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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:
25th July 1989 - 1st August 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Old standards: according to guideline 405 of february 1987 Vehicle used is unsual but also tested

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Remarks:
but according to 1985's version of guideline 405
GLP compliance:
yes (incl. certificate)
Remarks:
1989-08-16

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Name of test material (as cited in study report) : 50% HR 89/620005 in Diethyl phthalate
Physical state :clear, colorless liquid
Storage condition and handling : not mentionned

Test animals / tissue source

Species:
rabbit
Strain:
other: SPF female albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Strain: SPF albino Chbb:HM (C.H.Boehringer, Biberach: Himalaya)
- Sex: female
- Source: Dr. Karl Thomae GmbH, Biberach an der Riss
- Age: no data
- Weight at study initiation: 2500-2900 g
- Number of animals: 4
- Controls: internal control (right eye)
-Housing: single PPL cages 45x55 cm with perforated floor
- Diet : Free access to food pellets "Altromin 2123" from Chr. Petersen Ltd., DK-4100 Ringsted
- Water : free access
- Acclimatation period: 1 week

ENVIRONMENTAL CONDITIONS :
- The animal room temperature was 21±2°C
- Relative humidity of 55±15%
- 12-hour light/dark cycle
- Air change 6 times an hour

Test system

Vehicle:
other: Diethyl phtalate (DEP)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration : HR89/620001 in DEP : 50% (w/w)
Duration of treatment / exposure:
No removal after application. Once applied the test material remained in contact with the eye throughout the experiment.
Observation period (in vivo):
Observation at 1 hour, 24 hours, 48 hours, 72 hours and 7 days.
From the 24 hours observation, eyes were rinsed with sodium chloride after observations.
Number of animals or in vitro replicates:
4 rabbits (female)
Details on study design:
About 0.1 ml of the test article was placed in the left eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. The lids were then gently held together for about one second. The eyes were examined and the grade of ocular reaction was recorded 1 hour later. 24 hours later an examination was performed before and after installation of oculoguttae flouresceini. After the examination the eyes were rinsed with 20 ml of a 0.9% sodium chloride solution.

Once applied no removal of test substance

SCORING SYSTEM: see table below

TOOL USED TO ASSESS SCORE: ophtalmoscope and fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
mean
Time point:
other: over all time point
Score:
0.9
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4/4 animals affected
Irritation parameter:
iris score
Remarks:
Lesion
Basis:
mean
Time point:
other: over all time point
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: over all time point
Score:
2.1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4/4 animals affected
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: over all time point
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: 4/4 animals affected
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
mean
Time point:
other: over all time point
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 3/4 animals affected
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: over all time point
Score:
1.2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: 4/4 animals affected
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: over all time point
Score:
0
Irritant / corrosive response data:
no irritant
for further details see table below

Any other information on results incl. tables

Results:

Rabbit   1hr score 24 hrs score 48 hrs score 72 hrs score 7 days score
(weight) (Score after fluorescein) (Score after fluorescein) (Score after fluorescein) (Score after fluorescein) (Score after fluorescein)
4247-left Test material Area of opacity 2 4 4 3 0
/(2500g) Cornea 1 1 1 1 0
  Iris 0 0 0 0 0
  Conjunctiva Chemosis 1 1 0 0 0
  Redness 2 3 2 1 0
  Discharge 3 1 0 0 0
4247-right Test material Area of opacity 1 2 2 1  
  Cornea 1 0 0 0  
  Iris 0 0 0 0  
  Conjunctiva Chemosis 0 0 0 0  
  Redness 2 2 1 0  
  Discharge 3 0 0 0  
4253-left Test material Area of opacity 2 3 1 2 0
/(3000g) Cornea 1 1 1 0 0
  Iris 0 0 0 0 0
  Conjunctiva Chemosis 2 1 0 0 0
  Redness 2 3 2 1 0
  Discharge 3 1 0 0 0
4253-right Test material Area of opacity 0 0 0 0  
  Cornea 0 0 0 0  
  Iris 0 0 0 0  
  Conjunctiva Chemosis 0 0 0 0  
  Redness 2 1 0 0  
  Discharge 3 0 0 0  
4255-left Test material Area of opacity 3 4 3 3 0
/(2600g) Cornea 1 1 1 1 0
  Iris 0 0 0 0 0
  Conjunctiva Chemosis 1 1 0 0 0
  Redness 2 3 2 1 0
  Discharge 3 1 0 0 0
4255-right Test material Area of opacity 1 3 2 1 0
  Cornea 1 1 1 1 0
  Iris 0 0 0 0 0
  Conjunctiva Chemosis 0 0 0 0 0
  Redness 2 3 1 0 0
  Discharge 3 1 0 0 0
4256-left Test material Area of opacity 3 4 4 4 0
/(2300g) Cornea 1 1 1 1 0
  Iris 0 0 0 0 0
  Conjunctiva Chemosis 1 1 0 0 0
  Redness 2 3 2 2 0
  Discharge 3 0 0 0 0
4256-right Test material Area of opacity 0 3 2 1 0
  Cornea 0 1 1 1 0
  Iris 0 0 0 0 0
  Conjunctiva Chemosis 0 0 0 0 0
  Redness 2 3 2 1 0
  Discharge 3 1 0 0 0

F : Reading after instillation of oculoguttae fluoresceini

Left eye treated with 50% HR 89/620005

Right eye treated with the vehicle

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
A 50% solution of D-menthol in diethylphtalate causes only slight irritation to the rabbit eye, totally reversible within 7 days.
Thus D-menthol shall not be classified as eye irritant.
Executive summary:

The primary eye irritant effect of “HR 89/620005’ in a 50% solution (1:1) (w/w) was investigated according to the method recommended in the OECD Guideline No.405,“Acute Eye Irritation/Corrosion”, Feb. 1987. The basic method was extended to include treatment with a vehicle control in the opposite eye to be desed with tha test article.

Under the experimental conditions described in the authorized report, moderate to intense reactions of cornea and conjunctiva were seen in all the rabbits after treatment with both the test article and the vehicle. The following mean values, based on the results from the 24-, 48- and 72-hour readings, were calculated:

  Cornea opacity  Iris lesion   Redness of cojunctiva Oedenia of conjunctiva
Vehicle 0.5 0,0 1.2 0,0
HR 89/131136 0.9 0,0 2,1 0,3

As it can be seen from the data shown above, the test article formulation was more eye-irritating compare to the vehicle control.

According to the Official Journal of the European Communities, L 257, 1983, “HR 89/62005” in a 50% solution (w/w) shall not be classified as eye irritant.