6-methyl-1,2,3-oxathiazin-4(3H)-one 2,2-dioxide, potassium salt

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 500 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The quality of the whole data base is considered to be sufficient and not critical.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Acesulfame potassium was investigated for its effect on fertility, reproductive performance, pre- and postnatal development in male and female Wistar rats at dietary levels of 0, 0.3, 1.0 and 3.0% in three successive generations, each comprising two consecutive litters. A teratogenicity study was conducted with 15 females per group of the F2b and F3a generations. Rats from the F3b generation were submitted to clinical and pathological examination. Pups from the F1a litters were used for a chronic toxicity/carcinogenicity study at the same dietary levels as the parents.

Fertility, number of young per litter, birth weight, growth rate and mortality during the lactation period were not adversely affected and there were no indications of increased mortality in utero. Growth rate was slightly decreased in the top dose group of the F0 and F1 generations. In the teratogenicity studies, no adverse effects were seen in appearance, food consumption, autopsy of the dams, organ weights, or litter data; no visceral or skeletal abnormalities attributable to the treatment were observed. In the four-week feeding study with the F3b-generation rats body weights and food efficiency figures were slightly decreased in males at the highest dose level. The relative weights of the caecum were slightly increased in both sexes of the high-dose group and in males of the mid-dose group. These findings were considered to represent an adaptive condition. Gross and microscopic examination did not reveal any treatment-related pathological changes. In the teratogenicity studies general appearance, food consumption and autopsy findings, organ weights 'and litter data were not adversely affected at any dose level. Visceral and skeletal examination of fetuses did not reveal any teratogenic effects attributable to the feeding of the test substance. The only effects of the test substance which were considered treatment-related consisted of inconsistent, slight decreases in body weights in the top-dose group, and a slight increase in the weight of the caecum.

 

Finally, the NOAEL for fertility and reproductive performance was 3.0% (30000 ppm corresponding to about 1500 mg/kg bw/day) a dose level exceeded the current limit dose of 1000 mg/kg bw/day.

Short description of key information:
The NOAEL for fertility and reproductive performance was 3.0% (30000 ppm corresponding to about 1500 mg/kg bw/day) a dose level exceeded the current limit dose of 1000 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
Acesulfame potassium was investigated for its effect on fertility, reproductive performance, pre- and postnatal development in male and female Wistar rats in three successive generations, each comprising two consecutive litters. This study is assessed as appropriate and valid since it was performed comparable to an internationally accepted testing guideline with deviations that can be considered as minor. Reporting, assessment and data presentation in the study report was considered as appropriate considering the date of study and report.

Effects on developmental toxicity

Description of key information

Acesulfame potassium administered orally to pregnant rats or rabbits did not lead to any maternal or developmental toxicity and especially to no morphological alterations in the fetuses. 

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

900 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The quality of the whole data base is considered to be sufficient and not critical.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The prenatal developmental toxicity of Acesulfame potassium was investigated in pregnant female Wistar rats. Each 20 pregnant females received dietary dose levels of 0, 0.3%, 1.0% and 3.0% from implantation at gestation day (GD) 6 through GD 15 (counting from day 0 of pregnancy). A positive control group received 75000 IU Vitamin A palmitate/day dissolved in soybean oil.

Signs of maternal toxicity did not occur and food consumption and body weight/body weight gain was not adversely affected. Increased food consumption was noted but this can not be considered as adverse effects. The oral administration of the test substance to the dams at all 3 dose levels had no influence on the gestational parameters. Signs of prenatal developmental toxicity including morphological alterations were not observed at any concentration. The mean fetal weights were slightly increased but this can not be considered as adverse effect. The positive control group showed a wide range of known abnormalities and demonstrated the sensitivity of the test system.

 

Thus, Acesulfame potassium administered to pregnant Wistar rats orally via the diet at 0, 0.3%, 1.0% and 3.0 % from implantation at gestation day (GD) 6 through GD 15 (counting from day 0 of pregnancy) did not lead to any maternal or developmental toxicity and especially to no morphological alterations in the fetuses.

 

The no observed adverse effects level (NOAEL) for maternal toxicity as well as for developmental toxicity including teratogenicity was 3.0% in the diet (30000 ppm corresponding to about 1500 mg/kg bw/day) and was thus clearly above the current limit dose of 1000 mg/kg bw/day.

 

The prenatal developmental toxicity of Acesulfame potassium was investigated in pregnant rabbits. Each 12 – 14 pregnant females received the test substance dissolved in re-distilled water at dose levels of 0, 100, 300 and 900 mg/kg bw/day by gavage from implantation at gestation day (GD) 7 through GD 17 (counting from day 0 of pregnancy). The application volume was 5 mL/kg bw and the control group received the vehicle (water) for comparison.

Signs of maternal toxicity did not occur and food consumption and body weight/body weight gain was not adversely affected. The oral administration of the test substance to the dams at all 3 dose levels had no influence on the gestational parameters. Signs of prenatal developmental toxicity including morphological alterations were not observed at any concentration.

 

Finally, Acesulfame potassium administered to pregnant rabbit orally by gavage at dose levels of 0, 100, 300 and 900 mg/kg bw/day from implantation at gestation day (GD) 7 through GD 19 (counting from day 0 of pregnancy) did not lead to any maternal or developmental toxicity and especially to no morphological alterations in the fetuses.

 

The no observed adverse effects level (NOAEL) for maternal toxicity as well as for developmental toxicity including teratogenicity was 900 mg/kg bw/day.

Justification for selection of Effect on developmental toxicity: via oral route:
The prenatal developmental toxicity of Acesulfame potassium was investigated in pregnant female rabbits. This study is assessed as appropriate and valid since it was performed similar to internationally accepted testing guideline and reporting, assessment and data presentation in the study report was considered as appropriate.

Justification for classification or non-classification

Acesulfame potassium did not impair reproductive performance including fertility in rats and did not show any developmental toxicity in rats and rabbits up to the highest dose levels tested.

The study results triggers the following classification/labelling:

EU Directive 1999/45/EC (as amended):        none

Regulation (EC) No 1272/2008 (CLP):           none

GHS (rev. 4) 2011:                                      unclassified