A 90-day feeding study of lupin (Lupinus angustifolius) flour spiked with lupin alkaloids in the rat.

Three groups of 20 male and 20 female Sprague-Dawley rats were given diets based on lupin (Lupinus angustifolius) flour (55.4 g/100 g diet) that had been spiked to provide dietary concentrations of 250, 1050 or 5050 mg lupin alkaloids/kg diet. A control group of 20 males and 20 females received 50 mg/kg (derived from the background level of alkaloid in lupin flour). The rats were treated for a minimum of 90-98 days. A dose-related reduction in red blood cell count and haematocrit (HCT) occurred in both sexes after 45 days, and the mean cell volume (MCV) was decreased in all the male treatment groups. The reductions in HCT and MCV persisted in the males until termination of the study when decreased haemoglobin levels were also observed in the top-dose males. The relative liver weights of female rats showed a dose-related increase. Altered foci of liver parenchymal cells were seen in five females receiving dietary levels of 5050 mg/kg, in one female fed 250 mg/kg and in one male from each of the 250 mg/kg and 1050 mg/kg treatment groups. No foci were seen in the control group. Basophilic foci are uncommon in young rats suggesting that the low incidence in this study is compound related.

A 28-day feeding study with methyl isoeugenol in rats.

Methyl isoeugenol was administered in rodent diet for a minimum of 28 consecutive days to groups of 16 male and 16 female rats (Sprague-Dawley strain) at levels of approximately 30, 100 and 300 mg/kg body weight/day. A further group of 16 male and 16 female rats was given the rodent diet as a control. The administration of methyl isoeugenol in the diet did not adversely affect the growth or general health of the animals or their food intakes. Although high dose animals of both sexes had increased lymphocyte and total white blood cell counts, these are not considered, in isolation, to be an adverse effect of treatment. None of the minor variations observed in the serum chemical analyses or urine analyses is considered to be indicative of a treatment-related toxic effect. An increase in liver weight, adjusted for body weight, was seen in male and female rats receiving 300 mg methyl isoeugenol/kg body weight. Few histopathological abnormalities were observed. Although the incidence of kidney and Harderian gland lesions was higher for high dose animals compared with the controls, the lesions are of a type that occurs spontaneously and are thus not considered to be attributable to treatment with methyl isoeugenol. While the increased liver weight and white blood cell counts of rats given 300 mg methyl isoeugenol/kg body weight may represent effects of treatment, it is not considered that there is any reason to regard these as adverse effects.