Deoxynivalenol: Toxicology and potential effects on humans

Journal of Toxicology and Environmental Health - Part B: Critical Reviews

Volumn 8, Issue 1, 2005, Pages 39-69

  Pestka, James J ^a,b   Smolinski, Alexa T ^a  

^a Michigan State University   (United States)

^b MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MYCOTOXIN; TRICHOTHECENE; VOMITOXIN;

ANIMAL MODEL; ANOREXIA; BODY WEIGHT; BOVIDS; CAT; CEREAL; CHICKEN; CHRONIC DISEASE; CHRONIC TOXICITY; DIETARY INTAKE; DOG; ENZYME ACTIVATION; FOOD CONTAMINATION; GASTROENTERITIS; GASTROINTESTINAL TOXICITY; HISTOPATHOLOGY; HUMAN; HUMAN CELL; LD 50; MAJOR CLINICAL STUDY; MORTALITY; MOUSE; NONHUMAN; PROTEIN SYNTHESIS INHIBITION; REVIEW; RISK ASSESSMENT; RODENT; SIGNAL TRANSDUCTION; SPECIES DIFFERENCE; SWINE; TOXICOKINETICS; VOMITING;

ANIMALS; CEREALS; ENVIRONMENTAL EXPOSURE; ENVIRONMENTAL MONITORING; FOOD MICROBIOLOGY; FUSARIUM; HUMANS; MYCOTOXINS; RISK ASSESSMENT; SPECIES SPECIFICITY; TRICHOTHECENES;

ANIMALIA; BOVIDAE; CANIS FAMILIARIS; FELIS CATUS; GALLUS GALLUS; PRIMATES; RODENTIA; SUS SCROFA;

EID: 11244316554     PISSN: 10937404     EISSN: None     Source Type: Journal    
DOI: 10.1080/10937400590889458     Document Type: Review

References (181)

1. Abbas, H. K., Mirocha, C. J., Pawlosky, R. J., and Pusch, D. J. 1985. Effect of cleaning, milling, and baking on deoxynivalenol in wheat. Appl. Environ. Microbiol. 50:482-486.
2. Abbas, H. K., Mirocha, C. J., and Tuite, J. 1986. Natural occurrence of deoxynivalenol, 15-acetyl-deoxynivalenol, and zearalenone in refusal factor corn stored since 1972. Appl. Environ. Microbiol. 51:841-843.
3. Abouzied, M. M., Azcona, J. I., Braselton, W. E., and Pestka, J. J. 1991. Immunochemical assessment of mycotoxins in 1989 grain foods: Evidence for deoxynivalenol (vomitoxin) contamination. Appl. Environ. Microbiol. 57:672-677.
4. Anonymous. 1999. Outbreaks of Gastrointestinal illness of unknown etiology associated with eating burritos-United States. Morbid. Mortal. Weekly. Rep. 48:210.
5. Anonymous. 2002. Opinion of the Scientific Committee on Food on Fusarium toxins. Part 6: Group evaluation of T-2 toxin, HT-2 Toxin, Nivalenol and Deoxynivalenol. Report of European Commission Scientific Committee on Food, Brussels, Belgium.
6. Arnold, D. L., Karpinski, K. F., McGuire, P. F., Nera, E. A., Zawidzka, Z. Z., Lok, E., Campbell, J. S., Tryphonas, L., and Scott, P. M. 1986a. A short-term feeding study with deoxynivalenol (vomitoxin) using rats. Fundam. Appl. Toxicol. 6:691-696.
7. Arnold, D. L., McGuire, P. F., Nera, E. A., Karpinski, K. F., Bickis, M. G., Zawidzka, Z. Z., Fernie, S., and Vesonder, R. F. 1986b. The toxicity of orally administered deoxynivalenol (vomitoxin) in rats and mice. Food Chem. Toxicol. 24:935-941.
8. Association of Food and Drug Officials of the United States. 1975. Appraised of the safety of chemicals in foods, drugs and cosmetics. FDA, Washington, D.C.
9. Atroshi, F., Rizzo, A. F., Veijalaonen, P., Lindberg, L. A., Honkanen-Buzalsi, T., Andersson, K., Hirvi, T., and Saloniemi, H. 1994. The effect of dietary exposure to DON and T-2 toxin on host resistance and serum immunoglobulins of normal and mastitic mice. J. Anim. Physiol. Anim. Nutr. 71:223-233.
10. Azcona-Olivera, J., Ouyang, Y., Murtha, J., Chu, F. S., and Pestka, J. J. 1995a. Induction of cytokine mRNAs in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): Relationship to toxin distribution and protein synthesis inhibition. Toxicol. Appl. Pharmacol. 133:109-120.
11. Azcona-Olivera, J., Ouyang, Y. L., Warner, R. L., Linz, J. E., and Pestka, J. J. 1995b. Effects of vomitoxin (deoxynivalenol) and cycloheximide on IL-2, 4, 5 and 6 secretion and mRNA levels in murine CD4+ cells. Food Chem. Toxicol. 33:433-441.
12. Banotai, C., Azcona-Olivera, J. I., Greene-McDowelle, D. M., and Pestka, J. J. 1999a. Effects of vomitoxin ingestion on murine models for systemic lupus erythematosus. Food Chem. Toxicol. 37:533-543.
13. Banotai, C., Greene-McDowelle, D. M., Azcona-Olivera, J. I., and Pestka, J. J. 1999b. Effects of intermittent vomitoxin exposure on body weight, immunoglobulin levels and haematuria in the B6C3F1 mouse. Food Chem. Toxicol. 37:343-350.
14. Berek, L., Petri, I. B., Mesterhazy, A., Teren, J., and Molnar, J. 2001. Effects of mycotoxins on human immune functions in vitro. Toxicol. In Vitro 15:25-30.
15. Bergsjo, B., Matre, T., and Nafstad, I. 1992. Effects of diets with graded levels of deoxynivalenol on performance in growing pigs. Zentralbl. Veterinarmed. A 39:752-758.
