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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals and Animal Husbandry
Two New Zealand White rabbits were supplied by Harlan Laboratories U.K. Ltd., Loughborough, UK. At the start of the study the animals weighed 2.30 or 2.59 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each 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 animals were individually housed in suspended cages. Free access to mains drinking water and food (2030 Teklad Global Rabbit diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminantof 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 animals were 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: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit):
A volume of 0.1 mL of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.

- Concentration:
Not applicable

VEHICLE

- Amount(s) applied:
Not applicable

- Concentration:
Not applicable

- Lot/batch no.:
Not applicable

- Purity:
Not reported
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
Approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
2 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, an additional animal was treated)
Details on study design:
Procedure
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A volume of 0.1 mL of the test material, which was found to weigh approximately 91 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 shown in "Any other information on materials and methods incl. tables".
After consideration of the ocular responses produced in the first treated animal, a second animal was treated.
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 "Any other information on materials and methods incl. tables", (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 sourcefrom a standard ophthalmoscope.

Any clinical signs of toxicity, if present, were also recorded.

Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: conjunctival redness was observed at 1 hour observation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: conjunctival redness was observed at 1 hour observation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: conjunctival redness was observed at 1 hour observation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: conjunctival redness was observed at 1 hour observation
Irritant / corrosive response data:
Ocular Reactions
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation.
Both treated eyes appeared normal at the 48-hour observation.
Other effects:
Body weight
All animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 1              IndividualScores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex

Male #1

Male #2

IPR= 2

IPR = 2

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

1
Hour

24
Hours

48
Hours

72
Hours

CORNEA

 

 

 

 

 

 

 

 

E = Degree of Opacity

0

0

0

0

0

0

0

0

F = Area of Cornea Involved

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

D

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

A = Redness

2

1

0

0

2

1

0

0

B = Chemosis

2

1

0

0

1

0

0

0

C = Discharge

1

0

0

0

1

0

0

0

IPR= Initial pain reaction

The cornea and iris scores were 0 in both animals, the chemosis score was 0.33 in one animal and 0 in the second animal, and redness score was 0.33 in both animals at 24, 48, and 72-hour observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified