N,N,-diethyl-m-toluamide (DEET) suppresses humoral immunological function in B6C3F1 mice

Toxicological Sciences

Volumn 108, Issue 1, 2009, Pages 110-123

  Keil, Deborah E ^a   Mcguinn, W David ^c   Dudley, Andrew C ^d   Eudaly, Jackie G ^b,c   Gilkeson, Gary S ^b,d   Peden Adams, Margie M ^b,c  

^a UNIVERSITY OF NEVADA   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^d RALPH H JOHNSON VA MEDICAL CENTER   (United States)

Author keywords

DEET; Gulf War Illness; Immune function; PFC response; T cell subpopulations

Indexed keywords

DIETHYLTOLUAMIDE;

ADULT ANIMAL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIBODY RESPONSE; ARTICLE; BIOAVAILABILITY; BLOOD LEVEL; CD4 CD8 RATIO; CELL TYPE; CONTROLLED STUDY; DOSE RESPONSE; FEMALE; HEALTH HAZARD; HUMORAL IMMUNITY; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOTOXICITY; LYMPHOCYTE PROLIFERATION; MOUSE; MOUSE STRAIN; NATURAL KILLER CELL; NONHUMAN; PLAQUE FORMING CELL; RISK ASSESSMENT; SPLEEN WEIGHT; T LYMPHOCYTE SUBPOPULATION; THYMUS;

ANALYSIS OF VARIANCE; ANIMALS; ANTIBODY FORMATION; B-LYMPHOCYTES; BIOLOGICAL AVAILABILITY; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; DEET; FEMALE; HUMANS; IMMUNE TOLERANCE; IMMUNOSUPPRESSIVE AGENTS; INJECTIONS, INTRAVENOUS; INJECTIONS, SUBCUTANEOUS; INSECT REPELLENTS; KILLER CELLS, NATURAL; MALE; METABOLIC DETOXICATION, DRUG; MICE; MODELS, ANIMAL; PERSIAN GULF SYNDROME; SPLEEN; THYMUS GLAND;

HEXAPODA; MUS; RODENTIA;

EID: 61349146620     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfp001     Document Type: Article

References (76)

