The consequences of DEET toxicity are variable and unpredictable

Subject:   Before you use "Registered" DEET-----
Date:      Fri, 28 Apr 2000 08:30:21 -0400
From:        Stephen Tvedten <steve@getipm.com>
Organization:     Get Set Inc. (www.getipm.com)

To:     Lyndon Hawkins <hawkins@empm.cdpr.ca.gov>
          Senior Research Scientist
          State of California, Department of Pesticide Regulation - Integrated Pest Management

Dear Lyndon, Before you use any of your "registered" DEET, Joyce Shepard thought you may wish to read the following - I would also like to point out that the City of New York supplied 33% DEET to the children last year even though New York State Law said it is illegal to sell any DEET product containing over 30%! I would also like to point out that Culex pipens is not out during the day and the pictures of children using DEET during the day to "protect" themselves from a mosquito that is not out during the day deeply disturbs me. Of course the use/misuse of many of your "registered" POISONS often disturbs me.

MMWR; October 06, 1989 / 38(39);678-680 - Epidemiologic Notes and Reports Seizures Temporally Associated with Use of DEET Insect Repellent -- New York and Connecticut. In August 1989, epidemiologists from the New York State Department of Health (NYSDH) investigated five reports of generalized seizures temporally associated with topical use of N,N-diethyl-m-toluamide (DEET). Three of the case-patients, one from New York and two from Connecticut, were reported by a pediatric neurologist who practices in both states. One case was reported initially to an entomologist in New York, and one was reported directly to the NYSDH. The cases occurred in June through August 1989.

The patients, four boys aged 3-7 years and one 29-year-old man, had few prodromal symptoms and recovered quickly. All five had unremarkable medical histories, and none had had a previous seizure or neurologic event. All had normal nonfocal neurologic examinations after their seizures, and four had normal complete laboratory examinations and normal computerized tomography and/or magnetic resonance imaging examinations. Each had had topical cutaneous exposure to varying concentrations of DEET; four had had fewer than three applications. The interval between last use of DEET and onset of seizures ranged from 8 to 48 hours. One patient developed urticaria before his seizure; he was one of two patients who developed an urticarial reaction to phenytoin administered to control seizures.

While reinforcing the importance of DEET in preventing Lyme disease (LD (Lyme borreliosis)), health officials in New York, Connecticut, and New Jersey issued a health alert on August 22 advising caution in the use of DEET-containing repellents. The NYSDH is planning to conduct epidemiologic studies to evaluate the association between DEET and neurologic events. Reported by: S Oransky, MD, Hudson Valley Poison Control Center, Nyack; B Roseman, MD, Pediatric Neurologic Associates, White Plains; D Fish, PhD, Medical Entomology Laboratory, New York Medical College, Valhalla; T Gentile, MS, Center for Environmental Health, J Melius, MD, State Environmental Epidemiologist, New York State Dept of Health. ML Cartter, MD, JL Hadler, MD, State Epidemiologist, Connecticut State Dept of Health Svcs. Div of Environmental Hazards and Health Effects, Center for Environmental Health and Injury Control; Div of Vector-Borne Infectious Diseases, Center for Infectious Diseases; Div of Field Svcs, Epidemiology Program Office, CDC.

Editorial Note: For health officials in New York and Connecticut, two of the states where LD is of growing concern, inquiries about the potential adverse effects of insect repellents have increased. Recent anecdotal reports of seizures temporally associated with the use of DEET have heightened public awareness of DEET's potential adverse effects.

DEET has been marketed in the United States since 1956 and is used by an estimated 50-100 million persons each year. Since 1961, at least six cases of toxic systemic reactions from repeated cutaneous exposure to DEET have been reported (1-6). Six girls, ranging in age from 17 months to 8 years, developed behavioral changes, ataxia, encephalopathy, seizures, and/or coma after repeated cutaneous exposure to DEET; three died. Another six systemic toxic reactions have been reported following ingestion of DEET (7). Additionally, episodes of confusion, irritability, and insomnia have been reported by Everglades National Park employees following repeated and prolonged use of DEET (8).

DEET is partially absorbed through the skin and has been used to enhance dermal delivery of other drugs (9). Adverse reactions include allergic responses, direct neurotoxicity, and dermatitis. One of the girls who died after dermal exposure was partially deficient in the enzyme ornithine carbamoyltransferase (3); DEET may interfere with the urea cycle metabolic pathway (10).

Anecdotal reports of seizures are difficult to interpret. None of the recent cases in New York and Connecticut have been clearly established as DEET toxicity. In contrast to cases described in the medical literature, the New York and Connecticut patients were all male, DEET exposure was less intense, few prodromal symptoms or encephalopathy were seen, and recovery was more rapid and complete. With the dramatic increase in the prevalence of DEET use in areas with endemic LD, the reported cases of seizures temporally related to DEET use may be coincidental. However, these cases may represent a different, previously unreported spectrum of toxic reactions. Careful toxicologic and epidemiologic studies must be conducted, including adequate documentation of DEET levels in affected and unaffected persons.