16. Bergsjo, B., Herstad, O., and Nafstad, I. 1993a. Effects of feeding deoxynivalenol-contaminated oats on reproduction performance in White Leghorn hens. Br. Poult. Sci. 34:147-159.
17. Bergsjo, B., Langseth, W., Nafstad, I., Jansen, J.H., and Larsen, H.J. 1993b. The effects of naturally deoxynivalenol-contaminated oats on the clinical condition, blood parameters, performance and carcass composition of growing pigs. Vet. Res. Commun. 17:283-294.
18. Bhat, R. V., Beedu, S. R., Ramakrishna, Y., and Munshi, K. L. 1989. Outbreak of trichothecene mycotoxicosis associated with consumption of mould-damaged wheat production in Kashmir Valley, India. Lancet. 1:35-37.
19. Bondy, G. S., and Pestka, J. J. 1991. Dietary exposure to the trichothecene vomitoxin (deoxynivalenol) stimulates terminal differentiation of Peyer's patch B cells to IgA secreting plasma cells. Toxicol. Appl. Pharmacol. 108:520-530.
20. Bondy, G. S., and Pestka, J. J. 2000. Immunomodulation by fungal toxins. J. Toxicol. Environ. Health B 3:109-143.
21. Borison, H. L. 1989. Area postrema: Chemoreceptor circumventricular organ of the medulla oblongata. Prog. Neurobiol. 32:351-390.
22. Bunner, D. L., and Morris, E. R. 1988. Alteration of multiple cell membrane functions in L-6 myoblasts by T-2 toxin: An important mechanism of action. Toxicol. Appl. Pharmacol. 92:113-121.
23. Canady, R. A., Coker, R. D., Egan, S. K., Krska, R., Kuiper-Goodman, T., Olsen, M., Pestka, J., Resnik, S., and Schlatter, J. 2001. Deoxynivalenol. In Safety evaluation of certain mycotoxins in food, pp. 420-529. Geneva: World Health Organization.
24. CAST. 2003. Potential economic costs of mycotoxins in the United States. In Mycotoxins:Risks in plant, animal, and human systems, pp.136-142. Task Force Report No. 139. Ames, IA: Council for Agricultural Science and Technology.
25. Clark, D. E., Wellman, P. J., Harvey, R. B., and Lerma, M. S. 1987. Effects of vomitoxin (deoxynivalenol) on conditioned saccharin aversion and food consumption in adult rats. Pharmacol. Biochem. Behav. 27:247-252.
26. Cote, L. M., Dahlem, A. M., Yoshizawa, T., Swanson, S. P., and Buck, W. B. 1986a. Excretion of deoxynivalenol and its metabolite in milk, urine, and feces of lactating dairy cows. J. Dairy Sci. 69:2416-2423.
27. Cote, L. M., Nicoletti, J., Swanson, S. J., and Buck, W. 1986b. Production of deepoxydeoxynivalenol (DOM-1), a metabolite of deoxynivalenol, by in vitro rumen incubation. J. Agric. Food Chem. 1986:458-460.
28. Cote, L. M., Buck, W., and Jeffery, E. 1987. Lack of hepatic microsomal metabolism of deoxynivalenol and its metabolite, DOM-1. Food Chem. Toxicol. 25:291-295.
29. Debouck, C., Haubruge, E., Bollaerts, P., van Bignoot, D., Brostaux, Y., Werry, A., and Rooze, M. 2001. Skeletal deformities induced by the intraperitoneal administration of deoxynivalenol (vomitoxin) in mice. Int. Orthop. 25:194-198.
30. Dong, W., and Pestka, J. J. 1993. Persistent dysregulation of IgA production and IgA nephropathy in the B6C3F1 mouse following withdrawal of dietary vomitoxin (deoxynivalenol). Fundam. Appl. Toxicol. 20:38-47.
31. Dong, W., Sell, J. E., and Pestka J. J. 1991. Quantitative assessment of mesangial immunoglobulin A (IgA) accumulation, elevated circulating IgA immune complexes, and hematuria during vomitoxin-induced IgA nephropathy. Fundam. Appl. Toxicol. 17:197-207.
32. Dong, W., Azcona Olivera, J. I., Brooks, K. H., Linz, J. E., and Pestka, J. J. 1994. Elevated gene expression and production of interleukins 2, 4, 5, and 6 during exposure to vomitoxin (deoxynivalenol) and cycloheximide in the EL-4 thymoma. Toxicol. Appl. Pharmacol. 127:282-290.
33. Ehling, G., Cockburn, A., Snowdon, P., and Buschhaus, H. 1997. The significance of the fusaruim toxin deoxynivalenol (DON) for human and animal health. Fifth Eur. Fusaruim Sem. 25:443-447.
34. El Banna, A. A., Hamilton, R. M., Scott, P. M., and Trenholm, H. L. 1983. Nontransmission of deoxynivalenol (vomitoxin) to eggs and meat in chickens fed deoxynivalenol-contaminated diets. J. Agric. Food Chem. 31:1381-1384.
35. Eriksen, G. S., and Alexander, J. 1998. Fusarium toxins in cereals-A risk assessment. Copenhagen: Nordic Council of Ministers, TemaNord 502.
36. Fioramonti, J., Dupuy, C., Dupuy, J., and Bueno, L. 1993. The mycotoxin, deoxynivalenol, delays gastric emptying through serotonin-3 receptors in rodents. J. Pharmacol. Exp. Ther. 266:1255-1260.
37. Forsell, J. H., Witt, M. F., Tai, J. H., Jensen, R., and Pestka, J. J. 1986. Effects of 8-week exposure of the B6C3F1 mouse to dietary deoxynivalenol (vomitoxin) and zearalenone. Food Chem. Toxicol. 24:213-219.