1. Abou-Donia, M., Goldsein, L. B., Dechovskaia, A., Bullman, S., Jones, K. H., Herrick, E. A., Abdel-Rahman, A. A., and Khan, W. A. (2001). Effects of daily dermal application of DEET and permethrin, alone and in combination, on sensorimotor performance, blood-brain barrier, and blood-testis barrier in rats. J. Toxicol. Environ. Health A 62 523-541.
2. Abou-Donia, M. B., Wilmarth, K. R., Abdel-Rahman, A. A., Jensen, K. F., Oehme, F. W., and Kurt, T. L. (1996a). Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. Fundam. Appl. Toxicol. 34, 201-222.
3. Abou-Donia, M. B., Wilmarth, K. R., Jensen, K. F., Oehme, F. W., and Kurt, T. L. (1996b). Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin: Implications for Gulf War chemical exposures. J. Toxicol. Environ. Health 48, 35-56.
4. Abu-Qare, A., and Abou-Donia, M. (2000). Increased 8-hydroxy-2′-deoxyguanosine, a biomarker of oxidative DNA damage in rat urine following a single dermal dose of DEET (N, N-diethyl-m-toluamide), and permethrin, alone and in combination. Toxicol. Lett. 117, 151-160.
5. Abu-Qare, A., and Abou-Donia, M. (2001). DEET (N,N-diethyl-m-toluamide) alone and in combination with permethrin increased urinary excretion of 6β-hydroxylcortisol in rats, a marker of hepatic CYP3A induction. J. Toxicol. Environ. Health A 64, 373-384.
6. Amato, A. A., McVey, A., Cha, C., Matthews, E. D., Jackson, C. E., Kleingunther, R., Worley, L., Cornman, E., and Kagan-Hallet, K. (1997). Evaluation of neuromuscular symptoms in veterans of the Persian Gulf War. Neurology 48, 4-12.
7. Barnes, D. B., Hardin, J. M., and Pruett, S. B. (1992). Acute infection of mice with highly virulent group B streptococci as a host resistance model for immunotoxicity. Arch. Toxicol. 66, 423-429.
8. Barr, D. B., Barr, J. R., Maggio, V. L., Whitehead, R. D., Jr, Sadowski, M. A., Whyatt, R. M., and Needham, L. L. (2002). A multi-analyte method for the quantification of contemporary pesticides in human serum and plasma using high-resolution mass spectrometry. J. Chromatogr. Anal. B 778, 99-111.
9. Bryant, J., Day, R., Whiteside, T. L., and Herberman, R. B. (1992). Calculation of lytic units for the expression of cell-mediated cytotoxicity. J. Immunol. Methods 146, 91-103.
10. Burleson, G. R., and Burleson, F. G. (2008). Testing human biologicals in animal host resistance models. J. Immunotoxicol. 5, 23-31.
11. Carlson, D. B. (2006). Source reduction in Florida's salt marshes: Management to reduce pesticide use and enhance the resource. J. Am. Mosq. Control Assoc. 22, 534-537.
12. Chaney, L. A., Wineman, R. W., Rockhold, R. W., and Hume, A. S. (2000). Toxicol. Appl. Pharmacol. 165, 107-114.
13. Clewell, H. J., Anderson, M. E., and Barton, H. A. (2002). A consistent approach for the application of pharmacokinetic modeling in cancer and noncancer risk assessment. Environ. Health Perspect. 110, 85-93.
14. Cunningham, A. J., and Szenberg, A. (1968). Further improvements in the plaque forming technique for detecting single antibody forming cells. Immunology 14, 599-601.
15. Czuprynski, C. J., Brown, J. F., Maroushek, N., Wagner, R. D., and Steinburg, H. (1994). Administration of anti-granulocyte mAb RB6-8C5 impairs the resistance of mice to Listeria monocytogenes infection. J. Immunol. 152, 1836-1846.
16. Czuprynski, C. J., Brown, J. F., Young, K. M., and Cooley, A. J. (1989). Administration of purified anti-L3T4 monoclonal antibody impairs the resistance of mice to Listeria monocytogenes infection. Infect. Immun. 57, 100-109.
17. Dalrymple, S. A., Lucian, L. A., Slattery, R., McNeil, T., Aud, D. M., Fuchino, S., Lee, F., and Murray, R. (1995). Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: Correlation with inefficient neutrophilia. Infect. Immun 63, 2262-2268.