Clinicians evaluating patients with unexplained seizures should consider the possibility of exposure to DEET. However, since the exact circumstances under which DEET-related neurotoxicity may occur are unclear, DEET should not be accepted as the cause of a seizure until appropriate evaluation has reliably excluded other possible etiologies.

The optimal concentration of DEET for prevention of tick bites is unknown. However, repellents containing 20%-30% DEET applied to clothing are approximately 90% effective in preventing tick attachment (11). To minimize the possibility of adverse reactions to DEET, the following precautions are suggested: --Apply repellent sparingly only to exposed skin or clothing.-- Avoid applying high-concentration products to the skin, particularly of children. --Do not inhale or ingest repellents or get them into the eyes. --Wear long sleeves and long pants, when possible, and apply repellent to clothing to reduce exposure to DEET. --Avoid applying repellents to portions of children's hands that are likely to have contact with eyes or mouth. --Never use repellents on wounds or irritated skin. --Use repellent sparingly; one application will last 4-8 hours. Saturation does not increase efficacy. --Wash repellent-treated skin after coming indoors. --If a suspected reaction to insect repellents occurs, wash treated skin, and call a physician. Take the repellent can to the physician. Specific medical information about the active ingredients in insect repellents is available from the National Pesticide Telecommunications Network, telephone (800) 858-7378.

1. Edwards DL, Johnson CE. Insect-repellent-induced toxic encephalopathy in a child. Clin Pharm 1987;6:496-8.

2. Gryboski J, Weinstein D, Ordway NK. Toxic encephalopathy apparently related to the use of an insect repellent. N Engl J Med 1961;264:289-91.

3. Heick HMC, Shipman RT, Norman MG, James W. Reye-like syndrome associated with use of insect repellent in a presumed heterozygote for ornithine carbamoyl transferase deficiency. J Pediatr 1980;97:471-3.

4. de Garbino JP, Laborde A. Toxicity of an insect repellent: N-N-diethyltoluamide. Vet Hum Toxicol 1983;25:422-3.

5. Roland EH, Jan JE, Rigg JM. Toxic encephalopathy in a child after brief exposure to insect repellents. Can Med Assoc J 1985;132:155-6.

6. Zadikoff CM. Toxic encephalopathy associated with use of insect repellant. J Pediatr 1979;95:140-2.

7. Tenenbein M. Severe toxic reactions and death following the ingestion of diethyltoluamide-containing insect repellents. JAMA 1987;258:1509-11.

8. McConnell R, Fidler AT, Chrislip D, NIOSH. Everglades National Park health hazard evaluation report. Cincinnati, Ohio: US Department of Health and Human Services, Public Health Service, 1986; NIOSH health hazard evaluation report no. HETA-83-085-1757.

9. Windheuser JJ, Haslam JL, Caldwell L, Shaffer RD. The use of N,N-diethyl- m-toluamide to enhance dermal and transdermal delivery of drugs. J Pharm Sci 1982;71:1211-3. 10. Heick HMC, Peterson RG, Dalpe-Scott M, Qureshi IA. Insect repellent, N,N-diethyl-m-toluamide, effect on ammonia metabolism. Pediatrics 1988;82:373-6. 11. Schreck CE, Snoddy EL, Spielman A. Pressurized sprays of permethrin or DEET on military clothing for personal protection against Ixodes dammini (Acari: Ixodidae). J Med Entomol 1986;23:396-9.

An experimental anti-nerve gas drug that was prescribed by the Department of Defense for 695,000 soldiers during the Persian Gulf War may have boosted the toxicity of N,N-Diethyl-m-toluamide (DEET) in the field, triggering veterans' symptoms known as Persian Gulf War Syndrome, Senate Committee staff members noted recently.

Last year, a USDA scientist who was conducting research on cockroaches found evidence that could have important implications for Persian Gulf War veterans, Senate Veterans' Affairs Committee staff members said at a May 6 committee hearing on hazards of military research. The scientist, Dr. James Moss, found that when used in combination with pyridostigmine, DEET became 10 times as toxic as when used alone.

Senate Veterans' Affairs Committee staff members investigating the use of the anti-nerve gas enhancer pyridostigmine made a connection between DEET and other insecticides used by soldiers in the field to combat sand flies and scorpions, and their possible synergistic effects with pyridostigmine.

Pyridostigmine bromide, a carbamate, is a chemical that enhances the effectiveness of established drugs for treatment of nerve gas poisoning, but only when appropriate doses are selected.

The report stated, "DEET and many other pesticides were commonly used during the Gulf War. If individuals who took pyridostigmine pills become more vulnerable to pesticides (or vice versa), this could explain the serious neurological symptoms experienced by so many Gulf War veterans."