38. Forsell, J. H., Jensen, R., Tai, J. H., Witt, M., Lin, W. S., and Pestka, J. J. 1987. Comparison of acute toxicities of deoxynivalenol (vomitoxin) and 15-acetyldeoxynivalenol in the B6C3F1 mouse. Food Chem. Toxicol. 25:155-162.
39. Forsyth, D. M., Yoshizawa, T., Morooka, N., and Tuite, J. 1977. Emetic and refusal activity of deoxynivalenol to swine. Appl. Environ. Microbiol. 34:547-552.
40. Friend, D. W., Trenholm, H. L., Elliot, J. I., Thompson, B. K., and Hartin, K. E. 1982. Effect of feeding vomitoxin-contaminated wheat to pigs. Can. J. Anim. Sci. 62:1211-1222.
41. Gareis, M., Bauer, J., and Gedek, J. 1987. On the metabolism of the mycotoxin deoxynivalenol in the isolated perfused rat liver. Mycotoxin Res. 3:25-32.
42. Gauvreau, H. C. 2000. Toxicokinetic, tissue residue, and metabolic studies of deoxynivalenol (vomitoxin) in turkeys. PhD dissertation, Simon Fraser University, Vancouver, BC.
43. Greene, D. M., Azcona Olivera, J. I., and Pestka, J. J. 1994. Vomitoxin (deoxynivalenol)-induced IgA nephropathy in the B6C3F1 mouse: Dose response and male predilection. Toxicology 92:245-260.
44. Grove, J. F. 1988. Non-macrocyclic trichothecenes. Nat. Prod. Rep. 5:187-209.
45. Grove, J. F. 2000. Non-macrocyclic trichothecenes. Part 2. Prog. Chem. Org. Nat. Prod. 69:1-70.
46. Hamilton, R. M., Thompson, B. K., Trenholm, H. L., Fiser, P. S., and Greenhalgh, R. 1985a. Effects of feeding white Leghorn hens diets that contain deoxynivalenol (vomitoxin)-contaminated wheat. Poult. Sci. 64:1840-1852.
47. Hamilton, R. M., Trenholm, H. L., Thompson, B. K., and Greenhalgh, R. 1985b. The tolerance of white Leghorn and broiler chicks, and turkey poults to diets that contained deoxynivalenol (vomi toxin)-contaminated wheat. Poult. Sci. 64:273-286.
48. Hart, L. P., and Braselton, W. E. J. 1983. Distribution of vomitoxin in dry milled fractions of wheat infected with Gibberella zeae. J. Agric. Food Chem. 31:657-659.
49. Harvey, R. B., Kubena, L. F., Huff, W. E., Elissalde, M. H., and Phillips, T. D. 1991. Hematologic and immunologic toxicity of deoxynivalenol (DON)-contaminated diets to growing chickens. Bull. Environ. Contam. Toxicol. 46:410-416.
50. He, P., Young, L. G., and Forsberg, C. 1992. Microbial transformation of deoxynivalenol (vomitoxin). Appl. Environ. Microbiol. 58:3857-3863.
51. Hedman, R., and Pettersson, H. 1997. Transformation of nivalenol by gastrointestinal microbes. Arch. Tierernahr. 50:321-329.
52. Heller, R. A., Song, K., Onasch, M. A., Fischer, W. H., Chang, D., and Ringold, G. M. 1990. Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor. Proc. Natl. Acad. Sci. USA 87:6151-6155.
53. Huff, W. E., Doerr, J. A., Hamilton, P. B., and Vesonder, R. F. 1981. Acute toxicity of vomitoxin (deoxynivalenol) in broiler chickens. Poult. Sci. 60:1412-1414.
54. Huff, W. E., Kubena, L. F., Harvey, R. B., Hagler, W. M. Jr., Swanson, S. P., Phillips, T. D., and Creger, C. R. 1986. Individual and combined effects of aflatoxin and deoxynivalenol (DON, vomitoxin) in broiler chickens. Poult. Sci. 65:1291-1298.
55. Hughes, D. M., Gahl, M. J., Graham, C. H., and Grieb, S. L. 1999. Overt signs of toxicity to dogs and cats of dietary deoxynivalenol. J. Anim. Sci. 77:693-700.
56. Hunder, G., Schumann, K., Strugala, G., Gropp, J., Fichtl, B., and Forth, W. 1991. Influence of subchronic exposure to low dietary deoxynivalenol, a trichothecene mycotoxin, on intestinal absorption of nutrients in mice. Food Chem. Toxicol. 29:809-814.
57. IARC. 1993. Some naturally occurring substances: Food items and constituents, heterocyclcamines and mycotoxins. IARC Monog. Eval. Carcinogen. Risks Hum. 56:599.
58. Ihara, T., Sugamata, M., Sekijima, M., Okumura, H., Yoshino, N., and Ueno, Y. 1997. Apoptotic cellular damage in mice after T-2 toxin-induced acute toxicosis. Nat. Toxins. 5:141-145.
59. Ihara, T., Yamamoto, T., Sugamata, M., Okumura, H., and Ueno, Y. 1998. The process of ultrastructural changes from nuclei to apoptotic body. Virchows Arch. 433:443-447.
60. Iordanov, M. S., Paranjape, J. M., Zhou, A., Wong, J., Williams, B. R., Meurs, E. F., Silverman, R. H., and Magun, B. E. 2000. Activation of p38 mitogen-activated protein kinase and c-Jun NH(2)- terminal kinase by double-stranded RNA and encephalomyocarditis virus: Involvement of RNase L, protein kinase R, and alternative pathways. Mol. Cell Biol. 20:617-627.
61. Islam, Z., and Pestka, J. J. 2003. Role of IL-1{beta} in endotoxin potentiation of deoxynivalenol-induced corticosterone response and leukocyte apoptosis in mice. Toxicol. Sci. 74:93-102.
62. Islam, Z., Nagase, M., Yoshizawa, T., Yamauchi, K., and Sakato, N. 1998. T-2 toxin induces thymic apoptosis in vivo in mice. Toxicol. Appl. Pharmacol. 148:205-214.
