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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Peer-reviewed assessment report (attached in section 13)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Version / remarks:
US EPA FIFRA Guideline § 81-4
Deviations:
yes
Remarks:
Purity of the test compound was not determined by the laboratory prior to conduct of the test.
GLP compliance:
yes
Remarks:
self-certified to US EPA regulations at 40 CFR Parts 160, 792

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Chemical name
IUPAC: 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline
CAS: 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver PA USA

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
The eyes of all rabbits remained unwashed.
Observation period (in vivo):
96 h
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of all rabbits remained unwashed.

SCORING SYSTEM: The eyes were examined for ocular reactions in accordance with the method of Draize at approximately 1, 24, 48 and 72 hours, and, since conjunctival redness was still noted after 72 hours, on Day 4.

TOOL USED TO ASSESS SCORE: fluorescein; Sodium fluorescein was used to aid in revealing corneal damage at 72 hours.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
conjunctive - redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.444
Max. score:
2
Reversibility:
fully reversible within: 96h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.167
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritant / corrosive response data:
The left (control) eyes of all rabbits were free of evidence of ocular irritation and other findings for the duration of the study. The right (test) eye for one rabbit exhibited a positive conjunctival reaction and all animals had minor conjunctival irritation. There was no evidence of any damage to the iris or the cornea. All ocular irritation was reversible and completely subsided by Day 4 or earlier. There were no remarkable changes or differences observed in body weights during the study period. The maximum average score for ethoxyquin was 3.7 and was observed at one hour postinstillation.
Other effects:
There were no deaths during the study.

Any other information on results incl. tables

Table Eye irritation scores according to the Draize scheme - unwashed eyes

 

Cornea

Iris

Conjunctiva - Redness

Conjunctiva - Chemosis

Time / rabbit No.

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

1 h

0

0

0

0

0

0

0

0

0

0

0

0

1

1

1

2

1

1

1

0

1

1

0

1

24 h

0

0

0

0

0

0

0

0

0

0

0

0

1

1

1

1

0

1

0

0

1

1

0

0

48 h

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

1

0

0

0

0

0

1

0

0

72h

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

0

Mean scores 24-72 h

0.0

0.0

0.444

0.167

Additional criteria in Directive 93/21/EEC Point 3.2.6.2 fulfilled: No

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
As information was provided via a peer-reviewed assessment report, it can be considered as sufficiently reliable to assess the eye irritation potential of ethoxyquin in rabbits.
The “Primary Eye Irritation Score” for each observation time is calculated as the sum of all individual irritation scores at that time divided by the number of animals in the group. Taking these values for the 24-, 48- and 72-hour observations into account, overall mean scores for corneal opacity, iris lesions, redness of the conjunctivae and edema of the conjunctivae (chemosis) will result. In this study, only conjunctival redness and chemosis were observed and for these findings, low mean scores of 0.44 and 0.17 were calculated.
If the 1-hour values for conjunctiva redness and conjunctiva chemosis are included in that calculation, mean scores would augment to 0.624 and 0.289, respectively.
Based on these results and in accordance with Annex VI of Commission Directive 2001/59/EC, ethoxyquin shall not be classified as an eye irritant.
According to Regulation 1272/2008, a substance must be classified as Irritating to eyes (Category 2), if, when applied to the eye of an animal, a substance produces:
— at least in 2 of 3 tested animals, a positive response of:
— corneal opacity ≥ 1 and/or
— iritis ≥ 1, and/or
— conjunctival redness ≥ 2 and/or
— conjunctival oedema (chemosis) ≥ 2
— calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.
In the present study, ethoxyquin was tested on six rabbits. In none of the tested animals the above-mentioned scores met or exceeded the scores triggering classification, so also according to Regulation 1272/2008, ethoxyquin does not need to be classified as eye irritant.
Executive summary:

In a primary eye irritation study [US EPA FIFRA Guideline § 81-4], 0.1 ml of undiluted ethoxyquin was instilled into the conjunctival sac of the right eye of six New Zealand white rabbits.  Eyes were not washed.  Animals then were observed for ≥ 4 days.  Irritation was scored by the method of Draize.

There were no deaths during the study. The left (control) eyes of all rabbits were free of evidence of ocular irritation. The right (test) eye for one rabbit exhibited a positive conjunctival reaction and all animals had minor conjunctival irritation. There was no evidence of any damage to the iris or the cornea. All ocular irritation was reversible and completely subsided by Day 4 or earlier. There were no remarkable changes or differences observed in body weights during the study period. The maximum average score for ethoxyquin was 3.7 and was observed at one hour postinstillation.

In this study, ethoxyquin is not an eye irritant and does not need to be classified.