Threats from insect bites range from minor irritations to potential transmission of serious diseases. Mosquito-borne diseases such as yellow fever and malaria are rare in the United States. Since 1999, the increase in West Nile encephalitis has heightened public concerns about insect transmission of disease. Tick-borne diseases including Lyme disease and Rocky Mountain spotted fever continue to be a problem. Although insect bites often are considered primarily a nuisance, they are again becoming a greater cause for medical concern.
The process of preventmS msect mtes must take into account the balance between the efficacy of a product and any risks from that product. During the 50 years since World War II, millions of people have used the insect repellent DEET (N,N-diethyl-m-toluamide, now called N,N-diethyl-3methylbenzamide) without apparent adverse effects. However, during the past 30 years, there have been multiple reports of severe toxic reactions attributed to DEET.
This article discusses the relative efficacy of chemical and nonchemical insect repellents on the market. It focuses particularly on the toxicology of DEET and the relationship between the risk from potential toxicity from DEET and the benefits of insect-borne illness prevention.
EPIDEMIOLOGY OF INSECT-BORNE ILLNESS
Mosquito-borne illness is far less common in the United States than in countries in Central and South America and Africa. Worldwide, there are 300 to 500 million cases of malaria annually. It is estimated that almost all of the approximately 1,200 cases that occur in the United States each year originated from overseas travel, atthough the mosquito vector Anopheles does live in the extreme southern part of the country.
Arboviral encephalitis also occurs in the United States. These diseases include Eastern and Western equine encephalitis, St. Louis encephalitis, La Crosse encephalitis, and West Nile encephalitis. With the exception of West Nile virus encephalitis, the numbers of the other reported arboviral illnesses range from one to five cases of Eastern or Western Equine encephalitis per year to several hundred cases annually each of St. Louis and La Crosse encephalitis.1 In 2001, there were 216 reported cases of arboviral encephalitis, not including West Nile virus.2
Published Case Reports of Acute Encephalopathy Associated With
West Nile virus encephalitis was first reported in the United States in 1999 in New York, NY.3 Since then, the number of reported cases each year has increased, as has the number of states to which the virus has spread. In 2002, 4,156 human cases were reported in 40 states, with 284 deaths. The total number of cases reported for the year 2003 was 9,862 in 45 states and Washington, DC, with 222 deaths. The distribution of disease appears to be shifting westward. For example, in 2002 there were 884 cases in Illinois, and in 2003 there were 54. In Colorado, 14 cases were reported in 2002, and 2,947 cases were reported in 2003.3
Lyme disease reports have increased steadily during the past 2 decades. During the 1980s, the number of reported cases increased in the United States from 497 in 1982 to 8,803 in 1989.4 More recent data reported 17,029 cases in 200 1.2
Many products are marketed to the public for use as insect repellents. The most widely used and well-known is DEET, which initially was developed for use by the US Army and first marketed in the US in the early 1950s.
Numerous natural oils are also marketed for public use. The most common agent, citronella, is an active ingrethent in Skin-so-Soft Bug Guard® lotion (Avon), Natrapel® (Tender), and others. It is also commercially available as candles and as impregnated wristbands.
Other so-called natural oils have been used, including concentrated bath oil of uncertain ingrethents, oil of eucalyptus, cedar oil, lemongrass oil, and others.5 No controlled studies proving safety and efficacy of the natural oil products have been published in the medical literature. Additionally, no controlled or blinded studies comparing these products with DEET are published in the literature.
Permethrin is a synthetic derivative of the naturally occurring pyrethrin insecticide and is used primarily against ticks. Permethrin is an effective agent when applied to clothing and works to kill the insect rather than to repel it physically. Permethrin is often used with DEET or another agent but is generally not effective alone to repel mosquitoes. Another synthetic repellent contains the product ethyl butylacetylaminopropionate (IR3535) 7.5%, and is marketed as Skin-so-Soft Bug Guard Plus® (Avon).
A number of available mechanical products may also repel or kill mosquitoes, including devices based on ultraviolet light or sonic emission, traps based on carbon dioxide release, and coils that emit pyrethrin. These may be effective at reducing populations of mosquitoes in a fixed location, such as a backyard, but do not have the advantage of portability that a personally applied product has. In field studies, products that emit carbon dioxide and octenol (a mosquito attractant) were more effective than the traps that used light as the attractant. These studies are discussed later in this article.
