Pyrethroid Insecticides

During the 1920s, pyrethrin was studied because of its potential as a precursor for synthetic organic pesticides. The first pyrethroid pesticide, allethrin, was identified in 1949. It is a type I pyrethroid because of a carboxylic ester of cyclopropane. Type II was created with the addition of a cyano group in α position. Some phenylacetic 3-phenoxybenzyl esters missing the cyclopropane but with the cyano group are also considered type II. In the 1970s, pyrethroids transitioned from mere household products to pest control agents in agriculture. Later, pyrethroids have replaced organophosphate pesticides in most of their applications the same way the latter had replaced organochlorinated pesticides before. Works on the optimisation of pyrethroids has granted them better photostability without compromising their biodegradability, as well as selective toxicity, metabolic routes of degradation and more effectivity, translating into the use of smaller amounts. Most pyrethroids present different isomers, each with different biological activity and, therefore, different toxicity. Pyrethroids account for a quarter of the pesticides used nowadays. Pyrethroids’ relative molecular mass is clearly above 300 g mol⁻¹; they are highly hydrophobic, photosensitive and get easily hydrolysed, with degradation times below 60 days. They are not persistent and mammals can metabolise them. However, pyrethroids have been proven to bioaccumulate in marine mammals and humans. Studies in mammals reported carcinogenic, neurotoxic and immunosuppressive properties and potential for reproductive toxicity mainly. Acceptable daily intake values and no observed adverse effect level values have been established at 0.02–0.07 mg (kg body weight)⁻¹ day⁻¹ and 1–7 mg (kg body weight)⁻¹ day⁻¹.

In this chapter, an overview of different aspects of current analytical methodologies such as sample preparation, extraction, purification, and instrumental analysis for pyrethroids is discussed. Recent development in sample preparation and extraction is presented. Regarding instrumental analysis, gas chromatography (GC) coupled to electron capture detection or mass spectrometry (MS) including tandem MS is generally preferred for analysis of pyrethroids. Although liquid chromatography has been used as a possible solution to reduce isomerization of pyrethroids that can occur at higher temperature, the advantages and disadvantages of different instrumental techniques are discussed here.

Insecticides are natural and synthetic chemicals used to kill unwanted pests. However, humans and insect share similar molecular targets, and thus, insecticides are potentially hazardous to human health. Several health effects might be observed in experimental animals following controlled exposure to insecticides. Synthetic pyrethroids are still a relatively novel group of insecticides widely used not only in agriculture but also in human and veterinary medicine, forestry, and public health and for commercial pest control and residential consumer use. They play a unique role in fighting against malaria in tropical areas, where the WHO recommends pyrethroids among others for indoor residual spraying (IRS) and impregnation of bed nets to prevent mosquito biting.

Bearing in mind the widespread use of these substances around the world, one can expect that the exposure of human population is common and may pose a potential health risk. Human biomonitoring (HBM) is a scientific tool that allows to assess the extent of exposure based on the measurement of a given chemical or its metabolites in human body fluids or tissues.

The need to estimate the level of exposure in different populations has led to the development of a methodology based on the measurement of urinary metabolites, as synthetic pyrethroids are rapidly metabolized in humans and excreted mainly in the urine. Human biomonitoring is used commonly in epidemiological studies and provides valuable information on the aggregate exposure.

Numerous analytical methods have been developed for the determination of metabolites of synthetic pyrethroids in human urine capable of detecting both environmental and occupational exposure.

Here, in this chapter, we summarized recent achievements in the analysis of metabolites of synthetic pyrethroids in human urine, with both separation and non-separation methods and methods of sample preparation and some aspects of instrumental analysis.

