Propanoic acid, 2-hydroxy-2-methyl-, 2-propen-1-yl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Principles of method if other than guideline:

The intial weight of animal (no. 075) was above the preferrred range specified in the General Study Plan (2.0 - 3.0kg). This deviation has no impact on the integrity of the test.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

prop-2-en-1-yl 2-hydroxy-2-methylpropanoate

EC Number:

700-908-3

Cas Number:

19444-21-4

Molecular formula:

C7H12O3

IUPAC Name:

prop-2-en-1-yl 2-hydroxy-2-methylpropanoate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elvage Scientifique des Dombes 01400 Chatillon sur Chalaronne, France
- Age at study initiation: Approximately 8-12 weeks
- Weight at study initiation: 2810 - 3120 g
- Housing: Individual
- Diet (e.g. ad libitum): NAFAG No. 814 (NAFAG, Gossau/SG, Switzerland), available ad libitum.
- Water (e.g. ad libitum): Available ad libitum from automatic dispensers; source is municipal water supply.
- Acclimation period: 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50% ± 20%
- Air changes (per hr): 13-14/hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

The test article (0.1 ml) was instilled into the conjunctival sac of one eye of three rabbits; the second eye served as a control. The test eyes were gently washed with distilled water 24 hours after treatment. Eyes were examined for irritation at 1, 24, 48 and 72 hours and 7 days after treatment.

Observation period (in vivo):

7 days (sufficient to determine reversibilityof efects).

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes - washed with distilled water for 1 minute
- Time after start of exposure: 24 hours

SCORING SYSTEM: OECD/EEC - Grading of Ocular Lesions

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: for full results see table below

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

ca. 0

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: for full results see table below

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: for full results see table below

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 days

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: for full results see table below

Irritant / corrosive response data:

Scattered or diffused areas of corneal opacity (score of 1) in two animals (no. 106 and 075) and scattered areas of corneal opacity up to slightly opaque cornea (scores of 1-2) in one animal (no. 044) were scene from 1 hour through 3 days after treatment. Moderate hyperaemia of the iris (score of 1) was observed in one animal (no. 075) at the 48 hour reading only, in one animal (no. 106) from 24 hours through to 48 hours after treatment, and in one animal (no. 044) from 1 hour through to 72 hours after treatment. Diffuse, crimson coloured conjunctival redness (score of 2) and above normal swelling of the eyelids and nictitating membranes up to obvious swelling with partial eversion of lids (score of 1-2) were observed in all animals from 1 hour through 72 hours after treatment. All eye reactions were reversed by day 7. The results of the eye examinations for individual animals are presented I Table 1. Mean irritation scores for eye reaction according to OECD/EEC guidelines (24-72 hours) are presented I Table 2.

Other effects:

There was no mortality in the test.
There were no remarkable clinical observations.
Body weights were not affected by treatment. Body weights are presented in Table 3.

Any other information on results incl. tables

Table 1: Individual Eye Irritation Scores

SEX / ANIMAL NO.	F / 106		F/ 075		F / 044
	CORNEA
	CE	TE	CE	TE	CE	TE
AFTER 1 HOUR AFTER 24 HOURS AFTER 48 HOURS AFTER 72 HOURS AFTER 7 DAYS	0 0 0 0 0	1 1 1 1 0	0 0 0 0 0	1 1 1 1 0	0 0 0 0 0	1 2 1 1 0
	IRIS
AFTER 1 HOUR AFTER 24 HOURS AFTER 48 HOURS AFTER 72 HOURS AFTER 7 DAYS	0 0 0 0 0	0 1 1 0 0	0 0 0 0 0	0 0 1 0 0	0 0 0 0 0	1 1 1 1 0
AFTER 1 HOUR AFTER 24 HOURS AFTER 48 HOURS AFTER 72 HOURS AFTER 7 DAYS	0 0 0 0 0	2 2 2 2 0	0 0 0 0 0	2 2 2 2 0	0 0 0 0 0	2 2 2 2 0
AFTER 1 HOUR AFTER 24 HOURS AFTER 48 HOURS AFTER 72 HOURS AFTER 7 DAYS	0 0 0 0 0	2 1 1 1 0	0 0 0 0 0	2 2 2 1 0	0 0 0 0 0	2 2 1 1 0
CE: CONTROL EYE   TE: TEST EYE

 

Table 2: Summary Eye Irritation Indices (OECD/EEC)

Mean Scores for 24, 48 and 72 hour readings

SEX / ANIMAL NO.	F / 106	F/ 075	F / 044	MEAN
CORNEA	1	1	1.33	1.11
IRIS	0.67	0.33	1	0.67
CONJUNCTIVAL REDNESS	2	2	2	2
CONJUCTIVAL CHEMOSIS	1	1.67	1.33	1.33

 

 

Table 3: Body Weights (g)

SEX / ANIMAL NO.	F / 106	F/ 075	F / 044
AT TEST START AFTER 3 DAYS AT TEST END (7 DAYS)	3000 3020 3220	3120 3140 3250	2810 2840 2900

 

 

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the test results, CA 2215 A (Intermediate of CGA 276854) is not required to be classified for eye irritation according to Commission Directive 93/21/EEC, issued May 4, 1993.

Executive summary:

An eye irritation/corrosion test was conducted with test article CA 2215 A (Intermediate CGA 276854) (batch P.608005). The test article (0.1 ml) was instilled into the conjunctival sac of one eye of three rabbits; the second eye served as a control. The test eyes were gently washed with distilled water 24 hours after treatment. Eyes were examined for irritation at 1, 24, 48 and 72 hours and 7 days after treatment. 

The test article induced reactions of the cornea in all animals beginning 1hour after treatment and cleared within 7 days. Slight reactions of the iris were seen in all animals, which cleared within 7 days after treatment at the latest. Redness and swelling of the conjunctiva was observed in all animals between 1hour and 3 days after treatment. All eye reactions were clear by day 7 after treatment. There was no mortality, and no remarkable clinical observations. Body weights were not affected by treatment. 

According to the test results, CA 2215 A (Intermediate of CGA 276854) is not required to be classified for eye irritation according to Commission Directive 93/21/EEC, issued May 4, 1993.