63. Islam, Z., Moon, Y. S., Zhou, H. R., King, L. E., Fraker, P. J., and Pestka, J. J. 2002. Endotoxin potentiation of trichothecene-induced lymphocyte apoptosis is mediated by up-regulation of glucocorticoids. Toxicol. Appl. Pharmacol. 180:43-55.
64. Islam, Z., King, L. E., Fraker, P. J., and Pestka, J. J. 2003. Differential induction of glucocorticoid-dependent apoptosis in murine lymphoid subpopulations in vivo following coexposure to lipopolysaccharide and vomitoxin (deoxynivalenol). Toxicol. Appl. Pharmacol. 187:69-79.
65. Iverson, F., Armstrong, C., Nera, E., Truelove, J., Fernie, S., Scott, P., Stapley, R., Hayward, S., and Gunner, S. 1995. Chronic feeding study of deoxynivalenol in B6C3F1 male and female mice. Teratogen. Carcinogen. Mutagen. 15:283-306.
66. Jackson, L. S., and Bullerman, L. B. 1999. Effect of processing on Fusarium mycotoxins. Adv. Exp. Med. Biol. 459:243-261.
67. Ji, G. E., Park, S. Y., Wong, S. S., and Pestka, J. J. 1998. Modulation of nitric oxide, hydrogen peroxide and cytokine production in a clonal macrophage model by the trichothecene vomitoxin (deoxynivalenol). Toxicology 125:203-214.
68. Joffe, A. Z. 1978. Fusarium poae and F. sporotichiodes as principal causal agents of alimentary toxic aleukia. In Mycotoxic fungi, mycotoxins and mycotoxicoses: An encyclopedia and book, eds. T. D. Wyllie and L. G. Morehouse, pp. 21-86. New York: Marcel Dekker.
69. Khera, K. S., Whalen, C., Angers, G., Vesonder, R. F., and Kuiper-Goodman, T. 1982. Embryotoxicity of 4-deoxynivalenol (vomitoxin) in mice. Bull. Environ. Contam Toxicol. 29:487-491.
70. Khera, K. S., Arnold, D. L., Whalen, C., Angers, G., and Scott, P. M. 1984. Vomitoxin (4-deoxynivalenol): Effects on reproduction of mice and rats. Toxicol. Appl. Pharmacol. 74:345-356.
71. Khera, K. S., Whalen, C., and Angers, G. 1986. A teratology study on vomitoxin (4-deoxynivalenol) in rabbits. Food Chem. Toxicol. 24:421-424.
72. Knasmuller, S., Bresgen, N., Kassie, F., Mersch-Sundermann, V., Gelderblom, W., Zohrer, E., and Eckl, P. M. 1997. Genotoxic effects of three Fusarium mycotoxins, fumonisin B1, moniliformin and vomitoxin in bacteria and in primary cultures of rat hepatocytes. Mutat. Res. 391:39-48.
73. Kristensen, P., Irgens, L. M., Andersen, A., Bye, A. S., and Sundheim, L. 1997. Gestational age, birth weight, and perinatal death among births to Norwegian farmers, 1967-1991. Am. J. Epidemiol. 146:329-338.
74. Kubena, L. F., Swanson, S. P., Harvey, R. B., Fletcher, O. J., Rowe, L. D., and Phillips, T. D. 1985. Effects of feeding deoxynivalenol (vomitoxin)-contaminated wheat to growing chicks. Poult. Sci. 64:1649-1655.
75. Kubena, L. F., Harvey, R. B., Corrier, D. E., and Huff, W. E. 1987. Effects of feeding deoxynivalenol (DON, vomitoxin)-contaminated wheat to female White Leghorn chickens from day old through egg production. Poult. Sci. 66:1612-1618.
76. Kuiper-Goodman, T., Miller, J. D., and Trenholm, H. L. 1994. Prevention of mycotoxicoses through risk management and risk assessment. In Mycotoxins in grains, eds. J. D. Miller and H. L. Trenholm, pp. 439-469. St. Paul, MN:Eagan Press.
77. Lake, B. G., Phillips, J. C., Walters, D. G., Bayley, D. L., Cook, M. W., Thomas, L. V., Gilbert, J., Startin, J. R., Baldwin, N. C., and Bycroft, B. W. 1987. Studies on the metabolism of deoxynivalenol in the rat. Food Chem. Toxicol. 25:589-592.
78. Lewis, C. W., Smith, J. E., Anderson, J. G., and Freshney, R. I. 1999. Increased cytotoxicity of food-borne mycotoxins toward human cell lines in vitro via enhanced cytochrome p450 expression using the MTT bioassay. Mycopathologia. 148:97-102.
79. Li, F. Q., Li, Y. W., Luo, X. Y., and Yoshizawa, T. 2002. Fusarium toxins in wheat from an area in Henan Province, PR China, with a previous human red mould intoxication episode. Food Addit. Contam. 19:163-167.
80. Li, S., Ouyang, Y., Yang, G. H., and Pestka, J. J. 2000. Modulation of transcription factor AP-1 activity in murine EL-4 thymoma cells by vomitoxin (deoxynivalenol). Toxicol. Appl. Pharmacol. 163:17-25.
81. Li, S., Ouyang, Y. L., Dong, W., and Pestka, J. J. 1997. Superinduction of IL-2 gene expression by vomitoxin (deoxynivalenol) involves increased mRNA stability. Toxicol. Appl. Pharmacol. 147:331-342.
82. Lombaert, G. A., Pellaers, P., Roscoe, V., Mankotia, M., Neil, R., and Scott, P. M. 2003. Mycotoxins in infant cereal foods from the Canadian retail market. Food Addit. Contam. 20:494-504.
83. Lun, A. K., Young, L. G., Moran, E. T., Jr., Hunter, D. B., and Rodriguez, J. P. 1986. Effects of feeding hens a high level of vomitoxin-contaminated corn on performance and tissue residues. Poult. Sci. 65:1095-1099.
