Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Age at study initiation: no data
- Weight at study initiation: males 3.3 – 3.6 kg, females 4.0 - 4.6 kg
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1-20.9
- Humidity (%): 61.0-65.0
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye remained untreated and served as control
Amount / concentration applied:
0.1 mL of the test substance were applied, which corresponded to a mass of 40.6 to 48.2 mg of the test substance.
Duration of treatment / exposure:
test substance remained in the eye
Observation period (in vivo):
4-5 days
Duration of post- treatment incubation (in vitro):
not applicable
Number of animals or in vitro replicates:
2 males and 2 females
Details on study design:
Four rabbits (2 male, 2 female) each received a volume of 0.1 mL test substance into the conjunctival sac of the right eye. This volume, measured in a specially prepared syringe, corresponded to 40.6– 48.2 mg test substance. The left eye remained untreated and served as control. At first, only one animal was treated, as in case of severe intolerance reactions the other animals would not have been exposed for humane reasons. The other animals were treated one day later. During administration and observation on the administration day (first day of the test) the animals were kept in restraining cages for approximately 2 hours. No food or water was available during this time.

Clinical observation:
Conjunctivae, eyelids, cornea and iris were evaluated before administration, 0.5, 1 and 2 hours thereafter, and then every 24 hours until termination of the study. Clinical observation was performed in each animal as long as findings occurred. Evaluation of the local tolerance on the conjunctiva of the rabbits was performed according to the score system recommended for the EU (Annex to EEC guideline 92/69/EWG, dated 31 Jul 1992, for the 17th adaptation of the EEC guideline 67/548/EWG, B 5. Acute Toxicity (Eye irritation). Off J EEC, L383A, Luxembourg, 29 Dec 1992.). In addition, all other local findings at the eyes as well as all other reactions to treatment were recorded.

Results and discussion

Results of in vivo studyopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
reddening
Basis:
mean
Time point:
24/48/72 h
Score:
0.58
Max. score:
3
Reversibility:
fully reversible within: max. 5 days
Irritation parameter:
conjunctivae score
Remarks:
swelling
Basis:
mean
Time point:
24/48/72 h
Score:
0.25
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritant / corrosive response data:
According to the system of evaluation recommended for EU (Annex to EEC guideline 92/69/EWG, dated 31 Jul 1992, for the 17th adaptation of the EEC guideline 67/548/EWG, B 5. Acute Toxicity (Eye irritation). Off J EEC, L383A, Luxembourg, 29 Dec 1992.), the values of findings relevant for classification at the time-points 24, 48 and 72 hours after administration were 0 for cornea and iris for every single animal at each time point.
Conjunctivae (reddening): 24 h - 3 animals with the score 1 (slight) and 1 animal with the score 2 (moderate); 48/72 h - 3 animals with the score 0 (no reddening) and 1 animal with the score 1 (slight)
Conjunctivae (swelling): 24/48/72 h - 3 animals with the score 0 (no swelling) and 1 animal with the score 1 (slight)
Other effects:
The treatment did not cause any effects on body weight gain.

Any other information on results incl. tables

Details about frequency, intensity and duration of the findings are to be taken from Table 1.

Table 1: Summary of local findings after single administration of the test substance in the rabbit eye. A/B = summation of positive findings/number of animals concerned. x-y = first - last day of occurence of a finding.

            Right eye 0.1 ml test substance
      male     female
   A/B x-y   A/B  x-y
 Conjunctiva        
 Reddening (all conjunctiva incl. conjunctiva sklerae)        
 - clear injection of a few vessels  3/2 1 - 2  4/2  1 -4 
 -diffuse crimson, single vessels are difficult to notice 5/2  1 -1  6/2  1 -2 
Swelling (conjunctiva and third eyelid)         
 - slight (incl. membrana nicitans) 3/2  1 -1  6/1  1 -4 
 - clearly with partial ectropium 3/2  1 -1     
 - with half eyelid closure     3/1  1 -1 

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Remarks:
in the opinion of the study director
Executive summary:

A single conjunctival administration of the test substance (technical quality including impurities) into the conjunctival sac of the rabbit eye provoked slight irritation on administration day which decreased in severity from day 2 onwards and were fully reversible on day 5 after administration. Based on these findings, no irreversible effect is to be expected after contact of the human eye with the substance.