Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

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: OECD guideline, GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
2003-02-13

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification : SEPIWHITE MSH
Description : off-white powder
Batch number : 0214400005
Date received : 13 October 2003
Storage conditions : approximately 4°C in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
One New Zealand White rabbit was supplied by David Percival Ltd, Moston, Sandbach, Cheshire,
UK. At the start of the study the animal was in the weight range of 2.0 to 3.5 kg and was twelve
to twenty weeks old. After an acclimatisation period of at least five days the animal was given a
number unique within the study which was written with a black indelible marker-pen on the inner
surface of the ear and on the cage label.
The animal was housed in a suspended metal cage. Free access to mains drinking water and food
(Certified Rabbit Diet (Code 5322) supplied by International Product Supplies Limited,
Wellingborough, Northants, UK) was allowed throughout the study. The diet and drinking water
were considered not to contain any contaminant of a level that might have affected the purpose or
integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70%
respectively. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00
to 18:00) and twelve hours darkness.
The animal was provided with environmental enrichment items which were considered not to
contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: 2nd eye
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
not rinced
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.
Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular effects.
Number of animals or in vitro replicates:
1
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbit were
examined for evidence of ocular irritation or defect with the aid of a light source from a standard
ophthalmoscope.
A volume of 0.1 ml of the test material, which was found to weigh approximately 49 mg (as
measured by gently compacting the required volume into an adapted syringe) was placed into the
conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.
The upper and lower eyelids were held together for about one second immediately after treatment,
to prevent loss of the test material, and then released. The left eye remained untreated and was
used for control purposes. Immediately after administration of the test material, an assessment of
the initial pain reaction was made according to the six point scale.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours
following treatment, according to the numerical evaluation given in Appendix 2, (from Draize J H
(1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity
of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the
light source from a standard ophthalmoscope.
Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular
effects.
After consideration of the ocular responses produced in this animal, no additional animals were
treated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
24/48/72 h
Score:
<= 2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
<= 3
Reversibility:
fully reversible within: 14 Days
Irritation parameter:
cornea opacity score
Remarks:
degree of opacity
Basis:
animal #1
Time point:
24/48/72 h
Score:
<= 2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Remarks:
area of cornea involved
Basis:
animal #1
Time point:
24/48/72 h
Score:
<= 4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
The reactions noted in the treated eye at the 21-day observation were considered to be indicative of irreversible ocular damage.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was considered to be corrosive to the rabbit eye due to irreversible ocular
effects.
The test material was also considered to be irritant according to EU labelling regulations Commission Directive 2001/59/EC. It is reasonable to assume that the symbol “Xi”, the indication of danger “Irritant” and the highest risk phrase R 41 “RISK OF SERIOUS DAMAGE TO EYES” are therefore required.
Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

- Commission Directive 92/69/EEC Method B5 Acute Toxicity (Eye Irritation)

Result.

A single application of the test material to the non-irrigated eye of one rabbit produced scattered or diffuse to translucent corneal opacity, iridial inflammation and severe conjunctival irritation. Vascularisation with a localised ingrowth of vessels for 2 – 3 mm in length was noted in the treated eye 7 to 21 days after treatment. Reactions noted in the treated eye at the 21-day observation were considered to be indicative of irreversible ocular damage.

Conclusion.

The test material was considered to be corrosive to the rabbit eye due to irreversible ocular effects. The test material was also considered to be irritant according to EU labelling regulations Commission Directive 2001/59/EC.

It is reasonable to assume that the symbol “Xi”, the indication of danger “Irritant” and the highest risk phrase R 41 “RISK OF SERIOUS DAMAGE TO EYES” are therefore required.