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The Insect repellents: A silent environmental chemical toxicant to the health
Abstract
In recent years, a large number of insect repellents have been developed with the idea of consumer benefits. In addition to already known advantageous application of insect repellents, there is increasing concern about the potential toxicity in environment leading to health caused by random use of these compounds. An increasing number of evidence suggests that insect repellents may trigger undesirable hazardous interactions with biological systems with a potential to generate harmful effects including intermediate metabolites. Biotransformation followed by bioaccumulation (vice e versa) may be an important phenomenon for toxic response of this chemicals. In this review, we have summarized the current state of knowledge on the insect repellent toxicity, including biochemical pathway alteration under in vitro and in vivo conditions considering different classes of organisms, from lower to higher vertebrate. Furthermore, we have tried to incorporate the effects of insect repellent in light of some clinical reports. We hope this review would provide useful information on potential side effects of uncontrolled use of insect repellents.
... Insect repellent is used to inhibit mosquitos' action, but no one knows the effect on health for long-term use. In addition, active substances in insect repellent contain organophosphates that harm human health; they could have hazardous interactions with the biological system in the body [2]. Therefore, insect repellent must be used properly according to the type and doses of insect repellent. ...
... The electric mosquito-repellent liquid, which contains prallethrin 1.6% insecticides, might cause hematological toxicity, and the pyrethroid group in liquid insect repellent leads to biochemical, hematological, neurological changes cytokine disturbance, and mutagenic damage in tissues [6,7]. Not only could it contribute to pollutants in the air [8], but also the active substance in both electric insect repellent is leading to biotransformation and followed by bioaccumulation that might have a toxic response in the body [2]. ...
Organophosphate compounds in insect repellent have a role in contributing to mosquito mortality but have toxic effects for humans when exposed for a long time. The research is aimed to analyze the effect of insect repellent exposure in blood leukocyte profile and histopathologic findings in lungs. The study used thirty males Rattus novergicus, which were divided into three groups, such as electric liquid insect repellent (P1) with contain 0.031% dimefluthrin, anti-mosquito coils (P2) with 0.014% dimefluthrin, and electric mat mosquito repellent with 0.566% dimefluthrin for 8 hours in 20 days respectively. Leukocyte profiles were determined by using the blood smear method, and the lung’s health was identified by histopathologic findings. Based on the results study showed mosquito coils exposure increase the lymphocytes count. Meanwhile, the electric liquid-repellent increased the basophil’s numbers. The electric mat exposure had more eosinophils, neutrophils stab, neutrophils segment, and monocytes in the blood. The leukocyte profile of each group showed there were no statistically significant differences (P-value > 0.05). Based on histopathology, lung findings showed that the electric mat exposure contributed to cells degeneration 7.5% and pleural thickening 30%. The higher dimefluthrin concentrations in insect repellents could affect leukocyte profile and lungs health.
... contact, inhalation, and at times, ingestion (Dimitroulopoulou et al., 2015). Insect repellants which are usually directly applied to the skin contain picaridin in its formulation that may contribute to skin diseases such as acanthosis and hyperkeratosis (Roy et al., 2017). A further example in a report by Awodele et al. (2014) regarding workers at a paint manufacturing company exposed to significant concentrations of heavy metals in the pigments of paint such as lead, cadmium, arsenic as well as chromium, show that the workers suffered headaches, skin irritation, and eye irritation due to inhalation, dermal absorption, and eye exposure. ...
... Consumers may unintentionally ingest the chemical substances in products; for instance, a person eats, prepares food or smokes after applying insect repellent cream or lotion without washing his hands. One of the chemical ingredients contained in insect repellent such as N, N-diethyl-3methylbenzamide (DEET), upon ingestion, might cause symptoms of nausea, vomiting, hypotension and coma (Roy et al., 2017). Besides that, young children are more susceptible to ingest any chemical substance released from a product as they tend to put everything in their mouth. ...
The numerous formulated products which are introduced to the market consist of chemical ingredients that may cause various safety and health hazards to the consumers. Therefore, it is extremely important to practice a systematic methodology to formulate products with acceptable safety and health performances. This work presents an index-based methodology to assess the safety and health hazards of the ingredients during the early formulation stage of product design. Hence, new inherent safety and health sub-indexes are introduced to improve the current safety and health hazards that are needed in formulated product design. The inherent safety and health sub-indexes are assigned with scores based on the degree of potential hazards. A higher score indicates a higher safety risk or severe health effect, and vice versa. The proposed methodology will greatly assist the users to identify the adverse safety and health effects caused by the ingredients. Hence, it is pivotal to eliminate or reduce the safety and health impacts from product usage. A case study on common ingredients used in the formulation of paint is presented on this study to describe the proposed method.
... For the past decade, studies are being conducted on plant extracts to determine their efficacy as natural insect repellent. They discovered a plant which contain citronellal chemotypes that can be effectively used as insects repellent, for example, Lemon myrtle (Roy et al., 2017) and Lemongrass (Shah et al., 2011). ...
... In this study, the essential oil used as natural insect repellent is the Lemon myrtle (Backhousia citriodora), which is an Australian native rainforest tree. The aroma and taste of Lemon myrtle are similar to a blend of lemon, lemongrass and lime, which contained 90-98% (w/w) citral (Roy et al., 2017). Lemon myrtle has several health benefits, such as for stress and insomnia, sore throat, pimples and acne, odor fighting properties, insect bites, excellent cleaning, etc (Horn et al., 2012). ...
Microemulsions are typically isotropic (clear) solutions with very small droplets (~10 to 100 nm), possess low viscosity and are thermodynamically stable. These properties have attracted much interest in producing high value-added products. In addition, there are growing interests in replacing petrochemical-based ingredients with naturally-derived materials, such as palm methyl esters and palm-based surfactants in the microemulsion system. There are numerous applications of microemulsion, for example in multipurpose liquid cleaners. The most significant properties of microemulsion for liquid cleaner applications are the improved solubilisation capacity for both polar and non-polar soil compounds due to very low values of interfacial tension achieved between aqueous and oil phases and their spontaneous formation. Other examples of microemulsion products are multipurpose liquid cleaners consisting of natural insect repellent for hard surfaces of household and industrial applications, microemulsion-spray natural insects repellent, and microemulsion-aerosol insecticides. This paper highlights the research and development of palm-based microemulsion system consisting of natural insect repellent for multipurpose liquid cleaners.
... The most common biting midge control method is using chemical pesticides. However, extensive application of insecticidal chemicals has many side effects and is harmful to human health [12][13][14][15][16][17]. Many insect repellents may cause symptoms such as breathing problems, eye and skin irritation, cough, sneezing, headache, asthma, and itching [18]. ...
Biting midge Forcipomyia taiwana is one of the common pests in East Asia. Their nuisance and blood-sucking behavior causes problems not only for human health but also for some industries. This study aims to evaluate the effectiveness of spraying alkaline water on controlling biting midge population and potential side effects of such approach on non-target organisms. Laboratory experiments were conducted to evaluate the effect of alkaline water on oviposition site preference of female biting midges as well as crickets. Effect of alkaline water on distribution pattern of earthworms was also examined. Besides, we also performed field manipulative studies by long term spraying of alkaline water to evaluate the effects on biting midge density, microalgae abundance and ground arthropod communities. The results of laboratory experiments showed that female biting midges laid significantly fewer eggs in surface treated with alkaline water. However, alkaline water treatment did not significantly affect the oviposition site choice of crickets and distribution pattern of earthworms. Result of field manipulations showed that long-term spraying of alkaline water could significantly reduce the abundance of soil microalgae and density of biting midges, but did not affect the diversity of non-target ground arthropods. These results demonstrate that long-term spraying of alkaline water could decrease biting midge density without harming co-existing non-target organisms and therefore is a potentially eco-friendly approach to control such pest.
... Pollution associated to pesticide accumulation is an emergent global problem [39]. Even low-toxic products applied in low concentrations can be leached by rain and accumulate in aquatic environments, causing pollution and environmental imbalance. ...
Nano-emulsions of essential oils (EO) and their chemical constituents are promising raw materials for the ecological control of Tribolium castaneum. Curcuma longa Linn is a plant known for the properties of its rhizome which is used in food, health and hygiene products. Its leaves are by-products with no commercial value, but with unexplored bioactive volatile constituents. This study aims to evaluate the repellency of nano-emulsions containing the EO from leaves of C. longa or its three main chemical constituents against T. castaneum. The representative mixture of EO extracted in four different months showed p-cymene (26.0%), 1,8-cineole (15.1%) and terpinolene (15.5%) as major compounds. Nano-emulsions of EO (HLB 16.7), terpinolene (HLB 15.0), 1,8-cineole (HLB15.0) and p-cymene (HLB 15.0) were repellent at concentrations of 11 μg/cm2 (EO, terpinolene and p-cymene) and 1.1 μg/cm2 (1,8-cineole). The EO nano-emulsion droplet size increased linearly over time, remaining below 300 nm for 35 days and below 600 nm for 80 days. The EO nano-emulsion proved to be a green alternative to synthetic pesticides, as it was safe against the bioindicator Chlorella vulgaris. Terpinolene, 1,8-cineol and p-cymene were able to inhibit the enzyme telomerase from T. castaneum in an in silico assay, which may explain the repellency of these samples. This study provides ideas for the utilization of EO from leaves of C. longa as raw material of new environmentally friendly plant-derived nanobiopesticides.
... The partition coefficient octanolwater is of particular importance since it is associated with the ability of substances to penetrate through organic membranes [3]. Solubility in water is closely related to the ability of a substance to accumulate in water bodies, as well as to penetrate into groundwater [4]. All these physicochemical properties were studied only for a number of ecotoxicants, since some substances are either extremely difficult to separate in pure form, or they have not yet been synthesized. ...
Modern development vector of environmental monitoring leads to elaboration of analytical methods for qualitative and quantitative analysis of different ecotoxicants. Many studies face the lack of information on isomers and homologues of already studied compounds. This problem cannot always be solved experimentally due to the difficulty of separating or synthesizing certain compounds; the use of group theories of solutions will help partly; using them, solubility in water or partition coefficient between two immiscible solvents is calculated for ecotoxicants. These parameters are important for solving the analytical and ecological problems. The partition coefficient in the octanol – water system is associated with a possibility of accumulation of different compounds in living organisms; the partition coefficient in the hexane – acetonitrile system can be used in gas chromatographic analysis. Solubility in water is closely associated with accumulation of ecotoxicants in water bodies, as well as with their ability to be transferred. This paper presents the capabilities of the UNIFAC model for solving physicochemical problems using the example of calculating the properties of real ecotoxicants on the basis of the available thermodynamic data. All the obtained calculated values were compared with those determined experimentally. In the case of pyrene derivatives, solubility data were obtained for the first time using a correlation group model to calculate the heat of fusion and melting temperature.
... An example is spraying the air freshener with the intention to remove the musty odor as one of the symptoms of pre-SBS in addition to the use of insect repellent, whether electrically, burning, or spraying aerosols. However, several studies (23)(24)(25) are concerned about the use of these chemicals because they are harmful to the health of occupants. In practice, people find it difficult to change habits unless they attempt to reduce the use of chemical substances. ...
The condition of the space environment as a result of the interaction of physical, chemical, and biological factors, in a complex way, can have acute and chronic effects on the physical and psychological health of the occupants. This was the incidence of sick building syndrome, and efforts to reduce and eliminate the syndrome were presented in this case study. The aim was to produce healthy indoor quality and sustainable
use by its occupants. The methods used minimum Indonesian standards regarding procedures for planning the housing environment in urban areas. The analysis of changes in the indoor volume employed indoor height variables for a particular floor area to apply flexibility to various building layouts. The variability of changes in the pollutant exposure area and indoor air volume was expressed as a relative change. Setting indoor height was a significant determinant for maintaining healthy indoor air quality through diluting air against pollutants. An additional 0.5 m of room height could increase the air volume by 15%-20% greater than the increase in the pollutant area. It was an effective method both at the design and building renovation stages. The physical and thermal mitigation was generally performed at the building use stage. Some of the conducted approaches included air conditioning (AC), electric or manual ventilation, and chemical-phytotechnological mitigation indoors by adding chemicals to space. The methods of indoor depollution during the use of buildings are still necessary using physical and chemical-phytotechnological methods by placing decorative plants.
... This physical deterrence strategy could be preferable to chemical deterrents, which have been criticized for being harmful to nontarget organisms. 16,17 ■ MATERIALS AND METHODS Mosquito Rearing and Colony Maintenance. Ae. aegypti colonies were reared in an insectary kept at 28°C and 40% relative humidity, in a 12 h light, 12 h dark regime. ...
