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Abstract for RACB83072 - Sodium Saccharin (CASRN 128-44-9)


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings may or may not have been peer reviewed and were not evaluated in accordance with the Explanation of Levels of Evidence for Reproductive Toxicity criteria (see or with the Explanation of Levels of Evidence for Developmental Toxicity criteria (see established by the NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

Sodium Saccharin (CAS # 128-44-9): Reproduction and Fertility Assessment in CD-1 Mice When Administered in Drinking Water

two dimensional chemical structure

NTP Report # RACB83072


Sodium saccharin (NaSac), used as an artificial sweetener since the late 1800's, was tested for potential effects on reproduction and fertility in Swiss CD-1 mice using the RACB protocol. Data on food and water consumptions, body weights, and clinical signs from the dose-range-finding study (Task 1) were used to set exposure concentrations for the continuous cohabitation phase (Task 2) at 1.25, 2.5, and 5% w/v in the drinking water. While water consumption was decreased at the high dose by nearly equal to 10-20%, it was increased at the low and middle dose levels by nearly equal to 40% and 20%, respectively. Consequently, the high dose animals gained slightly less weight during Task 2. Measures of body weights and water consumption allowed the calculation of daily exposure estimates: 3.5, 5.9, and 8.1 g/kg/d.

In Task 2, 3, 0, 1, and 8 mice died in the control, low, middle, and high dose groups, respectively. The increased mortality at 5% NaSac was attributed to complications of dehydration. For the surviving pairs, there was no reduction in the mean number of litters/pair, although at the high dose, the number of live pups per litter decreased by 16% and the pup weight adjusted for litter size was decreased by 6%. There was no decrease in the viability of the offspring.

These effects were considered secondary to the decreased water intake seen at the high dose, and since the middle dose level had a relative increase in intake and showed no reproductive toxicity, Task 2 was judged to be essentially negative for reproductive toxicity, and the evaluation of the second generation was performed with only the controls and the middle dose level. Thus, the last litter from the control and middle dose groups was nursed, weaned, and reared to mating at nearly equal to 70-80 days of age. There was no effect of exposure to NaSac on viability or growth to weaning, or on body weights at the start of the cohabitation week. Water consumption was increased by nearly equal to 30 in the 2.5% NaSac group, although this did not translate to a change in body weight. In the mating trial, there were no differences due to NaSac consumption in the percent of F1 pairs mating or delivering a litter, or in the number, weight, or viability of pups in that litter.

After the F2 pups were evaluated and discarded, the F1 controls and 2.5% NaSac-exposed mice were killed and necropsied. There were no differences between the groups in terminal body weights or organ weights. The concentration, percent motile, or percent morphologically abnormal sperm in the epididymis were unchanged by NaSac exposure, as was the length or characteristics of the estrous cycle.

In summary, NaSac reduced fertility only at a concentration that also significantly reduced water consumption and increased mortality. At concentrations that increased water consumption, there were no measurable effects on reproductive performance or necropsy endpoints.

Report Date: April 1985

NTIS #PB85188258/AS

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