Commercial Mosquito Repellents and Their Safety Concerns

Hanem Fathy Khater, Abdelfattah M. Selim, Galal A. Abouelella, Nour A. Abouelella, Kadarkarai Murugan, Nelissa P. Vaz and Marimuthu Govindarajan

### Abstract

Mosquitoes are serious vectors of diseases threading millions of humans and animals worldwide, as malaria, filariasis, and important arboviruses like dengue, yellow fever, chikungunya, West Nile virus, and Zika viruses. The swift spread of arboviruses, parasites, and bacteria in conjunction with the development of resistance in the pathogens, parasites, and vectors represents a great challenge in modern parasitology and tropical medicine. Unfortunately, synthetic insecticides had led to some serious health and risk concerns. There are no vaccines or other specific treatments for arboviruses transmitted by mosquitoes. Accordingly, avoidance of mosquito bites remains the first line of defense. Insect repellents usually work by providing a vapor barrier deterring mosquitoes from coming into contact with the skin surface, and this chapter focused on assets and liabilities, mechanism of action, improving efficacy, safety, and future perspective of synthetic and natural repellents that could potentially prevent mosquito-host interactions, thereby playing an important role in reducing mosquito-borne diseases when used correctly and consistently.

Keywords: repellent plants, synthetic repellents, treated clothes, nanoparticles, microencapsulation

### 1. Introduction

Parasites since antiquity [1] are a serious threat for millions of humans and animals worldwide which bring about chronic debilitating, periodically disabling disease and are responsible for the overwhelming financial loss [2–6]. Mosquitoes (Diptera: Culicidae) [7, 8] are among them as they can act as vectors for serious parasites and pathogens, including malaria, filariasis, and important arboviruses, such as dengue, yellow fever, chikungunya, West Nile virus, and Zika viruses [9, 10]. Mosquito control and personal protection from mosquito bites are the most meaningful measures for controlling several life-threatening diseases transmitted exclusively by bites from bloodsucking mosquitoes. Repellents evolved, dates back to antiquity; the Pharaoh Sneferu, reigned from around 2613–2589 BCE and the founder of the fourth dynasty of Egypt, and Cleopatra VII, the last pharaoh of ancient Egypt, used bed nets as protection against mosquitoes; the ancient Egyptians used essential oils (EOs) for repelling insects, medicinal benefits, beauty

care, and spiritual enhancement and in literally all aspects of their daily life [1]. Insect-repellent plants have been applied traditionally for thousands of years through different civilizations [11]. Such plants were used in various forms such as hanged bruised plants in houses, crude fumigants where plants were burnt to drive away mosquitoes, and oil formulations applied to the skin or clothes [12]. Smoke is undoubtedly the most extensively exploited means of repelling mosquitoes, typically by burning plants in rural tropics and by utilizing spiral-shaped incenses like Katori Senk—an archetypal icon of the humid Japanese summers [13].

such as chloroquine is increased. Most of the commercial MRs are prepared using non-biodegradable, synthetic chemicals like N,N-diethyl-3-methylbenzamide (DEET), dimethylphthalate (DMP), and allethrin which may lead to the environment and, hence, the unacceptable health risks in the case of their higher exposure. With an increasing concern for public safety, a renewed interest in the use of natural products of plant origin is desired because natural products are effective, environmentally friendly, biodegradable, inexpensive, and readily available [7, 8, 13, 17, 20]. Repellent application is a reliable mean of personal protection against annoyance and pathogenic infections not only for local people but also for travelers in disease risk areas, particularly in tropical countries; therefore, this chapter focused on assets and liabilities, safety, and future perspective of synthetic and natural MRs that could potentially prevent mosquito-host interactions, thereby playing an important role in reducing mosquito-borne diseases when used correctly

Commercial Mosquito Repellents and Their Safety Concerns

DOI: http://dx.doi.org/10.5772/intechopen.87436

The history of synthetic repellents had been reviewed [12]; before World War II, MRs were primarily plant-based with the oil of citronella being the most widely used compound and the standard against which others were evaluated. At that time, the emergence of synthetic chemical repellents starts. There were only three principal repellents: dimethylphthalate discovered in 1929, Indalone® (butyl-3,3 dihydro-2,2-dimethyl-4-oxo-2H-pyran-6-carboxylate) patented in 1937, and Rutgers 612 (ethyl hexanediol), which became available in 1939. Later on and for military use, 6-2-2 of M-250 (a mixture of six parts DMP and two parts each Indalone® and Rutgers 612) was used [13]. The event of World War II was the primary switch on in the development of new repellent technologies because the Pacific and North African theaters posed significant disease threats to allied military personnel. Over 6000 chemicals had been tested from 1942 to 1947 in a variety of research institutions led to the identification of multiple successful repellent chemistries. Such great aim established several independent research projects that inevitably identified one of the most effective and widely used insect repellents to date, DEET. From then on, several compounds have been synthesized relying on previous research, which identified amide and imide compounds as highly successful contact repellents. Among these are picaridin, a piperidine carboxylate ester, and IR3535, which are currently considered DEET competitors in some repellency bioassays [21]. The chemical structures of some synthetic repellents are shown in

