Toxicity studies of chanoclavine in mice

Epichloë endophytes have been used successfully in pastoral grasses providing protection against insect pests through the expression of secondary metabolites. This approach could be extended to other plant species, such as cereals, reducing reliance on pesticides. To be successful, the selected endophyte must express secondary metabolites which are active against cereal insect pests without any secondary metabolite which is harmful to animals. Chanoclavine is of interest as it is commonly expressed by endophytes and has potential insect activity. Investigation of possible mammalian toxicity is therefore required. An acute oral toxicity study showed the median lethal dose of chanoclavine to be > 2000 mg/kg. This allows it to be classified as category 5 using the globally harmonized system of classification and labelling of chemicals and category 6.1E using the New Zealand HSNO hazard classes, the lowest hazard class under both systems of classification. A 3-week feeding study was also performed which showed chanoclavine, at a dose rate of 123.9 mg/kg/day, initially reduced food consumption but that this was resolved by day 7. No toxicologically significant effects on gross pathology, histology, haematology or blood chemistry were observed. These experiments showed chanoclavine to be of low toxicity and raised no food safety concerns.