be adopted instead of industrial agriculture. Multi-level approaches should be adapted for crops protection, rather than exclusively depending on pesticides. This will elevate landscape heterogeneity, increase suitable habitats for pollinators, and control pests naturally or biologically. Vegetation should be actively managed, which will increase functional biodiversity. Crops should be types-wise and cultivar-wise rotated to increase soil fertility and make crops resistant to the pest. Natural agents should be used for bio-control such as the introduction of beneficial insects, viruses, bacteria, and nematodes. This will also improve crop protection (Douglas and Tooker 2015).

Control and preventive measures against pesticides

Pesticides should be employed according to the regulation and should be used by following the stipulated regulations. Pesticides risk assessment and safety, biopesticides use in agriculture, and biotechnological advancement of agriculture should be exclusively included in future plans. The advanced form of constructed wetlands should be employed, which emerged as a more reliable management approach and treatment system for alleviating different nonpoint sources of pesticides including agricultural runoffs and draining. Through this advance system of wetlands, pesticides are evacuated via different processes such as biological processes including plant absorption or metabolism, physical processes including absorption, sedimentation, co-precipitation, and precipitation, chemical processes, e.g., hydrolysis, photolysis, cation exchange, oxidation, and reduction, and biochemical processes such as microbial deprivation (Vymazal and Březinová 2015).

Pesticides use should be avoided and restricted at local and home level via using lesser or no cosmetics. Biological pest management should be adapted. Pesticides should be locked and stored in childproof containers, cupboards, or cabinets. Pesticides with the least hazardous impacts and dangers should be used. The pesticides users, exposed masses, applicators, dealers, and farmers should be educated properly. They should be guided regarding manufacturers’ suggestions, instructions, protection equipment, and avoiding exposure of pregnant women, infants, toddlers, and children to the pesticides. Similarly, at the community level, organic farming and integrated pest management should be adopted at public buildings such as schools, hospitals, and public parks and mass awareness programs including workshops, seminars, and symposia should be arranged. The government should instruct children, pesticides dealers, pesticides applicators, pesticides users, and general masses about the hostile effects of pesticides, at the national level. The environmental protection and public health organizations should monitor and regularly assess pesticides concentration in the local environmental media. They should restrict the use of illegal and banned pesticides. Regular pesticide-based poisoning surveillance and epidemiological studies should be a part of their plan. Permissible limits for the pesticides should be established. These organizations should try to restrict pesticide use within their defined limits and should establish pesticide poisoning control and emergency center.

Conclusion

Pyrethroids have been reported from the soil, cash crops, land or terrestrial organisms, water, sediments, and aquatic organisms including fish. Therefore, it is threatening at a fish biodiversity standpoint, as pyrethroids implicated population decline of fish has been confirmed by various studies in the past. Moreover, different aquatic- and ecotoxicological studies revealed the severe toxic effects of synthetic pyrethroids on fish at various biological levels such as at molecular, cellular, histological, organismal, and population level. These studies provide a future window for further studies. To comprehensively appraise the hostile impacts of synthetic pyrethroids and explain the underlying mechanism more deeply, studies that can possibly link these different levels of biological impacts are highly recommended. Furthermore, toxicological studies regarding individual enantiomers of the pyrethroids should be undertaken. The knowledge from such experiments that are based on the enantioselective toxicity and chirality of the pyrethroids will help in developing environment-friendly pyrethroids. This will also enrich activity of pyrethroids against target insects without posing severe hostilities on nontarget organisms including fish.