Certain chlorine-substituted sugars with chemical similarities to sucralose
have been demonstrated previously to diminish or inhibit sperm glycolysis
and fertility in the rat (Ford and Waites, 1978a). In order to investigate
this potential for sucralose, epididymal spermatozoa were recovered from ra
ts exposed in vivo to oral doses of one of three of these substituted sugar
s: 6-chloroglucose (6-CG, 24 mg/kg/day, positive control), sucralose (500 m
g/kg/day, over 300 times the expected human daily intake), or a 6'-substitu
ted isomer of sucralose, trichloro de-oxy sucrose (TCDS, 100 mg/kg/day, a p
otential trace impurity in commercial sucralose); distilled water served as
the negative control. After incubation of the spermatozoa with D-[U-C-14]
glucose, measurements of (CO2)-C-14 and of ATP content showed no impairment
of the glycolytic ability of spermatozoa in any of the groups except for a
marked inhibition for those exposed to 6-CG, the positive control, In orde
r to determine whether other parameters of reproduction and fertility could
be affected, reproductive endpoints were examined following oral exposure
of male and female rats to sucralose. Sucralose was fed in the diet at conc
entrations of 0, 0.3, 1.0 and 3.0% (approx. 100, 365 and 1150 times the EDI
) to groups of 30 male and 30 female rats for 10 weeks prior to mating, and
continued through two subsequent generations until weaning of the F-2 pups
. Two litters were produced per generation. Food consumption and weight gai
n in the F-0 and F-1 generations were depressed in all sucralose groups bef
ore mating and in all four litters prior to meaning. The decrease in initia
l average weight for newborn pups probably reflects the increased litter si
zes noted for sucralose-treated groups and the reduced food consumption of
the dams during gestation and lactation. The latter is a result primarily o
f the unpalatability of sucralose to rats (McNeil, 1987). Caecal enlargemen
t (a common animal response to large doses of indigestible material) occurr
ed in both the F-0 and F-1 parents. Increased kidney weights, possibly asso
ciated with increased water intake, were observed primarily among animals r
eceiving 3% sucralose (no renal histopathology has been detected). Decrease
d thymus weights occurred in F-1 males and in both F-1 and F-2 females at t
he 3% level. Subsequent studies specifically designed to investigate the po
tential for adverse immune system effects of sucralose (McNeil, 1987) showe
d no adverse effects. These findings are consistent with investigations by
others showing that decreases in thymus weights occur in young rats in resp
onse to stressful conditions associated with reductions in weight gain. All
reproductive indices (oestrous cycles, mating behaviour, fertility, gestat
ion, maternal and foetal viability, foetal development, parturition, pup ma
turation and lactation) were comparable between the control and sucralose-t
reated groups. We conclude from these results that sucralose has no effect
on sperm glycolysis or on male or female reproductive performance in the ra
t. (C) 2000 Elsevier Science Ltd. All rights reserved.