Vomitoxin: Natural Occurrence on Cereal Grains and Significance as a Refusal and Emetic Factor to Swine R. F. Vesonder B.S. and C. W. Hesseltine Ph.D.* Fifty 12,13-epoxytrichothecenes have been reported in the literature; of these diacetoxyscirpenol, T-2 toxin, nivalenol and vomitoxin have been naturally occurring in cereal grains throughout the world. Vomitoxin is produced in ears of corn prior to harvest when wet, cool weather precedes which favours Gibberella zeae growth. This type of infected corn, which often contains vomitoxin, is associated with the refusal and emetic syndrome exhibited by swine. Since 1916, emesis in humans resulting from grains is indicated by growth of the mould Fusaria in the field is meagre. The ability ingestion of food prepared from Fusarium­ G. zeae (perfect stage of F. graminearuml of G. zeae to render grains unwholesome for infected cereal grains has been recorded in on the kernels and flowering head. On corn, consumption by swine and other farm several areas around the world. In the Soviet G. zeae occurs as a reddish mould that animals may be dependent on the type of Union, .it was known as the drunken bread begins as observable growth on the ear tip. hybrid, but studies of whether G. zeae intoxication. Sporadic food poisoning featur­ This condition is referred to as Gibberella or infection can be controlled by breeding 8 ing vomiting, nausea, somnolence, headache pink ear rot • new plants have not been conducted. and convulsion occurred in Japan during Outbreaks of barley scabbed with Emetic substances were extracted from the 1950's and the late 1940's. These dis­ G. zeae in the Midwest region of the U.S. naturally moulded barley with water3,9,'3. orders were associated with consumption were reported in 1919, 19289 and in the A water extract obtained from barley of rice contaminated with Gibberella zeae 1930'sto. This barley was rejected by swine. infected with G. saubentii has been reported and Fusarium nivale1 and of foods made Barley from the 1928 U.S. crop exported to to cause vomiting when intubated into 2 from G. zeae infected wheat flour • In the Germany was also toxic to swine. Swine swine'4. Swine also refused feed made from southern part of Korea in 1963, barley force-fed this barley became sick and barley naturally infected with Fusaria and infected with F. graminearum was reported vomited, and eventually death ensued from barley cultured with G. saubenetti. Water to cause in humans the toxic disturbances preference not to eat. Equines also rejected extracts from F. graminearum'contaminated of nausea, vomiting, abdominal pains and feed containing mouldy barley, but ~ttle barley administered intraperitoneally (ipl diarrhoea!. Comparable sYmptoms 'were and chickens were not susceptible. Farm caused toxic disturbances in suckling mice observed in swine and a few cattle. In a animal disorders due to ingestion of scabbed and pigs but had no apparent effect on similar phenomenon, involving swine con­ barley in the U.S. subsided as production rabbits, rats, mature mice and day·old 3 suming corn naturally contaminated with moved from the humid Midwest environ­ chicks • F. graminearum in the U.S., a new tricho­ ment to the West. G. zeae·infected corn (12 to 100% of thecene, vomitoxin, was isolated and shown Wheat also is susceptible to Gibberella kernels were infectedl produced in northern to be the causative agent4. Whether or not infection, but its involvement in the swine Indiana in 1965 has been investigated for the factor causing emesis in humans is . sYndrome of refusal and emesis appears to emetic and refusal factors"; hog farmers identical to that in swine is unknown, be less frequent than that of barley and reported that this corn was refused by swine particularly since several trichothecenes corn. Fusaria-infected corn now seems to and caused a few pigs to vomit. In feeding have been capable of causing various lab­ be the major grain in the U.S. which has tests, swine rejected the naturally infected oratory animals to vomit2,5,6. Vomitoxin detrimental effects on swine performance. corn and the corn amended with water was also shown to be the principal toxin In 1972, corn contaminated with G. zeae extracts obtained from this infected corn. responsible for the phenomenon of feed caused extensive losses to swine operations, In addition, swine vomited when this water refusal exhibited by swine'. reaching epidemic proportions in the U.S. extract was administered by stomach tube, Sporadic Fusaria outbreaks in the corn intravenously or ip. The substances extrac­ History of refusal and emetic factors belt also occurred in Indiana in 1958 and ted with water from this infected corn in scabbed grains 1965" and in