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Slaframine is an alkaloidal mycotoxin produced by the fungus Rhizoctonia leguminicola that causes profuse salivation (slobbers) in animals. Rhizoctonia leguminicola is a common fungal pathogen of red clover and causes a syndrome known as black patch disease in the plant. Slaframine is a piperidine or indolizidine alkaloid with the molecular formula C10H18N2O2. . This fungus can be present on clover, alfalfa, and other legumes. Cool, wet, humid weather promotes growth of the fungus and production of slaframine. Legume hays contaminated with slaframine causes slobber syndrome and the various animals are sensitive to its effects.

History
Initially outbreaks of profuse salivation in cattle were reported in the late 1940s and 1950s from agricultural experiment stations in the Midwestern United States. In 1956, the first case of fungal contamination of red clover with Rhizoctonia leguminicola was reported which was mainly associated with a pasture disease called black patch. This was so called because it derives its name from the appearance of affected areas in the field. Most of these cases were associated with the feeding of second-cutting red clover hay. The wet spring weather and abundant clover growth in Central Kentucky has made 2010 a bumper year for slaframine toxin, or “slobber toxin".

Metabolism
Liver is the major site of slaframine metabolism where it has been suggested that slaframine is metabolized in the liver by a microsomal flavoprotein oxidase to the ketoimine metabolite consisting of quaternary nitrogen separated from an acetate ester by two carbon atoms.(Figure 1) It is apparent to reveal that the more direct access to hepatic tissues provided by the route of administration, the shorter the time interval to the onset of salivation.

Toxicity
In horses, excessive salivation is usually the first sign of slaframine exposure (Figure 2). Signs typically develop within hours of exposure. The Slaframine poisoning or slobbers likely occur in a cooler and wetter spring or fall because these seasons are ideal for the growth of the fungus Rhizoctonia leguminicola. In the field conditions, the other clinical signs associated with the "slobbers syndrome" include salivation, lacrimation, feed refusal, bloating, stiff joints, diarrhea, and weight loss.

The clinical signs of slaframine toxicity are similar in all species. When animals are feed with slaframine contaminated forage then they salivate profusely. Experimentally, a single dose of slaframine produces salivation for 6-10 hours. However, clinically affected animals can slobber for several days because they have continued access to slaframine contaminated forages. Cyanosis and open-mouth breathing have been reported under experimental conditions in sheep, swine, and guinea pigs. Pigs also were observed to vomit, became dyspneic, and collapse with stiffened pelvic limbs.

Diagnosis and Treatment
Diagnosis of slaframine toxicity is generally done by observation of clinical signs (salivation) in animals consuming legume forage, particularly red clover hay. Further tests can identify the fungus Rhizoctonia leguminicola in the hay which usually can be easily isolated in cultures. Although chemical analysis for slaframine is not usually necessary, chromatographic methods for detecting the toxin in hay, plasma, or milk have been described. The slobber symptoms usually recover spontaneously when the contaminated hay is removed, however clinical signs may persist for 1-2 days following removal of the toxic forage. In severe cases, atropine may be of benefit to reverse the parasympathomimetic effects of slaframine, however it is unlikely to be completely resolving clinical signs.