Oil of Lemon Eucalyptus as an Insect Repellent

By Alexandra Connelly Frost, PhD

Dr. Frost is an Epidemiologist at the R. Stuart Dickson Institute for Health Studies, Carolinas HealthCare System, Charlotte, NC; she reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. 

Before synthetic repellents were developed in 1929, people routinely used natural compounds to protect against insect bites. During World War II, however, the United States government began testing more than 20,000 mosquito repellents to protect troops traveling to tropical areas. As a result, a highly effective synthetic repellent (N,N-diethyl-m-toluamide or DEET) was developed in 1953 and arrived on the market in 1956.1 Currently, DEET is the most popular commercial insect repellent, with close to 250 formulations sold worldwide. 

Despite its effectiveness, many consumers are reluctant to apply synthetic chemicals to their skin and seek natural alternatives to synthetic repellents. This desire has been exacerbated by reports that DEET is dangerous for children, possibly inducing encephalitis. These cases are extremely rare (17 suspected cases worldwide reported to date)2 and occurred in children that orally ingested DEET or were repeatedly exposed to high concentrations.3 Nonetheless, many would rather err on the side of caution.

Commercially available insect repellents fall into one of two classes: synthetic chemicals or plant-derived essential oils.4 Currently, there are only five active ingredients registered for topical use in the United States: two are synthetic (DEET and IR3535) and three are plant-derived (picaridin [KBR 3023], citronella, and p-menthane-3,8-diol [PMD]).1 

One plant-derived alternative that has sparked particular attention of late is oil of lemon eucalyptus. In fact, the Centers for Disease Control and Prevention (CDC) recently reported that oil of lemon eucalyptus (PMD is the active ingredient) is one of only three products (DEET, picaridin, and PMD) recommended to protect against West Nile virus, a serious virus spread by mosquitoes that can cause neurological disease or even death.5 The Environmental Protection Agency (EPA) lists PMD as effective against mosquitoes, biting flies, and gnats.6 

Botany and Pharmacology 

Eucalyptus ssp. is a genus of trees and shrubs in the family Myrtaceae that originated in Australia, but now commonly grows in almost all tropical and subtropical areas. Eucalyptus trees are characterized by vertically hanging, white, leathery leaves and ragged bark.7 There are close to 600 species of eucalyptus, one of which is Eucalyptus citriodora Hook. E. citriodora is also known as citron-scented gum, lemon eucalyptus, lemon-scented gum, Corymbia citriodora, and spotted gum. E. citriodora has been credited with anti-inflammatory, antibacterial, and antifungal activity; and, recently has gained popularity as an insect repellent.8 

E. citriodora leaves contain many compounds with pesticide activity including: aromadendrene, citronellal, citronellic acid, citronellol, citronellyl acetate, p-cymene, limonene, linalool, alpha-pinene, PMD, tannin, terpinene, terpinolene, and ursolic acid.8 PMD has been identified as the compound that provides the strongest insect protection in this plant. Of note, E. citriodora 
also contains citronellol, which is the active ingredient in oil of citronella products. Oil of citronella, however, is not obtained from E. citriodora, rather from perennial grasses indigenous to tropical Asia (C. nardus and C. winterianus).9 Oil of citronella is reported to have considerably shorter repellent times than DEET and PMD alternatives, with complete protection times 
averaging only about 20 minutes at concentrations of 10%.4 

Research Studies 

In the late 1980s, a worldwide survey was conducted by the U.S. military to identify repellents not produced in the United States. Of the 65 formulations not produced in the United States, 33 contained DEET and the remainder contained natural oils or undisclosed ingredients. One of the natural formulas identified was quwenling. This formula sparked the interest of researchers because it had become China’s repellent of choice.10 Quwenling was made from the waste distillate after extraction of lemon eucalyptus oil; the main ingredient in this distillate was PMD.11 Quwenling has been a popular insect repellent in China for more than two decades.1 

As mentioned previously, PMD is the main ingredient in quwenling; however, products containing PMD are relatively new to the U.S. market. There is a paucity of information on the efficacy of these products in peer-reviewed literature. This will likely change over time as PMD is more widely used and evaluated in the United States. Results of studies from the current literature are discussed in the next several paragraphs. 