Mosquito-borne diseases such as dengue, chikungunya, and malaria have long been a health and economic burden in our society. Such illnesses develop after the pathogen, here arboviruses, are transmitted to humans by female mosquitoes during blood meals. In the case of dengue and chikungunya, such pathogens are transmitted to humans by infected Aedes aegypti females. Prior to feeding the insects rest on vertical surfaces. In this work, a surface roughness threshold was observed for live Aedes aegypti colonies, and below a root-mean-squared roughness of S q < 0.124 μm the mosquitoes were physically incapable of gripping vertical substrates. This roughness threshold was unaffected by surface wettability or relative humidity. The importance of topographical feature height was understood using a claw-hooking model considering friction. Local defects above this threshold allowed claw hooking to take place, emphasizing the importance of surface uniformity. An antimosquito coating was developed that reduced surface roughness below this threshold when it was applied to realistic surfaces such as wood, brick, wall laminates, and tile. Lowering the surface roughness below the threshold reduced the number of mosquitoes capable of landing on the surfaces by 100%: i.e., no mosquitoes were able to adhere to the treated surfaces. The ability to completely inhibit Aedes aegypti females from landing on surfaces represents a new vector-borne disease control strategy that does not suffer from the nontarget toxicity, resistance, or ecosystem disruption associated with conventional chemical control strategies.
... Few reports on the impact of UV filters on aquatic species are available in literature indicating their role as hormone disruptor, growth inhibitor and bioaccumulator (Wang et al., 2021b). Furthermore, insect repellents are personal care products used to prevent different surfaces (skin/clothing etc.) from the attack of insects and their associated diseases (Roy et al., 2017). N,N-diethyl-m-toluamide (DEET) is one of the most common active component in insect repellents and has proven to be slightly toxic to aquatic lives causing neurotoxicity of its neuronal targets (Campos et al., 2016). ...
Due to rapid urbanization and globalization, an enormous use of pharmaceuticals and personal care products (PPCPs) has resulted their excessive release in water bodies leading to several environmental issues. This release into the environment takes place via household sewage, hospital effluents, manufacturing units and landfill sites etc. The pharmaceuticals and personal care products (PPCPs) are recently listed as emerging contaminants having many adverse effects towards aquatic life, human beings, and the whole ecosystem. The alarming threats of PPCPs demand efficient methods to cope up their hazardous impacts. The conventional wastewater remediations are not specifically designed for the removal of PPCPs and hence, they require advanced technologies and materials for their elimination to ensure water safety. Among various methods employed so far, photocatalysis is considered to be one of the most cost effective and eco-friendly method but it requires a suitable candidate as a photocatalyst. Thanks to the magnetic nanocomposites which have improved the limitations (poor stability, agglomeration, and difficult separation, etc.) of classically used nanomaterials. Magnetic nanocomposites contain at least one component having magnetic properties making their separation easy from the aqueous media after the photodegradation phenomenon. These can be further functionalized with other materials to obtain maximum advantage as photocatalyst. Few examples of such functionalized nanocomposites are inorganic material based magnetic nanocomposites, carbon based magnetic nanocomposites, biomaterial based magnetic nanocomposites, metal-organic framework based magnetic nanocomposites and polymer based magnetic nanocomposites etc. This review covers the global environmental issue of water pollution especially with respect to the PPCPs, their occurrence in aqueous environment and toxic effects on living beings. A comprehensive discussion of the recently reported functionalized magnetic nanocomposites for the photocatalytic removal of PPCPs from water is the main aim of this review. The synthetic/morphological approaches of various functionalized magnetic composites and their mechanism of action are also elaborated. The possible research challenges in the field of magnetic nanocomposites and future research directions are discussed to apply magnetic nanocomposites for wastewater treatment in near future.
... Although synthetic repellents tend to be more effective and/or longer-lasting than botanical repellents [2], concerns have been raised over the safety of these repellents to the human being as well as potential toxicity to the ecosystem and the resistance to synthetic repellents [3][4]. Recent studies have found essential oils as potential candidates for mosquito repellents. ...
Dengue is a mosquito-borne viral disease that has caused millions of dengue virus infections per year in the world. Mosquito repellent is an effective way to prevent mosquito bites and the spread of mosquito-borne disease. In this study, we extracted essential oil from the bark of Cinnamomum cassia collected in Viet Nam and analyzed its chemical composition. We then evaluated the spatial repellent of the essential oil basing on WHO guidelines. The essential oil was hydro-distilled and extracted with chloroform to obtained an average yield of 2.55% (w/w). The main component of oil is trans-cinnamaldehyde with a content of 99.24%. The repellent index of essential oil at concentrations of 25%, 15%, 5%, 1% and DEET 10% after 90 minutes was 73.33%, 57.14%, 33.33%, 17.65% and 12.50%, respectively. In conclusion, the Cinnamomum cassia essential oil is an effective and promising repellent in preventing dengue mosquitoes.
... Insect repellents are PCPs that, through their application on the skin, clothing or other surfaces have the ability to deter insects from approaching and resting (Fink et al., 2017). These compounds play an important role to prevent mosquito bites (Roy et al., 2017). One of the most common uses is on human skin, particularly in tropical environments and in temperate zones during the summer season where mosquitoes are particularly abundant. ...
Personal care products (PCPs) are part of the large and growing family of emerging contaminants (ECs). Many daily products such as sunscreens, toothpaste, make-up products, perfume, and others, fall under this definition, and their use is increasing exponentially. Furthermore, the degradation of some components of these products is limited. Indeed, they are able to easily reach and accumulate in aquatic systems, representing a new class of contaminants. Moreover, due to their chemical properties, they can interfere at different biological levels, and for this reason, they need to be thoroughly investigated. We have reviewed the literature on PCPs, with a special focus on the adverse effects on the freshwater zebrafish (Danio rerio). The aim of this work is to provide a careful assessment of the toxicity of these compounds, in order to raise awareness for more conscious and responsible use.
... Synthetic pesticides are used for public health sprays as chemicals with insecticidal properties such as organochlorines, organophosphorus, carbamates, pyrethroids, synthetic pyrethroid pyrroles, and phenyl pyrazole (Schofield, 1993;Pal, 1994). The excessive, unlimited, uninterrupted, indiscriminate, and continuous application of synthetic insecticides as principal agents results in the unwarranted toxic or lethal effects on non-target organisms, the development of resistance in mosquitoes, and more importantly, potential toxicity in the environment and adverse effects on human health, posing a great threat to life and the environment (Shrivastava et al., 2002;Kawada et al., 2009;Koures et al., 2012;Raveen et al., 2014;Rathy et al., 2014;Hemlatha et al., 2015;Roy et al., 2017). So, there is an urgent need for an alternative source to synthetic insecticides across the globe. ...
Mosquitoes are considered a most common human enemy; causes mortality, morbidity, monetary and social disruption. It plays a significant role in endemic conditions for Malaria, Japanese encephalitis (JE), Dengue, Yellow fever, Chikungunya, and Filariasis etc. The prolonged use of synthetic insecticides raises the risk of unintended harmful or fatal consequences such as biological amplification, mosquito resistance development, and negative impacts on environmental quality and non-target species, including human health. So that there is urgent need to find natural and environmentally safe phytochemicals as an alternative to synthetic pesticides from indigenous plant sources that are accessible to the whole local community. Phytochemicals are botanicals that are naturally occurring pesticides produced from floral resources, and they are a viable alternative to synthetic insecticides in Integrated Mosquito Management (IMM). Plant based insecticides are less toxic, delay the development of resistance because of its structure and easily biodegradable. In this article, we have summarized the recent studies published in 2020 and 2021 on the biopesticide effect of botanicals with their suitable solvents which possess strong potential against mosquitoes larva. We also focused on their mode of action on the target population, variance in larvicidal efficacy among Culex, Aedes, and Anopheles mosquitoes, polarity of solvents employed during extraction, active component, and prospective improvements in biological control.
... Most of the popular commercial tick repellents and acaricidal products are based on synthetic chemicals (Bissinger and Roe 2010). Previous studies have investigated potential issues using synthetic chemicals, due to their potential to pollute and persist in the environment, causing bioaccumulation, which results in toxicity towards humans and other animals (Roy et al. 2017). ...
Repellent and acaricidal activity of essential oils extracted from three varieties of basil (Ocimum basilicum L.) were evaluated on blacklegged ticks (Ixodes scapularis Say) and American dog ticks (Dermacentor variabilis Say) in laboratory conditions. Essential oils were extracted and characterized through gas chromatography-mass spectrometry, and tested at different concentrations for long-term repellent activity using horizontal bioassays. In addition, basil essential oils were combined with an inert material (i.e., granite rock dust) with known insecticidal and miticidal properties to assess acaricidal activities against adult ticks. Among the tested basil varieties, var. Jolina essential oil at 15% vol/vol concentration repelled 96% of tested ticks up to 2 h post-treatment. The EC50 for I. scapularis nymphs was 4.65% vol/vol (95% confidence interval: 4.73–4.57). In acaricidal tests, the combination of essential oil from var. Aroma 2 at 10% wt/wt with rock dust resulted in 100% tick mortality after only 24 h post-exposure, with a LD50 of 3.48% wt/wt (95% CI 4.05–2.91) for freshly prepared treatment tested on I. scapularis adults. The most common compounds detected in basil essential oils by GC–MS were linalool (52.2% in var. Nu Far, 48.2% in Aroma 2, 43.9% in Jolina), sabinene (6.71% in Nu Far, 8.99% in Aroma 2, 8.11% in Jolina), eugenol (11.2% in Jolina, 8.71% in Aroma 2), and estragole (18.2% in Nu Far). The use of essential oils alone and in combination with rock dust provides an innovative and environmentally friendly approach for managing ticks and inhibiting vector-borne disease transmission.
... The widespread utilization of synthetic pesticides poses hazards for both the environment and human health due to their toxicity and poor biodegradability [1,2]. In addition, the use of some chemical pesticides or their residues may be hazardous for non-target organisms, including humans and beneficial organisms [3,4]. ...
Chemical insecticides have many harmful effects, including as foodborne residues and environmental contaminants, as well as side effects on natural enemies and serious risks for human health. The use of plant-derived essential oils (EOs) as effective bio-agents has become an essential component of integrated pest management. In this study, the contact toxicity, deterrent, and repellent activities were evaluated for essential oils obtained from Mentha piperita, Mentha longifolia, Salvia officinalis, and Salvia rosmarinus, grown at high altitudes in the Taif region, KSA, on Aphis punicae. Furthermore, the toxicity of these EOs against the predator Coccinella undecimpunctata was estimated. A total of 17, 14, 16, and 26 compounds were identified in the EOs of M. piperita, M. longifolia, S. officinalis, and S. rosmarinus, respectively. They showed a variation in the major compounds: M. piperita (Carvone, 61.16%), M. longifolia (Pulegone, 48.6%), S. officinalis (Eucalyptol, 33.52%), and S. rosmarinus (α-pinene, 36.65%). A contact toxicity test on A. punicae imago and C. undecimpunctata larvae showed that LC50 were approximately four-fold greater for all tested EOs towards aphids compared to towards the predator, while the two species of Salvia sp. were more effective than the other two species of Mentha sp. The LC50 values on A. punicae ranged from 1.57 to 2.97 µg/mL, while on C. undecimpunctata larvae, they ranged from 5.96 to 10.33 µg/mL. Furthermore, the EOs of two species of Salvia sp. showed excellent repellence and deterrence against A. punicae. In conclusion, the tested EOs, especially those from Salvia sp., have been shown to be promising natural aphicides, repellent, and deterrent against A. punicae, and they are safe for important insect predators
... In the absence of vaccines, repellents could be an option to minimise the risk of contracting different mosquito-borne diseases (Islam et al. 2017). Synthetic repellents and insecticides are used to control Ae. aegypti; however, the frequent use of this substance results in vector resistance and environmental contamination (Roy et al. 2017). Currently, DEET (N,N-diethyl-meta-toluamide), the most frequently used mosquito repellent, represents an important tool for mosquito control (Zhu et al. 2018;Dennis et al. 2019). ...
Essential oils have been tested as insect repellents with moderate results. The most important characteristics of these oils are that they possess a high chemical diversity of compounds, are cheap, and are easily accessible. Recently, mixtures of essential oils have shown a higher repellent activity than a single essential oil, probably by increasing the effectiveness with the number of chemicals in the mixture. The repellent effect of essential oils from citronella (Cymbopogon nardus), mint (Mentha arvensis), rosemary (Rosmarinus officinalis L.), clove (Eugenia caryophyllata), and their mixture was evaluated against Aedes aegypti. The mixture of citronella, mint, and clove essential oils (1:1:1) was also evaluated in an adulticidal bioassay. Additionally, chemical identification was performed using these commercial essential oils. The 1:1:1 mixture of citronella, mint, and clove essential oils was as effective as the commercial repellent DEET at lower doses (5%), and it is a good candidate for an adulticide at higher doses (20–25%). The chemical constituents of the essential oils were mostly terpenes and oxygenated terpenoids. These findings were discussed in terms of economic and environmental frameworks.
