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

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1989-Oct-23 through 1989-Nov-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically reliable study with sufficient information for evaluation and assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Principles of method if other than guideline:

The study was performed to investigate the properties of Acesulfame potassium as an artificial sweetener when administered incorporated into the diet to rats with streptozotocin induced diabetic status for 28 days.

GLP compliance:

yes (incl. QA statement)

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

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

IUPAC Name:

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

Constituent 2

Reference substance name:

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

EC Number:

259-715-3

EC Name:

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

Cas Number:

55589-62-3

Molecular formula:

C4H5NO4S.K

IUPAC Name:

potassium 6-methyl-2,2,4-trioxo-3,4-dihydro-1,2λ⁶,3-oxathiazin-3-ide

Constituent 3

Reference substance name:

Acesulfame potassium

IUPAC Name:

Acesulfame potassium

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Acesulfam K
- Physical state: white powder
- Lot/batch No.: 89 284/188 1958
- Stability under test conditions: stable
- Storage condition of test material: stored at room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 4 - 5 weeks
- Weight at study initiation: 80 - 120 g
- Fasting period before study: no
- Housing: individual in macrolone cages
- Diet: ad libitum
- Water: ad libitum (tap water):

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES:
From: 1989-Oct-23
To: 1989-Nov-20

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): once for the study period
- Mixing appropriate amounts with (Type of food): standard laboratory chow (Ssniff R 10; Ssniff Spezialdiäten GmbH, Soest, Germany)
- Storage temperature of food: room temperature

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples of each test diet preparation (top, middle, and bottom) for groups 2 to 5 were together with a reference sample of the control article and were analyzed for test article concentrations.

Duration of treatment / exposure:

28 day

Frequency of treatment:

daily

Post exposure period:

none

Doses / concentrations

Remarks:

Doses / Concentrations:

Basis:
nominal in diet
0, 1000, 3000, 10000, 30000 ppm

No. of animals per sex per dose:

10

Control animals:

yes, plain diet

Details on study design:

Wistar rats of both sexes were rendered diabetic by a single i.v. dose of streptozotocin (60 mg/kg bw) 12 days prior to the commencement of the study. Groups of 20 male and 20 female rats were selected from the diabetic animals, only those with blood glucose levels greater than 300 mg% being
used

Examinations

Examinations:

Morbidity/mortality: All animals were examined twice daily at the beginning and end of the workingday for morbidity and mortality.
Clinical signs: All animals were examined at least once daily for signs of ill health or overt signs of toxicity and each finding was recorded.
Body weight: Body weight of male and female animals was recorded once weekly during the treatment period.
Food consumption: Food consumption of males and females was recorded three times weekly during the treatment period.
Clinical chemistry: glucose, triglycerides

Positive control:

None

Results and discussion

Details on results:

Mortality:
No animal died during the course of the study

Clinical findings:
Major clinical findings observed in all animals of either sex followingsingle streptozotocin treatment were excessive water consumption and polyuria which is considered to be due to the induced diabetic status. There were no clinical changes directly attributable to dietary administration of Acesulfam K.

Body weight:
Body weights/body weight gain were not affected by treatment

Food consumption:
Group mean food consumption was statistically significantly slightly reduced in group 5 males on days 5 to 8 and group 4 and 5 femaleson days 1 to 3.

Clinical chemistry:
Blood chemistry parameters examined once predose revealed extremely increased glucose and markedly increased triglyceride levels in all animals of all groups and of either sex due to the single intravenous streptozotocin administration to all animals. Examination of cholesterol, triglycerides, and lipoproteins did not reveal any pathologically relevant change of the serum lipoprotein constellation.

Applicant's summary and conclusion

Conclusions:

Acesulfame potassium was well tolerated when administered for 28 days at dietary concentrations of 1000, 3000, 10000,and 30000 ppm to male and female Sprague-Dawley rats with streptozotocin induced diabetic status.

Executive summary:

Administration of Acesulfame potassium mixed to the basic powdered diet at1000, 3000, 10000 and 30000 ppm did not elicit any toxic effects on male and female animals throughout the four week study period.

 

Minimal statistically significant reductions in food consumption seen on single occasions are considered to be of minor nature and may be rather associated with the induced diabetic status and its concomitant variability of individual data than directly related to Acesulfame potassium as an artificial sweetener.

 

Clinical findings such as excessive water consumption and polyuria observed in all animals of either sex throughout the study were considered to be related to the streptozotocin induced diabetic status.

 

Extremely increased blood sugar and markedly increased triglyceride levels seen in all animals of either sex at the predose examination were in accordance with the expected and required precondition of a diabetic status at the start of treatment with Acesulfame potassium.

 

Conclusion:

Acesulfame potassium was well tolerated when administered for 28 days mixed to the basic powdered diet at concentrations of 1000, 3000, 10000 and 30000 ppm.