Toxicology of novel macrocyclic trichothecenes, baccharinoid B4, myrotoxin B, and roritoxin B

Baccharinoid B4, Myrotoxin B and Roritoxin B, some recently identified macrocyclic trichothecenes, were tested in Swiss mice with respect to their toxicity after oral and topical application. For oral dosing, the mycotoxins were dissolved in propylene glycol, and doses from 0 to 8.0 mg/kg body weight (BW) were employed. For topical application, toxins were dissolved in DMSO. A dose of 40 mg/kg BW was applied, except for Roritoxin B, where a dose of 10 mg/kg BW was also utilized. Animals were observed until death, or until 14 days after application and histopathological examinations were performed. It was found that Baccharinoid B4 was only moderately toxic, but this macrocyclic trichothecene appeared to exert its toxicity particularly on the intestine. Myrotoxin B was found to be quite toxic, and Roritoxin B was determined to be the most potent and toxic macrocyclic trichothecene of the three investigated. Oral administration of Roritoxin B resulted in death of 70-90% of mice at doses up to 1.0 mg/kg BW, and topical application of 10 or 40 mg/kg BW caused 100% death within 18 hours after application.