84. Lun, A. K., Moran, E. T., Jr, Young, L. G., and McMillan, E. G. 1988. Disappearance of deoxynivalenol from digesta progressing along the chicken's gastrointestinal tract after intubation with feed containing contaminated corn. Bull. Environ. Contam Toxicol. 40:317-324.
85. 3H-deoxynivalenol in colostomized and intact chickens. Bull. Environ. Contam Toxicol. 42:919-925.
86. Luo, Y., Yoshizawa, T., and Katayama, T. 1990. Comparative study on the natural occurrence of Fusarium mycotoxins (trichothecenes and zearalenone) in corn and wheat from high- and low-risk areas for human esophogeal cancer in China. Appl. Environ. Microbiol. 56:3723-3726.
87. Luo, X. 1994. Food poisoning caused by Fusarium toxins. Proc. Second Asian Conf. Food Safety, pp. 129-136.
88. McMullen, M., Jones, R., and Gallenberg, D. 1997. Scab of wheat and barley: A re-emerging disease of devastating impact. Plant Dis. 81:1340-1348.
89. Meky, F. A., Hardie, L. J., Evans, S. W., and Wild, C. P. 2001. Deoxynivalenol-induced immunomodulation of human lymphocyte proliferation and cytokine production. Food Chem. Toxicol. 39:827-836.
90. Meky, F. A., Turner, P. C., Ashcroft, A. E., Miller, J. D., Qiao, Y. L., Roth, M. J., and Wild, C. P. 2003. Development of a urinary biomarker of human exposure to deoxynivalenol. Food Chem. Toxicol. 41:265-273.
91. Miller, J. D., Greehalgh, R., Wang, Y. Z., and Lu, M. 1991. Trichothecene chemotype of three Fusarium species. Mycologia. 83:121-130.
92. Miura, K., Nakajima, Y., Yamanaka, N., Terao, K., Shibato, T., and Ishino, S. 1998. Induction of apoptosis with fusarenon-X in mouse thymocytes. Toxicology 127:195-206.
93. Moon, Y., and Pestka, J. J. 2002. Vomitoxin-induced cyclooxygenase-2 gene expression in macrophages mediated by activation of ERK and p38 but not JNK mitogen-activated protein kinases. Toxicol. Sci. 69:373-382.
94. Morooka, N., Uratsuji, N., Yoshizawa, T., and Yamamoto, H. 1972. Studies on the toxic effects of barley infected with Fusarium spp. J. Food Hyg. Soc. Jpn. 13:368-375.
95. Morrissey, R. E. 1984. Teratological study of Fischer rats fed diet containing added vomitoxin. Food Chem. Toxicol. 22:453-457.
96. Morrissey, R. E., and Vesonder, R. F. 1985. Effect of deoxynivalenol (vomitoxin) on fertility, pregnancy, and postnatal development of Sprague-Dawley rats. Appl. Environ. Microbiol. 49:1062-1066.
97. Morrissey, R. E., Norred, W. P., and Vesonder, R. F. 1985. Subchronic toxicity of vomitoxin in Sprague-Dawley rats. Food Chem. Toxicol. 23:995-999.
98. Nejdfors, P., Ekelund, M., Jeppsson, B., and Westrom, B. R. 2000. Mucosal in vitro permeability in the intestinal tract of the pig, the rat, and man. Scand. J. Gastroenterol. 35:501-507.
99. Ossenkopp, K. P., Hirst, M., and Rapley, W. A. 1994. Deoxynivalenol (vomitoxin)-induced conditioned taste aversions in rats are mediated by the chemosensitive area postrema. Pharmacol. Biochem. Behav. 47:363-367.
100. Ouyang, Y. L., Azcona Olivera, J. I., and Pestka, J. J. 1995. Effects of trichothecene structure on cytokine secretion and gene expression in murine CD4+ T-cells. Toxicology. 104:187-202.
101. Ouyang, Y. L., Azcona Olivera, J. I., Murtha, J., and Pestka, J. J. 1996a. Vomitoxin-mediated IL-2, IL-4, and IL-5 superinduction in murine CD4+ T cells stimulated with phorbol ester calcium ionophore: Relation to kinetics of proliferation. Toxicol. Appl. Pharmacol. 138:324-334.
102. Ouyang, Y. L., Li, S., and Pestka, J. J. 1996b. Effects of vomitoxin (deoxynivalenol) on transcription factor NF- kappa B/Rel binding activity in murine EL-4 thymoma and primary CD4+ T cells. Toxicol. Appl. Pharmacol. 140:328-336.
103. Øvernes, G., Matre, T., Sivertsen, T., Larsen, H. J., Langseth, W., Reitan, L. J., and Jansen, J. H. 1997. Effects of diets with graded levels of naturally deoxynivalenol-contaminated oats on immune response in growing pigs. Zentralbl. Veterinarmed. A. 44:539-550.
104. Penner, K., Gray, J., and Pestka, J. J. 2003. Human cytokine mRNA response to deoxynivalenol using whole blood cultures. Toxicologist 72(1):121.
105. Pestka, J. J., and Casale, W. L. 1990. Naturally occurring fungal toxins. Adv. Environ. Sci. Technol. 23:613-638.
106. Pestka, J. J., and Zhou, H. R. 2003. Hck- and PKR-dependent mitogen-activated protein kinase phosphorylation and AP-1, C/EBP and NF-κB activation precedes deoxynivalenol-induced TNF-α and MIP-2 expression. Toxicologist 72:121.
107. Pestka, J. J., Lin, W. S., and Miller, E. R. 1987a. Emetic activity of the trichothecene 15-acetyldeoxynivalenol in swine. Food Chem. Toxicol. 25:855-858.
108. Pestka, J. J., Tai, J. H., Witt, M. F., Dixon, D. E., and Forsell, J. H. 1987b. Suppression of immune response in the B6C3F1 mouse after dietary exposure to the Fusarium mycotoxins deoxynivalenol (vomitoxin) and zearalenone. Food Chem. Toxicol. 25:297-304.
