Metabolism and Toxicity of Trichothecenes

Eriksen, GS. 2003. Metabolism and toxicity of trichothecenes. Doctoral thesis. ISSN 1401-6249, ISBN 91-576-6411-0 Trichothecenes are mycotoxins commonly found in cereals. The toxins are mainly produced by Fusarium fungi, which infect cereals in the field. Trichothecenes have been associated with outbreaks of diseases both in humans and in farm animals. Trichothecenes are closely related toxins based on a C-15 skeleton with an epoxide ring. The microbiological transformation of trichothecenes to the less toxic de-epoxide in the gut has been studied in this thesis. It was found that the micro-organisms in faeces from pigs in the Uppsala area had the ability to transform the trichothecenes nivalenol (NIV) and deoxynivalenol (DON) to their corresponding de-epoxy metabolites. The pig intestinal micro-organisms did not acquire the de-epoxidation ability during a seven week long exposure to low levels of DON in the feed, but the ability was transferred between animals by spreading faeces from pigs with an intestinal deepoxidation ability in the pens of pigs lacking this ability. The faecal microorganisms in humans were not able to transform trichothecenes to their de-epoxy metabolite. The de-epoxides of NIV and DON were shown to be 51 and 24 times less cytotoxic than the corresponding toxin with an intact epoxide ring, verifying that the de-epoxidation is a detoxification of trichothecenes. The absorption, metabolism and excretion of 3-acetylDON in pigs with a known intestinal de-epoxidation ability were also studied. The toxin was rapidly deacetylated and absorbed into the blood. DON was detected in plasma from 20 minutes after feeding. A maximum plasma concentration of 51.9 ± 6.8 ng/ml was reached three hours after feeding. The toxin was rapidly excreted and the DON concentration in plasma declined rapidly after reaching the peak concentration. No accumulation occurred in plasma during the three days exposure period. No deepoxy DON was present in plasma or urine, indicating that the de-epoxidation of trichothecenes occurs in the distal parts of the gastrointestinal tract where the absorption is low. DON and conjugated DON were the only metabolites detected in plasma and urine, while de-epoxy DON and DON were detected in faeces. Studies where the trichothecenes DON, NIV and T-2toxin were given to farm animals via their feed have been reviewed. It was concluded that pigs are more sensitive to trichothecenes in feed than other farm animals. Guideline limits of 0.3 mg DON and 0.2 mg T-2/HT-2 toxins/kg feed are proposed to ensure that no negative effects will occur in pigs. Similarly, guideline values of 0.5 mg T2/HT-2 toxins and 2.5 mg DON/kg feed are proposed in chicken feed. Ruminants are more resistant to trichothecenes and no guideline value is proposed for feed for ruminants.