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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Klimisch score 1; GLP study according to guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): C-SAT090071
- Physical state: liquid
- Analytical purity: ca. 83 % with 8-10 % impurities (nonylphenol)
- Lot/batch No.: 5138
- Expiration date of the lot/batch: 30-4-2013
- Stability under test conditions: stable
- Storage condition of test material: room temperature

Test animals / tissue source

Species:
rabbit
Strain:
other: Crl:CHBB (HM) Russian rabbit
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 9-12 months
- Weight at study initiation: 2.3-3.3 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +- 3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animals
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
single application
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to OECD 405 guideline

TOOL USED TO ASSESS SCORE: light and fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean (24/48/72 hours)
Score:
1.33
Reversibility:
fully reversible within: 7d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean (24/48/72 hours)
Score:
1
Reversibility:
fully reversible within: 7d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean (24/48/72 hours)
Score:
0.67
Reversibility:
fully reversible within: 7d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean (24/48/72 hours)
Score:
0.67
Reversibility:
fully reversible within: 7d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean (24/48/72 hours)
Score:
0.67
Reversibility:
fully reversible within: 7d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean (24/48/72 hours)
Score:
0.33
Reversibility:
fully reversible within: 7d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean (24/48/72 hours)
Score:
2.33
Reversibility:
fully reversible within: 7d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean (24/48/72 hours)
Score:
1.67
Reversibility:
fully reversible within: 7d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean (24/48/72 hours)
Score:
1.67
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean (24/48/72 hours)
Score:
2
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean (24/48/72 hours)
Score:
1.33
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean (24/48/72 hours)
Score:
1.67
Reversibility:
fully reversible within: 7d

Any other information on results incl. tables

One hour after the application of the test item, animal No. 4409 showed scattered or

diffuse areas of opacity with details of iris clearly visible on about one quarter of the

cornea area, some hyperaemic conjunctival blood vessels, a swelling above normal

and a moderate flow of tears. Some hyperaemic conjunctival blood vessels, as

welling above normal and a mild flow of tears were observed in animal No. 4410.

Animal No. 4414 showed an iris with markedly deepened rugae, congestion,

swelling, moderate circumcorneal hyperaemia and an existing reaction to light, a

conjunctiva with diffuse crimson colour and individual vessels not easily discernible,

an obvious swelling with partial eversion of Iids as weil as a moderate flow of tears.

24 hours after the application of the test item, scattered or diffuse areas of opacity

with details of iris clearly visible on more than three quarters of the cornea area, an

iris with markedly deepened rugae, congestion, swelling, moderate circumcorneal

hyperaemia and an existing reaction to light, a conjunctiva with diffuse crimson

colour and individual vessels not easily discernible, a swelling with Iids about half

closed and a moderate flow of tears were observed in animal No. 4409. Anima!

No. 441 0 showed scattered or diffuse areas of opacity with details of iris clearly

visible on about one quarter of the cornea area, an iris with markedly deepened

rugae, congestion, swelling, moderate circumcorneal hyperaemia and an existing

reaction to light, a conjunctiva with diffuse crimson colour and individual vessels not

easily discernible, an obvious swelling with partial eversion of Iids and a moderate

flow of tears. Scattered or diffuse areas of opacity with details of iris clearly visible on

about one quarter of the cornea area, an iris with markedly deepened rugae,

congestion, swelling, moderate circumcorneal hyperaemia and an existing reaction to

light, a conjunctiva with diffuse crimson colour and individual vessels not easily

discernible, a swelling with Iids about half closed and a moderate flow of tears were

observed in animal No. 4414.

After the instillation of Fluorescein, animal No. 4409 showed an easily discernible

translucent area with details of the iris slightly obscured on more than half, but less

than three quarters of the cornea area. An easily discernible translucent area with

details of the iris slightly obscured was observed on more than one quarter, but less

than half of the cornea area of animal No. 4410, whereas animal No. 4414 showed

scattered or diffuse areas of opacity with details of iris clearly visible on more than

one quarter, but less than half of the cornea area.