109. Pestka, J. J., Moorman, M. A., and Warner, R. L. 1989. Dysregulation of IgA production and IgA nephropathy induced by the trichothecene vomitoxin. Food Chem. Toxicol. 27:361-368.
110. Pestka, J. J., Dong, W., Warner, R. L., Rasooly, L., and Bondy, G. S. 1990a. Effect of dietary administration of the trichothecene vomitoxin (deoxynivalenol) on IgA and IgG secretion by Peyer's patch and splenic lymphocytes. Food Chem. Toxicol. 28:693-699.
111. Pestka, J. J., Dong, W., Warner, R. L., Rasooly, L., Bondy, G. S., and Brooks, K. H. 1990b. Elevated membrane IgA+ and CD4+ (T helper) populations in murine Peyer's patch and splenic lymphocytes during dietary administration of the trichothecene vomitoxin (deoxynivalenol). Food Chem. Toxicol. 28:409-420.
112. Pestka, J. J., Azcona Olivera, J. I., Plattner, R. D., Minervini, F., Doko, M. B., and Visconti, A. 1994a. Comparative assessment of fumonisin in grain-based foods by ELISA, GC-MS, and HPLC. J. Food Prot. 57:169-172.
113. + cells. Food Chem. Toxicol. 32:1125-1136.
114. Pieters, M. N., Fiolet, D. C. M., and Baars, A. J. 1998. Deoxynivalenol: Derivation of concentration limits in wheat and wheat containing food products. National Institute of Public Health and the Environment, Report 388802 018: 1-32.
115. Prelusky, D. B. 1996. A study on the effect of deoxynivalenol on serotonin receptor binding in pig brain membranes. J. Environ. Sci. Health B 31:1103-1117.
116. Prelusky, D. B., and Trenholm, H. L. 1991a. Non-accumulation of residues in swine consuming deoxynivalenol-contaminated diets. J. Food Sci. 57:801-802.
117. Prelusky, D. B., and Trenholm, H. L. 1991b. Tissue distribution of deoxynivalenol in swine dosed intravenously. J. Agric. Food Chem. 39:748-752.
118. Prelusky, D. B., and Trenholm, H. L. 1993. The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swine. Nat. Toxins 1:296-302.
119. Prelusky, D. B., Trenholm, H. L., Lawrence, G. A., and Scott, P. M. 1984. Nontransmission of deoxynivalenol (vomitoxin) to milk following oral administration to dairy cows. J. Environ. Sci. Health B 19:593-609.
120. 14C-labeled deoxynivalenol to White Leghorn hens. Fundam. Appl. Toxicol. 7:635-645.
121. Prelusky, D. B., Veira, D. M., Trenholm, H. L., and Hartin, K. E. 1986b. Excretion profiles of the mycotoxin deoxynivalenol, following oral and intravenous administration to sheep. Fundam. Appl. Toxicol. 6:356-363.
122. 14C-labeled deoxynivalenol in swine. Fundam. Appl. Toxicol. 10:276-286.
123. Prelusky, D. B., Yeung, J. M., Thompson, B. K., and Trenholm, H. L. 1992. Effect of deoxynivalenol on neurotransmitters in discrete regions of swine brain. Arch. Environ. Contam. Toxicol. 22:36-40.
124. Prelusky, D. B., Rotter, B. A., and Rotter, R. G., Miller, and Trenholm. 1994a. Toxicology of mycotoxins. 359-403. In Mycotoxins in grain: Compounds other than aflatoxin, eds. J. D. Miller and H. L. Trenholm, pp. 359-403, St. Paul, MN: Eagan Press.
125. Prelusky, D. B., Gerdes, R. G., Underhill, K. L., Rotter, B. A., Jui, P. Y., and Trenholm, H. L. 1994b. Effects of low-level dietary deoxynivalenol on haematological and clinical parameters of the pig. Nat. Toxins 2:97-104.
126. Proctor, R. H., Hohn, T. M., and McCormick, S. P. 1995. Reduced virulence of Gibberella zeae caused by disruption of a trichothecene toxin biosynthetic gene. Mol. Plant Microbe Interact. 8:593-601.
127. Rasooly, L., and Pestka, J. J. 1992. Vomitoxin-induced dysregulation of serum IgA, IgM and IgG reactive with gut bacterial and self antigens. Food Chem. Toxicol. 30:499-504.
128. Rasooly, L., and Pestka, J. J. 1994. Polyclonal autoreactive IgA increase and mesangial deposition during vomitoxin-induced IgA nephropathy in the BALB/c mouse. Food Chem. Toxicol. 32:329-336.
129. Rasooly, L., Abouzied, M. M, Brooks, K. H., and Pestka, J. J. 1994. Polyspecific and autoreactive IgA secreted by hybridomas derived from Peyer's patches of vomitoxin-fed mice: Characterization and possible pathogenic role in IgA nephropathy. Food Chem. Toxicol. 32:337-348.
130. Rizzo, A. F., Atroshi, F., Ahotupa, M., Sankari, S., and Elovaara, E. 1994. Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin. Zentralbl. Veterinarmed. A 41:81-90.
131. Robbana-Barnat, S., Loridon-Rosa, B., Cohen, H., Lafarge-Frayssinet, C., Neish, G. A., and Frayssinet, C. 1987. Protein synthesis inhibition and cardiac lesions associated with deoxynivalenol ingestion in mice. Food Addit. Contam. 4:49-56.
132. Robbana-Barnat, T., Lafarge Frayssinet, C., Cohen, H., Neish, G. A., and Frayssinet, C. 1988. Immunosuppressive properties of deoxynivalenol. Toxicology 48:155-166.
133. Rogers, C. G., and Heroux-Metcalf, C. 1983. Cytotoxicity and absence of mutagenic activity of vomitoxin (4-deoxynivalenol) in a hepatocyte-mediated mutation assay with V79 Chinese hamster lung cells. Cancer Lett. 20:29-35.