... Outro prejuízo ambiental referente ao uso de inseticidas está relacionado aos efeitos em organismos não alvo, como animais aquáticos, répteis, anfíbios, plantas e polinizadores 15 . Não só os inseticidas ambientais, mas aqueles aplicados na pele apresentam risco ao meio ambiente 16 . Avaliar os potenciais prejuízos para os organismos não alvo, bem como a persistência no ambiente, faz parte do processo de registro de um produto para que este seja seguro para seres humanos, e para os ecossistemas onde serão inseridos 17 ...
Introdução: Arboviroses transmitidas pelo Aedes aegypti têm grande relevância para a saúde pública, sendo o controle químico do vetor uma importante estratégia de mitigação. Entretanto, o uso intensivo de pesticidas está associado a seleção de insetos resistentes e impacto ambiental. Por isso, é essencial desenvolver e regulamentar novos produtos, eficazes e sustentáveis. Objetivo: Descrever os requisitos para regulação de inseticidas e repelentes no Brasil, à luz de orientações internacionais. Comparar os ativos regulamentados no país com os disponíveis nos Estados Unidos (EUA) e União Europeia (UE). Por fim, realizar um levantamento de estudos ecotoxicológicos dos ativos empregados no controle vetorial. Método: Revisão narrativa de instrumentos regulatórios nacionais e internacionais, literatura científica, consulta a agências regulatórias e ao ECOTOX Knowledgebase. Resultados: As normas brasileiras trazem exigências consoantes com as internacionais. Todos os ativos disponíveis nos EUA têm monografia aprovada pela Anvisa; já a UE mostrou-se mais restritiva. Há menos repelentes tópicos disponíveis no Brasil e na UE, comparando-se com EUA. Muitos dos inseticidas aprovados para controle vetorial representam risco para organismos não alvo. Ainda assim, não identificamos quaisquer estudos para alguns dos produtos no banco de dados pesquisado. Conclusões: A UE mostrou-se a agência mais restritiva com relação ao registro de inseticidas. Existe a necessidade de guias com orientações específicas sobre o desenvolvimento de produtos inovadores para o controle do mosquito, bem como de ferramentas de busca com maior transparência na página da agência brasileira. Finalmente, esta revisão reitera a importância de análises ecotoxicológicas mais abrangentes para os produtos em questão, considerando seu potencial dano ambiental.
... IR3535 is a transparent, colorless, odorless liquid mixture that has proven to be safe, as demonstrated by acute toxicity, local tolerability, phototoxicity and repeated-dose toxicity assays. 15 Further, IR3535 is non-genotoxic and has thus been considered a safe insect repellent ingredient by the US Environmental Protection Agency since 1999. Moreover, this compound is classified as a hypoallergenic substance based on skin irritation tests. ...
BACKGROUND
IR3535 is among the most widely used synthetic insect repellents, particularly for the mitigation of mosquito-borne diseases such as malaria, yellow fever, dengue, and Zika, as well as to control flies, ticks, fleas, lice, and mites. These insects are well-known vectors of deadly diseases that affect humans, livestock, and crops. Moreover, global warming could increase the populations of these vectors.
RESULTS
Here, we performed IR3535 dose-response analyses on Drosophila melanogaster, a well-known insect model organism, using electrophysiology and binary food choice assays. Our findings indicated that bitter-sensing gustatory receptor neurons (GRNs) are indispensable to detect IR3535. Further, potential candidate gustatory receptors were screened, among which GR47a was identified as a key molecular sensor. 0.1%–0.4% ranges of IR3535 affected larval development and mortality. Additionally, DEET (i.e., another commonly used insecticide) was found to exert synergistic effects when co-administered with IR3535.
CONCLUSION
Our findings confirmed that IR3535 directly activates bitter-sensing GRNs, which are mediated by GR47a. This relatively safe and highly potent insecticide can be largely used in combination with DEET to increase its efficiency to protect livestock and crops. Collectively, our findings suggest that the molecular sensors elucidated herein could be used as targets for the development of alternative insecticides.
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... Synthetic pesticides are used for public health sprays as chemicals with insecticidal properties such as organochlorines, organophosphorus, carbamates, pyrethroids, synthetic pyrethroid pyrroles, and phenyl pyrazole (Schofield, 1993;Pal, 1994). The excessive, unlimited, uninterrupted, indiscriminate, and continuous application of synthetic insecticides as principal agents results in the unwarranted toxic or lethal effects on non-target organisms, the development of resistance in mosquitoes, and more importantly, potential toxicity in the environment and adverse effects on human health, posing a great threat to life and the environment (Shrivastava et al., 2002;Kawada et al., 2009;Koures et al., 2012;Raveen et al., 2014;Rathy et al., 2014;Hemlatha et al., 2015;Roy et al., 2017). So, there is an urgent need for an alternative source to synthetic insecticides across the globe. ...
Mosquitoes are counted as the oldest human enemy; play a significant role in the health
hazardous of the community. It has endemic conditions for Malaria, Japanese encephalitis (JE), Dengue, Yellow fever, Chikungunya, and Filariasis, etc. However, JE cases are recently declined, it showed 44,000 new cases and 6000 fatalities from between 2008 to 2014 in Uttar Pradesh and Bihar. The prolonged use of synthetic insecticides raises the risk of unintended harmful or fatal consequences such as biological amplification, mosquito resistance development, and negative impacts on environmental quality and non-target species, including human health. Phytochemicals are botanicals that are naturally occurring pesticides produced from oral resources, and they are a viable alternative to synthetic insecticides in Integrated Mosquito Management. Plant-based insecticides are less toxic, delay the development of resistance because of their structure, and easily biodegradable. Secondary metabolites derived from botanicals act as both a larvicidal agent and a defense mechanism in and of themselves. In this article, we have summarized the recent studies on the effectiveness of phytochemical compounds such as Saponine, steroids, isoavonoids, essential oils, alkaloids and tannins have strong potential especially against mosquito's larva. We also focused on their mode of action on the target population, variance in larvicidal efficacy among Culex, Aedes, and Anopheles mosquitoes, the polarity of solvents employed during extraction, active component nature, and prospective improvements in biological control. This review will reveal the idea of natural plant sources that are cost-effective and eco-friendly
than synthetic chemicals against the mosquito and it will help reduce the risk of vector-borne diseases.
... 9 Therefore, the uncontrolled consumption of synthetic repellents in general and DEET as a special case has risen many warnings about their safety on personal basis in addition to their probable effect on environmental pollution. 10 Thiamine hydrochloride (TH) or vitamin B1 is essential for aerobic metabolism, cell growth, transmission of nerve impulses and acetylcholine synthesis. Its deficiency causes disorders like beriberi, Wernicke-Korsakoff syndrome, optic neuropathy, Leigh's disease, African Seasonal Ataxia, and central pontine myelinolysis. ...
Thiamine hydrochloride (TH) was thought to exert a good insect repellent activity. The purpose of this work was to develop a formulation that releases TH in sustained regimen on human skin. Long lasting protection against mosquito bites was achieved. Pullulan acetate (PA) was used to prepare TH nanospheres. Optimal system was incorporated in Pluronic® hydrogel. Formulae were tested for in-vitro release and ex-vivo permeation. Complete protection time (CPT) was done adopting Kaplan-Meier survival function for the synthetic repellent (DEET), TH solution and nanospheres in hydrogel. Release profile of TH solution, nanospheres and nanosphere-loaded hydrogel (DG) demonstrated an added effect of DG, where t 1/2 was 11.2±1.4 h. SEM for DG showed homogenous dispersion of nanospheres inside the matrix of the gel. Ex-vivo permeation showed only 0.761±0.04% of TH in hydrogel permeated the skin after 12h, while 44.98±3.2% permeated when TH solution was applied. Clinical study revealed a significant difference in CPT between TH solution with either DEET or (DG) (p<0.05), and no significant difference between DEET and DG with CPT 400±31 and 360±18 min, respectively (P > 0.05). The high efficacy of TH-loaded hydrogel rendered it a successful alternative for DEET, offering long protection against mosquito bites.
... The most widely marketed insect repellent worldwide is n,n-diethyl-meta-toluamide (DEET) because it is a broadspectrum repellent that is effective against various mosquito species and ticks. However, since treatment with synthetic chemicals such as DEET is associated with human health risks [14], most people hesitate to apply DEET products to their skin or clothing and deliberately look for other DEET-free repellent products. For these reasons, alternative natural repellents are now very appreciated by consumers, and essential oils of aromatic plants are considered the most promising candidates [15,16]. ...
Arthropod-borne infectious diseases cause many deaths and a major economic burden worldwide. Repellents play an important role in protecting people from infectious biting arthropods. The repellency of veratraldehyde, a known food additive, and the WJ-1041 formulation containing 10% veratraldehyde was tested against Aedes albopictus and Culex pipiens pallens females and Haemaphysalis longicornis nymphs using arm-in-cage, indoor or filter paper tests. Veratraldehyde exhibited repellency similar to or lower than that of n,n-diethyl-meta-toluamide (DEET) against A. albopictus, but in H. longicornis, the activity of veratraldehyde was better than that of DEET. The repellency of the 10% veratraldehyde solution was comparable to that of 20% DEET against the two mosquitoes. When comparing repellency between the WJ-1041 formulation (10% veratraldehyde) and 10% DEET against C. pipiens pallens, A. Albopictus and H. longicornis, the two showed similar repellency and complete protection time (CPT) values. However, there was a small difference depending on the tested insects. The absorption of veratraldehyde via skin was minimal, if at all. The pharmacokinetic parameters (Cmax and Tmax) of veratraldehyde in blood samples of rats were not different from those of the control group. Based on these results, veratraldehyde has high potential to be commercialized as a repellent agent against infectious disease-borne pests in the near future.
... Age ( Various scientific studies have shown the adverse impact of insect repellent and incense smoke exposure through animal and epidemiological studies [93][94][95]. Liu et al. found that a large concentration of volatile organic compounds (VOCs), PAHs, aldehydes and fine particles, which pose an acute and chronic health risk, could be generated by mosquito coils [96]. Besides, mosquito coils are the most toxic insect repellents than mat and liquid repellents [93] due to a higher lipid peroxidation response and increased freeradical substances that can alter the cell membrane and cause damage to DNA [95]. ...
This study aimed to assess the association of exposure to particle-bound (PM2.5) polycyclic aromatic hydrocarbons (PAHs) with potential genotoxicity and cancer risk among children living near the petrochemical industry and comparative populations in Malaysia. PM2.5 samples were collected using a low-volume sampler for 24 h at three primary schools located within 5 km of the industrial area and three comparative schools more than 20 km away from any industrial activity. A gas chromatography–mass spectrometer was used to determine the analysis of 16 United States Environmental Protection Agency (USEPA) priority PAHs. A total of 205 children were randomly selected to assess the DNA damage in buccal cells, employing the comet assay. Total PAHs measured in exposed and comparative schools varied, respectively, from 61.60 to 64.64 ng m−3 and from 5.93 to 35.06 ng m−3. The PAH emission in exposed schools was contributed mainly by traffic and industrial emissions, dependent on the source apportionment. The 95th percentiles of the incremental lifetime cancer risk estimated using Monte Carlo simulation revealed that the inhalation risk for the exposed children and comparative populations was 2.22 × 10−6 and 2.95 × 10−7, respectively. The degree of DNA injury was substantially more severe among the exposed children relative to the comparative community. This study reveals that higher exposure to PAHs increases the risk of genotoxic effects and cancer among children.
... Furthermore, synthetic repellents' application to exposed skin to protect from mosquito bites is a common approach for reducing the transmission of mosquito-borne diseases and irritating bites [16]. However, there are concerns about their toxicity and safety [17,18]. These limitations have necessitated researchers to develop new compounds to combating mosquitos and preventing mosquito bites. ...
It is estimated that one million deaths per year are caused by mosquito-borne diseases worldwide. While preventing such diseases is possible and, of course, more manageable than attended to treat patients. Prevention of these diseases is based on improving the environment (e.g., decreased stagnant water) and controlling mosquitoes in immature and adult forms. Resistances among mosquitoes, environmental pollution, and adverse effects on non-target species, such as humans, are some of the major disadvantages of using chemical insecticides. Essential oils (EO)s with a wide range of activities on mosquitoes, including ovicide effect, larvicide effect, pupicide effect, adulticide effects, and repellent effect, are proper alternatives for synthetic ones. However, their practical usage is questioned due to their volatility and lower efficiency than synthetic samples. In recent years, researchers have attended to overcome these challenges by formulating EOs into nanoformulations. In this study, existing reports on exploiting EO-based nanoformulations in mosquito control have been categorized as larvicides, repellents, and adulticides. Moreover, by discussing the reported results, the appropriate nanoformulations for each purpose have been suggested; polymeric nanoparticles are more suitable for larvicides, lipid nanocarriers are more suitable for repellents nanoemulsions are more suitable for adulticide.