18. Dixit, R. (2007). Pharmacokinetics and toxicokinetics: Fundamentals and applications in toxicology. In Veterinary Toxicology: Basic and Clinical Principles (R. C. Gupta, Ed.), pp. 25-41. Academic Press, New York, NY.
19. Duke, S. S., Schook, L. B., and Holsapple, M. P. (1985). Effects of N-notrodimethylamine on tumor susceptibility. J. Leukoc. Biol. 37, 383-394.
20. Dunn, P. L., and North, R. J. (1991). Early gamma-interferon production by natural killer cells is important in defense against murine listeriosis. Infect. Immun 59, 2892-2900.
21. Faustman, E. M., and Omenn, G. S. (2001). Risk assessment. In Casarett and Doull's Toxicology: The Basic Science of Poisons, 6th edn (C. D. Klaassen, Ed.), pp. 83-104. McGraw-Hill Companies, Inc, New York, NY.
22. Feldmann, R. J., and Maibach, H. I. (1970). Absorption of some organic compounds through the skin of man. J. Invest. Dermatol. 54, 399-404.
23. Frost, S. D. (2000). Gulf War syndrome: Proposed causes. Cleve. Clin. J. Med. 67, 17-20.
24. Gilbert, I. H. (1966). Evaluation and use of mosquito repellents. JAMA 196, 253-255.
25. Gouge, S. F., Daniels, D. J., and Smith, C. E. (1994). Exacerbation of asthma after pyridostigmine during operation desert storm. Military Med. 159, 108-111.
26. Gryboski, J., Weinstein, D., and Ordway, N. K. (1961). Toxic encephalopathy apparently related to the use of an insect repellent. N. Engl. J. Med. 264, 289-291.
27. Haley, R. W., and Kurt, T. L. (1997). Self-reported exposure to neurotoxic chemical combinations in the gulf war. JAMA 277, 231-237.
28. Jerne, N. K., and Nordin, A. A. (1963). Plaque formation in agar by single antibody producing cells. Science 140, 405.
29. Keil, D. E., Mehlmann, T., Butterworth, L., and Peden-Adams, M. M. (2007). Gestational exposure to PFOS suppresses immunological function in F1 mice. Toxicol. Sci. 103, 77-85.
30. Kerkvleit, N. I., and Brauner, J. A. (1990). Flow cytometric analysis of lymphocyte subpopulations in the spleen and thymus of mice exposed to an acute immunosuppressive dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Environ. Res. 52, 146-154.
31. Lau, C., Anitole, K., Hodes, C., Lai, D., Pfahles-Hutchens, A., and Seed, J. (2007). Perfluoroalkyl acids: A review of monitoring and toxicological findings. Toxicol. Sci. 99, 366-394.
32. Luster, M. I., Munson, A. E., Thomas, P. T., Holsapple, M. P., Fenters, J. D., White, K. L., Jr, Lauer, L. D., Germolec, D. R., Rosenthal, G. J., and Dean, J. H. (1988). Development of a testing battery to assess chemical-induced immunotoxicity: National Toxicology Program's guidelines for immunotoxicity evaluation in mice. Fundam. Appl. Toxicol. 10, 2-19.
33. Luster, M. I., Portier, C., Pait, D. G., Rosenthal, G. J., Germolec, D. R., Corsini, E., Blaylock, B. L., Pollock, P., Kouchi, Y., Craig, W., et al. (1993). Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests. Fundam. Appl. Toxicol. 21, 71-82.
34. Luster, M. I., Portier, C., Pait, D. G., White, K. L., Gennings, C., Munson, A. E., and Rosenthal, G. J. (1992). Risk assessment in immunotoxicology. I. Sensitivity and predictability of immune tests. Fundam. Appl. Toxicol. 18, 200-210.
35. McCain, W. C., Lee, R., Johnson, M. S., Whaley, J. E., Ferguson, J. W., Beall, P., and Leach, G. (1997). Acute oral toxicity study of pyridostigmine bromide, permethrin, and DEET in the laboratory rat. J. Toxicol. Environ. Health 50, 113-124.
36. McConnell, R., Fidler, A. T., and Chrislip, D. (1986). NIOSH Health Hazard Evaluation Report No. HETA 83-085-1757, Evergalades Nation Park, Everglades, FL. NTIS Accession No. PB87-189270AS. pp. 107.
37. National Research Council. (1994a). Science and Judgment in Risk Assessment. National Academy Press, Washington, DC.