DEET AND ITS USE
DEET repels all insects and many arthropods, including ticks. Most commonly used formulations are available in concentrations ranging from 5% to 100% (95% active ingrethent). DEET has been marketed as a child-safe product, such as in Off!® Skintastic and Skintastic Family Formula® (SC Johnson) and Cutter® All Family (Spectrum), with concentrations between 4.75% and 10% DEET. Most other products contain between 15% and 30% DEET. Some brands and formulations are available in concentrations as high as 95% and are usually found in sporting goods stores and hunting and fishing sections of most discount department stores, in sections apart from most pesticide products.
United States Poison Control Annual Reports of Calls related to DEET29-35
According to the manufacturer's label, proper use of these products includes single daily application, application only to exposed skin rather than to occluded surfaces, and removal of the product by washing after returning indoors. The mechanism of action of DEET is not well known, but DEET acts as a barrier on the skin and decreases the ability of the insect to recognize human skin.
Toxicoloty of DEET
Toxicokinetics of DEET in animals.
The absorption, biodistribution, metabolism, and excretion of DEET in animal models have been reviewed a number of times.5·6 In guinea pigs, 19% to 48% of DEET penetrates across the epidermis to the subcutaneous layer within 6 hours. In a study using radio-labeled DEET (C14), absorption in a dog was 7.9% to 12.8%.6 There is also evidence that DEET may persist on the skin for an extended period of time. After application of C14 DEET to the skin of mice, washed off after 2 hours, 21% of the radio-labeled C14 was found on the skin 36 days later.7
DEET is rapidly absorbed and distributed in the blood stream in mice. Dermally applied, radio-labeled DEET was found within 2 hours in the blood, lacrimal glands, liver, kidney, nasal mucosa, and urine.8 Urinary excretion is the primary mode of elimination, most of which is excreted in the form of inactive metabolites.7
Toxicokinetics of DEET in humans. There is evidence in some human studies that the absorption, distribution, metabolism, and excretion are similar to the kinetics in laboratory animals.6,8,9 DEET is well absorbed across intact human skin. Using human skin-graft tissue, the permeability of skin has been shown to increase with increasing concentrations of DEET. Permeability is enhanced when DEET is dissolved in a 30% to 40% ethanol, of which many commercial products are formulated.10
DEET is rapidly absorbed, with peak levels occurring within 6 to 8 hours after dosing. Excretion is also rapid, with nearly all of the radio-labeled DEET recovered between 12 and 24 hours after dosing. DEET appears to be entirely metabolized before urinary excretion.9 Two other studies demonstrated a small amount of DEET excreted unchanged following administration over a larger body surface area.11,12 Skin permeability has been shown to decrease when combined with a polyethylene glycol vehicle.13 At present, no commercial formulation has been made with this solvent.
Animal models. Central nervous system toxicity from DEET is a primary finding in rats. Excitation, posturing, tremors, coma, seizures, and ataxia were noted following doses approaching or exceeding the oral LD50 (dosage causing death in 50% of exposed laboratory animals) of 1,800 mg/kg. Dogs displayed tremors and hyperactivity following daily oral intake of 0.1 mL/kg and 0.3 mL/kg of 85% DEET during a 13- week period. Other neurologic and or behavioral effects include shaking, prostration, and loss of balance. Other toxic efforts found in animals include vomiting, progressive weight loss, and skin irritation.6
Human models. In humans, DEET can be irritating to skin and mucosal surfaces. Patients have reported paresthesias, mild irritation, and contact dermatitis.14·15 One case of generalized urticaria has also been reported.16
A number of the neurological findings reported in animals appear to be consistent with human reports of exposure. Toxic encephalopathy has been reported following cutaneous exposure and ingestion.15'27 Table 1 (see page 446) reports the major details surrounding the 22 reported cases (17 children and five adults) of toxic encephalopathy following DEET exposure. Patients have presented with slurred speech, confusion, headache, restlessness and irritability, ataxia, and seizures.22,28
The concentration of DEET is not consistent in relation to severity of exposure. In some patients, toxicity occurred following cutaneous exposure to 10% DEET Unfortunately, some reports lack sufficient detail to exclude other possible causes. Two of the reported deaths occurred following intentional ingestion of 95% DEET. On these occasions, the onset of seizures and mental status changes was within 1 to 2 hours of exposure.22
Reports to Poison Control Centers
Another mechanism to evaluate potential toxicity to DEET is by analyzing poison control center reporting data. All calls to US poison control centers are reported in aggregate form and classified by severity of outcome. Exposures are analyzed by medical outcomes and categorized into various groups. Asymptomatic outcomes are classified as no effect, and minor symptoms that resolve rapidly and are not life-threatening are classified as minor effect. Moderate effect includes symptoms that are more pronounced or prolonged because of exposure. These symptoms are not lifethreatening, but patients may require some treatment. Symptoms that are lifethreatening or result in residual disability or disfigurement are classified as major effect. Outcomes also include death.2835 These data are limited by insufficient information surrounding details ofexposure with the exception of the most serious exposures or outcomes.