... Citronellal gets a lot of attention for its repellency efficiency against mosquito 20,21,32,59,60 , although its exact mode of action is still unknown. This lack of knowledge regarding the mechanism involved in its activity can be attributed to the inconsistency of the diverse methods used to determine the repellency of volatiles in insects [60][61][62][63][64][65][66][67][68] . In this study, we used a Y-tube olfactory meter which included in its design, most of the critical elements necessary for determining the mosquito-repellent activity of citronellal in vitro. ...
Anopheles gambiae s.s. is a key vector of Plasmodium parasites. Repellents, which may be a promising alternative to pesticides used to control malaria mosquitoes. Although citronellal is a known mosquito repellent, its repellency characteristics are largely unknown. Determining the specific odorant-binding proteins (OBPs) and odorant receptors (ORs) that detect and transfer the citronellal molecule in A. gambiae s.s. will help to define the mode of action of this compound. In this research, we assessed the repellent activity of citronellal in A. gambiae s.s. using a Y-tube olfactory meter, screened candidate citronellal-binding OBPs and ORs using reverse molecular docking, clarified the binding properties of predicted proteins for citronellal using fluorescence competition binding assay. Results showed that citronellal had a dosage effect on repelling A. gambiae s.s.. The 50% repellent rate was determined to be 4.02 nmol. Results of simulated molecular docking showed that the only proteins that bound tightly with citronellal were AgamOBP4 and AgamORC7. Fluorescence competitive binding assays confirmed the simulations. This research determined that citronellal was captured by AgamOBP4 and transmitted to AgamORC7 in A. gambiae s.s.. Our study will be beneficial in the further understanding the repellent mechanism of citronellal against A. gambiae s.s..
... Furthermore, the long-term exposure of DEET and some other pesticides produced mood and cognitive changes in animal experiments that had consistency with neuro-inflammatory changes in hippocampal brain areas experienced by GW veterans [13,14]. Even, some neurotoxicity signs and genotoxic effects were reported to be received by DEET in a few pieces of research [15]. Although, the environmental risk assessment results of DEET indicate that is unlikely to produce an adverse biological effect in aquatic systems [16]. ...
With the increasing concern of emerging contaminants (ECs), advanced oxidation processes (AOPs) have been widely investigated to fulfill the drinking water quality because of the potential adverse health effects of ECs. Accordingly, N,N-diethyl-meta-toluamide (DEET) is selected as a model compound belonging ECs to monitor its ultrasonic oxidation which is one of the most popular AOPs in a dual frequency ultrasonic reactor (DFUR) using low-frequency probe (20 KHz) and high-frequency transducer (640 KHz) type sources. DFUR was calorimetrically optimized in terms of power densities of both ultrasonic sources in order to provide the highest sonochemical yield with efficient energy output. Pseudo-first order kinetic equation was applied to results by measuring the concentration decreasing during the oxidation reactions. The pseudo-first-order rate constants, k, increased from 7.8x10-3 min-1 (640 kHz, R2=0.930) to 13.5x10-3 min-1 (DFUR, R2=0.990), by contrast, the rate constant was only 0.7x10-3 min-1 (R2=0.281) for 20 kHz low-frequency ultrasonic source. DEET oxidation was evaluated with the presence of different gas saturation (Ar, Air, O2, and N2); addition of hydrogen peroxide (PO), persulfate (PS) and monoperoxysulfate (MPS) and PO concentration effect (molar ratio of DEET:PO; 1:1, 1:2, 1:5, 1:10 and 1:20). The DEET oxidation rate was calculated as 35.8 x10-3 min-1 (R2=0.994) in the presence of Argon gas saturation, while it was 13.5 x10-3 min-1 (R2=0.990) when no gas bubbling. Therefore, the main degradation pathway was predicted as pyrolysis taking place inside the cavitation bubble where DEET molecules can reach. On the other side, a lower degradation rate in the presence of PO, PS, and MPS than that of no additives has indicated that the bulk phase degradation pathway for some part of DEET molecules are still occurred.
... Since the transmission of these viruses depends on the presence of the competent mosquito vectors Aedes aegypti and Aedes albopictus [3][4][5], measures such as repellent-or insecticide-treated nets, indoor spraying, or personal protection measures are needed to protect people from mosquito-borne infections [6]. To date, mosquitoes are mainly controlled by synthetic insecticides and repellents, but besides the quick development of resistance by insect pests, their use is often prohibitively expensive, unsustainable, and it poses relevant risks to humans and environmental health [7]. ...
Mosquito-borne arboviruses diseases cause a substantial public health burden within their expanding range. To date, their control relies on synthetic insecticides and repellents aimed to control the competent mosquito vectors. However, their use is hampered by their high economic, environmental, and human health impacts. Natural products may represent a valid eco-friendly alternative to chemical pesticides to control mosquitoes, and mosquito-borne parasitic diseases. The aim of this work was to combine the chemical and sensorial profiles with the bioactivity data of Salvia spp. essential oils (EOs) to select the most suitable EO to be used as a repellent and insecticide against the invasive mosquito Aedes albopictus (Diptera: Culicidae), vector of pathogens and parasites, and to describe the EOs smell profile. To do this, the EOs of four Salvia species, namely S. dolomitica, S. dorisiana, S. sclarea, and S. somalensis were extracted, chemically analyzed and tested for their bioactivity as larvicides and repellents against Ae. albopictus. Then, the smell profiles of the EOs were described by a panel of assessors. The LC50 of the EOs ranged from 71.08 to 559.77 μL L−1 for S. dorisiana and S. sclarea, respectively. S. sclarea EO showed the highest repellence among the tested EOs against Ae. albopictus females (RD95 = 12.65 nL cm−2), while the most long-lasting, at the dose of 20 nL cm−2, was S. dorisiana (Complete Protection Time = 43.28 ± 3.43 min). S. sclarea EO showed the best smell profile, while S. dolomitica EO the worst one with a high number of off-flavors. Overall, all the EOs, with the exception of the S. dolomitica one, were indicated as suitable for “environmental protection”, while S. dorisiana and S. sclarea were indicated as suitable also for “Body care”.
... Although synthetic insecticides such as organophosphate, pyrethroid, etc. have reduced the Aedes mosquito population successfully, the continuous increase in the use of the synthetic insecticides has led to mosquito resistance [6], and more importantly, potential toxicity in the environment and adverse effects on human health [7,8]. Besides, repellents are often used to protect against mosquito bites by applying on human skin. ...
Dengue is one of the most dangerous vector-borne diseases transmitted by Aedes mosquitoes. The use of mosquito repellents to protect human hosts and insecticides to reduce the mosquito population is a crucial strategy to prevent the disease. Here, we reported larvicidal and repellent activities of Mentha arvensis L. essential oil against Aedes aegypti, the main vector of the disease. The essential oil was extracted by hydro-distillation from the aromatic plant grown in Vietnam. The yield was 0.67% based on the weight of fresh leaves. The essential oil was analyzed by gas chromatography-mass spectrometry (GC-MS). The main components were menthol (66.04%), menthyl acetate (22.19%), menthone (2.51%), and limonene (2.04%). Toxicity test on Aedes aegypti larvae showed that the median lethal concentrations, LC50 and LC90 were 78.1 ppm (part per million) and 125.7 ppm, respectively. Besides, the essential oil showed excellent repellency on Aedes aegypti mosquitoes. At 25%, 50%, and 100% concentration, the respective complete protection times (CPTs) were 45 min, 90 min, and 165 min. When adding 5% vanillin to the essential oil (25%), the complete protection time of the essential oil increased up to 120 min. In conclusion, the EO from Mentha arvensis L. has been shown to be a promising natural larvicide and repellent against Aedes aegypti mosquitoes.
... (Hemiptera: Micronectidae) in Vietnam (Nam et al. 2000), and water scavenger beetle Hydrochara affinis (Coleoptera: Hydrophilidae) in Korea (Baek et al. 2014). Despite the limitations in application, environment-friendly mosquito control programs, including biological control, are encouraged by some mosquito control agencies or academic societies such as Society for Vector Ecology, in order to circumvent the harm caused by insecticide application to natural ecosystems and humans (Yanola et al. 2015, Roy et al. 2017. ...
In order to elucidate the poorly understood relationships between mosquito larvae and their predatory aquatic insects in urban and suburban areas of tropical Southeast Asia, where vector‐borne diseases are prevalent, aquatic insects were sampled from 14 aquatic habitats in residential areas of Chiang Mai, northern Thailand, during the rainy season (July to November) in 2016. Correlations among biological variables, densities of major predatory aquatic insect groups (i.e., Odonata, Coleoptera, and Hemiptera: OCH group) in wetlands and artificial lentic habitats, and the density of mosquito larvae were analyzed. Among the sampled mosquito larvae, Culex spp. were the most abundant, and both OCH density and water quality were major determinants of Culex spp. density (rs = −0.302 and −0.396, respectively). Logistic regression analyses indicated that the probability of Culex spp. occurrence was significantly and negatively correlated with OCH density. Furthermore, high macrophyte abundance was associated with higher predator density, potentially reducing mosquito density. Hemipteran predators were most negatively correlated with Culex spp. density, regardless of whether macrophyte abundance was high or low (rs = −0.547 and −0.533, respectively). Therefore, hemipteran predators were the most important aquatic insect predators in the urban and suburban residential areas of Chiang Mai, Thailand, and OCH species, such as the hemipteran Micronecta scutellaris, could be used as biological control agents against mosquitoes in the region.
... In the Po lagoons, we have also identified icaridin (or picaridin), i.e. another insect repellent (Table 3). Developed more recently than DEET, icaridin represents with the previous compound the two most common synthetic substances of this group of consumer products (Roy et al., 2017). It is characterized by moderate hydrophobicity (log K ow 2.57) and toxicity to aquatic organisms (Liu et al., 2018). ...
A comprehensive analytical screening has been applied for the first time to surficial sediment samples collected from seven lagoons of the Po River Delta. This screening has been used to gain further insights into the exposure conditions potentially present in the Po lagoons. Despite a certain degree of variability was observable within the lagoons, this study confirmed the general tendency that the northernmost Caleri lagoon is less contaminated than the other lagoons of the delta, which conversely are more exposed to river waters and particularly to the Po River. This screening identified 23 suspect and 8 target contaminants in the investigated lagoons. The target contaminants were quantified by means of authentic analytical standards, and showed concentration values ranging from 0.01 ng/g for irbesartan, to 80 ng/g for DEET, respectively. The surveyed molecules included pharmaceuticals, industrial chemicals, personal care products, pesticides as well as illicit substances mainly originating from inland waters and the anthropic activities of their (sub)basins. Notably, many of these chemicals, such as flame retardants (TPhP, TCEP, TCPP), phthalates (DnBP, DiBP, DnOP), synthetic hormones (norethisterone, trenbolone) and several parabens (methyl-, ethyl-, butylparaben) are endocrine disruptors and have been detected in all Po Delta lagoons. This study showed that the lagoons of the Po Delta are exposed to a multitude of chemicals substances whose multiple interactions are very likely. As suggested by other studies conducted in this area, the disrupting activities of chemicals capable to interfere with the endocrine system of aquatic organisms should be thoroughly investigated.
... DEET, DEPA, IR3535, and Picaridin) are commonly used as active ingredient in insect repellent products 22 . However, an increasing number of evidences suggest that such synthetic repellents may trigger undesirable hazardous interactions with biological systems, with a potential to generate harmful effects 7,22,23 . As an alternative, over the last 50 years, many plant species have been screened as potential sources of repellents and insecticides. ...
Abstract Repellents are a main tool to prevent the outbreak of mosquito-borne diseases that represents a threat for millions of people worldwide. Plant-based products are very promising, low-toxic and eco-friendly alternative to synthetic repellents. Here, we performed an olfactory screening of the essential oils (EOs) of Artemisia verlotiorum Lamotte (Asteraceae), Lavandula dentata L. (Lamiaceae), and Ruta chalepensis L. (Rutaceae) for their possible use as ingredients in topical repellents. The EOs smell profiles were then matched with their repellence against the mosquito Aedes albopictus (Skuse) (Diptera Culicidae). To obtain a more complete bioactivity description, we also tested the EOs oviposition deterrence and the larvicidal activity. The best smell profile was associated with A. verlotiorum EO, while R. chalepensis EO showed the lowest overall pleasantness. All the EOs had a significant activity as skin repellent against Ae. albopictus, deterred the oviposition in the field, and exerted a clear larvicidal activity. Beside the best smell profile, A. verlotiorum EO showed also the longest lasting repellent effect, assuring the complete protection of the treated skin against Ae. albopictus for a time 60% longer than the synthetic repellent DEET.
... Synthetic contact insecticides, fumigation, and insect repellents, such as pyrethroids-cyfluthrin and deltamethrin-phosphine, methyl bromide, and DEET (N,N-diethyl-3-methyl-benzamide) have been applied to protect stored crops and products over long periods. However, random use of these conventional insecticides and repellents has triggered severe environmental and health problems [7][8][9][10]. Botanical insecticides have long been thought to be attractive alternatives for pest control because of their safety and eco-friendly properties [11][12][13]. ...
