Title: Alternative Sweeteners

Neohesperidin Dihydrochalcone 95
other bitter-tasting substances, such as paracetamol, dextromethorphan, and other
pharmaceuticals (66), or the formulation of special foods such as energy-boosting
drinks (67).
The ability of neohesperidine DC to mask the unpleasant taste of many
pharmaceuticals and to improve the organoleptic properties of other sweeteners
led us to think about the potential use of this substance also in medicated feedstuffs.
The positive effect of neohesperidine DC in feedstuffs for farm animals
has been demonstrated, in particular when used as a flavor modifier in blends
with saccharin because of the ability of neohesperidine DC not only to reduce
saccharin aftertaste but also to mask the bitter taste of some components of feed.
Surprisingly, neohesperidine DC has also been shown to act as an attractant for
certain fish such as sea bass and rainbow trout, which suggests its use as an
ingredient in new feeds for cultured fish (68).
V. TOXICOLOGY AND METABOLISM
The safety assessment of neohesperidine DC can be based on data from a number
of toxicological studies conducted at the Western Regional Research Laboratory,
Albany, California. These studies include subacute feeding trials in rats, a threegeneration
reproduction and teratogenicity study in rats, a 2-year chronic
carcinogenicity/toxicity in rats, and a 2-year feeding study in dogs (69). The data,
summarized by Horowitz and Gentili (11), showed no evidence of any increased
incidence of tumors that could be associated with the ingestion of neohesperidine
DC, as well as no adverse effect of toxicological significance even in the highdose
group.
Neohesperidine DC has been checked for mutagenicity in the Ames test;
it is nonmutagenic, regardless of which of the various Salmonella tester strains
is used (70–73). In mice, the compound causes no increase in the normal frequency
of micronucleated polychromatic erythrocytes in bone marrow (74).
In 1985–86 a new, detailed study on the ‘‘subchronic (13-wk) oral toxicity
of neohesperidine DC in rats’’ was carried out at the TNO-CIVO Toxicology
and Nutrition Institute in the Netherlands (75). Neohesperidine DC was fed to
groups of 20 male and 20 female Wistar rats at dietary levels of 0, 0.2, 1.0, and
5.0% for 91 days. Only at the 5% level were there any treatment-related effects
(i.e., marginal changes in body weight and food consumption, cecal enlargement,
and slight changes in some of the clinical chemistry variables). These phenomena
were judged to be of little, if any, toxicological significance. Neither the lowdose
nor intermediate-dose groups showed any compound-related effects, and
none of the groups showed any ophthalmoscopical, hematological, or histopathological
changes. It was concluded that the intermediate dose, which translates to
about 750 mg of neohesperidine DC per kg body weight per day, was the no-