DEET (N,N-diethyl-3-methylbenzamide) is the standard and most effective broad-spectrum insect-repellent component with a long-lasting effect on mosquitoes, ticks, as well as biting flies, chiggers, and fleas. DEET was discovered as a mosquito repellent by the US Department of Agriculture and patented by the US Army in 1946. It was allowed for public use in 1957, and since then it has been a standard repellent for several insects and arthropods [14]. DEET is the most studied insect repellent and mainly used as a positive control to compare the efficacy of many repellent substances. DEET has a dose-dependent response: the higher the concentration, the longer the protection. DEET, 20–25%, is the conventional concentration used in commercial products. The shorter protection time depended on the mixture as well [14]. In fact, DEET plays a limited role on

and consistently.

Figure 1.

2.1 DEET

147

2. Synthetic repellents

Mosquitoes have been considered as a major obstacle to the tourism industry and socioeconomic development of developing countries particularly in the tropical and endemic regions [14]. Mosquito problems are ancient as old as the pyramids, and the presence of malaria in Egypt from circa 800 BCE onward has been confirmed using DNA-based methods, and antigens produced by Plasmodium falciparum leading to tertian fever in mummies from all periods were detected, and all mummies were suffering from malaria at the time of their death [1]. Herodotus noted down that the builders of the Egyptian pyramids (circa 2700–1700 BCE) were given large amounts of garlic almost certainly to protect them against malaria [1]. Despite recent considerable efforts to control vector-borne diseases, malaria alone produces 250 million cases per year and 800,000 deaths including 85% of children under 5 years [15]. Global warming has moved the mosquitoes on the way to some temperate and higher altitudes, affecting people who are vulnerable to such diseases [16]. Recently, malaria is a great problem in Africa, but it was well controlled in Egypt [1]. Ahead of the development and commercial success of synthetic insecticides in the mid-1930–1950s, botanical insecticides were the leading weapons for insect control. Synthetic insecticides are distinguished by their efficacy, speed of action, ease of use, and low cost. Therefore, they drove many natural control methods as botanicals, predators, and parasitoids to shadows [8, 17, 18]. Insecticidal treatment of house walls, in particular, could provide a very helpful reduction of mosquito incidence, but such measures need financial and organizational demand, but poor rural areas in endemic regions do not have sufficient resources for such costly protective measures. Because of health and environmental concerns [8, 17], there is an urgent need to identify new nonhazardous vector management strategies that replace harmful chemical insecticides and repellents. There are no vaccines or other specific treatments for arboviruses transmitted by mosquitoes; therefore, avoidance of mosquito bites remains the first line of defense [9, 18]. Hence, the use of the mosquito repellents (MRs) on exposed skin area is highly recommended.

Insect repellents usually work by providing a vapor barrier deterring mosquitoes from meeting the skin surface. Insect repellents had been used for thousands of years against biting arthropods. Several species of primates were observed anointing their pelage via rubbing millipedes and plants as Citrus spp., Piper marginatum, and Clematis dioica. Wedge-capped capuchins (Cebus olivaceus) were observed rubbing the millipede Orthoporus dorsovittatus onto their coat during the period of maximum mosquito activity [19]. Such millipede contains benzoquinones and insect-repellent chemicals, and it was hypothesized that the anointing behavior was intended to deter biting insects. Laboratory studies revealed a significant repellent effect of benzoquinones against Aedes (Stegomyia) aegypti (the yellow fever mosquito) and Amblyomma americanum (the lone star tick). Such anointing behavior to deter blood-feeding arthropods is also common among birds, and it could be genetically expressed as an "extended phenotype" as it has an obvious adaptive advantage. Evidence for this lies in the fact that benzoquinones applied to filter paper elicited anointing activity among captive-born capuchins [12]. The World Health Organization (WHO) also recommends repellents for protection against malaria as the resistance of Plasmodium falciparum to anti-malarial drugs

#### Commercial Mosquito Repellents and Their Safety Concerns DOI: http://dx.doi.org/10.5772/intechopen.87436

such as chloroquine is increased. Most of the commercial MRs are prepared using non-biodegradable, synthetic chemicals like N,N-diethyl-3-methylbenzamide (DEET), dimethylphthalate (DMP), and allethrin which may lead to the environment and, hence, the unacceptable health risks in the case of their higher exposure. With an increasing concern for public safety, a renewed interest in the use of natural products of plant origin is desired because natural products are effective, environmentally friendly, biodegradable, inexpensive, and readily available [7, 8, 13, 17, 20]. Repellent application is a reliable mean of personal protection against annoyance and pathogenic infections not only for local people but also for travelers in disease risk areas, particularly in tropical countries; therefore, this chapter focused on assets and liabilities, safety, and future perspective of synthetic and natural MRs that could potentially prevent mosquito-host interactions, thereby playing an important role in reducing mosquito-borne diseases when used correctly and consistently.