134. Rotter, B. A., Rotter, R. G., Thompson, B. K., and Trenholm, H. L. 1992. Investigations in the use of mice exposed to mycotoxins as a model for growing pigs. J. Toxicol. Environ. Health 37:329-339.
135. Rotter, B. A., Thompson, B. K., Lessard, M., Trenholm, H. L., and Tryphonas, H. 1994. Influence of low-level exposure to Fusarium mycotoxins on selected immunological and hematological parameters in young swine. Fundam. Appl. Toxicol. 23:117-124.
136. Rotter, B. A., Prelusky, D. B., and Pestka, J. J. 1996. Toxicology of deoxynivalenol (vomitoxin). J. Toxicol. Environ. Health 48:1-34.
137. Schaafsma, A. W. 2002. Economic changes imposed by mycotoxins in food grains: Case study of deoxynivalenol in winter wheat. Adv. Exp. Med. Biol. 504:271-276.
138. Scott, P. M. 1996. Mycotoxins transmitted into beer from contaminated grains during brewing. J. AOAC Int. 79:875-882.
139. Shifrin, V. I., and Anderson, P. 1999. Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis. J. Biol. Chem. 274:13985-13992.
140. Shinozuka, J., Guanmin, L., Uetsuka, K., Nakayama, H., and Doi, K. 1997. Process of the development of T-2 toxin-induced apoptosis in the lymphoid organs of mice. Exp. Anim. 46:117-126.
141. Shinozuka, J., Suzuki, M., Noguchi, N., Sugimoto, T., Uetsuka, K., Nakayama, H., and Doi, K. 1998. T-2 toxin-induced apoptosis in hematopoietic tissues of mice. Toxicol. Pathol. 26:674-681.
142. Sugita-Konishi, Y., and Pestka, J. J. 2001. Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model. J. Toxicol. Environ. Health A 64:619-636.
143. Sugita-Kinoshi, Y., Hara-Kudo, Y., Kasuga, F., and Kumagai, S. 1998. The effects of trichothecenes on host defense against infectious diseases. Mycotoxins 47:19-23.
144. Sundstol-Eriksen, G., and Pettersson, H. 2003. Lack of de-epoxidation of type B trichothecenes in incubates with human faeces. Food Addit. Contam. 20:579-582.
145. Sun, X. M., Zhang, X. H., Wang, H. Y., Cao, W. J., Yan, X., Zuo, L. F., Wang, J. L., and Wang, F. R. 2002. Effects of sterigmatocystin, deoxynivalenol and aflatoxin G1 on apoptosis of human peripheral blood lymphocytes in vitro. Biomed. Environ. Sci. 15:145-152.
146. Swamy, H. V., Smith, T. K., MacDonald, E. J., Boermans, H. J., and Squires, E. J. 2002. Effects of feeding a blend of grains naturally contaminated with Fusarium mycotoxins on swine performance, brain regional neurochemistry, and serum chemistry and the efficacy of a polymeric glucomannan mycotoxin adsorbent. J. Anim. Sci. 80:3257-3267.
147. Swanson, S. P., Helaszek, C., Buck, W. B., Rood, H. D., Jr., and Haschek, W. M. 1988. The role of intestinal microflora in the metabolism of trichothecene mycotoxins. Food Chem. Toxicol. 26:823-829.
148. Szelenyi, I., Herold, H., and Gothert, M. 1994. Emesis induced in domestic pigs: A new experimental tool for detection of antiemetic drugs and for evaluation of emetogenic potential of new anticancer agents. J. Pharmacol. Toxicol. Methods 32:109-116.
149. Szkudelska, K., Szkudelski, T., and Nogowski, L. 2002. Short-time deoxynivalenol treatment induces metabolic disturbances in the rat. Toxicol. Lett. 136:25-31.
150. Trenholm, H. L., Hamilton, R. M., Friend, D. W., Thompson, B. K., and Hartin, K. E. 1984. Feeding trials with vomitoxin (deoxynivalenol)-contaminated wheat: Effects on swine, poultry, and dairy cattle. J. Am. Vet. Med. Assoc. 185:527-531.
151. Trenholm, H. L., Thompson, B. K., Hartin, K. E., Greenhalgh, R., and McAllister, A. J. 1985. Ingestion of vomitoxin (deoxynivalenol)-contaminated wheat by nonlactating dairy cows. J. Dairy Sci. 68:1000-1005.
152. Tryphonas, H., O'Grady, L., Arnold, D. L., McGuire, P. F., Karpinski, K., and Vesonder, R. F. 1984. Effect of deoxynivalenol (vomitoxin) on the humoral immunity of mice. Toxicol. Lett. 23:17-24.
153. Tryphonas, H., Iverson, F., So, Y., Nera, E. A., McGuire, P. F., O'Grady, L., Clayson, D. B., and Scott, P. M. 1986. Effects of deoxynivalenol (vomitoxin) on the humoral and cellular immunity of mice. Toxicol. Lett. 30:137-150.
154. Ueno, Y. 1983. Trichothecenes: Chemical, biological, and toxicological aspects. In Trichothecenes, ed. Y. Ueno, pp. 135-146. Amsterdam: Elsevier Press.
155. Ueno, Y. 1984. Toxicological features of T-2 toxin and related trichothecenes. Fundam. Appl. Toxicol. 4:S124-S132.
156. Vesonder, R. F., Ciegler, A., and Jensen, A. H. 1973. Isolation of the emetic principle from Fusarium-infected corn. Appl. Microbiol. 26:1008-1010.
157. Wang, X., Martindale, J. L., Liu, Y., and Holbrook, N. J. 1998. The cellular response to oxidative stress: influences of mitogen- activated protein kinase signalling pathways on cell survival. Biochem. J. 333 (Pt 2):291-300.
158. Warner, R. L., Brooks, K., and Pestka, J. J. 1994. In vitro effects of vomitoxin (deoxynivalenol) on lymphocyte function: enhanced interleukin production and help for IgA secretion. Food Chem. Toxicol. 32:617-625.