Schreck et al studied the effectiveness of quwenling through a series of tests that involved application of quwenling (30% active ingredients, or AI) on the forearm of a volunteer, from the wrist to the elbow.9 After 15 minutes, the volunteer’s arm (a protective glove covered the hand) was exposed sequentially for three minutes in four cages, each containing 200 blood-hungry female mosquitoes of four different species (Aedes aegypti, Aedes albopictus, Anopheles quadrimaculatus, and Anopheles albinmanus). Volunteers were also taken to the Everglades National Park to test the repellent in an authentic environment. Treated arms were exposed continuously to the natural environment to calculate time until first bite. The same tests were done with a DEET standard (15% AI) and the two repellents were then compared. Collectively, the results from these series of tests suggested that quwenling was not as effective as DEET in terms of duration of protection: The mean number of hours until the first bite by Aedes aegypti was 1.1 hours with quwenling and 4.8 hours with DEET. 

Fradin et al compared several different insect repellents on the national market by using arm-in-cage studies with variable protocols depending on the time at first bite.4 This study reported that 11 of 12 non-DEET repellents had mean protection times from Aedes aegypti mosquitoes of less than 23 minutes, whereas DEET topical formulas provided mean protection times ranging from 88 minutes (4.75% DEET) to 301 minutes (23.8% DEET). After the study was started, a new botanical product was introduced in the United States under the trade names of Repel Lemon Eucalyptus Insect Repellent (Wilson Pharmaceutical Company) and Fite Bite Plant Based Insect Repellent (Travel Medicine). The authors evaluated this product using the same method that they used for the products originally specified in the study using six test subjects. The lemon eucalyptus repellent had a mean protection time of 120 minutes, which made it the most effective of all non-DEET repellents tested in this study and more effective than low-concentration DEET products (6.65% and lower); however, the concentration of lemon eucalyptus or PMD was not stated in the study. Another important point from this study was that wristband repellents were not effective, regardless of the formula.4 

In 2002, Barnard et al tested IR3535, KBR 3023, PMD repellent (40% PMD), and DEET (25%) against Ochlerotatus taeniorhynchus in the Everglades National Park.12 During seven, three-minute observation periods over six hours, bites were surveyed on test subjects. The PMD repellent had a mean complete protection time of 3.7 hours (compared to 5.6 hours with DEET) and an overall mean percent repellency of 89%. Authors stated that all three non-DEET repellents were effective insect repellents for human use. 

In 2004, Barnard and Xue tested 12 commercially available synthetic and botanical insect repellents against Aedes albopictis, Culex nigripalpus, and Ochlerotatus triseriatus by exposing treated forearms to three-minute cage exposures every 30 minutes until the subject received two or more mosquito bites in the same observation period or one bite in two consecutive observation periods.11 When estimated mean time of protection was averaged over the three species, Repel Lemon Eucalyptus Insect Repellent (26% oil of lemon eucalyptus or 65% PMD) provided more than seven hours of protection from mosquitoes of these species. Repel’s protection time was comparable to the 15% DEET formula in the study. 

Similarly, Govere et al reported that 0.574 g of quwenling (Mosiguard towelettes) was comparable to 15% DEET for protection against Anopheles arabiensis mosquitoes in their arm-in-cage study.13 Both formulas protected against this species of mosquitoes for 5-6 hours of one-minute, hourly cage exposures. 

Trigg also found spray, gel, and stick formulations of 50% PMD effective against An. gambiae and An. funestus mosquitoes in the field in Tanzania.14 Their results, however, are misleading: They reported six hours and 42 minutes average time until first bite when the first five hours were spent unexposed to mosquitoes before the trial began at 10 pm. Once they went into the field where the experiment tool place, it took an average of one hour and 42 minutes using PMD spray compared to one hour and 55 minutes using DEET spray until the first bite was received. 

Hadis et al reported comparable efficacy of DEET and PMD (greater then 90% for both) in terms of mean number of bites and average percent protection at concentrations of 40% and 75%, respectively, against Mansonia mosquitoes.15 They did not compare time until first bite for the different repellents, but rather the overall effectiveness during the test period (from 7:00 to 7:30 pm) in Pugnudo, Ethiopia. Both the time to first bite and the average number of bites over a time period are important in terms of disease protection. 