Between 1985 and 1988, there were 9,086 reported human exposures. Approximately two-thirds of these patients had either no adverse effect or minor effects with rapid resolution. There was one reported death from suicidal ingestion of 8 oz of repellent containing DEET. Five patients in this study were reported as having a major or potentially life-threatening effect.28 The 1996 to 2002 annual reports of the American Association of Poison Control Centers Toxic Exposure Surveillance System were reviewed for DEET exposure and subsequent adverse events.29*35 The results are shown in Table 2 (see page 449). On average, 6,649 exposures to insect repellents have been reported to US poison control centers each year. No deaths were reported during this time period. Of a total of 46,541 reports, 46 were classified as having a major effect. Of the 48% of exposures having sufficient data to state an outcome, almost half (46%) had no effect or a minor effect. Since 2001, DEET-containing products were reported separately from non-DEET products.
These data suggest children's exposures are of generally more concern than adult exposures. It is unclear whether people are more likely to report a child's exposure or whether children are more likely to have a significant effect. It is also unclear whether children represent the majority of the major or moderate effects and whether exposures were oral or from cutaneous applications.
DEET may be measured in the blood and tissues. Metabolites may be measured in the urine. There is scant data on what constitutes an abnormal DEET measurement in the blood. Of the cases in which death following oral ingestion was reported, blood levels of DEET have ranged between 16.8 and 24 mg/dL.21 Urine metabolites in patients with reported toxicity following dermal application range from 0.3 pg/mL to 1.6 pg/mL.21·24·25
COMPARISON OF EFFICACY BETWEEN DEET AND ALTERNATIVES
Measuring the duration of action of DEET is the primary method of determining the efficacy. This can be measured by a number of methods, including the "arm in a cage" method and field studies.5·36"39
"Arm in a Cage" Study
Recently, multiple concentrations of DEET, along with several other commercially available insect repellent products containing citronella, IR3535, or other naturally occurring oils, were tested in a blinded fashion using the "arm in a cage" method.5 In this study, the investigators did not apply a uniform amount of repellent to each subject, but allowed the subject to apply the product as they interpreted the directions. This was done to attempt to replicate "real world" conditions.
Duration of action of DEET increased as the concentration increased. DEET 4.75% had a mean complete protection time of 88.4 minutes, with a range of 45 to 120 minutes. DEET 6.65% worked for 1 12 minutes, with a range of 90 to 170 minutes. DEET 20% worked for 234 minutes, with a range of 180 to 325 minutes. The highest DEET concentration tested in this study was 23.8%; the mean protection time was 301 minutes, with a range of 200 to 360 minutes.
As DEET concentration increased, each product had a statistically different mean protection time regardless of trade name. One product containing 2% soybean oil but no DEET had a mean protection time of 94.6 minutes, which placed it in the same category of efficacy as 4.75% DEET. However, the range of protection time was wider, at 16 to 195 minutes.5
Products containing citronella lotion or oil had a mean protection time between 2.8 and 19.7 minutes, with ranges between 1 and 60 minutes. The best performing of these agents contained either 10% citronella alone or 12% citronella with multiple other oils. The performance was significantly less than the lowest concentrated formulation of DEET available on the market.5
The product containing 7.5% IR3535 had a mean protection time of 22.9 minutes and a range of 10 to 60 minutes.5 The product's manufacturer, Avon, disputed this study by claiming repellency of 3 hours; however, no supporting data were offered.40 Three other products were tested, each of which were wristbands containing either 9.5% DEET or 25% citronella. Each had a mean protection time of less than a minute.5
In one field study, when compared with no protection, 3% citronella candles decreased mosquito landing rates from about 10 bites per 5 minutes to 6 bites per 5 minutes.36 Although this difference was statistically significant, there was no comparison of the citronella candles with DEET protection. The clinical significance of such a decrease in number of bites is unclear.