Toxic and repellent effects of the essential oil from Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. were evaluated against Lasioderma serricorne and Liposcelis bostrychophila. The essential oils (EOs) from roots (ER) and leaves (EL) of A. heterotropoides were obtained separately by hydrodistillation and characterized by gas chromatography-mass spectrometry (GC-MS) analysis. Major components of ER and EL included methyleugenol, safrole, and 3,5-dimethoxytoluene. Both ER and EL of A. heterotropoides showed certain toxicity and repellency against L. serricorne and L. bostrychophila. 3,5-Dimethoxytoluene, methyleugenol, and safrole were strongly toxic via fumigation to L. serricorne (LC50 = 4.99, 10.82, and 18.93 mg/L air, respectively). Safrole and 3,5-dimethoxytoluene possessed significant fumigant toxicity against L. bostrychophila (LC50 = 0.83 and 0.91 mg/L air, respectively). The three compounds all exhibited potent contact toxicity against the two insect species. Here, the EL of A. heterotropoides was confirmed to have certain toxicity and repellency against stored product insects, providing a novel idea for the comprehensive use of plant resources.
Personal care products (PCPs) are products used in cleaning, beautification, grooming, and personal hygiene. The rise in diversity, usage, and availability of PCPs has resulted in their higher accumulation in the environment. Thus, these constitute an emerging category of environmental contaminants due to the potential of its constituents (chemical and non-chemical) to induce various physiological effects even at lower concentrations (ng/L). For analyzing the impact of the PCPs constituents on the non-target organism about 300 article including research articles, review articles and guidelines were studied from 2000 to 2023. This review aims to firstly discuss the fate and accumulation of PCPs in the aquatic environment and organisms; secondly provides overview of environmental risks that are linked to PCPs; thirdly review the trends, current status of regulations and risks associated with PCPs and finally discuss the knowledge gaps and future perspectives for future research. The article discusses important constituents of PCPs such as antimicrobials, cleansing agents and disinfectants, fragrances, insect repellent, moisturizers, plasticizers, preservatives, surfactants, UV filters, and UV stabilizers. Each of them has been found to display certain toxic impact on the aquatic organisms especially the plasticizers and UV filters. These continuously and persistently release biologically active and inactive components which interferes with the physiological system of the non-target organism such as fish, corals, shrimps, bivalves, algae, etc. With a rise in the number of toxicity reports, concerns are being raised over the potential impacts of these contaminant on aquatic organism and humans. The rate of adoption of nanotechnology in PCPs is greater than the evaluation of the safety risk associated with the nano-additives. Hence, this review article presents the current state of knowledge on PCPs in aquatic ecosystems.
Ethyl 3-(N-butylacetamido) propanoate (EBAAP) is one of the most widely used mosquito repellents worldwide, and is also commonly used to produce cosmetics. Residues have recently been detected in surface and groundwater in many countries, and their potential to harm the environment is unknown. Therefore, more studies are needed to fully assess the toxicity of EBAAP. This is the first investigation into the developmental toxicity and cardiotoxicity of EBAAP on zebrafish embryos. EBAAP was toxic to zebrafish, with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). EBAAP exposure also reduced body length, slowed the yolk absorption rate, induced spinal curvature and pericardial edema, decreased heart rate, promoted linear lengthening of the heart, and diminished cardiac pumping ability. The expression of heart developmental-related genes (nkx2.5, myh6, tbx5a, vmhc, gata4, tbx2b) was dysregulated, intracellular oxidative stress increased significantly, the activities of catalase (CAT) and superoxide dismutase (SOD) decreased, and malondialdehyde (MDA) content increased significantly. The expression of apoptosis-related genes (bax/bcl2, p53, caspase9, caspase3) was significantly upregulated. In conclusion, EBAAP induced abnormal morphology and heart defects during the early stages of zebrafish embryo development by potentially inducing the generation and accumulation of reactive oxygen species (ROS) in vivo and activating the oxidative stress response. These events dysregulate the expression of several genes and activate endogenous apoptosis pathways, eventually leading to developmental disorders and heart defects.
Repellent and acaricidal activities of essential oils (EO) extracted from common yarrow (Achillea millefolium L.) and main chemical components were evaluated against Ixodes scapularis and Dermacentor variabilis adult ticks and nymphs. Flowers and leaves were collected from two locations, Harvest Moon trail (HMT) and Port Williams (PW) in Nova Scotia (Canada), and EO were extracted via hydro-distillation. Samples were analyzed using GC-MS, and differences in chemical composition and quantity of compounds detected were reported in relation to the collection site and plant parts. EO were both rich in germacrene D (HMT EO 21.5 ± 1.31% wt; PW EO 25.5 ± 0.76% wt); however, HMT flower EO has a higher concentration of camphor (9.9 ± 0.08% wt) compared to PW flower EO (3.0 ± 0.01% wt). Significant acaricidal activity was reported against I. scapularis adult ticks, particularly for HMT flower EO with a LD50 of 2.4% v/v (95% confidence interval = 1.74–3.35) at 24 h post-exposure. Germacrene D had the lowest LD50 of 2.0% v/v (95% CI 1.45–2.58) among the four compounds after 7 days. No significant acaricidal effect was observed on D. variabilis adult ticks. Yarrow PW flower EO exerted repellent activity towards I. scapularis nymphs (100% repellency up to 30 min); however, repellency significantly declined over time. Yarrow EO exert promising acaricidal and repellent properties, that may be used to manage Ixodes ticks and the diseases they vector.
The use of formulations containing botanical products for controlling insects that vector human and animal diseases has increased in recent years. Plant extracts seem to offer fewer risks to the environment and to human health without reducing the application strategy’s efficacy when compared to synthetic and conventional insecticides and repellents. Here, we evaluated the potential of extracts obtained from caninana, Chiococca alba (L.) Hitchc. (Rubiaceae), plants as a tool to be integrated into the management of Aedes aegypti, one of the principal vectors for the transmission of arborviruses in humans. We assessed the larvicidal and repellence performance against adult mosquitoes and evaluated the potential undesired effects of the extracts on non-target organisms. We assessed the susceptibility and predatory abilities of the nymphs of Belostoma anurum, a naturally occurring mosquito larva predator, and evaluated the C. alba extract’s cytotoxic effects in mammalian cell lines. Our chromatographic analysis revealed 18 compounds, including rutin, naringin, myricetin, morin, and quercetin. The methanolic extracts of C. alba showed larvicidal (LC50 = 82 (72–94) mg/mL) activity without killing or affecting the abilities of B. anurum to prey upon mosquito larvae. Our in silico predictions revealed the molecular interactions between rutin and the AeagOBP1 receptor to be one possible mechanism for the repellent potential recorded for formulations containing C. alba extracts. Low cytotoxicity against mammalian cell lines reinforces the selectivity of C. alba extracts. Collectively, our findings highlight the potential of C. alba and one of its constituents (rutin) as alternative tools to be integrated into the management of A. aegypti mosquitoes.
Essential oils are volatile compounds that contain chemical constituents with different biological activities, including repellent activity. Thus, the investigation of aromatic species with repellent potential against insect vectors, such as Aedes aegypti (Linnaeus 1762) has increased. The present study evaluated the spatial activity index, the chemical composition of the essential oil from Croton tetradenius leaves, as well as the effective repellent concentration and protection time against female Ae. aegypti mosquitoes. For the biological assays, mosquitoes with up to seven days of emergence were used, which were subjected to different essential oil concentrations in a non-ionic emulsion. The chemical composition was determined by gas chromatography, coupled with mass spectrometry and flame ionization detector. The essential oil showed a higher repellent spatial activity for the concentrations of 200 and 300 mg/cm². The estimated concentration of 14.1 and 163.4 mg/cm² showed an effective repellency of 50 and 99%, respectively. Regarding the protection time, 84% landing inhibition, and 100% blood-feeding inhibition were observed for the concentration of 200 mg/cm² within 240 min. Thirty-three compounds were identified in the chemical characterization, and camphor (30.25%), p-cymene (13.39%), α-terpinene (10.59%), and γ-terpinene (5.32%) were the major compounds. Therefore, the essential oil from Croton tetradenius leaves proved to be a promising repellent alternative in protecting against the Aedes aegypti mosquito.
Pyrethroid insecticides are one of the most widely used insecticides globally, posing a severe threat to human health and the environment. In this study, we applied high-throughput organic analysis testing combined with high-volume solid-phase extraction (Hi-throat/Hi-volume SPE) to elucidate the occurrence of 11 pyrethroid insecticides in lake water (n = 37), tributary river water (n = 15), and tap water (n = 6) in the Taihu Lake Basin. Permethrin was found to be the major contributing pyrethroid insecticide (detection rate = 100%). The concentrations of pyrethroid insecticides from different lake regions were revealed in the following descending order: southern > eastern > western > northern. The principal component analysis and multiple linear regression demonstrated that landscape maintenance, agricultural cultivation, and livestock breeding were the main sources of pyrethroid insecticides in the Taihu Lake surface water. Moreover, runoff input plays an important role in their accumulation, while the surrounding rivers contribute 2292 kg of pyrethroid insecticides to Taihu Lake annually. The risk assessment analysis demonstrated that pyrethroid insecticides pose a high risk to both the ecological environment and the surrounding human populations, thereby necessitating effective countermeasures. Furthermore, the pyrethroid insecticides in the Yangtze River Delta region have to be controlled. Overall, this is the first study focused on China that revealed the residue levels in water sources and tap water.
Arthropod-borne viral diseases are important public health threats in tropical countries. In the Americas, diseases such as Dengue, Zika, Chikungunya, Mayaro, and Yellow fever, which are mainly transmitted by Aedes aegypti L. are responsible for high rates of morbidity and mortality in the populations. The incidence of those viruses has increased in the last few years, due to the decrease of vector control programs, as well as, the resistance of this vector in front of many products that have been used in this proposal. Plant-based products such as essential oils are a promising alternative for A. aegypti control. In this context, the present work aims to investigate the seasonality effect on the larvicidal potential and safety of essential oils from 4 endemic plants of the Brazilian Amazon, as well as to verify their larvicidal activity and safety. The species were collected in the rainy and dry periods (Eugenia uniflora L., Lantana camara L., Ocimum basilicum L., Plectranthus neochilus Schlrt.). The essential oils were extracted by hydrodistillation and chemical composition was determined by gas chromatography coupled to mass spectrometry. The larvicidal activity was performed according to the methodology recommended by the World Health Organization. The safety of the oil use was evaluated against two non-target organisms: Artemia salina Leach and Danio rerio Hamilton Buchanan. Essential oils of E. uniflora, L. camara, O. basilicum, P. neochilus, presented as major compounds, in both collection periods, the substances Curzerene, Germacrene D, Methyl chavicol and, Caryophyllene, respectively. However, showed a qualitative and quantitative variation of this composition. All oils showed promising results against Ae. aegypti larvae with LC50 between 41.7 - 275.8 μg/mL. They were efficient against Ae. aegypti but showed high toxicity to non-target organisms, requiring additional safety studies. Despite these results showing that those essential oils are not ideal larvicides because they presented toxicity to non-target organisms, bioprospection is a promising tool to help reduce the dissemination of arboviruses, and they can use in artificial breeders of Ae. aegypti larvae, where water will not be reused for human consumption or have other cohabiting organisms.
Mosquitoes have already developed resistance toward most of the commercial synthetic repellents. Therefore, searching for new potential alternatives is the need of the hour. In the study, we evaluated the repellency of six citrus-derived essential oils against Aedes aegypti using the arm-in-cage method. The results showed more than 50 percent repellency up to 4 h exposure time at 1 mg/cm2 area for three Citrus spp. with maximum repellency of 81 percent for C. aurantifolia. Therefore, two of the major constituents of C. aurantifolia EO, namely citral and limonene, were chosen further for the repellency test. The results showed higher efficacy of compounds than crude oil. EC50 for commercial standard repellent DEET was determined for comparison under the same experimental conditions. To understand the possible mode of action of citral, limonene and DEET, in-silico interactions of these compounds with odorant-binding proteins (OBP1 and OBP22) and acetylcholinesterase (AChE) enzymes were studied. The findings revealed positive docking of all of these compounds having affinity values in the range of − 6.0 to − 6.9 kcal/mol. Overall, the study demonstrated that limonene and essential oils of Citrus aurantifolia could be the best potential alternative for synthetic repellents.
