Carbonic acid, ethyl methyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 March - 19 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 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

Details on test material:

Sponsor's identification: ETHYL METHYL CARBONATE

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues 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: 2.68 - 3.16 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): 17-22 °C
- Humidity (%): 44-56%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml unchanged test material

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1 hour and 24, 48 and 72 hours following treatment

Number of animals or in vitro replicates:

6

Details on study design:

In order to minimise pain on instillation of the test material, one drop of local anaesthetic "Ophthaine", 0.5% proxymetacaine hydrochloride, E.R. Squibb & Sons Limited, Hounslow, Middlesex, U.K.) was instilled into both eyes of these animals I - 2 minutes before treatment.

SCORING SYSTEM:
A modified version of the system described by Kay J.H. and Calandra J.C., J. Soc. Cosmet. Chem., 1962 13 281-289 was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material. In addition, the number of rabbits showing a positive effect was recorded.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
- light source from a standard ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 hour

Score:

4.8

Max. score:

13

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 hours

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48, 72 hours

Score:

0

Max. score:

0

Irritant / corrosive response data:

No corneal effects were noted during the study. Iridial inflammation was noted in one treated eye one hour after treat¬ment. No other iridial effectswere noted. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Minimal conjunctival redness persisted in one treated eye at the 24-hour observation. Treated eyes appeared normal 24 to 48 hours after treatment.

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 maximum group mean score of 4.8 to the rabbit eye according to a modified Kay and Calandra classification system. In addition, positive effects were noted in 1/6 rabbits. based on these data, ETHYL METHYL CARBONATE does not need to 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 primary eye irritation assay was to provide information on possible health hazards in case of acute eye contact with a test material and serve as a a rational basis for risk assessment to the eye 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

No corneal effects were noted during the study. Iridial inflammation was noted in one treated eye one hour after treatment. No other iridial effectswere noted. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment.The test material produced a maximum group mean score of 4.8.  Minimal conjunctival redness persisted in one treated eye at the 24-hour observation. Treated eyes appeared normal 24 to 48 hours after treatment.

Conclusion
The test material, ETHYL METHYL CARBONATE, produced a maximum group mean score of 4.8 to the rabbit eye according to a modified Kay and Calandra classification system. In addition, positive effects were noted in 1/6 rabbits. based on these data, ETHYL METHYL CARBONATE does not need to be classified according to EU Directive 67/548/EC amended and repealed by EU Regulation No. 1272/2008 and CLP.