38. National Research Council. (1994b). Risk Characterization. National Academy Press, Washington, DC.
39. National Research Council. (1996). Understanding Risk: Informing Decisions in a Democratic Society. National Academy Press, Washington, DC.
40. Osmitz, T. G., and Murphy, J. V. (1997).Neurological effects associated with use of the insect repellent N,N-diethyl-m-toluamide (DEET). J. Toxicol. 35, 435-441.
41. Peden-Adams, M. M., EuDaly, J. G., Dabra, S., EuDaly, A., Heesemann, L. M., Smythe, J., and Keil, D. E. (2007a). Suppression of humoral immunity following exposure to the perfluorinated insecticide sulfluramid. J. Environ. Sci. Health A 70, 1-12.
42. Peden-Adams, M. M., EuDaly, J., EuDaly, E., Dudley, A. C., Zeigler, J., Lee, A., Robbs, J., Gilkeson, G., and Keil, D. E. (2001). Evaluation of immunotoxicity induced by single or concurrent exposure to N,N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel. Toxicol. Ind. Health 17, 192-209.
43. Peden-Adams, M. M., Keller, J. M., EuDaly, J. G., Berger, J., Gilkeson, G. S., and Keil, D. E. (2007b). Suppression of humoral immunity following exposure to perfluorooctane sulfonate (PFOS). Toxicol. Sci. 104, 144-154.
44. Peden-Adams, M. M., Keller, J. M., EuDaly, J. G., Berger, J., Gilkeson, G. S., and Keil, D. E. (2008). Suppression of humoral immunity following exposure to perfluorooctane sulfonate (PFOS). Toxicol. Sci. 104 144-154.
45. Pruett, S. B., Fan, R., Zheng, Q., Myers, L. P., and Hebert, P. (2000). Modeling and predicting immunological effects of a chemical stressor (3,4-dichoropropionanilide) using the area under the corticosterone concentration versus time curve. Toxicol. Sci. 58, 77-87.
46. Qiu, H., Jun, H. W., and McCall, J. W. (1998). Pharmacokinetics, formulation, and safety of insect repellent N,N-diethyl-3-methylbenzamide (DEET): A review. J. Am. Mosq. Control Assoc. 14, 12-27.
47. Reifenrath, W. G., Hawkins, G. S., and Kurtz, M. S. (1991). Percutaneous penetration and skin retention of topically applied compounds: An in vitro-in vivo study. J. Pharm. Sci. 80, 526-532.
48. Reifenrath, W. G., and Robinson, P. B. (1982). In vitro skin evaporation and penetration characteristics of mosquito repellents. J. Pharm. Sci. 71, 1014-1018.
49. Renwick, A. G. (1995). Toxicokinetics. In General and Applied Toxicology: College Edition, 2nd edn (B. Ballantyne, T. Marrs, and P. Turner, Eds.), pp. 111-142. Stockton Press, New York. NY.
50. Robbins, P. J., and Cherniack, M. G. (1986). Review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET). J. Toxicol. Environ. Health 18 503-525.
51. Roland, E. H., Jan, J. E., and Rigg, J. M. (1985). Toxic encephalopathy in children after brief exposure to insect repellents. Can. Med. Assoc. 132, 155-156.
52. Rook, G., and Zumla, A. (1998). Is the Gulf War syndrome an immunologically mediated phenomenon? Hospital Med. 59, 10-11.
53. Schimidt, D. H., Acree, F., Jr, and Bowman, N. C. (1959). Fate of C-14-diethyltoluamide applied to guinea pigs. J. Econ. Entomol. 52, 928-930.
54. Schoenig, G. P., Hartnagel, R. E., Jr, Schardein, J. L., and Vorhees, C. V. (1993). Neurotoxicity Evaluation of N,N-Diethyl-m-toluamide (DEET) in rats. Fundam. Appl. Toxicol. 21, 355-365.
55. Schoenig, G. P., Osimitz, T. G., Gabriel, K. L., Hartnagel, R., Gill, M. W., and Goldenthal, E. I. (1999). Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m-toluamide (DEET). Toxicol. Sci. 47, 99-109.
56. Schoenig, G. P., and Osimitz, T. G. (2001). Chapter 63 DEET. In Handbook of Pesticide Toxicology, 2nd edn (R. I. Krieger, Ed.), pp. 1439-1459. Academic Press. A Harcourt Science and Technology Company, San Diego, CA.
57. Selgrade, M., Cooper, K. D., Devlin, R. B., van Loveren, H., Baigini, R. E., and Luster, M. I. (1995). Immunotoxicity - Bridging the gap between animal research and human health effects. Fundam. Appl. Toxicol. 24, 13-21.