Another study compared various insect repellent products to negative controls (unprotected people) and positive controls (skin application of 22% DEET).37 Tested products included citronella candles, DEET-impregnated wristbands, mosquito smoke coils containing a pyrethroid, an insect-killing grid using ultraviolet light with 1octen-3-ol as attractants, a sonic mosquito repeller, and the mosquito plant (Pelargonium citrosum). DEET protected against mosquito bites and mosquito-landing rates much better than any of the other products. Only two tested products protected better than the negative controls. The wristband had a slightly better protection than no protection, but the subjects reported the majority of bites occurring on head and neck sites rather than sites adjacent to the wrist bands. This supports the assertion that, as with DEET, any protection should cover all susceptible skin to be effective.
The other product that fared better than no protection was the mosquito smoke coils, but they were susceptible to changes in wind speed and direction. When the smoke plume blew away from the volunteers, they reported more bites. When completely enveloped in the smoke, subjects reported a moderate degree of protection. However, according to the manufacturer's label, consumers should avoid prolonged inhalation of the smoke.4' When mosquito-coil machines were evaluated for toxic emissions in a separate study, the authors found that burning one coil releases the amount of particulate matter less than 2.5 mm that is the equivalent of burning between 75 and 137 cigarettes. The amount of formaldehyde that was released was equivalent to burning 5 1 cigarettes.41
One study compared DEET with IR3535 and found that, at 20% concentration, both products showed equal repellency against most genera of mosquitoes except Anopheles?* Most protection times were in the range of 8 to 10 hours for this study, with the exception of about 3.5 hours and 5 hours, respectively, for Anopheles. A separate study did not show equal results between the two agents for protection against Ochlerotatus, a mosquito commonly found in the Southeastern states and a vector for Venezuelan equine encephalitis virus.39 DEET 25% protected for approximately 5.5 hours, and IR3535 25% protected for approximately 3 hours.
There appears to be a discrepancy in the performance of IR3535 in the "arm in a cage" study versus field study. Equal efficacy in field study,38 particularly in the considerably longer mean protection time, differed from the findings of the "arm in a cage" study.5 This may partially be due to the higher concentration used in the field study. Differences in results may also be related to differences in amounts used because of individual interpretation of product directions.5 As this is a relatively new product, further study will be helpful in evaluating its efficacy.
No study or manufacturer can make the claim that a product prevents humans from contracting mosquitoborne illness. It is important to emphasize that additional methods of prevention should be included to prevent illness, such as wearing clothing that completely covers the skin and avoiding possible exposure during dusk or dawn, when mosquitoes are most prevalent. It has been demonstrated that application of DEET to clothing is particularly effective for ticks.42
The American Academy of Pediatrics recommends that DEET should be used in concentrations between 10% and 30%, and the choice of concentrations may be based, in part, on the length of time a person is likely to be exposed. For example, if a child requires only 1 to 2 hours of protection, 10% DEET is usually sufficient. DEET should not be applied more than once a day, and DEET should not be used on children younger than 2 months. Products that combine DEET with a sunscreen should be avoided, due to the need to frequently reapply sunscreen.42
In comparison trials, DEET is more effective than any other insect repellent. Despite some reports of serious adverse events, when comparing the thousands of other reports of exposure and millions of past users, DEET has a good safety record. The appropriate and safest concentration to use on children remains unclear, however. Due to potential absorption through the skin, prudence would dictate that the lowest effective concentration for the time period of exposure be used. Because research has shown that solvents with less skin permeation may be used as an alternative to the ethanol used in some commercial DEET preparations, manufacturers could develop products that are less likely to be absorbed. Pediatricians should be familiar with the duration of action of various formulations of DEET and the efficacy (and in some cases lack of efficacy) of other products in order to advise patients on safe but effective methods of insect control.
