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Effects on fertility

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2-Generation Developmental Toxicity Study in Rats

In order to complete the study of long-term effects of Sucrose Acetate Isobutyrate (SAIB), a possible incidental food additive, a study of its effect on reproduction of rats was undertaken. A group of fifteen female and five male albino rats (Holtzman) sixty-six days old were isolated and fed Purina Lab Chow to which 5.0% SAIB was added. The SAIB was dissolved in acetone, mixed with the Purina Lab Chow and the acetone allowed to evaporate. A similar group of control rats were fed Purina Lab Chow vhich had a comparable volume of acetone mixed with it and then evaporated. The diets were fed to these groups and their offspring throughout the course of this study. Weights of the animals, food consumption , and feed efficiencies were measured up to the time the animals were bred. After about one month of feeding, the rats on each diet were regrouped in five cages each cage consisting of one male and three females. The surviving F1 generation was necropsied after the last litter was weaned. Organs were examined grossly and microscopically for pathology. No abnorality attributable to the compound was noted. Organ weights showed a marked uniformity between the SAIB and control groups. Coupled with a lack of demonstrable histopathology attributable to the compound it is concluded that 5.0% SAIB in the diet over a period of two generations produced no untoward effect.


3-Generation Developmental Toxicity Study in Rats

Groups of 30 male and 30 female immature rats (FO animals) were fed diets that contained 0, 0.5, 1.0, or 2.0 g of sucrose acetate isobutyrate (SAIB)/kg of body weight (g/kg). Males and females received the test diets for 10 and 2 weeks, respectively. In addition, females received test diets continuously throughout mating, gestation, and lactation, until necropsy. The FO animals were then mated to produce F1 litters. Groups of 30 male and 30 female F1 animals were fed diets that contained 0, 0.5, 1.0, or 2.0 g of SAIB/kg for at least 10 weeks postweaning, and the breeding program was repeated to produce F2a animals. After weaning of the F2a litters, the Fl adults were remated to produce F2b litters, which were used for teratologic evaluation. The F2a animals (30/sex/group) were fed test diets containing 0, 0.5, 1.0, or 2.0 g of SAIB/kg for at least 10 weeks postweaning and then mated to produce F3 litters. Adult F2a males were sacrificed and discarded after the completion of mating. The study was completed when the adult F2a females were sacrificed on Day 14 of the F3 gestation, and the uterus was examined for the number of implantations. Antemortem data (i.e., antemortem observations, body weights, and food consumptions), reproduction data, and litter data were recorded. Test diets were fed continuously throughout the study. All FO and Fl adults were examined macroscopically, and reproductive organs and gross lesions were co:lected and preserved for possible examination. Tissues "masses" found in the peritoneal cavity were examined microscopically. The results of the study are summarized as follows:

  • Survival was 100% for males and females in all groups in the FO, Fl, and F2a generations.
  • There were no treatment-related antemortem observations.
  • Body weights were slightly (3% to 6%), but significantly, lower only during the first half of lactation at 1.0 and 2.0 g/kg for FO females and on Day 21 of lactation at 0.5 and 2.0 g/kg for F1 females.
  • There were no consistent statistically significant differences in body weight gains.
  • Food consumptions for F2a males and females were significantly lower during the premating period.
  • There was a significant trend in decreased fertility for F1 females during mating for the F2a litters; however, there were no statistically significant differences between the control and treated groups and no effect of continued SAIB treatment on subsequent matings (i.e., for F2b or F3 litters). The single observation of reduced fertility is not considered to be test material-related.
  • Fetal viability for F2b litters was significantly decreased at 2.0 g/kg based on analysis of variance, however, not when the values were compared by Student's t-test. This observation is not considered to be test material-related.
  • There were no treatment-related effects on fetal development through the period of organogenesis (i.e., Days 6 through 15 of gestation) based on teratologic evaluation of the F2b liiters.
  • There were no treatment-related macroscopic or microscopic changes.

Effects on developmental toxicity

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Teratology study in Rabbits

Inseminated female New Zealand White SPF rabbits randomly assigned to one control and three treatment groups of 16 animals each were used to determine the teratogenic potential of Sucrose Acetate Isobutyrate (SAIB). Dosage levels of 250, 425 and 600 mg/kg body weight/dose at volumes of SAIB of 0.685, 0.84, and 1.0 ml/kg body weight, respectively, were administered orally by gavage twice daily on days 7 through 19 of gestation to yield total daily doses of 500, 850 and 1,200 mg/kg body weight/day at total daily volumes of 1.37 1.68, and 2.00 ml/kg body weight, respectively (contained in a volume of 0.92 ml/kg body weight corn oil). The control group received the vehicle only, corn oil, on a comparable regimen at a total daily volume of 0.92 ml/kg. Cesarean sections were performed on all surviving females on gestation day 29 and the fetuses were removed for teratologic evaluation. Two high dose animals died on gestation day 17. One death was determined to be due to mucoid enteritis and the other was from unknown cause(s). The remaining animals on study survived to scheduled sacrifice. There was a slight increase in the incidence of labored breathing in all treated groups. No other meaningful differences in maternal antemortem and necropsy observations, body weight gain, food consumption or Cesarean section observations relative to those of the control group were seen at 1,200 mg/kg/day or less. No evidence of an adverse effect on fetal morphology was seen at any tested level. In conclusion, the 1,200 mg/kg/day level was determined to be the "no observable effect level" with respect to developmental toxicity, including teratogenesis, in this study.

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