58. Selgrade, M. K. (1999). Use of immunotoxicity data in health risk assessment: Uncertainties and research to improve the process. Toxicology 133, 59-72.
59. Selgrade, M. K. (2007). Immunotoxicity the risk is real. Toxicol. Sci. 100, 328-332.
60. Selim, S., Hartnagel, R. E., Jr, Osimitz, T. G., Gabriel, K. L., and Schoenig, G. P. (1995). Absorption, metabolism, and excretion of N,N diethyl-m-toluamide following dermal application to human volunteers. Fundam. Appl. Toxicol. 25, 95-100.
61. Smith, C. N., Gilbert, I. H., Gouck, H. K., Bowman, M. C., Acree, F., and Schmidt, C. H. (1963). Factors affecting the protection period of mosquito repellents. U.S. Dept. Agric. Tech. Bull. 1285, 1-36.
62. Soetekouw, P. M., de Vries, M., van Bergen, L., Galama, J. M., Keyser, A., Bleijenberg, G., and van der Meer, J. W. (2000). Somatic hypotheses of war syndromes. Eur. J. Clin. Invest. 30, 630-641.
63. Spencer, T. S., Hill, J. A., Feldmann, R. J., and Maibach, H. I. (1979). Evaporation of diethyltoluamide from human skin in vivo and in vitro. J. Invest. Dermatol. 72, 317-319.
64. Stinecipher, J., and Shah, J. (1997). Percutaneous permeation of n,n-diethyl-m-toluamide (DEET) from commercial mosquito repellents and the effect of solvent. J. Toxicol. Environ. Health 52, 119-135.
65. Sudakin, D. L., and Trevathan, W. R. (2003). DEET: A review and update of safety and risk in the general population. J. Toxicol. Clin. Toxicol. 41, 831-839.
66. Tawatsin, A., Thavara, U., Chansang, U., Chavalittumrong, P., Boonruad, T., Wongsinkongman, P., Bansidhi, J., and Mulla, M. S. (2006). Field evaluation of deet, Repel Care, and three plant based essential oil repellents against mosquitoes, black flies (Diptera: Simuliidae) and land leeches (Arhynchobdellida: Haemadipsidae) in Thailand. J. Am. Mosq. Control Assoc. 22, 306-313.
67. U.S. EPA. (1998a). DEET reregistration eligibility decision (RED). EPA738-R-98-010.
68. U.S. EPA. (1998b). Health effects test guidelines. OPTTS 870.7800. Immunotoxicity. http://www.epa.gov/opptsfrs/publications/ OPPTS_Harmonized/870_Health_EffectsTest_Guidelines/Series/870-7800.pdf
69. U.S. EPA. (1994). Methods for derivation of inhalation reference concentrations and application of inhalation dosimetry EPA/600/8-90/ 066F. U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Washington, DC.
70. U.S. EPA. (2003). Framework for cumulative risk assessment. U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Washington Office, Washington, DC, EPA/630/P-02/001F.
71. Veltri, J. C., Osimitz, T. G., Bradford, D. C., and Page, B. C. (1994). Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N,N-diethyl-m-toluamide (DEET) from 1985-1989. Clin. Toxicol. 32, 1-16.
72. Voidani, A., and Thrasher, J. D. (2004). Cellular and humoral immune abnormalities in Gulf War veterans. Environ. Health Perspect. 112, 840-846.
73. Wiltrout, R. H., Herberman, R. B., Zhang, S.-R., Chirigos, M. A., Ortaldo, J. R., Green, K. M., Jr, and Talmadge, J. E. (1985). Role of organ-associated NK cells in decreased formation of experimental metastases in lung and liver. J. Immunol. 134, 4267-4275.
74. Wittich, A. C. (1996). Gynecologic evaluation of the first female soldiers enrolled in the Gulf War Comprehensive Clinical Evaluation Program at Tripler Army Medical Center. Military Med. 161, 635-637.
75. Wu, W. J., and Pruett, S. B. (1999). Ethanol decreases host resistance to pulmonary metastases in a mouse model: Role of natural killer cells and the ethanol-induced stress response. Int. J. Cancer 82, 886-892.
76. Zadikoff, C. M. (1979). Toxic encephalopathy associated with use of insect repellant. J. Pediatr. 95, 140-142.