1 . American Academy of Pediatrics. Arboviruses. In: Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Dis· eases. 26th ed. EIk Grove Village, IL: American Academy of Pediatrics; 2003:199-202.
2. Centers for Disease Control and Prevention. Summary of notifiable diseases - United States, 2001 . MMWR Morb Mortal WIcIy Rep. 2003;50(53):i-xxiv, 1-108.
3. Centers for Disease Control and Prevention. West Nile Virus Activity in the United States (reported as of May 21, 2004). Atlanta, GA: CDC; 2003. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/surv &control03Maps.htm. Accessed June 7. 2004.
4. Lyme disease surveillance - United States, 1989-1990. MM WR Morb Mortal WkIy Rep. 1 99 1;40(25):4 17-421.
5. Fradin M, Day J. Comparative efficacy of insect repellents against mosquito bites. N Eng J Med. 2002:347( 1 ): 1 3- 1 8.
6. Robbins P, Cherniack M. Review of the biodistribution and toxicity of the insect repellent N,N-Diethyl-m-Toluamide (DEET). J Toxicol Environ Health. 1986;18(4):503525.
7. Dormán D. Diethyltoluamide (DEET) insect repellent toxicosis. Vet Clin North Am Small AnimPract. 1 990;20(2):387-390.
8. Bloomquist L, Thorsell W. Distribution and fate of the insect repellent C-N,N-diethyl-mtoluamide in the animal body. II. Distribution and excretion after cutaneous application. Acta Pharmacol Toxicol. 1977:4 1 (3): 235243.
9. Selim S. Hartnagel RE Jr, Osimitz TG. Gabriel KL, Schoenig GP. Absorption, metabolism, and excretion of N,N-diethyl-mtoluamide following dermal application to human volunteers. Fundam Appi Toxicol. 1995:25(1 ):95-100.
10. Stinecipher J. Shah J. Percutaneous permeation of N.N-diethyl-m-toluamide (DEET) from commercial mosquito repellents and the effect of solvent. J Toxicol Environ Health. 1997:52(2): 119-135.
11. Moody RP, Benoit FM. Riedel D, Ritter L. Dermal absorption of the insect repellent DEET (N,N-diethyl-m-toluamide) in rats and monkeys: effect of anatomical site and multiple exposure. J Toxico/ Emiron Health. 1989;26(2):137-147.
12. Wu A1 Pearson LM, Shekoski DL, et al. High resolution gas chromatography/mass spectrometric characterization of urinary metabolites of N ,N-diethyl-m-toluamide (DEET) in man. Journal of High Resolution Chromatography & Chromatography Communications. 1979:2(9):558-562.
13. Ross J, Shah J. Reduction in skin permeation of N,N-diethyl-m-toluamide (DEET) by altering the skin/vehicle partition coefficient. Journal of Controlled Release. 2000;67(23):2 11-221.
14. Roland EH, Jan J, Rigg RM. Toxic encephalopathy in a child after brief exposure to insect repellents. Can Med Assoc J. 1985; 132(2): 155- 156.
15. Seizures temporally associated with use DEBT insect repellent - New York and Connecticut. MMWR Morb Mortal WkIy Rep. 1989;38(39):678-680.
16. Wantke F, Focke M, Hemmer W, Götz M, Jarisch R. Generalized urticaria induced by a diethyltoluamide-containing insect repellent in a child. Contact Dermatitis. 1996;35(3): 186-1 87.
17. Gryboski J, Weinstein D, Ordway NK. Toxic encephalopathy apparently related to the use of an insect repellent. N Eng J Med. 1961;264:289-291.
18. Zadikoff CM. Toxic encephalopathy associated with the use of insect repellent. J Pediatr. 1979;95(1):140-142.
19. Heick HM, Shipman RT, Norman MG, James W. Reye-like syndrome associated with use insect repellent in a presumed heterozygote for ornithine carbamoyl transferase deficiency. J Pediatr. 1980;97(3):47 1-473.
20. de Garbino JP, Laborde A. Toxicity of an insect repellent: N-N-diethyltoluamide. Vet Hum Toxicol. 1983;25(6):422-423.