Microencapsulation is a promising method for controlling and prolonging the release of safer, bio-based insect repellents, which can be used for protection against many vector-borne endemic diseases. Geraniol is an effective insect repellent; however, its encapsulation in gelatin/gum Arabic, and its long-term retention have not been studied to date. In this study, complex coacervation was used to obtain novel geraniol-containing microcapsules using gelatin/gum Arabic. The effect of processing conditions on the size and morphology of the microcapsules and the subsequent release properties was investigated. Optimal conditions included a coacervation pH of 4.45 and a crosslinking pH of 6.0. Lower mixing rates produced single core capsules with larger particle size (93 µm). Higher mixing rates resulted in multi-core capsules with smaller average particle sizes (34 µm). The geraniol contents of microcapsules were found to be 90%, 68%, and 73% for mixing rates of 700 RPM, 1000 RPM, and 1300 RPM, respectively. Microcapsule formulations showed excellent release profiles into humid air without any burst release, with retentions of 80%, 74%, and 76% at 26 days for mixing rates 700 RPM, 1000 RPM, and 1300 RPM, respectively. Encapsulation of geraniol results in longer-lasting retention compared to similar systems; hence it can be used as textile coatings for use in insect repellent clothing or incorporated into various carrier solutions for application as an area treatment. Our research highlights the possibility of tuning diffusion characteristics based on microcapsule morphology opening new applications for this technique.
Metabolic resistance-associated enzymes primarily detoxify xenobiotics and endogenous substances. Insecticides that could inhibit these enzymes may potentiate their toxic effect on the targeted pest by hampering the metabolic detoxification pathways. In a recent investigation, we identified eugenol as a potential larvicide against Aedes aegypti. Therefore, the goal of this work was the in-silico study of eugenol with metabolic detoxification enzymes while using the organophosphate temephos as a control. Temephos is said to inhibit acetylcholinesterase (AChE), an important enzyme of the central nervous system. So, AChE was also used for docking study. Modeller9.21 software was used to create models of the said enzymes. Ligands were eugenol and temephos, and the receptors were detoxifying enzymes and AChE. Docking was performed using autodock vina software, and their binding interactions are presented using UCSF Chimera and ligplot. Results revealed good docking of both the compounds, with binding affinity values ranging from –5.4 to –6.9 kcal/mol for detoxifying enzymes, which appeared to be in a comparable range. Again, both the ligands docked well with the AChE enzyme with binding affinity value of –6.5 kcal/mol for eugenol and –7.9 kcal/mol for temephos. Since, ligands act by binding to receptors, it is thought that eugenol and temephos work in a similar way and might block metabolic detoxification enzymes. In light of the negative environmental consequences and side effects of temephos, eugenol, which has a comparable binding affinity for the metabolic enzymes studied, might be recommended as a viable alternative to temephos for use as a mosquito larvicide.
Pharmaceuticals and personal care products (PPCPs) are chemicals of anthropogenic origin. With the developing technology, the intensive use and unconscious disposal of PPCPs, whose varieties, numbers, and spread around the world have increased rapidly, have been a serious concern in recent years. Medical and personal wastes, sewage, and industrial and agricultural activities are the main sources of PPCPs. Not only drugs used by people, but also medicines, fertilizers, and similar substances used in agricultural activities can leak into the soil and mix with groundwater and drinking water and cause serious pollution. Although PPCPs are not classified as persistent organic pollutants, many of them exhibit properties similar to persistent organic pollutants. Because PPCPs are continuously discharged into the environment, they are included in the so-called pseudo-persistent class. This review summarizes current information on the classification of PPCPs, their occurrence in the environment, their impact on the functioning of the ecosystem, their transport to soil and water, their infiltration, and environmental exposure to PPCPs.
The use of household insecticides is an alternative solution to prevent mosquito bites.Most of the household insecticides sold in Indonesia have pyrethroid active ingredients, permethrin,which is available in the aerosol formulation. Inappropriate use of household insecticides can reducemosquito susceptibility. The objectives of this study are to describe the use of household insecticidesand susceptibility of Aedes sp. against permethrin in Sorosutan Yogyakarta. This study used a crosssectionalsurvey design. This study was conducted in December 2018–April 2019 in 354 householdsin Sorosutan which were randomly selected based on proportional sampling. Interviews about thehousehold insecticides were conducted with the owner or resident of the house. The susceptibilitytests used impregnated paper with permethrin 0.75%. The survey results showed that 25.14% ofthe houses use household insecticides. The insecticide used were aerosol, electric mosquito repellents,and mosquito coils containing active ingredients of the pyrethroid group, namely dimefl uthrin,transfl uthrin, prallethrin, cypermethrin, and metofl uthrin. The susceptibility test results showed adecrease in mosquito susceptibility where the population of Aedes sp. in Sorosutan has been resistantagainst permethrin. The continuous use of insecticides with pyrethroid active ingredients can developmosquito resistance against permethrin because all pyrethroids have the same mode of action. Thisstudy concludes that only a small proportion (25,14%) of the households used insecticides with theactive ingredients used mainly in the pyrethroid group (dimefl uthrin, transfl uthrin, prallethrin,cypermethrin, and metofl uthrin) and the population of Aedes sp. in Sorosutan has been resistant topermethrin.
Due to the extensive use and incomplete removal, pharmaceutical and personal care products (PPCPs) are introduced into the water continuously. It has been proved that the unique properties of PPCPs are influential to organisms and the environment, and gradually affect human health. In this paper, the toxicological effects of typical PPCPs, and the environmental behavior of PPCPs in aquatic are reviewed. The risk assessments of PPCPs in the water are summarized. The research directions of environmental toxicology research of PPCPs in the future are proposed. Many PPCPs were found to be toxic or even highly toxic toward aquatic organisms, and have the potential for bioaccumulation. It is essential to study the acute and long-term toxicity of PPCPs and their metabolites, evaluate the environmental behaviors and make a reasonable assessment of ecotoxicology and human health risks of PPCPs.
Studies have reported the presence of ethyl butylacetylaminopropionate (IR3535) in waters, and the content of this repellent is expected to rise significantly in the future. There are extremely scarce data in the literature regarding the behavior of IR3535 and its derivatives in water. The present work reports the results obtained from experiments conducted under controlled conditions aiming at investigating the transformation of IR3535 in chlorinated water, in addition to an attempt to identify its disinfection by-products (DBPs). The work also reports the findings of analyses conducted in swimming pool water samples which sought to investigate the presence and content of IR3535 and its targeted DBPs in these samples. The results obtained in the controlled experiments show that IR3535 is not completely degraded under the chlorinated conditions evaluated and 9 DBPs were tentatively identified. The presence of IR3535 was detected in both adults and children’s pool water samples at concentrations ranging from 62 ng L⁻¹ to 114 ng L⁻¹. Some of the DBPs identified in the controlled experiments were also detected in the pool water samples. The toxicity of the 9 DBPs identified was evaluated using the QSAR model, where some by-products presented mutagenic and carcinogenic properties.
Background
N’,N’-diethyl-m-toluamide (DEET) is the most widely used repellent substance worldwide. It is formulated as aerosol, solution, lotion, gel and patches. However, the official compendia report monographs to analyze only DEET drug substance and solution.
Objective
In this study an isocratic HPLC method was validated to assay DEET in lotion, gel and solution, under the same analytical conditions.
Method
The method was validated according to ICH requirements and DEET detection was achieved at around 11 min, using C-18 column, a mobile phase composed by methanol, acetonitrile and water pH 4.5 (45:10:45), flow rate at 1 mL min-1 and detection at 270 nm.
Results
A linear relationship was observed in the range of 2.5 to 100 µg mL-1, the method was precise (relative standard deviation < 2%) and accuracy was demonstrated by DEET recovery values ranging from 99.5 to 100.2%. The specificity was studied by a forced degradation test, where degradation products were observed after alkaline degradation and ultraviolet radiation. Appropriate resolution between DEET, degradation products and excipient peaks indicated the method specificity. Robustness was evaluated by a full factorial design, and no effect on DEET assay was observed under simultaneous variation in analytical parameters. The method was applied to assay nine marketed formulations, demonstrating its good applicability.
Conclusion
The validated HPLC method was successfully applied to the quantitative analysis of DEET in lotion, gel and solution, contributing to improve the quality control and the efficacy of these formulations.
The ubiquity of lizard in homes and has caused huge problem to human. They are one of the very important agents to transmit Salmonella that cause food poisoning towards human being. Through this research the potential of Kaffir lime peel toward lizard was reported. The process to produce Kaffir lime extract is hydrodistillation extraction method. The repellency test of essential oil will be assess at different concentration (0%, 25%, 50%, 75% and 100%). The duration of observation will be test from 3 to 6 hour duration. The results has shown that the concentration up to 50% and above of essential oil from Kaffir lime peel extraction may reflect the lizards in a state of discomfort.
Trichloroethylene (TCE), a commonly used industrial solvent and degreasing agent, is known to cause trichloroethylene hypersensitivity syndrome (THS) with multi-system damage, including skin, liver and kidney. Clinical evidence have shown that the kidney injury occurs in THS and our previous studies suggested that the terminal complement complex C5b-9 deposited in impaired renal tubules induced by TCE with unclear mechanisms. In the present study, we questioned whether activation of the complement system with renal deposition of C5b-9 contributes to TCE-induced kidney injury in THS. We established a BALB/c mouse model of TCE sensitization with or without pretreatment of exogenous CD59, a C5b-9 inhibitory protein. H&E staining, PAS staining, and biochemical detection of urinary proteins were performed to assess renal function. Deposition of C5b-9 and expression of CD59 were evaluated by immunohistochemistry. Sub-lytic effects of C5b-9 in tubular epithelial cells were assessed by lactate dehydrogenase (LDH) cytotoxicity assay. Expression of endocytosis receptors megalin and cubilin on proximal tubules were assessed by immunofluorescence and qRT-PCR. We found that TCE sensitization induced structural and functional changes of renal tubules in mice, associated with the deposition of sub-lytic C5b-9 on proximal tubular epithelial cells. TCE sensitization decreased proximal tubule uptake of filtered proteins and renal expression of megalin and cubilin, phenotypes that were attenuated by pretreatment with exogenous CD59. Overall, our findings reveal a novel mechanism underlying sub-lytic C5b-9 acting on megalin and cubilin, contributes to the renal tubules damage by TCE exposure.
Despite the ubiquitous occurrence of N,N-diethyl-m-toluamide (DEET) in aquatic systems, assessments evaluating the toxicity of DEET on phytoplankton species are summed to a single study on a unicellular green alga. In particular, the toxicological effects of DEET in dinoflagellates are unknown. In this study, we employed the mixotrophic dinoflagellate Gymnodinium instriatum as a study system to evaluate acute effects of DEET on the oxygen flux of laboratory cultures. This study reports an inhibitory reaction model of DEET described by the equation y = 4.99x(0.54), where y represents the percent inhibition of oxygen flux and x represents DEET concentration in mg L(-1) (r(2) = 0.98). Based on this model, the effective concentration of DEET needed to reduce O2 flux by 50 % (EC50) for this species was found to be at 72.9 mg L(-1). The reported EC50 is more than five times lower than the EC50 reported previously for the unicellular green algae Chlorella protothecoides. This study raises the question of the potential toxicological effects of DEET in dinoflagellates, in particular those populations inhabiting systems characterized by low water circulation such as enclosed bays and lagoons.
A 37-year-old male with prior medical history of profound developmental delay experienced seizure and cardiac arrest following ingestion of 6 ounces of a 40% N, N-diethyl-meta-toluamide (DEET) containing solution. The patient was unresponsive, acidemic, tachycardic and hypotensive on presentation. Over three hospital days, the patient's vitals recovered to baseline but he remained unresponsive and areflexic with fixed and dilated pupils. Non-contrast brain magnetic resonance imaging showed cerebral edema, transtentorial and tonsillar herniations. A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method was utilized for the analysis of postmortem plasma blood and urine samples of a lethal case of DEET intentional ingestion. The method combined the use of C18 SepPak cartridges for solid phase extraction and reversed-phase HPLC. One urine and five blood samples from this patient were analyzed for DEET concentration. Mixtures of serum/urine postcentrifuge were eluted and reduced to 1 mL using a solvent evaporator. Blood in ethylenediaminetetraacetic acid (EDTA), whole blood, serum, blood with heparin and urine DEET concentrations were 9.84, 9.21, 10.18, 8.66dl and 0.642 mg/dL, respectively. All samples were collected <1 h postingestion. Although seizures and cardiac toxicity have been described in other case reports, this case is atypical due to the exceptional dose ingested and the timing of the fluid test samples being drawn so soon following exposure. Although a widely used and extremely safe insect repellent, DEET can be highly toxic in large but easily obtainable doses.
N,N-diethyl-m-toluamide (DEET) has been registered for commercial use as an insect repellent for over five decades, and is used widely across the world. Concerns over the safety of DEET first emerged during the 1980s after reports of encephalopathy following DEET exposure, particularly in children. However, the role of DEET in either the illness or deaths was and remains purely speculative. In response to these cases a number of reviews and investigations of DEET safety were carried out. Here we examine the methods used and information available to determine the safety of DEET in humans. Animal testing, observational studies and intervention trials have found no evidence of severe adverse events associated with recommended DEET use. Minor adverse effects noted in animal trials were associated with very large doses and were not replicated between different test species. The safety surveillance from extensive humans use reveals no association with severe adverse events. This review compares the toxicity assessment using three different models to define the risk assessment and safety threshold for DEET use in humans and discusses the clinical consequences of the thresholds derived from the models.
