Title: Alternative Sweeteners

38 Auerbach et al.
Table 4 Major Safety Studies Completed
Genetic toxicology
Three-month dog (0.5, 1, 2% of the diet)
Three-month rat (0.5, 1, 2% of the diet)
Rat teratology (100, 300, 1000 mg/kg/day)
Rabbit teratology (100, 300, 1000 mg/kg/day)
One-month mouse (1, 2, 5% of the diet)
Twelve-month rat (0.01, 0.03, 0.1, 0.3, 1% of the diet)
Eighteen-month dog (10, 30, 100, 500 mg/kg/day)
Rat reproduction (0.1, 0.3, 1% of the diet)
Twenty-four-month mouse oncogenicity (0.1, 0.3, 0.7% of the diet)
Twenty-four-month rat oncogenicity (0.1, 0.3, 1% of the diet; two
species)
Rat, neurobehavioral (3 studies)
Man, metabolism
Man, no effects (15 mg/kg/day, 14 days)
Man, no effects (10 mg/kg/day, 90 days)
Diabetic men and women, no effects (10 mg/kg/day, 90 days; two
studies)
related increase in liver weight secondary to the induction of hepatic microsomal
metabolizing enzymes, a common adaptive response of the liver to xenobiotics.
This high-dose effect abated during chronic studies and after cessation of treatment.
At a dose in man of 15 mg/kg/day (44 times the mean chronic intake
estimate and equivalent to consumption of 18 liters of alitame-sweetened carbonated
beverage per day by a 60-kg individual), no enzyme induction was observed
over a 14-day period.
Furthermore, neither enzyme induction nor any other effects were observed
over a 90-day period in a double-blind toleration study of 130 subjects of both
sexes of three races (Caucasian, African-American, and Asian) receiving 10 mg
alitame/kg/day, a dose equivalent to consumption of 12 liters carbonated beverage
per day.
No evidence of carcinogenic potential was noted in rats and mice treated
for 2 years at doses as high as 564 and 1055 mg/kg/day, respectively. Alitame,
in doses as high as 1000 mg/kg/day during organogenesis, was devoid of embryotoxic
or teratogenic potential in rats and rabbits. In two-generation reproduction
studies there were no compound effects on mating behavior, pregnancy rate,
the course of gestation, litter size, or maternal or offspring survival.
Mutagenicity assays, both in vitro and in vivo, revealed no genotoxicity at
gene or chromosomal levels in microbial and mammalian test systems. Alitame
had no detectable activity in a battery of pharmacological systems used to assess