Short-term toxicity studies of loline alkaloids in mice

Epichloë endophytes have been used successfully in pastoral systems to reduce the impact of insect pests through the expression of secondary metabolites by these organisms. The use of endophytes could be extended to other plant species, such as cereal crops, where the production of bioactive secondary metabolites would reduce the reliance on pesticides for insect control. Research is currently underway to select chemically-favourable endophytes for inoculation into modern cereal crops. The success of this approach is dependent on the selection of an appropriate secondary metabolite target which must not only be effective against insect pests but also be safe for grazing animals. Furthermore, since these compounds may enter the human food chain through the ingestion of animal products, they must be safe for monogastric animals. The loline alkaloids have been identified as possible target metabolites as they are associated with potent effects on insects and low toxicity to grazing animals. The purpose of the current study was to generate toxicological data on the loline alkaloids in a monogastric system using mice. Male and female mice were fed 415 mg/kg/day total lolines for a 3 week period through the incorporation of endophyte-infected meadow fescue seed into their diet. Control groups fed normal mouse food and a diet containing endophyte-free meadow fescue seed were also utilized. The loline treatment caused no statistically significant effect on gross pathology, histology, haematology, blood chemistry, heart rate, blood pressure or motor coordination. Reduced weight gain and food consumption were noted in the loline groups in the initial stages of the experiment, but food consumption of all groups was equivalent on a food intake per gram of body weight basis by day 7. This experiment raises no food safety concerns for the loline alkaloids and further research will be conducted to yield an association between loline-producing endophytes and modern cereal crops.