As a consequence of their increasing use, pyrethroid insecticides are recognized as a threat for nontarget species and ecosystem health. The present chapter gives a state-of-art overview of individual pyrethroid occurrence in waters and sediments worldwide, together with recent reports of their quantification in the atmospheric gas and aerosol phases. Degradation rates, transport processes, and partitioning of pyrethroids between environmental phases are reviewed. River flow efficiently transports pyrethroids to river mouths and estuaries, while pyrethroid impact on the marine environment remains difficult to appraise due to lack of comprehensive studies. Nevertheless, aquaculture arises as an important but poorly understood environmental burden. Owing to their large organic carbon pool, sediments may act as a sink for pyrethroids and impair nontarget aquatic species. Partitioning potential of pyrethroids is compared to that of other well-known legacy pollutants in the light of their position in the phase space defined by key physicochemical properties (K_OW and H′). The transport and partition of pyrethroids away from their source are strongly dependent on their half-life, but their quasi constant emissions in urban and agricultural area may compensate for their degradation, therefore sustaining the occurrence and behavior of some individual pyrethroids as “quasi persistent organic pollutants.”

Pyrethroids are one of the most heavily used insecticide classes globally because they have low mammalian toxicity. However, they are highly toxic to arthropods. Pyrethroids are ubiquitous in the aquatic environment as a result of urban (landscaping, structural pest control, home, and garden) and agricultural runoff and spray drift, often at levels that exceed water quality benchmarks established for the protection of aquatic life. Pyrethroids also enter the aquatic compartment through direct application to treat crustacean parasites in commercial fisheries. Here, we briefly review the acute and sublethal toxicities of pyrethroids with a focus on aquatic invertebrates. Our primary focus is on evidence of the evolution of adaptive pyrethroid resistance in aquatic invertebrates (sea lice (Lepeophtheirus salmonis), mosquitoes (Anopheles gambiae and A. coluzzi) black flies (Simulium spp.), and amphipods (Hyalella azteca)) driven by target and nontarget applications of pyrethroids in the aquatic environment. We explore the human health, evolutionary, ecological, and risk assessment implications of the evolution of pyrethroid resistance and suggest using resistance in the model invertebrate H. azteca to further our understanding of evolutionary toxicology in wild populations.

Pyrethroids are chiral insecticides due to the occurrence of up to three asymmetric carbons. Each stereogenic centre generates two possible spatial configurations (R- or S-enantiomers), which are non-superimposable mirrored forms. Two chiral carbons on the cyclopropane ring generate four enantiomers on Type I pyrethroids, while a third chiral centre on Type II pyrethroids generates eight enantiomers. The chiral nature of enzymatic sites favours specific insecticidal activity only for some enantiomers in commercial formulations. On the other hand, there is an overabundance of enantiomers with no desired activity or even undesired side effects. In this sense, in addition to the previously described toxicity of insecticide enantiomers to nontarget organisms, adverse effects, such as endocrine disruption, have been reported for enantiomers with low or no insecticidal action. In addition, the different metabolic pathways of pyrethroid enantiomers have consequences for their persistence and bioaccumulation profiles in biological systems. Therefore, a stereochemical approach is required to better understand the undesired impacts of pyrethroids on the environment and on human health, since the studies point to patterns of toxicity and persistence at enantiomeric levels. The occurrence of degradation/persistence patterns in environmental samples may be useful for understanding enantiomeric fate, contributing to more accurate risk assessments aimed at preventing or mitigating the impacts of continuous pyrethroid release into the environment.

Synthetic pyrethroids such as cypermethrin and deltamethrin have been widely used in Chile to treat sea lice on salmon since 2007. The environmental risks of aquaculture practices are evaluated through the use of several tools such as fugacity-based models for predicting environmental dynamics and the fate of pyrethroids after their release into the marine environment and the determination of pyrethroid occurrence in environmental samples (i.e., water and sediment). For seawater, passive sampling devices (PSDs) are proposed as a good alternative for field monitoring. Finally, by means of ecotoxicological bioassays, the effects of pyrethroids on native biota were assessed. The results show that the application of pyrethroids may trigger some unintended risks to nontarget organisms, particularly copepods, since modeled and observed concentrations in water (dissolved phase) are in the range of fractions of ng L⁻¹, but higher cypermethrin and deltamethrin concentrations in sediment in the range of 1,323 and 1,020 ng g⁻¹, respectively, have been observed. These measured concentrations were in the range of concentrations toxic to native invertebrate species in Chile. We conclude that a stricter process should be followed when pyrethroids, particularly cypermethrin, are recommended for use in combating sea lice in the Chilean salmon farming industry. Risk assessment procedures and the establishment of stricter regulations on matters such as the maximum allowable concentrations around the cages when these pesticides are applied and recommended.

