Isopropyl 2-methylbutyrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 to 16 May 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target chemicals are similar and a base set of studies has confirmed similar results.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Purity is similar with insignificant impurities.

3. ANALOGUE APPROACH JUSTIFICATION
Please see attched justification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

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:

Butanoic acid, 2-methyl-, ethyl ester

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

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 20010036
- Expiration date of the lot/batch: no data
- Purity test date:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: cool and dry
- Stability under test conditions: 360 days

Test animals / tissue source

Species:

rabbit

Strain:

other: SPF Albino rabbits of stock Chbb:HM (SPF) – Little russian

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 libitum. 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:

unchanged (no vehicle)

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: Alll scoring was on a 0 to 4 scale with 0 being no or little effect to 4 being extreme effect.

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

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Any other information on results incl. tables

- 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;:

 

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:

GHS criteria not met

Conclusions:

According to EU guidelines this substance is not classfied as irritating.