northwest Ohio in 1970, were separated into two fractions, based 12 Cereal grains that cause swine or farm 1975 and 1977 • Low temperature with on their solubility in methanol. Swine animals with simple stomachs to vomit on concomitant high moisture conditions, ingesting corn amended with the methanol­ ingestion and refuse feed usually connotes which usually resUlts in a delayed harvest, soluble fraction vomited initially but would a scab condition in grain. This disease in appears to favour G. zeae corn infection. return to eat without further symptoms of This was the situation in 1966 and 1972. nausea or other effects. Hence, it was In addition, the 1972 corn crop was not proposed that the water extract of G. zeae­ Ronald F. Vesonder is a resaarch chamist in the dried immediately because of energy shor­ infected corn contained a methanol·soluble Mycotoxin Microbiology end Biochemistry tages for operating dryers; this introduced emetic factor and a methanol·insoluble R8lIesrch. Fermentation Laboratory; andCliffordW. a storage variable. refusal factor. Hease/tine ia Chief olthe Fermenlstion Laboratory 81 the Northern Regional Research Canter. Unusually wet weather preceded harvest . Emetic substances associated with Fusaria Northern Regional Research center. Agricultural in northwest Ohio in 1977. Conditions were species isolated from cer~als have been Resaarch. Science and Education Administretion. conducive to G. zeae growth on corn reported, using pigeons as an assay tool'6. U.S. Department of Agriculture. Peoria. Illinois intended for swine feed, and much of this Emetic factors were produced on corn 61604. 12 corn was found to contain vomitoxin • inoculated in the field with OF. graminearum tThe mention of firm names or trade produClsdoes Even with these documented cases, informa­ and from liquid culture media fermented not imply that they are endorsed or recommended by tha US Department of Agriculture over other tion concerning environmental conditions with a strain of F. moniliforme, F. roseum, firms or similar products not mentioned. and factors governing production of refusal F. poae, F. culmorum and F. nivale. The and emetic factors on grains infected with emetic principle elaborated by F. monili· form" was lethal to the pigeon in 12 hours of nine corn samples collected by the Food 1.88 bs, 3H, CH 3-G=C; 2.16 m, 2H, CH 2; when injer.ted through the wing vein. In and Drug Administration from the Midwest 3.10 ABq, J=4 Hz, CH,; 3.60 d,1!::!, CH; Japan, at about the same time, nivalenol, in 1972, vomitoxin was found at levels 3.82 s, 2!:!, CH, -OH; 4.50 m, 1H, CH-OH; 8 trichothecene produced by F. nivale ranging from 15-28 ppm. These findings 4.80 m, 1H, CH-OH; O-CH-HC=C; 6.60 m, cultured on liquid media was reported',". show vomitoxin to be the main tricho­ CH=C. The mass spectrum of vomitoxin This Fu:;arium strain was isolated from thecene involved in the syndrome of refusal showed a molecular ion at 296.157, and mouldy rice that caused nausea and vomit­ and emesis exhibited by swine in the U.S. loss of CH 3, H,O, hydroxymethyl or ing in 25 young people. The emetic-produc­ in 1972. formaldehyde as characterized by fragment ing Fusaria strain6 described subsequently iOn peaks at m/e 281, 278, 265 and 286, received much attention by investigators respectively. The most prominent ion, throughout the world. In a screen of Fusaria Classification of Fusaria involved in at m/e 248, which corresponds to loss of species using chemical and bioassay methods, fusariotoxicoses both water and formaldehyde, is consistent it was found that the F. poae strain pro­ Since Link's description of the genus for keto at C-8, hydroxyl at C-7 and duced the trichothecenes T-2 toxin, HT-2 Fusarium in 1809, classification of this hydroxymethyl at C-B. toxin and neosolaniol on a peptone-supple­ species has followed many schemes: The Vomitoxin was converted into its tri­ mented Czapek-Dox media at 25 and thousand Fusaria that had been described acetate with acetic anhydridepyridine (m.p. I8 27°C . Trichothecenes were not detected by the 1930's was lumped into sixteen 155-156° C) with a molecular ion 422.155. in the culture liquor for F. moniliforme and groups, six subgroups and 142 species The NMR spectrum in CDCI 3: 8 0.96 S, F. nivale strains. The PD strains on moist varieties'3; About 50 species were recognised CH 3; 1.86 s, 3H, CH 3; 1.90 s, 3H, CH 3; corn at 5 and 25° C and on Richards solu­ in the Fusarium genus"; All Fusaria were 2.12 s, 3!:!, CH 3; 2.20 s, 3H, CH 3; 2.95 ABq, tion at 25° C have been studied'. Extracts reduced to nine species",'6; and there are J=4, Hz 2H, CH-CH,-O; 3.89 d, CH" obtained from the F. poae strain cultured several other classification systems""'.