Carbonic acid, ethyl methyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 March - 14 March 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted in accordance with Japanese MAFF "Good Laboratory Practice Standards for Toxicological Studies" (59 NohSan No. 3850, August 10 1984) and Safepharm Standard Operating Procedures. The study was performed to assess the irritancy potential of the test material following a single, 4-hour, semi-occluded application to the intact rabbit skin (Safepharm Standard Method Number JMAFF 5). The method was designed to comply with requirements of the Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 59 NohSan No. 4200, January 28 1985.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 59 NohSan No. 4200, January 28 1985.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

433-480-9

EC Name:

-

Cas Number:

623-53-0

Molecular formula:

C4H8O3

IUPAC Name:

ethyl methyl carbonate

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.47 - 2.75 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-20 °C
- Humidity (%): 41-56%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml unchanged (no vehicle)

Duration of treatment / exposure:

four hours

Observation period:

24, 48 and 72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage: 100
- Type of wrap if used: gauze patch secured in position with a strip of surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: four hours after application

SCORING SYSTEM:

Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Oedema Formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately I millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the six test rabbits (24 values) and this total was divided by 12 to give the primary irritation index of the test material. The Jest material was classified according to the following scheme:

Primary Irritation Index Classification of Irritancy
0 Non-irritant
0 - 2 Mild irritant
2 - 5 Moderate irritant
5 - 8 Severe irritant

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48 hours

Score:

0.08

Max. score:

1

Reversibility:

fully reversible

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

0

Irritant / corrosive response data:

Very slight erythema was noted at one treated skin site one hour after patch removal. Very slight erythema developed at another treated skin site at the 24-hour observation and persisted at this treated skin site at the 48-hour observation.
All treated skin sites appeared normal at the 72-hour observation.

Any other information on results incl. tables

see attachment

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material, ETHYL METHYL CARBONATE, produced a primary irritation index of 0.08 and should thus not be classified according to EU Directive 67/548/EC amended and repealed by EU Regulation No. 1272/2008 and CLP.

Executive summary:

Purpose
The purpose of this assay was to identify the skin irritation/corrosion potential of the test material when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. This study should provide a rational basis for risk assessment to the irritating potential of the test item in man.

Study Design
The method was designed to comply with requirements of the Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 59 NohSan No. 4200, January 28 1985.

Results

A single 4-hour, semi-occluded application of the test material to the intact skin of six rabbits produced very slight erythema.. All treated skin sites appeared normal at the 72-hour observation.
The test material produced a primary irritation index of 0.08 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Conclusion
The test material, ETHYL METHYL CARBONATE, produced a primary irritation index of 0.08 and should thus not be classified according to EU Directive 67/548/EC amended and repealed by EU Regulation No. 1272/2008 and CLP.