21. Snyder JW, Poe RO, Stubbins JF, Garrettson LK. Acute manic psychosis following the dermal application of N,N-diethyl-m-toluamide (DEET) in an adult. J Tox Clin Tox. 1986;24(5):429^39.
22. Tenenbein M. Severe toxic reactions and death following the ingestion of diethyltoluamide-containing insect repellents. JAMA. 1987:258(1 1):1509-1511.
23. Edwards DL, Johnson CE. Insect-repellentinduced toxic encephalopathy in a child. Clinical Pharmacy. 1987;6(6):496-498.
24. Lipscomb J, Kramer J, Leikin J. Seizure following brief exposure to the insect repellent N,N-diethyl-m-toluamide. Ann Emerg Med. 1 992:2 1(3):3 15-3 17.
25. Hampers LC, Oker E, Leikin JB. Topical use of DEET insect repellent as a cause of severe encephalopatiiy in a healthy adult male. Acad Emerg Med. 1 999;6( 1 2): 1 295- 1 267.
26. Petrucci N, Sardini S. Severe neurotoxic reaction association with oral ingestion of lowdose diethyltoluamide-containing insect repellent in a child. Pediatr Emerg Care. 2000;16(5):341-342.
27. Briassoulis G, Narlioglou M, Hatzis T. Toxic encephalopathy associated with use of DEET insect repellents: a case analysis of its toxicity in children. Hum Exp Toxicol. 2001;20(1):8-14.
28. Veltri JC, Osimitz TG, Bradford DC, Page BC. Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N,N-diethyl-m-toluatnide (DEET) from 1985-1989. J Toxicol Clin Toxicol. 1994:32(1): 1-16.
29. Litovitz TL, Smilkstein M, Felberg L, et al. 1996 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Enter Med. 1997;l5(5):447-500.
30. Litovitz TL, Klein-Schwartz W, Dyer KS, et al. 1997 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emer Med. 1998;16(5):443-497.
31. Litovitz TL, Klein-Schwartz W, Caravati EM, et al. 1998 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emer Med. 1999;17(5):435-487.
32. Litovitz TL, Klein-Schwartz W, White S, et al. 1 999 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emer Med. 2000; 18(5):5 17-574.
33. Litovitz TL, Klein-Schwartz W, White S. et al. 2000 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emer Med. 2001;19(5):337-195.
34. Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, et al. 2001 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emer Med. 2002;20(5):39M52.
35. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emer Med. 2003;21(5):353^21.
36. Lindsay LR, Surgeoner GA, Heal JD, GaIUvan GJ. Evaluation of the efficacy of 3% citronella candles and 5% citronella incense for protection against field populations of AEDES mosquitoes. J Am Mosq Contr Assoc. 1996:12(2 Pt l):293-294.
37. Jensen T, Lampman R, Slamecka MC, Novak RJ. Field efficacy of commercial anti-mosquito products in Illinois. J Am Mosq Contr Assoc. 2000; 16(2): 148-152.
38. Thavara J, Tawatsin A, Chompoosri J. Laboratory and field evaluation of the insect repellent 3535 (ethyl butylaminopropionate) and DEET against mosquito vectors in Thailand. JAm Mosq Contr Assoc. 2001; 17(3): 190- 195.
39. Barnard DR, Bernier UR, Posey KH, Xue RD. Repellency of IR3535, KBR3023, paramenthane-3,8-diol, and DEET to black salt marsh mosquitoes (Diptera: Culicidae) in the Everglades National Park. J Med Entomol. 2O02;39(6):895-899.
40. Teal JJ. Insect repellents and mosquito bites. N Engl J Med. 2002;347(2l): 17 19-1721 -
41 . Liu W, Zhang J, Hashim JH, et al. Mosquito coil emissions and health implications. Environ Health Perspect. 2003; 1 1 1 ( 1 2): 1 454- 1 460.
42. Young D, Evans S. Safety and efficacy of DEET and permethrin in the prevention of arthropod attack. Mil Med. 1998;163(5):324330.
43. American Academy of Pediatrics Committee on Environmental Health. Pesticides. In: Etzel RA, ed. Pediatric Environmental Health. 2nd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003:348-350.
Published Case Reports of Acute Encephalopathy Associated With
United States Poison Control Annual Reports of Calls related to DEET29-35