The theoretical risks associated with wearing an insect repellent should be weighed against the reduction or prevention of the risk of fatal or debilitating diseases including malaria, dengue, yellow fever and filariasis. With over 48 million European residents travelling to regions where vector borne diseases are a threat in 2009, restricting the concentration of DEET containing repellents to 15% or less, as modelled in the 2010 EU directive, is likely to result in extensive sub-therapeutic activity where repellents are infrequently applied. Future European travellers, as a consequence of inadequate personal protection, could potentially be at increased risk of vector borne diseases. Risk assessments of repellents should take these factors into account when setting safe limits.
The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (five males and five females) after dermal application of approx. 3g of a formulation containing 20% IR3535(®), i.e. the total amount of IR3535(®) applied were between 1.94 and 3.4mmol/person (418-731mg/person). Blood and urinary concentrations of IR3535(®) and its only metabolite, IR3535(®)-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535(®) were at or below the limit of quantification (0.037μmol/L). IR3535(®)-free acid peaked in plasma samples 2-6h after dermal application. C(max) mean values were 5.7μmol/L in males, 3.0μmol/L in females and 4.2μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9μmol/Lh in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535(®) and IR3535(®)-free acid were detectable, however, only very small amounts of IR3535(®) were found. Concentrations of IR3535(®)-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4h and 8h after dermal application). Overall, IR3535(®) and IR3535(®)-free acid excreted with urine over 48h representing 13.3±3.05% of the dose applied. Since IR3535(®) is rapidly and extensively metabolized, and IR3535(®)-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535(®)-free acid and IR3535(®) represents the total extent of absorption of IR3535(®) in humans. Based on the results of this study, the skin penetration rate of IR3535(®) is 13.3% in humans after dermal application.
In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.
We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort.
Studies were identified from the AHS publication list available at http://aghealth.nci.nih.gov as well as through a Medline/PubMed database search in March 2009. We also examined citation lists. Findings related to lifetime-days and/or intensity-weighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposure-response relationships.
We reviewed 28 studies; most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios (or odds ratios) and positive exposure-response patterns were reported for 12 pesticides currently registered in Canada and/or the United States (alachlor, aldicarb, carbaryl, chlorpyrifos, diazinon, dicamba, S-ethyl-N,N-dipropylthiocarbamate, imazethapyr, metolachlor, pendimethalin, permethrin, trifluralin). However, estimates of association for specific cancers were often imprecise because of small numbers of exposed cases, and clear monotonic exposure-response patterns were not always apparent. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposure-response patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed for alachlor, carbaryl, metolachlor, pendimethalin, permethrin, and trifluralin.
Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted.
The aim of this study was to evaluate the repeated-dose 14-day dermal toxicity of different combinations of some synthetic pyrethroid insecticides, piperonyl butoxide, and tetramethrin in rats. A total of 70 adult Wistar rats were randomly divided into 7 (6 experimental and 1 control) groups. Different combinations of insecticides were dermally applied to the rats in the experimental groups for 14 days. Clinical observations were performed daily; hematologic and biochemical parameters were also determined. Gross necropsy and histopathologic examinations were performed systematically, and organ weights were recorded. Although the administered doses of the insecticides were relatively lower than their acute dermal toxicity values, a high mortality rate (27 of 60 experimental animals, 45%) was observed. Furthermore, the insecticide combinations caused decreased body weights and feed consumptions, increased organ weights, and hematologic, biochemical, and common histopathologic changes. As a result, the findings showed that although pyrethroids are considered to be of low acute toxicity, they become more toxic when combined with piperonyl butoxide or tetramethrin in certain doses.
Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate. Women of reproductive age (20-40 years) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. Our findings strongly suggest that health-risk assessments for phthalate exposure in humans should include diethyl, dibutyl, and benzyl butyl phthalates.
Four synthetic mosquito repellents (Autan [10% KBR3023], IR3535 [7.5%], Off! [15% deet], Skinsations [7% deet]) and eight natural (primarily plant extracts and/or essential oils) product-based repellents (Bite Blocker [2% soybean oil], ByGone, GonE!, Natrapel [10% citronella], Neem Aura, Sunswat, MosquitoSafe [25% geraniol], and Repel [26% p-menthane-3,8-diol]) were tested in the laboratory against Aedes albopictus Skuse, Culex nigripalpus Theobald, and Ochlerotatus triseriatus (Say). When estimated mean protection time (eMPT) responses for each repellent were averaged for all three mosquito species, Autan, Bite Blocker, Off!, and Repel prevented biting for > or =7.2 h; IR3535, MosquitoSafe, and Skinsations for 3.2-4.8 h; and ByGone, Natrapel, GonE, NeemAura, and SunSwat for 0.9-2.3 h. Against Ae. albopictus, the eMPT for Off! and Repel exceeded 7.0 h and ranged from 5.0 to 5.7 h for Autan, Bite Blocker, and Skinsations. Bygone, GonE, NeemAura, and SunSwat provided 0.2 h protection against Ae. albopictus and Oc. triseriatus, whereas Autan, Bite Blocker, Off., and Repel prevented bites by Oc. triseriatus for > or =7.3 h. All 12 repellents provided an eMPT > or =2.8 h against Cx. nigripalpus (maximum: 8.5 h for Bite Blocker). When the average eMPT for each repellent (for all species) was divided by the eMPT for 7% deet (Skinsations), the order of repellent effectiveness and the corresponding repellency index (R,) was Repel (1.7) > Bite Blocker (1.5) = Autan (1.5) = Off! (1.5) > Skinsations (1.0) > IR3535 (0.8) > MosquitoSafe (0.6) > Natrapel (0.5) > Neem Aura (0.3) = SunSwat (0.3) = Bygone (0.3) > GonE (0.2).
Synthetic insect repellents, IR3535 and KBR 3023 (also known as picaridin, or by the trade name Bayrepel®), were tested in Burkina Faso against mosquito vectors of disease to compare their relative efficacy and persistence profiles
to those of the ‘gold standard’ DEET. Collection of >49 000 mosquitoes (∼95% belonging to the Anopheles gambiae complex) showed that after an exposure of 10 h, KBR 3023 produced the highest protection against anophelines, followed by
DEET, then IR3535. The response of aedines was more variable. By fitting a logistic plane model we estimated 95% effective
dosages (ED95) for An. gambiae s.l., as well as a decay constant characterizing the exponential loss of repellent from the skin, with time. The ED95 values for DEET, IR3535, and KBR 3023 were 94.3, 212.4, and 81.8 μg/cm2 respectively. The decay constants were estimated at −0.241, −0.240, and −0.170 h−1 respectively. The corresponding estimates of half-life were 2.9, 2.9, and 4.1 h. Immunoenzymatic detection of the circumsporozoite
protein (CSP) of Plasmodium falciparum in 842 An. gambiae s.l. showed that CSP-positive mosquitoes were equally frequent in treated and control subjects, indicating that the repellents
could produce a reduction in the number of malaria infectious bites.
The mosquito repellent activity of 38 essential oils from plants at three concentrations was screened against the mosquito Aedes aegypti under laboratory conditions using human subjects. On a volunteer's forearm, 0.1 mL of oil was applied per 30 cm2 of exposed skin. When the tested oils were applied at a 10% or 50% concentration, none of them prevented mosquito bites for as long as 2 h, but the undiluted oils of Cymbopogon nardus (citronella), Pogostemon cablin (patchuli), Syzygium aromaticum (clove) and Zanthoxylum limonella (Thai name: makaen) were the most effective and provided 2 h of complete repellency.
From these initial results, three concentrations (10%, 50% and undiluted) of citronella, patchouli, clove and makaen were selected for repellency tests against Culex quinquefasciatus and Anopheles dirus. As expected, the undiluted oil showed the highest protection in each case. Clove oil gave the longest duration of 100% repellency (2–4 h) against all three species of mosquito. Copyright
For the use of topical insect repellents, DEET and picaridin, human health risk assessments were conducted for various population subgroups. Acute, subchronic, and chronic dermal exposures were examined. No-observed-effect-levels (NOELs) of 200, 300, and 100mg/kg body weight (BW) were used as endpoints for DEET for acute, subchronic, and chronic exposures, respectively. For picaridin, a NOEL of 2000 mg/kg BW/day for acute exposure and a NOEL of 200 mg/kg BW/day for subchronic and chronic exposures were used. Daily exposures to several population subgroups were estimated. Risks were characterized using the Margin of Exposure (MOE) method (NOEL divided by the estimated exposure), whereby estimated MOEs were compared to an MOE of 100. Estimates of daily exposures ranged from 2 to 59 mg/kg BW/day for DEET and 2 to 22 mg/kg BW/day for picaridin. Children had the lowest MOEs. However, none of the estimated exposures exceeded NOELs for either repellent. At 40% DEET for acute exposure, children < or = 12 years had MOEs below 100. For subchronic and chronic exposures children at > or = 25% DEET and at 15% picaridin had MOEs below 100. Therefore, we found no significant toxicological risks from typical usage of these topical insect repellents.
N,N-diethyl-3-methylbenzamide (DEET) is a broad-spectrum insect repellent used by millions of people since the 1950s. Ethyl 3-[acetyl(butyl)amino]propanoate (IR3535) is a repellent developed more recently that is still not used as extensively. This study compares the behavioral and toxicological effects of both substances in fifth-instar nymphs of the blood-sucking bug Rhodnius prolixus Stål (Hemiptera: Reduviidae), one of the main vectors of American trypanosomiasis (Chagas disease). Repellency was quantified using filter paper discs as experimental arenas. Half the discs were treated with solution of repellent in acetone, and the other half with acetone alone. The lowest observed effect level was identical for both substances, 74 μg/cm2. Nymph age (between 1-3 h and 99 d from last ecdysis) had no influence on repellency. Topical application of 750 mg of DEET per nymph produced a mortality rate between 0% (24 h after application) and 40% (7 d later). The same dose of IR3535 produced no mortality during the same period of time. Simultaneous treatment with piperonylbutoxide (a mixed function microsomal oxidase inhibitor) synergized the lethal effect of DEET. Only DEET increased locomotor activity in nymphs exposed to a treated surface. Nymph antennectomy abolished DEET repellency but not its effect on locomotor activity. The concentrations of both these compounds required to produce either behavioral or toxicological effects are too high to have any practical applications in the control of R. prolixus.
Repellent efficacy of the Off! Clip-on Mosquito Repellent device (S. C. Johnson and Son, Inc., Racine, WI) containing Metofluthrin was evaluated on six human volunteers against the container-breeding mosquito Aedes albopictus (Skuse) and the salt marsh mosquito Aedes taeniorhynchus (Wiedemann) at two field locations in northeastern Florida. The device repelled mosquitoes by releasing a vaporized form of the pyrethroid insecticide metofluthrin ([AI] 31.2%) and provided 70% protection from Ae. albopictus bites for > 3 h. For the second field trial, a repellent device that was used in the first trial was tested after being open for >1 wk. This device provided 79% protection from Ae. taeniorhynchus bites for 3 h. Our field results showed that the repellent device was 70 and 79% effective at repelling Ae. albopictus and Ae. taeniorhynchus from human test subjects in both field locations in northeastern Florida.
Metofluthrin (commercial name: SumiOne(®), Eminence(®)) is a novel pyrethroid insecticide developed by Sumitomo Chemical Co., Ltd. Metofluthrin has extremely high insecticidal activity to various pest insects, especially to mosquitoes. In addition, Metofluthrin has relatively high volatility and low mammalian toxicity. Metofluthrin is therefore suitable for use not only in conventional mosquito control formulations such as coils and liquid vaporizers, but also in a variety of novel devices that do not require heating, such as fan vaporizers and paper and resin emanators. Here we describe the insecticidal activity of Metofluthrin mainly against mosquitoes in various formulations in both laboratory and field trials.
Prenatal exposure to endocrine disruptors has the potential to impact early brain development. Neurodevelopmental toxicity in utero may manifest as psychosocial deficits later in childhood. This study investigates prenatal exposure to two ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and social behavior in a sample of adolescent inner-city children. Third trimester urines of women enrolled in the Mount Sinai Children's Environmental Health Study between 1998 and 2002 (n=404) were analyzed for phthalate metabolites and BPA. Mother-child pairs were asked to return for a follow-up assessment when the child was between the ages of 7 and 9 years. At this visit, mothers completed the Social Responsiveness Scale (SRS) (n=137), a quantitative scale for measuring the severity of social impairment related to Autistic Spectrum Disorders (ASD) in the general population. In adjusted general linear models increasing log-transformed low molecular weight (LMW) phthalate metabolite concentrations were associated with greater social deficits (β=1.53, 95% CI 0.25-2.8). Among the subscales, LMWP were also associated with poorer Social Cognition (β=1.40, 95% CI 0.1-2.7); Social Communication (β=1.86, 95% CI 0.5-3.2); and Social Awareness (β=1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social Motivation. No significant association with BPA was found (β=1.18, 95% CI -0.75, 3.11). Prenatal phthalate exposure was associated with childhood social impairment in a multiethnic urban population. Even mild degrees of impaired social functioning in otherwise healthy individuals can have very important adverse effects over a child's lifetime. These results extend our previous finding of atypical neonatal and early childhood behaviors in relation to prenatal phthalate exposure.
