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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-Jul-13 through 2012-Jul-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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 potassium
- Physical state: white, crystalline powder
- Analytical purity: 100%
- Lot/batch No.: 0000522972
- Expiration date of the lot/batch: 08 October 2012
- Stability under test conditions: stable
- Storage condition of test material: Controlled Room temperature (15-25 °C, below 70 RH%), protected from humidity

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: young adult
- Weight at study initiation: 220 - 253 g
- Fasting period before study: no
- Housing: individual caging
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7 – 26.6 °C
- Humidity (%): 30 - 70
- Air changes (per hr): 15-2ß
- Photoperiod (hrs dark / hrs light): 12 h/12h

IN-LIFE DATES: From: 13-Jul-2012 To: 27-Jul-2012

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: shaved back
- % coverage: 10%
- Type of wrap if used: Sterile gauze pads in contact with the skin using a patch of adhesive hypoallergenic plaster.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
- Concentration (if solution): neat
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- not applicable

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation: on day of treatment: 1 and 5h, thereafter daily; body weight: days 0, 7, 14
- Necropsy of survivors performed: yes

Statistics:

Not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item did not cause any mortality at the dose level of 2000 mg/kg bw.

Clinical signs:

other: SYSTEMIC CLINICAL SIGNS: No clinical signs were observed during the treatment with the test item or thereafter within the 14 day observation period. LOCAL DERMAL SIGNS: No dermal signs were observed after treatment with the test item.

Gross pathology:

There was no evidence of any observations at the dose level of 2000 mg/kg bw at necropsy.

Other findings:

Not applicable

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of Acesulfame potassium after a single dermal administration was found to be greater than 2000 mg/kg bw in male and female CRL:(WI) rats.

Executive summary:

The acute dermal toxicity study was performed with Acesulfame potassium in Wistar rats (CRL:(WI)) in compliance with OECD Guideline No. 402,Commission Regulation (EC) No 440/2008, B.3 and OPPTS 870.1200.

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24 -hour exposure followed by a 14‑day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

The test item did not cause any mortality at the dose level of 2000 mg/kg bw.

 

No clinical signs were observed during the treatment with the test item or thereafter within the 14 day observation period. No dermal signs were observed after treatment with the test item. There were no effects on body weight or body weight gain in any animal during the study. There was no evidence of any observations at the dose level of 2000 mg/kg bw at necropsy.

The median lethal dose ofAcesulfame Potassiumafter a single dermal administration was found to be greater than 2000 mg/kg bw in male and female CRL:(WI) rats. Acesulfame Potassiumis non-toxic after acute dermal 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