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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 October 1989 - 8 November 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study following OECD guideline 405 with minor deviations: no certificate of analysis and low housing temperature conditions
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
No certificate of analysis and low housing temperature
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
417-790-1
EC Name:
-
Cas Number:
78418-01-6
Molecular formula:
C15H20O4
IUPAC Name:
2-Hydroxy-5-(1-oxooctyl)benzoic acid
Constituent 2
Reference substance name:
MEXORYL SAB
IUPAC Name:
MEXORYL SAB
Details on test material:
- Name of test material (as cited in study report): ER 195
- Physical state: white crystalline powder
- Lot/batch No.: DG6
- Storage condition of test material: room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David percival Ltd, Moston, U.K.
- Age at study initiation: between 12 and 16 weeks
- Weight at study initiation: 2.31 - 2.92 kg
- Housing: individually housed in metal cages
- Diet (e.g. ad libitum): rabbit diet (Preston Farmers limited, New Leake, U.K.), ad libitum
- Water (e.g. ad libitum): normal drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-19
- Humidity (%): 50-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 23 October 1989 To: 8 November 1989

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approximately 65 mg
Duration of treatment / exposure:
Eye was not washed after exposure
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: no removal of substance

SCORING SYSTEM: by Kay J.H. and Calandra J.C., 1962

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48,72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
4
Reversibility:
other: the animal was killed after 72 h observation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
not specified
Remarks:
animal killed after 72 h observation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.3
Max. score:
3
Reversibility:
not specified
Remarks:
animal killed after 72 h observation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks:
animal killed after 72 h observation
Irritant / corrosive response data:
Diffuse corneal opacity, iridial inflammation and moderate or severe conjunctival irritation were noted in all treated eyes one hour after treatment and
in two treated eyes at subsequent 24, 48 and 72-hour observations.
In one animal, the corneal opacity in the treated eye increased and areas of opalescent corneal opacity with iridial inflammation and moderate to severe conjunctival irritation were noted in this treated eye at the 48 and 72-hour observation. Other adverse effects noted on the nictitating and/or conjunctival membranes of this treated eye were pale appearance, small green-coloured or white areas and areas of haemorrhage. A blood stained discharge was also noted. For humane reasons this animal was killed after the 72-hour observation.
In another animal, diffuse corneal opacity, iridial inflammation and minimal conjunctival irritation persisted in the treated eye on day seven. No corneal opacity, iridial inflammation or conjunctival irritation was noted on day fourteen. Circumcorneal vascularisation and convoluted eyelids were also apparent during this period. The nictitating membrane was also pale in appearance.
The corneal opacity in the eye of the third treated animal increased and opalescent corneal opacity with pannus formation, indicative of irreversible ocular damage, had developed on day fourteen. The iridial inflammation could not be assessed at this time; minimal conjunctival irritation with convoluted eyelids were also noted. For humane reasons this animal was killed on day fourteen.
Other effects:
No data

Any other information on results incl. tables

Individual and mean scores for cornea, iris and conjunctivae

Rabbit number & sex

Time after treatment

Corneal opacity

Iridial inflammation

Conjunctival redness

Conjunctival chemosis

178 male

24 h

1

1

2

3

 

48 h

1

1

3

3

 

72 h

1

1

3

2

Total

 

3

3

8

8

Mean

 

1.0

1.0+

2.7+

2.7+

156 male

24 h

1

1

2

2

 

48 h

1

1

3

3

 

72 h

1

1

3

3

Total

 

3

3

8

8

Mean

 

1.0

1.0+

2.7+

2.7+

162 female

24 h

2

1

2

3

 

48 h

3

1

2

3

 

72 h

3

1

3

3

 Total    8  3  7  9
 Mean    2.7+  1.0+  2.3  3.0+

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material ER 195, was found to be at least severe irritant to the rabbit eye and should be classified R41 according to the criteria of Annex VI to the Directive 67/548/EEC and category 1 according to CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy (two males and one female) adult rabbits of the New Zealand White strain were exposed to 65 mg of undiluted ER 195 in their right eye while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 24, 48 and 72 h after dosing and graded according to Kay J. H. and Calandra J. C. (1962).

Diffuse corneal opacity, iridial inflammation and moderate or severe conjunctival irritation were noted in all treated eyes one hour after treatment and in two treated eyes at subsequent 24, 48 and 72-hour observations.

In one animal, the corneal opacity in the treated eye increased and areas of opalescent corneal opacity with iridial inflammation and moderate to severe conjunctival irritation were noted in this treated eye at the 48 and 72-hour observation. Other adverse effects noted on the nictitating and/or conjunctival membranes of this treated eye were pale appearance, small green-coloured or white areas and areas of haemorrhage. A blood stained discharge was also noted. For humane reasons this animal was killed after the 72-hour observation.

In another animal, diffuse corneal opacity, iridial inflammation and minimal conjunctival irritation persisted in the treated eye on day seven. No corneal opacity, iridial inflammation or conjunctival irritation was noted on day fourteen. Circumcorneal vascularisation and convoluted eyelids were also apparent during this period. The nictitating membrane was also pale in appearance.

The corneal opacity in the eye of the third treated animal increased and opalescent corneal opacity with pannus formation, indicative of irreversible ocular damage, had developed on day fourteen. The iridial inflammation could not be assessed at this time; minimal conjunctival irritation with convoluted eyelids were also noted. For humane reasons this animal was killed on day fourteen.

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 1, 2.7 for cornea score, 1, 1, 1 for iris score, 2.7, 2.7, 2.3 for conjunctivae score and 2.7, 2.7, 3 for chemosis score.

Under these test conditions, ER 195, was found to be at least severe irritant to the rabbit eye and should be classified R41 according to the criteria of Annex VI to the Directive 67/548/EEC and category 1 according to CLP Regulation (EC) N° (1272-2008).