Recently, it has also been shown that burning E citriodora leaves could provide a cost-effective means of household protection in addition to mosquito nets in sub-Sahara Africa where 90% of deaths from malaria occur and much of the exposure time is before individuals go to bed (where they are protected by mosquito nets) in the evening.16 

Mechanism of Action 

Curiously, none of the above articles discussed the mechanism by which PMD repels insects. The mode of action of many repellents is unclear, but it is believed that these products do not repel insects, they simply mask or confuse the attractive signals that humans emit so that mosquitoes are unable to locate us. Mosquitoes have specific sensory receptors that provide them with the information they need to detect a source, orient to it, and travel to it to sample a blood meal. Host location is determined by many factors including lactic acid, ammonia, carbon dioxide, octenol, phenols, temperature, and humidity.17 For example, DEET interferes with the transmission of spikes from a lactic acid-excited neuron stimulated by lactic acid from a host.16 The precise mechanism for PMD has not been reported. 

Adverse Effects 

All pesticides distributed or sold in the United States must be registered by the EPA. To be registered, the manufacturer must present scientific studies showing that they can be used without posing unreasonable risks to humans or the environment. As part of the registra-tion process, the EPA collects and reviews a complete set of studies from the pesticide producers describing 
the health and environmental effects of the product. 

Accordingly, the EPA imposes regulations to manage any of the risks the pesticide might pose. PMD was registered with the EPA as a product that can be used against public health pests in March of 2000.18 

In animal studies evaluated by the EPA during the registration process of PMD, the only adverse effect that PMD showed was eye irritation.6 Eye irritation, however, has not been reported in peer-reviewed, epidemiologic literature. However, one peer-reviewed research study reported that a subject experienced significant skin irritation at the site of application.4 

There are special warning labels on products containing PMD advising users not to get the product in their eyes and to avoid spraying directly on or near the face. Users are also advised not to use PMD on the faces or hands of small children.6 PMD is not to be used on children younger than three years of age (the product has not been adequately tested in this population).19 

Dosage and Formulation 

There are a few oil of lemon eucalyptus repellents on the market in the United States. EPA-registered lemon eucalyptus repellents include: Repel Lemon Eucalyptus Insect Repellent Lotion and Spray Lotion, Survivor Lemon Eucalyptus Insect Repellent Lotion, and Off! Botanicals Insect Repellent. Repel Lemon Eucalyptus Insect Repellent Lotion and Spray Lotion and Survivor Lemon Eucalyptus Insect Repellent contain 30% oil of lemon eucalyptus (65% PMD). Off! Botanical Insect Repellent contains 10% PMD. Of note, most commercial products contain a synthetic PMD molecule, but the active ingredient was originally isolated from waste distillate of lemon eucalyptus oil extract.11 

In general, it appears that PMD is roughly half as effective as DEET by level of concentration; therefore, a 30% PMD product would be about as effective as a 15% DEET product. Keep in mind, however, that the innate attractiveness of human subjects to mosquitoes ranges from 30% to 70%; therefore, different concentrations and intervals of application may be effective depending on the individual.20 

Important Information on Using Pesticides 

Patients should be particularly vigilant between dusk and dawn—the prime mosquito-biting hours—and should follow instructions on the product label carefully. General instructions specified by the EPA are as follows: only apply repellents to exposed skin and/or clothing; never use repellents over cuts, wounds, or irritated skin; do not apply to eyes and mouth; apply sparingly around ears; when using sprays do not spray directly onto face (spray on hands first and then apply to face); do not allow children to handle the products and do not apply to children’s hands; do not spray in enclosed areas; avoid breathing a repellent spray; do not use repellent near food; after returning indoors, bathe or wash treated skin with soap and water; and finally, always store repellents and pesticides out of the reach of children (regardless of whether they are botanical or synthetic).21 When using an insect repellent, the EPA recommends that users always check the container to make sure that the product has an "EPA-approved" label and registration number. Patients should always read the label of any product they are using, even if they have used the same product before, as safety and efficacy information is updated and reflected on product labels.21 

In case of a rash or an adverse reaction from a repellent, patients should: stop using the product, wash the area with soap and water, and call the local poison control center for guidance. If a severe reaction occurs, patients should call 911 and make sure to take the insect repellent product to the hospital.21 

Conclusion and Recommendation 

In the United States, where the greatest disease threat from a mosquito bite is West Nile virus, PMD-based repellents are a safe and effective alternative to synthetic formulas; however, at concentrations tested, DEET formulas usually provided protection for a longer period of time.

