Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 18, 1988 - October 21, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to OECD Test Guideline No. 405, 1987 and under GLP Standards (EPA, USA, 1983, OECD, 1981)

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
yes
Remarks:
No control; left (undiluted) eye; right (diluted) eye
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Directive 84/449/EEC
Deviations:
not applicable
Principles of method if other than guideline:
Not relevant
GLP compliance:
yes
Remarks:
Statement of Compliance

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Vitamine-A-Palmitate 1.7 ml mlU/g
- Physical state: Liquid
- Analytical purity: confidential
- Lot/batch No.: confidential
- Expiration date of the lot/batch: October, 1989
- Stability under test conditions: stable for at least 2 hours, stabilized with Tocopherol

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Füllinsdorf (Switzerland)
- Age at study initiation:
Male: 14 weeks
Females: 15 weeks
- Weight at study initiation:
Male: 2.5 kg
females: 2.5-2.8 kg
- Housing: Individually in stainless steel cages equipped with an automatic cleaning and drinking system
- Diet: ad libitum pelleted standard rabbit maintenance diet
- Water: ad libitum community tap water
- Acclimation period: Four days under laboratory conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (ºC): 20 ± 3
- Humidity (%): 40 - 70
- Air changes (pr hour): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: No data

Test system

Vehicle:
other: unchanged (no vehicle, 100%) or diluted in neantine (diethylphtalate, 30%)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted (100%) and diluted (30%)
Duration of treatment / exposure:
72 hours (not rinsed)
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: subjective numerical according to OECD Guideline 405 (corneal, iridic and conjunctival irritation (redness/chemosis)).

TOOL USED TO ASSESS SCORE: slit-lamp 30 SL/M and Varta Cliptrix diagnostic-lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24,48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: undiluted test substance
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: undiluted test substance
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24, 48, 72 hours
Score:
0.1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: undiluted test substance
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: undiluted test substance
Other effects:
Yellow and slightly yellow staining of the eyelashes by pigment or  coloring of the test article was observed in the animals treated with the undiluted (100 %) test article from 1 to 24 hours (1/3 rabbits), and from  1 to 72 hours (2/3 rabbits) after treatment. Yellow and slightly yellow staining was observed in all rabbits (3/3) treated with the diluted (30%)  test article 1 hour after treatment.

Any other information on results incl. tables

Table 1: Individual Draize scores, cumulative scores (cumul score), and  mean 

cumulative scores (mean cum score) for the undiluted test substance(instilled 

into the left eye without rinsing)

animal  cornea   iris   conjunctivae   cumul   mean cum
no                      redn.  chem.   score   score
---------------------------------------------------------
1-hour reading
1       0        0      2      0       2
2       0        0      2      0       2
3       0        0      2      0       2       2.00
- - - - - - - - - - - - - - - - - - - - - - - - - - - - -
24-hour reading
1       0        0      1      0       1
2       0        0      0      0       0
3       0        0      0      0       0       0.33
- - - - - - - - - - - - - - - - - - - - - - - - - - - - -
48-hour reading
1       0        0      0      0       0
2       0        0      0      0       0
3       0        0      0      0       0       0.00
- - - - - - - - - - - - - - - - - - - - - - - - - - - - -
72-hour reading
1       0        0      0      0       0
2       0        0      0      0       0
3       0        0      0      0       0       0.00
---------------------------------------------------------
total mean score (24-72 h) = 0.33 (mean of 3)
---------------------------------------------------------

Mean scores 24 - 72 h reading
Animal   Cornea   Iris   Conjunctivae
                         Redness  Chemosis
---------------------------------------------
1        0        0      0.3      0
2        0        0      0        0
3        0        0      0        0

Mean scores 24 - 72 h reading
Animal   Cornea   Iris   Conjunctivae
                         Redness  Chemosis
---------------------------------------------
1-3      0        0      0.1      0


Table 2: Individual Draize scores, cumulative scores (cumul score), and  mean 

cumulative scores (mean cum score) for the 30% solution of the test  substance 

in diethylphthalate (instilled into the right eye without  rinsing)

animal  cornea   iris   conjunctivae   cumul   mean cum
no                      redn.  chem.   score   score
---------------------------------------------------------
1-hour reading
1       0        0      2      0       2
2       0        0      1      0       1
3       0        0      1      0       1       1.33
- - - - - - - - - - - - - - - - - - - - - - - - - - - - -
24-hour reading
1       0        0      0      0       0
2       0        0      0      0       0
3       0        0      0      0       0       0.00
- - - - - - - - - - - - - - - - - - - - - - - - - - - - -
48-hour reading
1       0        0      0      0       0
2       0        0      0      0       0
3       0        0      0      0       0       0.00
- - - - - - - - - - - - - - - - - - - - - - - - - - - - -
72-hour reading
1       0        0      0      0       0
2       0        0      0      0       0
3       0        0      0      0       0       0.00
---------------------------------------------------------
total mean score (24-72 h) = 0.00 (mean of 3)
---------------------------------------------------------



Applicant's summary and conclusion