159. Wehner, F. C., Marasas, W. F., and Thiel, P. G. 1978. Lack of mutagenicity to Salmonella typhimurium of some Fusarium mycotoxins. Appl. Environ. Microbiol. 35:659-662.
160. Wong, S. S., Zhou, H. R., Marin-Martinez, M. L., Brooks, K., and Pestka, J. J. 1998. Modulation of IL-1 beta, IL-6 and TNF-alpha secretion and mRNA expression by the trichothecene vomitoxin in the RAW 264.7 murine macrophage cell line. Food Chem. Toxicol. 36:409-419.
161. Wong, S. S., Schwartz, R. C., and Pestka, J. J. 2001. Superinduction of TNF-α and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization. Toxicology 161:139-149.
162. Wong, S. S., Zhou, H. R., and Pestka, J. J. 2002. Effects of vomitoxin (deoxynivalenol) on the binding of transcription factors AP-1, NF-κB and IL-6 in RAW 264.7 macrophage cells. J. Toxicol. Environ. Health A 65:1161-1180.
163. Worrell, N. R., Mallett, A. K., Cook, W. M., Baldwin, N. C., and Shepherd, M. J. 1989. The role of gut micro-organisms in the metabolism of deoxynivalenol administered to rats. Xenobiotica 19:25-32.
164. Yan, D., Rumbeiha, W. K., and Pestka, J. J. 1998a. Experimental murine IgA nephropathy following passive administration of vomitoxin-induced IgA monoclonal antibodies. Food Chem. Toxicol. 36:1095-1106.
165. Yan, D., Zhou, H. R., Brooks, K. H., and Pestka, J. J. 1998b. Role of macrophages in elevated IgA and IL-6 production by Peyer's patch cultures following acute oral vomitoxin exposure. Toxicol. Appl. Pharmacol. 148:261-273.
166. Yang, G. H., Jarvis, B. B., Chung, Y. J., and Pestka, J. J. 2000. Apoptosis induction by the satratoxins and other trichothecene mycotoxins: Relationship to ERK, p38 MAPK, and SAPK/JNK activation. Toxicol. Appl. Pharmacol. 164:149-160.
167. Yordanova, P., Islam, Z., and Pestka, J. J. 2003. Kinetics of deoxynivalenol (vomitoxin) distribution and clearance in the mouse. Toxicologist 72(1):253.
168. Yoshino, N., Takizawa, M., Akiba, H., Okumura, H., Tashiro, F., Honda, M., and Ueno,Y. 1996. Transient elevation of intracellular calcium ion levels as an early event in T-2 toxin-induced apoptosis in human promyelotic cell line HL- 60. Nat. Toxins 4:234-241.
169. Yoshizawa, T. 1983. Red-mold diseases and natural occurrence in Japan. In Trichothecenes - Chemical, biological, and toxicological aspects, ed. Y. Ueno, pp. 195-209. New York: Elsevier.
170. Yoshizawa, T., and Morooka, N. 1973. Deoxynivalenol and its monoacetate: New mycotoxins from Fusarium roseum and moldy barley. Agric. Biol. Chem. 37:2933-2934.
171. Yoshizawa, T., and Morooka, N. 1974. Studies on the toxic substances in the infected cereals (III). Acute toxicities of the new trichothecene mycotoxins: Deoxynivalenol and its monoacetate. J. Food Hyg. Soc. Jpn. 15:261-269.
172. Yoshizawa, T., and Morooka, N. 1977. Trichothecenes in mold infested cereals in Japan. In Mycotoxins in human and animal health, eds. J. V. Rodricks, C. W. Hesseltine, and M. A. Mehlman, pp. 309-321. Park Forest South, IL:Pathotox.
173. Yoshizawa, T., Cote, L. M., Swanson, S. P., and Buck, W. B. 1986. Confirmation of DOM-1, a de-epoxidation metabolite of deoxynivalenol, in biological fluids of lactating cows. Agric. Biol. Chem. 50:227-229.
174. Yoshizawa, T., Yamashita, A., and Luo, Y. 1994. Fumonisin occurrence in corn from high- and low-risk areas for human esophageal cancer in China. Appl. Environ. Microbiol. 60:1626-1629.
175. Young, J. C., Fulcher, R. C., Hayhoe, J. H., Scott, P. M., and Dexter, J. E. 1984. Effect of milling and baking on deoxynivalenol (vomitoxin) content of eastern Canadian wheats. J. Agric. Food Chem. 32:659-664.
176. Young, L. G., McGirr, L., Valli, V. E., Lumsden, J. H., and Lun, A. 1983. Vomitoxin in corn fed to young pigs. J. Anim. Sci. 57:655-664.
177. Zhou, H. R., Yan, D., and Pestka, J. J. 1997. Differential cytokine mRNA expression in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): Dose response and time course. Toxicol. Appl. Pharmacol. 144:294-305.
178. Zhou, H. R., Yan, D., and Pestka, J. J. 1998. Induction of cytokine gene expression in mice after repeated and subchronic oral exposure to vomitoxin (deoxynivalenol): Differential toxin-induced hyporesponsiveness and recovery. Toxicol. Appl. Pharmacol. 151:347-358.
179. Zhou, H. R., Islam, Z., and Pestka, J. J. 2003a. Rapid, sequential activation of mitogen-activated protein kinases and transcription factors precedes proinflammatory cytokine mRNA expression in spleens of mice exposed to the trichothecene vomitoxin. Toxicol. Sci. 72:130-142.
180. Zhou, H. R., Harkema, J. R., Hotchkiss, J. A., Yan, D., Roth, R. A., and Pestka, J. J. 2000. Lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) synergistically induce apoptosis in murine lymphoid organs. Toxicol. Sci. 53:253-263.
181. Zhou, H. R., Lau, A. S., and Pestka, J. J. 2003b. Role of double-stranded RNA-activated protein kinase (PKR) in deoxynivalenol-induced ribotoxic stress response. Toxicol. Sci. 74:335-344.