When traveling to a tropical or malaria endemic area, it is still advisable to use a DEET repellent because oil of lemon eucalyptus has not been adequately tested against mosquitoes that spread malaria. DEET is the safest, best studied, and longest-lasting repellent against malaria-carrying mosquitoes, according to the CDC. Refer to the CDC Travelers’ Health web site (www.cdc.gov/travel/bugs.htm) for specific recommendations concerning protection from insects when traveling outside the United States.19 The CDC (www.cdc.gov) and EPA (www.epa.gov) are the most reliable resources for updates on safety and efficacy of all pesticides.

References

1. Buka RL. Sunscreens and insect repellents. Curr Opin Pediatr 2004;16:378-384. 

2. Briassoulis G, et al. Toxic encephalopathy associated with use of DEET insect repellents: A case analysis of its toxicity in children. Hum Exp Toxicol 2001;20:8-14. 

3. Sudakin DL, Trevathan WR. DEET: A review and update of safety and risk in the general population. J Toxicol Clin Toxicol 2003;41:831-839. 

4. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med 2002;347:13-18. 

5. Kuehn BM. CDC: New repellents for West Nile fight. JAMA 2005;293:2583. 

6. U. S. Environmental Protection Agency. p-Menthane-3,8-diol (011550) Fact Sheet. Available at www.epa.gov/pesticides/biopesticides/ingredients/factsheets/factsheet_011550.htm. Accessed June 23, 2005. 

7. Funk & Wagnalls New World Encyclopedia. EBSCOhost Research Databases. Available at: www.epnet.com.libproxy.lib.unc.edu/. Accessed June 15, 2005. 

8. United States Department of Agriculture. Dr. Duke’s Phytochemical and Ethnobotanical Databases [online database]. Agricultural Research Service, National Genetic Resources Program. Available at: www.ars-grin.gov/duke/. Accessed June 23, 2005. 

9. Environmental Protection Agency. Available at: www.epa.gov/REDs/factsheets/3105fact.pdf. Accessed July 6, 2005.

10. Schreck CE, Leonhardt EA. Efficacy assessment of quwenling, a mosquito repellent from China. J Am Mosq Control Assoc 1991;7:433-436. 

11. Barnard DR, Xue RD. Laboratory evaluation of mosquito repellents against Aedes albopictus, Culex nigripalpus, and Ochierotatus triseriatus (Diptera: Culicidae). J Med Entomol 2004;41:726-730. 

12. Barnard DR, et al. Repellency of IR3535, KBR3023, para-menthane-3,8-diol, and deet to black salt marsh mosquitoes (Diptera: Culicidae) in the Everglades National Park. J Med Entomol 2002;39:895-899. 

13. Govere J, et al. Efficacy of three insect repellents against the malaria vector Anopheles arabiensis. Med Vet Entomol 2000;14:441-444. 

14. Trigg JK. Evaluation of a eucalyptus-based repellent against Anopheles spp. in Tanzania. J Am Mosq Control Assoc 1996;12(2 pt 1):243-246. 

15. Hadis M, et al. Field trials on the repellent activity of four plant products against mainly Mansonia popu-lation in western Ethiopia. Phytother Res 2003;17:202-205. 

16. Seyoum A, et al. Field efficacy of thermally expelled or live potted repellent plants against African malaria vectors in western Kenya. Trop Med Int Health 2003;8:1005-1011. 

17. Davis EE, Bowen MF. Sensory physiological basis for attraction in mosquitoes. J Am Mosq Control Assoc 1994;10(2 pt 2):316-325. 

18. U.S. Environmental Protection Agency. Pesticides: Regulating Biopesticides. Available at www.epa.gov/pesticides/biopesticides/. Accessed June 23, 2005. 

19. Centers for Disease Control and Prevention. Updated information regarding mosquito repellents. Available at: www.cdc.gov/ncidod/dvbid/westnile/RepellentUpdates.htm. Accessed June 23, 2005. 

20. Schreck CE et al. Mosquito attraction to substances from the skin of different humans. J Am Mosq Control Assoc 1990;6:406-410. 

21. U.S. Environmental Protection Agency. How to use insect repellents safely. Available at: www.epa.gov/pesticides/factsheets/insectrp.htm. Accessed June 23, 2005.