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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 May to 16 May 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl 2-methylbutyrate
EC Number:
231-225-4
EC Name:
Ethyl 2-methylbutyrate
Cas Number:
7452-79-1
Molecular formula:
C7H14O2
IUPAC Name:
ethyl 2-methylbutanoate
Constituent 2
Reference substance name:
Ethyl Methylbutyrate-2
IUPAC Name:
Ethyl Methylbutyrate-2
Constituent 3
Reference substance name:
Ethyl-2-methylbutyrate
IUPAC Name:
Ethyl-2-methylbutyrate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Ethyl Methylbutyrate-2
- Physical state: Colourless to slight yellowish, liquid
- Analytical purity: 99.4%
- Lot/batch No.: 20010036
- Stability: 360 days
- Storage condition of test material: cool and dry
- Other:
- Test concentration: undiluted
- Arrival of test article: 17/4/2000

Test animals / tissue source

Species:
rabbit
Strain:
other: SPF Albino rabbits of stock Chbb:HM (SPF) – Littlerussian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: BI Pharma KG, 88397 Biberach
- Age at study initiation: No details provided in report
- Weight at study initiation: 1.9 - 2.1 kg bw
- Housing: During a pre-period of at least one week and throughout the experiment the rabbits were caged individually in PPO cages (floor area: 2576 sq.cm) with perforated floor.
- Diet (e.g. ad libitum): A pelleted complete rabbit diet “Altroimin 2123” from Altromin, D-32791 Lage, Lippe, was available ad libiturn. Analyses for major nutritive components and relevant possible contaminants are performed regularly on the diet. Certificates of analysis are retained.
- Water (e.g. ad libitum): The animals had free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth. Analyses for relevant possible contaminants are performed regularly. Certificates of analysis are retained.

ENVIRONMENTAL CONDITIONS
The study took place in animal room No. 6 provided with filtered air at the following conditions:
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness. Light was on from 6 am to 6 pm

Test system

Vehicle:
not specified
Controls:
other: The untreated right eye
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
4 female (The study was initiated with one rabbit. Since no marked eye irritation was seen in this animal another three rabbits were included in the study with time difference).
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were examined and the grade of ocular reaction was recorded one hour and 24 hours later. After the first 24 hour reading Fluorescein was instilled. After rinsing with 20 ml 0.9% sodium chloride solution the eyes were examined again using UV-light to detect possible corneal damage.
- Time after start of exposure: 24 hours

SCORING SYSTEM: See attached report for details

TOOL USED TO ASSESS SCORE: The day before testing both eyes of the animals were examined with a hand held inspection lamp fitted with white and UV light and magnifying glass with, 2 x magnification to ensure there were no defects or irritation. The examination was performed before and after instillation of Fluorescein.

The eyes were examined and the grade of ocular reaction was recorded one hour and 24 hours later. After the first 24 hour reading Fluorescein was instilled. After rinsing with 20 ml 0.9% sodium chloride solution the eyes were examined again using UV-light to detect possible corneal damage.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Reversibility:
fully reversible within: 7 days

Any other information on results incl. tables

See Table 1 of attached report for individual results.

- One hour after application of the test article animals No. 1770 and No. 1773 showed a diffuse, crimson red conjunctiva with individual vessels not easily discernible, an obvious swelling with partial eversion of lids and a discharge with moistening of the lids and hairs just adjacent to lids in animals No. 1771 and No. 1772 were observed a diffuse, crimson red conjunctiva with individual vessels not easily discernible, an obvious swelling with partial eversion of lids and a discharge different from normal.

 

- 24 hours after application of the test article animals No. 1770 and No. 1772 showed some conjunctival vessels definitely injected and a swelling above normal. In animal No. 1771 were observed a diffuse, crimson red conjunctiva with individual vessels not easily discernible as well as an obvious swelling with partial eversion of lids. Animal No. 1773 showed a diffuse, crimson red conjunctiva with individual vessels not easily discernible as well as a swelling above normal.

 

- 48 hours after application of the test article in animals No. 1770 and No. 1771 were observed some conjunctival vessels definitely injected and a swelling above normal. Animals No 1772 and No. 1773 showed some conjunctival vessels definitely injected.

 

- 72 hours after application of the test article in animals No. 1770 and No. 1773 were observed some conjunctival vessels definitely. Animal No. 1771 showed some conjunctival vessels definitely injected and a swelling above normal. In animal No. 1772 was observed a conjunctival swelling above normal.

 

- 7 days after application of the test article all four animals were free of any signs of eye irritation.

 

The following mean values were obtained from the data presented in Table 1 of attached report:

 

cornea opacity         0.0

iris lesion                  0.0

redness of conjunctiva   1.1

oedema of conjunctiva (chemosis) 0.8

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the directive of the EEC commission 93/21/EEC of May 4, 1993 ETHYL METHYLBUTYRATE-2, Batch No 20010036, shall not be classified as eye irritating.
Executive summary:

The local effect of ETHYL METHYLBUTYRATE-2 was investigated according to the method recommended in the OECD Guideline No. 405, “Acute Eye Irritation/Corrosion”, Feb. 1987, and EEC Guideline B.5 “Acute Toxicity (Eye irritation)”, Jan. 1997.

Four female albino rabbits were exposed to 0.1 ml of the test article in the left eye. The eyes were examined and the changes were graded according to a numerical scale one hour, 24, 48 and 72 hours as well as 7 days after dosing.

 

Slight to well-defined signs of irritation were observed on the treated eyes. All effects were fully reversible within 7 days.

 

The following mean values, based on the results from the 24, 48 and 72 hour readings, were calculated:

 

Animal No. Cornea opacity Iris lesion Redness of conjunctiva Oedema of conjunctiva

1770 0.00 0.00 1.00 0.67

1771 0.00 0.00 1.33 1.33

1772 0.00 0.00 0.67 0.67

1773 0.00 0.00 1.33 0.33

 

According to the directive of the EEC commission 93/21/EEC of May 4, 1993 ETHYL METHYLBUTYRATE-2, Batch No. 20010036, shall not be classified as eye irritating.