A 90-day feeding study of the alkaloids of Lupinus angustifolius in the rat.
Groups of 20 Sprague-Dawley rats of each sex were fed diets containing lupin alkaloid at dose levels of 0, 100, 330, 1000 and 5000 ppm supplemented with maltodextrin to attain a level of 4.5%, for 13 wk (equivalent to average daily intakes of lupin alkaloid of approximately 0, 10, 30, 100 and 500 mg/kg body weight/day, respectively, over the course of the study). A further group of rats was fed control (basal) diet over the same period. All control and high-dose animals underwent an ophthalmological examination before the start of the study and before autopsy. Blood samples were collected from all rats prior to the start of treatment, during wk 6 and prior to autopsy for haematological and clinical chemistry examination. All animals were monitored daily for change in clinical condition, and body weight and food intake were measured twice weekly. A range of tissues were preserved for histological examination at autopsy. There was an initial drop in food intake by all rats in the 1000 and 5000 ppm groups and thereafter the intake was between 90% and 95% of that of the controls. In general, no other effects related to treatment were seen. On the basis of the lower body weights and food intakes of the groups fed the alkaloid at levels of 1000 and 5000 ppm, a no-observed-adverse-effect level (NOAEL) of 330 ppm is seen under the conditions of this study. It is likely that these effects are entirely due to the antipalatability effect of the lupin alkaloids. In view of the growth rates, haematology, clinical chemistry and histological findings, a speculative NOAEL of 1000 ppm may be more appropriate.