The report went on to note that two antidotes to nerve agents, atropine and pyridine-2-aldozime methochloride (2-PAM), are enhanced if pyridostigmine has already been given. "It should be noted," the staff report said, "that 2-PAM itself may intensify the effects of carbamate poisoning, so that if a soldier had an adverse reaction to pyridostigmine [from its combination with pesticides] the use of 2-PAM could make the reaction worse."

REF: Kansas Pesticide Newsletter, 17(6), June 18, 1994, (as seen in Pesticide & Toxic Chemical News 22{28}).

Fundam Appl Toxicol 1996 Dec;34(2):201-22 Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. Abou-Donia MB, Wilmarth KR, Abdel-Rahman AA, Jensen KF, Oehme FW, Kurt TL Department of Pharmacology, Duke University Medical Center, Durham, North Carolina, 27710, USA.

The operating environment of the service personnel during the Persian Gulf War involved psychological, biological, and chemical elements including exposure to pesticides such as the insect repellent DEET (N,N-diethyl-m-toluamide) and the insecticide chlorpyrifos (O,O-diethyl O-3,5,6-trichloropyridinyl phosphorothioate) and to pyridostigmine bromide (PB,3-dimethylaminocarbonyloxy-N-methylpyridinium bromide) that was administered as a prophylactic agent against possible nerve gas attack. The present study was designed to determine the toxicity produced by individual or coexposure of hens 5 days/week for 2 months to 5 mg PB/kg/day in water, by gavage; 500 mg DEET/kg/day, neat, sc; and 10 mg chlorpyrifos kg/day in corn oil, sc. Coexposure to various binary treatments produced greater neurotoxicity than that caused by individual exposures and was characterized by severe neurologic deficit and neuropathological alterations. Also, neurotoxicity was further enhanced following concurrent administration of the three chemicals. Severe inhibition of plasma butyrylcholinesterase (BuChE) activity was produced in hens treated with PB (activity 17% of control) compared to those treated with chlorpyrifos (activity 51% of control) or DEET (activity 83% of control). BuChE inhibition was further increased in binary and tertiary treatment groups compared to individual treatment groups. In contrast, a significant inhibition of brain acetylcholinesterase (AChE) was produced in hens administered chlorpyrifos alone (activity 67% of control), while those given chlorpyrifos in combination with other compounds exhibited a significant inhibition of brain AChE activity ranging from 43 to 76%. Brain neurotoxicity target esterase (NTE) was not inhibited in any of the individual treatment groups or PB/DEET, but was significantly inhibited and had activity expressed as a percentage of control in groups administered combined chlorpyrifos with PB of 73% or DEET of 74% and in the tertiary treatment group of 71%. We hypothesize that test compounds may compete for xenobiotic metabolizing enzymes in the liver and blood and may also compromise the integrity of the blood-brain barrier, leading to an increase in their "effective concentrations" in the nervous system to levels equivalent to the toxic doses of individual compounds. This is consistent with the present observation of increases in (1) the inhibition of brain AChE and NTE, (2) the extent of neurologic dysfunction, and (3) the severity and frequency of neuropathologic lesions in the combined treatment groups compared to those administered individual compounds.

OBJECTIVE: To describe a case of N,N-diethyl-m-toluamide (DEET)-induced cardiovascular toxicity in an adult and reviews other cases that have been reported in the published literature. Human and animal data available on DEET pharmacokinetics are reviewed and factors that predispose an individual to DEET toxicity are identified. DATA SOURCES: Case report information was obtained through personal contact with the patient during hospitalization and by telephone, and also from the patient's medical records. Computerized literature searches were conducted with the following systems to obtain medical literature on DEET toxicity: TOXLINE, International Pharmaceutical Abstracts, and MEDLINE. Index Medicus was searched manually. STUDY SELECTION: All reported cases of DEET toxicity in children and adults were reviewed. DATA EXTRACTION: Case reports were evaluated for the quantity of the DEET exposure (topical or oral), the clinical manifestations of the exposure, and the outcome of the exposure. DATA SYNTHESIS: This case is similar in some aspects to those already in the literature; however, very few cases of DEET toxicity in adults have been reported. Cardiovascular toxicity in humans related to DEET application has not been previously reported in the published medical literature. DEET exposure (topical or oral) results in a highly variable clinical course. Whether the outcome is death or recovery without sequelae is difficult to predict. CONCLUSIONS: Adults, as well as children, are at risk for toxicity from insect repellents. The use of highly concentrated DEET-containing insect repellents should be avoided to reduce the risk of toxicity in both children and adults. The consequences of DEET toxicity are variable and unpredictable.

So Lyndon, Rather than slather yourself with DEET, I would suggest sitting in the breeze (of a fan) and enjoy the freedom from pests and "registered" pesticides! Hopefully the breeze is not considered an "illegal alternative" in California!

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