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Turmeric (Curcuma longa L.) extracts have a long history of use worldwide, but a major limitation of these extracts is their extremely low oral bioavailability, caused by low absorption, rapid metabolism and rapid excretion following ingestion. Thus, a new highly bioavailable turmeric extract formulation (comprising turmeric extract, acacia gum, sunflower oil and quillaia extract) has been developed and is intended for use as a food ingredient. Safety of this novel extract was evaluated using the standard Tier 1 battery of in vitro genotoxicity tests (bacterial reverse mutation test and an in vitro mammalian cell micronucleus test) followed by repeated-dose 28- and 90-day oral toxicity studies in rats. In the 90-day study, male and female Sprague-Dawley rats were dosed once daily, by oral gavage, either with the vehicle or the test item at 500, 1500 or 3000 mg/kg body weight/day. Clinical examinations were conducted regularly, and body weights and food consumption were recorded weekly throughout the study. At the end of the study, blood samples were analyzed for clinical pathology parameters, before a macroscopic necropsy was conducted and a full list of tissues were examined histopathologically. There was no evidence of genotoxicity in vitro. No test item-related adverse effects were observed in the 28- or 90-day studies; therefore, 3000 mg/kg body weight/day (the maximum feasible dose and highest dose tested in rats) was established as the no-observed-adverse-effect level.

Ryokucha saponin (RSP), which is one of the ingredients of green tea, was administered orally to rats for 3 months at dose levels of 50, 150 and 500 mg/kg/day to assess any toxic effects. As positive control, 1200 mg/kg/day of quillaia saponin (QSP), which contains saponins equivalent in amount to those in 500 mg RSP/kg/day, was administered. The no-effect level of RSP was 50 mg/kg/day and the lowest-observed-effect level of RSP was 150 mg/kg/day for both sexes, so that the true no-effect level of RSP was estimated to be between these dose levels. In addition, it was confirmed that the toxicity of RSP at 500 mg/kg/day was less than that of QSP at 1200 mg/kg/day and RSP was demonstrated to be safer than QSP, which is a permitted food additive.

Detergent-disrupted influenza virus vaccines, formulated as Iscoms™, or oil-in-water (o/w) emulsions, were administered parenterally to mice and evaluated for immunogenicity and protective efficacy. Both formulations enhanced both primary and secondary serum antibody responses. The magnitude of these responses with o/w emulsions was further enhanced by the addition of the non-ionic block copolymer L121 in the emulsion. Four weeks after primary immunization, mice were challenged by exposure to an aerosol containing infectious virus. Resistance to challenge in terms of survival rate and weight change correlated well with serum antibody titre for all formulations. Two major differences were observed between the adjuvant formulations. Iscom™ vaccines, formulated with Quil-A or the less toxic Quillaia saponin preparation Iscoprep™ 703, induced specific cytotoxic T-lymphocyte responses, whereas the o/w-based vaccines did not. In addition, dose-site reactivity studies in sheep showed that Iscom™ vaccines were less reactive than o/w-based vaccines, the degree of reactivity of the latter increasing sharply with increasing L121 concentration. On the basis of these studies, Iscoms™ were chosen for development as a potential adjuvant for human influenza vaccines.

Groups of 48 male and 48 female mice were fed quillaia extract in the diet at levels of 0 (control), 0·1, 0·5 or 1·5% for 84 wk. The material had no adverse effect on the death rate or the incidence of histopathological findings, including tumours. However, there was a lower rate of body-weight gain at the 1·5% dietary level, and there were isolated statistically significant differences between the treated and control animals, mainly at the 1·5% dietary level, in the haematological examinations and in some absolute and relative organ weights of both sexes. It is concluded that, in mice, quillaia extract fed at levels up to 1·5% in the diet (approximately 2·2g/kg/day) did not exert a carcinogenic effect. The no-untoward-effect level from this study is considered to be 0·5% in the diet, giving an intake of approximately 0·7 g quillaia extract/kg/day.

1. Saponins are steroid or triterpene glycosides which occur in a number of important food plants, including such staples as soya beans (Glycine max) and chickpeas (Cicer arietinurn). They are known to be hypocholesterolaemic.2. Some saponins form an insoluble complex with cholesterol which prevents its absorption from the small intestine. Others cause an increase in the faecal excretion of bile acids, an indirect route for elimination of cholesterol.3. We have investigated the effects of different saponins on absorption of the bile salt sodium cholate from perfused loops of small intestine, in vivo, in the rat. Purified saponins from soapwort (Suponaria Officinalis), soya beans and quillaia (Quillata suponaria) reduced the rate of absorption of the bile salt; soya-bean and soapwort saponins substantially so but quillaia saponin to a much lesser extent.4. These results were explained by the formation of large mixed micelles by bile acid and saponin molecules in aqueous solution. These aggregates can have molecular weights in excess of 106daltons, consequently the bile acid molecules incorporated in them are not available for absorption.5. Control of plasma cholesterol and nutrient absorption through dietary saponins could provide substantial health and nutritional benefits in humans.

Groups of 48 male and 48 female rats were fed quillaia extract in the diet at levels of 0 (controls), 0.3, 1.0 and 3.0% for 2 yr. The material had no adverse effects on death rate, water consumption, serum chemistry or haematological parameters or on the incidence of histopathological findings, including tumours. In the males given the 3% dietary level, the death rate, total leucocyte count at wk 108, incidence of kidney lesions and weights of the kidneys, heart and thyroid were all below the control values. These differences were explicable, however, in terms of a lowered body weight consequent on a decreased food intake. It is concluded that, in rats, quillaia extract fed at levels up to 3.0% in the diet did not have any carcinogenic effect. The no-untoward-effect level established in this was 3.0% in the diet, approximately equivalent to an intake of 1.5 g/kg/day.

Quillaia extract was fed to groups of 15 male and 15 female rats for 13 wk at dietary concentrations of 0 (control), 0·6, 2·0 or 4·0%. There was a transitory reduction in the rate of body-weight gain, associated with a reduced intake of food and water, but by the end of the study the weights of the treated rats did not differ significantly from those of the controls. The feeding of quillaia saponin did not affect the results of haematological examinations (including erythrocyte fragility tests in hypotonic saline), serum and urine analyses, renal concentrating ability or the urinary cell excretion. The relative liver weight was reduced in males given 2·0 or 4·0% quillaia and the relative stomach weight was increased in both sexes at the same levels. No histopathological effects attributable to treatment were found. The no-untoward-effect level in this study was 0·6% of the diet, equivalent to an intake of approximately 400 mg/kg/day.