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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:
2001-06-14 to 2001-07-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Guideline 11 Nousan No. 6283 (October 1, 1999); First Revision: 12 Nousan 8628 (December 6, 2000)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products Inc. Denver, PA, USA
- Age at study initiation: Young adult
- Weight at study initiation: 2577 to 2758 grams
- Housing: individual housing in suspended wire mesh cages
- Diet: 150 g/day, standard laboratory rabbit diet PMI Nutrition International, Inc. Certified Rabbit LabDiet® 5322
- Water: ad libitum, municipal water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66-77
- Humidity (%): 48-80
- Air changes (per hr): no data
- Photoperiod: 12 hour light/dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its one control. The test article was introduced into the conjunctival sac of one eye, the untreated eye serving as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml
- Concentration: The test article was applied unchanged as received
Duration of treatment / exposure:
Eyes were not rinsed after treatment.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no washing was done

SCORING SYSTEM: in accordance with Draize, as published in the guidelines in Subsection F. Hazard Evaluation: Human and Domestic Animals distributed in 1984 and the EPA-OPPTS Health Effects Test Guidelines (1998).

TOOL USED TO ASSESS SCORE: A direct ophthalmoscope was used during these observations to examine the corneal tissue. In addition, both eyes were further examined at 24 hours and at all subsequent observations with sodium fluorescein.

PREPARATION and SELECTION of ANIMALS: Both eyes of all rabbits were examined for ocular abnormalities prior to initiation of dosing. The pre-initiation examination included the use of sodium fluorescein and a direct ophthalmoscope for detection of corneal abnormalities. Only rabbits with no
pre-existing ocular abnormalities were assigned to study.
Both eyes of all rabbits were examined macroscopically for ocular irritation in accordance with the method of Draize at approx. 1, 24, 48, 72 h, 4, 7, 14 d

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
other: #1, #2
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: day 14
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: day 21
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal: #1, #2
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
fully reversible within: 17 days
Irritant / corrosive response data:
Positive corneal, iridal and conjunctival findings were noted for all animals. Corneal neovascularization was noted for two animals on study days 7 through 14 or 17. Iridal irritation subsided by study day 7, and corneal and conjunctival irritation completely subsided by study termination (study day 21).
The Maximum Average Score for the test substance was 50.3 at 48 hours post-instillation.
Other effects:
There were no deaths or remarkable body weight changes during the study period.

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time

Score at time point / Reversibility

Cornea opacity

Cornea - Area  involved

Iris

Conjunctivae

Redness

Conjunctivae

Chemosis

Conjunctivae

Discharge

Fluorescein test (% of cornea retaining stain)

Max. score: 4

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

Max.: 100 %

1 hour

1/1/1

1/1/1

1/1/1

2/2/1

3/2/3

3b/3b/3b

no

24 hours

1/1/1

4/4/1

1/1/0

3/2/2

4/3/3

3b,p/3b,p/3b,p

yes 75/65/10

48 hours

2/2/1

4/4/1

1/1/0

3/3/2

4/4/3

3b,p/3b/3b,p

yes 65/45/5

72 hours

2/2/1

4/3/1

1/1/0

3/2/2

3/4/2

3b,p/3b/1b,p

yes 50/30/0

4 days

2/2/1

4/3/1

1/1/0

3/2/2

3/3/2

2b,p/2b/1b,p

yes 50/20/0

7 days

2k/1k/0

2/1/0

0/0/0

2/2/1

2/2/1

1b/0/0

yes 15/5/0

10 days

1k/1k/0

1/1/0

0/0/0

1/2/1

1/1/1

0/0/0

yes 0/0/0

14 days

1k/1k/0

1/1/0

0/0/0

1/1/0

0/1/0

0/0/0

yes 0/0/0

17 days*

0/1k/-

0/1/-

0/0/-

0/1/-

0/0/-

0/0/-

yes 0/0/-

21days**

-/0/-

-/0/-

-/0/-

-/0/-

-/0/-

-/0/-

yes -/0/-

* only the two animals with responses at 14 days examined

** only the animal with responses at 17 days examined

b = clear discharge, p = purulent discharge in conjunctival sac, k = corneal neovascularization

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes)
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
Interpretation is based on effects on the cornea, iris and conjunctiva calculated as mean scores following grading at 24, 48 and 72 hours after instillation of the test material, in consideration of reversibility. Slight to moderate effects of cornea and iris were observed and moderate to severe conjunctivae and chemosis scores. All symptoms were fully reversible within 21 days.
Executive summary:

In a primary eye irritation study according to US Guideline EPA OPPTS 870.2400 (1998), OECD Guideline 405 (1987), EU Guideline B.5 (1992) and Japanese Guideline Nousan No. 6283 (1999), revised Nousan 8628 (2000), 0.1 ml of oleic-acid based IQAC, DMS quaternised (according to sponsors information: 80 % of CAS No. 72749-55-4, 15 % of CAS No. 9004-96-0 (Oleic acid, ethoxylated) and 5 % of CAS No. 25322-68-3 (Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated)) was instilled into the conjunctival sac of three White New Zealand rabbits. The eyes were not rinsed after substance application. Animals then were observed for 21 days. Irritation was scored by the method of Draize.

Positive corneal, iridal and conjunctival findings were noted for all animals. Corneal neovascularization was noted for two animals on study days 7 through 14 or 17. Iridal irritation subsided by study day 7, and corneal and conjunctival irritation completely subsided by study termination (study day 21).

The test substance induced a maximum mean total score of 50.3 (maximum possible mean total score of 110) at 48 hours post-instillation. Mean scores following grading at 24, 48 and 72 hours after instillation of the test material for corneal opacity were >/= 1but < 3, for iritis >/= 1 but < 1.5 and for conjunctival redness and oedema >/= 2. All effects were completely reversible in all animals within 21 days.