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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-Jan-13 through 1987-Feb-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Japanese Minitry of Health and Welfare (MHW)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

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): Acesulfame K
- Physical state: white crytsal
- Analytical purity: 99.4%
- Lot/batch No.: CM0879585
- Stability under test conditions: stable

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Laboratory Animals (Hamamatsu City, Shizuoka Pre., Japan )
- Age at study initiation: 4 weeks
- Weight at study initiation: males: 96 - 110 g, females: 84 - 96 g
- Fasting period before study: 16 h
- Housing: 5 per cage
- Diet: ad libitu4m (commercial laboratory chew (CE-2, CLEA Japan, Inc.)
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21° C - 25°C
- Humidity (%): 45% - 65%
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES:
From: 1987-Feb-10
To: 1987-Feb-24

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: solubility

MAXIMUM DOSE VOLUME APPLIED:
4 mL/kg bw

Doses:

4167, 5000, 6000, 7200, 8640, 10368 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and deaths: daily; body weight: days -1, 3, 7, 10, 14
- Necropsy of survivors performed: yes

Statistics:

Student's t-test or Welch's t-test.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

5 438 mg/kg bw

Based on:

test mat.

95% CL:

>= 4 839 - <= 5 994

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

5 565 mg/kg bw

Based on:

test mat.

95% CL:

>= 5 083 - <= 6 071

Mortality:

Dead animals were observed from 20 min. to 24 hr. after administration in both sexes.
0 mg/kg bw: males: 0/10; females: 0/10
4167 mg/kg bw: males: 0/10; females: 0/10
5000 mg/kg bw: males: 4/10; females: 4/10
6000 mg/kg bw: males: 8/10; females: 6/10
7200 mg/kg bw: males: 9/10; females: 9/10
8640 mg/kg bw: males: 9710; females: 10/10
10368 mg/kg bw: males: 10/10; females: 10/10

Clinical signs:

other: Dose dependent effects consisted of a decrease in spontaneous movement, crawling, convulsions, diarrhea. All surviving animals recovered within 2 days after administration.

Gross pathology:

Macroscopic findings in dead rats of both sexes included hemorrhage in the gastric mucosa and hyperemia in the small intestine and caecum in many cases and sporadic congestion in the lung and sporadic petechial hemorrhage in the thymus. The autopsy of survivors exhibited no macroscopic abnormalities in any organs.

Other findings:

Not applicable

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 values and 95% confidence limits were 5438 (4839-5994) mg/kg bw for males and 5565 (5083-6071) mg/kg bw for females.

Executive summary:

The oral acute toxicity of Acesulfame potassium was examined in rats (10 males and10 females/group).The oral LD50 values and 95% confidence limits were 5438 (4839 -5994) mg/kg bw for males and 5565 (5083 -6071) mg/kg bw for females. Major symptoms observed were a decrease in spontaneous movement, crawling, convulsions and diarrhea. The suppression of body weight gains was trendently observed at 4167 and 5000 mg/kg bw males, and at 5000 mg/kg bw females. There was no difference in body weight between the treated groups and control group at the end of observation period. The autopsy of dead animals revealed hemorrhage in the gastric mucosa, hyperemia in the small intestine and cecum, congestion in the lung, and petechial hemorrhage in the thymus. The autopsy of surviving animals exhibited no macroscopic abnormalities in any organs in either sex.

Acesulfame K was non-toxic after acute oral administration.

The study result 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