48 hours after the application of the test item, scattered or diffuse areas of opacity

with details of iris clearly visible on more than three quarters of the cornea area, an

iris with markedly deepened rugae, congestion, swelling, moderate circumcorneal

hyperaemia and an existing reaction to light, a conjunctiva with diffuse beefy red

colour and an obvious swelling with partial eversion of Iids were observed in animal

No. 4409. Anima I No. 4410 showed scattered or diffuse areas of opacity with details

of iris clearly visible on about one quarter of the cornea area, an iris with markedly

deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia and an

existing reaction to light, a conjunctiva with diffuse crimson colour and individual

vessels not easily discernible, an obvious swelling with partial eversion of Iids and a

mild flow of tears. A conjunctiva with diffuse crimson colour and individual vessels

not easily discernible as weil as an obvious swelling with partial eversion of Iids were

observed in animal No. 4414.

After the instillation of Fluorescein, animal No. 4409 showed scattered or diffuse

areas of opacity with details of iris clearly visible on more than one quarter, but less

than half of the cornea area. Scattered or diffuse areas of opacity with details of iris

clearly visible were observed on about one quarter of the cornea area of animal

No. 4410 and No. 4414.

72 hrs after the application of the test item, animal No. 4409 showed scattered or

diffuse areas of opacity with details of iris clearly visible on more than one quarter,

but less than half of the cornea area, a conjunctiva with diffuse crimson colour and

individual vessels not easily discernible as weil as a swelling above normal. Some

hyperaemic conjunctival blood vessels were observed in animal No. 4410 and

No. 4414.

After the instillation of Fluorescein, animal No. 4409 showed scattered or diffuse

areas of opacity with details of iris clearly visible on about one quarter of the cornea

area.

Seven days after the application of the test item, no ocular reactions were observed

in the eye of animal No. 4409, but tight scab was revealed on the upper eyelid.

Anima I No. 4410 showed moderate formation of scab on the upper eyelid and loss of

hair around the eye. Mild formation o scab and loss of hair around the eye was

observed in animal No. 4414.

Fourteen days after the application of the test item, animal No. 4409 still showed a

hairless fringe of the eye but scab not any longer. The upper eyelid of animal

No. 4410 was very hairless but free of scab. The loss of hair on the upper eyelid of

animal No. 4414 was mild and scab was not present any longer.

Twenty-one days after the application of the test item, animal No. 4409, No. 4410

and No. 4414 was free of signs of irritation. The hair was grown again in the

adjacency of the eye.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is classified as irritating to eyes according to category 2 of the regulation (EC) No 1272/2008 (2008)7, because of the data concerning the opacity of the cornea obtained after the use of fluorescein.
Executive summary:

The local effect of Ethanone, 1-(2-hydroxy-5-nonylphenyl)-, oxime, branched was investigated according to the method recommended in the OECD Guideline 405 (2002) and the council regulation (EC) No 440/2008 part B.5. (2008).

During an initial test, an amount of 0.1 ml of the undiluted test item was applied in one eye of a female albino rabbit. The eye was examined and the changes were graded according to a numerical scale after 1 hr, 24 hrs, 48 hrs and 72 hrs as well as on day 7,14 and 21. Well defined changes were observed in the treated eye. Since the animal used during the initial test did not show corneal defects on day 7, two more female albino rabbits were treated with 0.1 ml of the undiluted test item each. Likewise ocular defects were graded after 1 hr, 24 hrs, 48 hrs and 72 hrs as well as on day 7, 14 and 21. The two test animals showed also well defined changes concerning eyes. All observed effects were fully reversible within 7 days.

Based on the results of the study described in this report Ethanone, 1-(2-hydroxy-5-nonylphenyl)-, oxime, branched

• shall not be classified as irritating to eyes according to annex VI of the directive 67/548/EEC (2009)3 as well as the directive 2006/12 11EC (2006, 2007)4.S.

• shall be classified as irritating to eyes according to category 2B of the GHS (2007)6, because of the data concerning the opacity of the cornea obtained after the use of Fluorescein.

• shall be classified as irritating to eyes according to category 2 of the regulation (EC) No 1272/2008 (2008)7, because of the data concerning the opacity of the cornea obtained after the use of Fluorescein.