Pyrethroids are used throughout the world in agricultural settings and inside and outside of residences to control pests. This has resulted in their increase in air concentration leading to inhalation, and to a lesser extent dermal, exposures to applicators, their families, and the general public. Applicators need to wear appropriate personal protection equipment (PPE) to avoid high exposures during or after spraying of crops. The various uses of the pyrethroids and pyrethrins are regulated and education often mandated to minimize potential exposures. Outdoor levels are predominantly influenced by agricultural applications which can result in drift of the pesticides to the surrounding residential communities. Drift contributions decrease with distance from application and depend upon wind conditions, temperature, and precipitation. Only a limited number of studies have directly measured pyrethroid air concentrations due to the effort involved. Rather, air concentrations and the resulting exposure estimates rely on mathematical modeling to predict the transport and distribution of pyrethroids and on biomarker measurements to determine uptake in individuals. Urinary metabolites are the most common biomarkers. However, most of the metabolites are not specific to individual pyrethroids; rather, they provide evidence that an individual or population were exposed to one or more pyrethroid pesticide. Recently, silicone bracelets have been deployed to evaluate relative personal inhalation exposures to pyrethroids as part of a scan for multiple semi-volatile organic compounds. When pyrethroids are sprayed indoors, they are absorbed onto surfaces and by house dust. The absorbed pyrethroids subsequently equilibrate with the indoor air and are distributed throughout the home resulting in multiple exposures over an extended time period. Inhalation of pyrethroids usually contributes only a small portion (<10%) of the total exposure in the general population, with ingestion of foods grown or stored with pesticides to increase crop yield having the largest contribution. Inhalation exposures can be significant though following the use pesticide application devices that release larger amounts into the air or if individuals enter a treated area without adequate ventilation or prior to the pyrethroid air concentration declining sufficiently.

For decades, the global demand for food has been increasing as a result of population growth and changes in diets. Together with this demand, the ample use of pesticides and insecticides in every step of the production chain has grown. Pyrethroids are systemic pesticides widely used in both agriculture and veterinary. They are often found on the surface of fruits and leafy vegetables or deposited on the lipid bilayer in products of animal origin. Considering the high use of pyrethroids all around the world, the potential risks of human exposure to residues in food products are a matter of great concern. Risk assessment is the scientific basis for risk management according to various international agencies. The vast majority of pesticide residue risk assessments in food are based on the toxicological evaluation of individual compounds, but assessments of cumulative exposure to multiple residues have gained notoriety. The evaluation of the “daily intake” is of great importance for human and environment safety.

The aim of this review is to provide a broad summary of the latest state of knowledge about the potential long-term adverse effects of pyrethroids on human health. The oldest and recent epidemiological studies mainly addressed respiratory, neurological, hormonal, and reproductive outcomes in adults after environmental and occupational exposures. Although several of these studies have suggested negative effects, especially on male hormonal and sperm parameters, findings were often equivocal or inconsistent across studies, and no firm and reliable conclusions can be reached yet. Regarding developmental outcomes, there is increasing evidence that fetal exposure to pyrethroids may be associated with poorer children’s neurodevelopment. Prevention measures should be considered to reduce exposure of pregnant women and children to these widely used insecticides.

This chapter summarizes the main conclusions drawn from the 11 different chapters of this book, as well as the future trends in the field of research on pyrethroid insecticides. The chapter is divided into five sections. First of all, we discuss the different pyrethroid insecticides produced and used regularly, their various applications, and their physicochemical properties, with special attention to their stereochemistry, evaluating the different isomers and enantiomers for each pyrethroid. After that, we present the developments in analytical methodologies for pyrethroid determinations in environmental and food matrices, as well as the analysis of urinary metabolites. Then, the environmental fate in aquatic ecosystems, with special attention to salmon industry, was presented, as well as pyrethroid presence in other environmental compartments such as soil or air. Bioavailabilty and bioaccumulation in terrestrial and aquatic wildlife are also discussed. And finally, the human exposure to pyrethroid insecticides through inhalation and food ingestion and the risk associated to the long-term exposure are summarized.