Imidazolium compounds, 1-[2-(2-carboxyethoxy)ethyl]-1(or 3)-(2-carboxyethyl)-4,5-dihydro-2-norcoco alkyl

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 15 to 29 June 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Animals were observed until Day 7 instead of Day 21

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

1

Reference substance name:

Imidazolium compounds, 1-[2-(2-carboxyethoxy)ethyl]-1(or 3)-(2-carboxyethyl)-4,5-dihydro-2-norcoco alkyl

EC Number:

272-897-9

EC Name:

Imidazolium compounds, 1-[2-(2-carboxyethoxy)ethyl]-1(or 3)-(2-carboxyethyl)-4,5-dihydro-2-norcoco alkyl

Cas Number:

68919-40-4

Molecular formula:

R_C8 H14 N2 O4 Na With R=Cn H2n+1 n=8, 10, 12, 14, 16, 18

IUPAC Name:

disodium 3-({2-[N-(2-hydroxyethyl)hexadecanamido]ethyl}amino)propanoate 3-[(2-hexadecanamidoethyl)(2-hydroxyethyl)amino]propanoate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 8803149
- Expiration date of the lot/batch: not specified
- Purity test date: not specified

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyer town, PA.
- Age at study initiation: not specified (young animals)
- Weight at study initiation: 2.48 to 2.61 kg
- Housing: in suspended wire mesh cages
- Diet (e.g. ad libitum): purina rabbit pellets ad libitum
- Water (e.g. ad libitum): water at libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 5°C
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 15 June 1988 To: 22 June 1988

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL sample of the test material was placed in the conjunctival sac of the right eye of each rabbit.
- Concentration (if solution): as such

Duration of treatment / exposure:

single adminstration on Day 0

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: recording of grade of ocular lesions (cornea, iris, conjunctivae)

Pre-screening: All rabbits used in this study received a pre-screening examination designed to detec pre-exicsting ocular irritation or corneal change.

Dose application: A 0.1 mL of test material was placed in the conjunctival sac of the right eye of each rabbit. The left eye served as control and was not treated. The lids of the treated eye were gently held together for 1 second before releasing them to prevent loss of the test material.

Observation: The ocular reactions were graded at 24, 48, 72 hours and on Days 4 and 7 using the grading system as the one described in the OECD 405 guideline.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

On the basis of the results of this in vivo study in rabbit, the registered substance is considered a severe eye irritant (Eye Damage 1, H318) according to criteria of CLP and GHS UN.

Executive summary:

The registered substance (product name = Miranol C2M AA) has been tested for acute ocular irritation in 3 New-Zealand White rabbits according to Draize test, and in compliance with Good Laboratory Practice. The test article, a liquid, was instillated as such in a single dose of 0.1 ml into the conjunctival sac of the right eye of the animal. The left eye remained untreated and served as a control. The eyes were not rinsed. Ocular examinations were performed at 24, 48, 72 hours after treatment, and at day 4 and 7.

 

Corneal opacity (score 2) was observed in all three rabbits at 24 hours. The reaction was still present in two animals at day 7 with grade 2, and with grade 1 in one animal. The mean scores (24-48-72 hours) calculated for each animal were 2.0 - 2.0 - 2.0. Iris reaction was observed between 24 hours and day 4 in one animal, and starting at day 3 in a second animal, whereas no reaction was observed in the third one. The mean scores (24-48-72 hours) calculated for each animal were 1.0 - 0.0 - 0.3.

Conjunctival redness (score 2 to 3) and chemosis (score 1 to 3) were observed and persisted until day 7 in all three animals. The mean scores (24-48-72 hours) calculated for each animal were 3.0 - 2.0 – 2.0 for redness, and 2.7 – 2.0 - 1.3 for chemosis.

In addition, ocular discharge was observed all three animals throughout the observation period.

 

On the basis of these results the registered substance is considered a severe eye irritant (Eye Damage 1, H318) according to criteria of CLP and GHS UN.