Preservatives and fragrances are important and frequent skin sensitizers, found in a wide range of products intended for personal and occupational use.
To examine the use of preservatives and fragrances in certain cosmetics and detergents on the market. The product types studied were shampoos, hair conditioners, liquid soaps, wet tissues, washing-up liquids, and multi-purpose cleaners.
Ingredient labels of 204 cosmetic products and ingredient data sheets of 97 detergents, available on company websites, were examined.
The preservatives most frequently identified were phenoxyethanol, methylparaben, sodium benzoate, propylparaben, and methylchloroisothiazolinone/methylisothiazolinone. Parabens were found in 44% of cosmetics and 9% of detergents; formaldehyde-releasers in 25% of cosmetics and 8% of detergents; and isothiazolinones in 23% of cosmetics and 28% of detergents. The fragrances most frequently identified were linalool, limonene, hexyl cinnamal, butylphenyl methylpropional, and citronellol. Eighty-eight per cent of the products contained fragrances, and any of the 26 fragrances requiring labelling were found in half of the cosmetics and one-third of the detergents.
Several preservatives and fragrances with well-known skin-sensitizing potential were common in the examined product types. Such products may be used several times a day by consumers and workers.
Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are capable of enhancing skin permeation of each other when applied simultaneously. We carried out a cellular study in rat astrocytes and neurons to assess cell toxicity of DEET and oxybenzone and a 30-day study in Sprague-Dawley rats to characterize skin permeation and tissue disposition of the compounds. Cellular toxicity occurred at 1 µg/mL for neurons and 7-day treatment for astrocytes and neurons. DEET and oxybenzone permeated across the skin to accumulate in blood, liver, and brain after repeated topical applications. DEET disappeared from the application site faster than oxybenzone. Combined application enhanced the disposition of DEET in liver. No overt sign of behavioral toxicity was observed from several behavioral testing protocols. It was concluded that despite measurable disposition of the study compounds in vivo, there was no evidence of neurotoxicological deficits from repeated topical applications of DEET, oxybenzone, or both.
This study investigated the stereoselective biotransformation and resulting estrogenic activity of the pyrethroid insecticide, permethrin (PM). Results of both in vivo (male Japanese medaka, vitellogenin (VTG) protein in plasma) and in vitro (primary rainbow trout hepatocyte VTG-mRNA expression) assays indicated stereoselective estrogenic activity of PM. 1S-cis-PM was observed to have significantly higher activity (P ≤ 0.05) than the 1R-cis enantiomer in both in vivo and in vitro evaluations. All enantiomers of PM were oxidized to a 4'-hydoxy PM (4OH PM) metabolite and underwent esterase cleavage to 3-phenoxybenzyl alcohol (3-PBOH) and 3-(4'-hydroxyphenoxy)-benzyl alcohol) (3,4'-PBOH). Racemic 4OH PM as well as 3-PBOH, and 3,4'-PBOH possessed significant (P ≤ 0.05) estrogenicity. 1S-trans-PM underwent esterase cleavage more extensively than the corresponding 1R-trans-PM. Inhibition studies with ketoconazole confirmed cytochrome P450-catalyzed hydroxylation as well as esterase cleavage of PM for all stereoisomers. These studies indicated stereoselectivity in the estrogenic activity of PM resulting from stereoselective biotransformation of the parent compound to more estrogenic metabolites.
Comparative inhalation toxicity studies of aerosols of insect repellents N,N-diethylbenzamide (DEB), N,N-diethylphenylacetamide (DEPA), and N,N-diethyl-3-methylbenzamide (DEET) were carried out in mice. The respiratory pattern was monitored using a computer program that recognizes the modifications of the breathing pattern. Exposure to the aerosols caused a dose-dependent decrease in normal breath, with an increase in airway obstruction. All the three insect "sensilla irritants" showed no significant mammalian sensory irritation. The acute LC(50) value for a 4-h exposure of DEB, DEPA, and DEET aerosols in male mice was found to be >2.5 g/m(3), 1714 mg/m(3), and 1369 mg/m(3), respectively. Irreversible depression in respiratory frequency was observed after exposure to DEB aerosol at a concentration of 277 mg/m(3) and above, which did not revert back to normal level even after aerosol exposure was stopped. At a concentration of 156 mg/m(3) of DEB, no respiratory depression was observed. DEPA and DEET caused no depression in respiratory frequency up to a concentration 1292 and 950 mg/m(3), respectively. Hence the two insect repellents DEET and DEPA do not cause any harmful effect to the respiratory parameters in acute exposure, showing that they are more suitable chemicals to be used as insect repellents as compared to DEB.
Species differences in the intrinsic clearance (CL(int)) and the enzymes involved in the metabolism of pyrethroid pesticides were examined in rat and human hepatic microsomes. The pyrethroids bifenthrin, S-bioallethrin, bioresmethrin, beta-cyfluthrin, cypermethrin, cis-permethrin, and trans-permethrin were incubated in rat and human hepatic microsomes in the presence or absence of NADPH. Metabolism was measured using a parent depletion approach. The CL(int) of the pyrethroids was 5- to 15-fold greater in rat relative to human microsomes except for trans-permethrin, which was approximately 45% greater in human microsomes. The metabolism of bifenthrin, S-bioallethrin, and cis-permethrin in rat and human hepatic microsomes was solely the result of oxidative processes. The metabolism of bioresmethrin and cypermethrin in human hepatic microsomes was solely the result of hydrolytic processes. Bioresmethrin and cypermethrin in rat hepatic microsomes and beta-cyfluthrin and trans-permethrin in microsomes from both species were metabolized by both oxidative and hydrolytic pathways. The metabolism of trans-permethrin was reduced when incubated with its diastereomer, cis-permethrin, in both rat and human hepatic microsomes. Rat cytochrome P450 (P450) isoforms that showed activity toward several pyrethroids included CYP1A1, CYP1A2, CYP2C6, CYP2C11, CYP3A1, and CYP3A2. Human P450 isoforms that showed activity toward multiple pyrethroids were CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Species-specific differences in metabolism may result in variable detoxification of pyrethroids, which may in turn result in divergent neurotoxic outcomes. These species differences and isomer interactions in metabolism of pyrethroids should be considered when assessing the potential adverse health effects of pyrethroid pesticides.
The tissue distribution of 14C-labelled N,N-diethyl-m-toluamide (DEET), a widely used mosquito repellent, was studied by means of whole-body autoradiography after cutaneous application to mice. The early picture was very similar to that previously observed after intravenous injection of the substance, with high concentration of radioactivity mainly in the lacrimal gland, liver, bile, intestinal contents, kidney, urine, and nasal mucosa. Urinary excretion in mice was highest early after application whereas in a human volunteer maximal excretion appeared only after several hours. In mice a low but significant excretion persisted throughout the observation time of one month, probably emanating from the considerable amount of radioactivity remaining in the smeared skin area, as observed both autoradiographically and by means of quantitative measurements.
Groups of 15 male and 15 female rats were given diets containing 0 (control), 0·2, 1·0 or 5·O% diethyl phthalate (DEP) for 16 wk. Consumption of diet containing 5% DEP was associated with a reduction in food intake and in the rate of body-weight gain, and similar effects were seen in the females given 1% DEP. No statistically significant effects on water intake or on the results of the haematological examinations, serum-enzyme levels, urinary cell-excretion rate, renal concentration tests or histological examination were seen in the treated animals. However, there were increases at wk 16 in the relative liver weight of females at all treatment levels and of males fed the highest level. There were also increases in the absolute and relative weights of stomach and small intestine in rats of both sexes; in the females these were statistically significant at all dietary levels at wk 16.
The pyrethroid insecticide permethrin was tested for its ability to induce sister chromatid exchanges (SCE), micronuclei (MN) and structural chromosome aberrations (CA) in cultured human peripheral blood lymphocytes. Permethrin was tested in the range of 5-500 micrograms/ml in the absence and in the presence of a rat liver activation system (S9 mix). Small elevations in the SCE frequencies were found and even though statistically significant may have no biological meaning, the more so since there was no dose-effect relationship. Permethrin induced both MN and CA when it was evaluated in the absence of a metabolic activation system. Nevertheless, it cannot be said that S9 mix suppressed the activity in itself. The effect of permethrin seemed to be time of exposure dependent. Permethrin could be characterized as a S-phase independent agent with greater potential for inducing chromosomal damage than sister chromatid exchanges.
1. The pharmacokinetics and metabolism of (1R, cis)- and (1R, trans)-isomers of tetramethrin (i.v. 0.25 mg/kg) were studied in rats. 2. The experimental data for the time course of the concentration of tetramethrin isomers in plasma fit a pharmacokinetic two-compartmental open model. Plasma levels of both isomers were similar. The terminal half-life of the trans-isomer in plasma was greater (125 min) than the cis-isomer (72 min). 3. The concentrations of the two metabolites, 3,4,5,6-tetrahydrophthalimide (TPI) and N-(hydroxymethyl)-3,4,5,6-tetrahydrophthalimide (MTI), were consistently higher in the plasma of rats treated with the trans-isomer than in those treated with the cis-isomer. 4. In rats treated with the trans-isomer, the majority of radioactivity excreted after 96 h was found in urine. The faeces was the major excretory route for rats treated with the cis-isomer (26% urine, 69% faeces with cis-isomer; 64% urine, 29% faeces with trans-isomer). 5. Metabolism of each isomer was rapid and complete. Parent chemical was not detected in urine and only small quantities of the intact cis-isomer were found in the faeces. MTI, TPI, and cyclohexane-1,2-dicarboximide (HPI) were detected in both urine and faeces. 6. The amount of radioactivity excreted into the bile was similar for both isomers. However, levels of the intact parent compound and TPI were higher in the bile isolated from rats treated with the trans-isomer. The trans-isomer was found to undergo enterohepatic circulation.
This article reviews 573 cases of acute pyrethroid poisoning reported in the Chinese medical literatures during 1983-1988. There were 325 cases of acute deltamethrin poisoning (occupational 158, accidental 167), 196 patients of acute fenvalerate poisoning (occupational 63, accidental 133, including 2 cases of ingestive fenvalerate-organophosphate mixture poisoning), 45 cases of acute cypermethrin poisoning (occupational 6, accidental 39) and 7 cases of other pyrethroid poisoning (occupational 2, accidental 5). The clinical manifestations have been reviewed and analysed. The diagnosis, gradation and differential diagnosis of occupational acute pyrethroid poisoning have been discussed.
1. The toxicokinetics of cis- and trans-tetramethrin isomers were investigated using the isolated perfused rat liver preparation. 2. The concentration of cis- and trans-tetramethrin decreased rapidly in the plasma perfusate and was initially replaced by N-(hydroxymethyl)3,4,5,6-tetrahydrophthalimide (MTI) and then by 3,4,5,6-tetrahydrophthalimide (TPI). Plasma perfusate concentrations of the intact cis-isomer were higher than those of the trans-isomer. Concentrations of MTI and TPI were higher in livers treated with the trans-isomer. 3. Tetramethrin and its metabolites were rapidly excreted in the bile. Bile from livers perfused with trans-isomer contained higher concentrations of parent isomer and metabolites MTI and TPI, than did bile from livers treated with the cis-isomer.
This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the [14C]phthalate diester was applied in a dose of 157 mumol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of 14C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of 14C excreted in the first 24 hr decreased significantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied 14C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal and showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased.
Certain types of plastic materials require the addition of appreciable quantities of plasticizers to impart specific physical-chemical properties to the final item. Presently, many vinyl devices used with drug products may contain plasticizers of the phthalate type. For this reason, a series of phthalic acid esters were evaluated for parenteral toxicity including LD50 values and hexobarbital narcosis. Experiments utilized in the study also included i.p. injections in mice for acute toxicity profiles, i.v. administration in rabbits for blood pressure and respiration effects, and intradermal injections into rabbits for irritation effects. A further study was conducted to note what effects repeated i.p. doses of the phthalates would have on mice over a period of time, examining the effects on organs, weight gain, and the blood. Finally, tissue culture experiments were conducted to attempt to correlate certain of the toxicity manifestations. The most salient feature of the toxicity of these compounds was the central depression on the animals and the rather low order of toxicity by the parenteral route of administration.