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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:
02 November 2009 to 19 November 2009.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

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:
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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Sponsor's identification : MnO2
Appearance : Black powder
Date received : 08 September 2008
Storage conditions : Room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Limited, Hillcrest, Belton, Loughborough, UK
- Weight at study initiation: 2.31 to 2.82 kg
- Housing: The animals were individually housed in suspended cages
- Diet: Free access to mains drinking water and food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water:Free access to mains drinking water was allowed throughout the study.
- Acclimation period: of at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70% respectively
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.1 mL of the test material, which was found to weigh approximately 32 mg
- Concentration (if solution): A volume of 0.1 mL of the test material, which was found to weigh approximately 32 mg

VEHICLE
Not applicable
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
APPLICATION OF TEST SUBSTANCE:
Initially a single rabbit was treated with 0.1 mL (32 mg) of test material. The test material was administered 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 test material and then released. The left eye served as a control and remained untreated. Immediately after administration of the test material an assessment of the initial pain reaction was made. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

SCORING SYSTEM:
Assessment of ocular damage/irritation was made 1, 24, 48 and 72 hours post dosing using the scoring system from Draize JH (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 at this point along with any clinical signs of toxicity if present. Individual bodyweights were recorded on day 0 and 3. The numerical values corresponding to each animal, tissue and observation time were recorded. These scores were then assessed using a modified version of the system described by Kay JH and Calandra JC (1962), J. Soc. Cosmet. Chem. 13, 281-289. If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.

TOOL USED TO ASSESS SCORE:
Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 68633 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
80
Reversibility:
other: no effect
Irritation parameter:
cornea opacity score
Basis:
animal: 68650 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
80
Reversibility:
other: no effect
Irritation parameter:
cornea opacity score
Basis:
animal: 68672 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
80
Reversibility:
other: no effect
Irritation parameter:
iris score
Basis:
animal: 68633 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
10
Reversibility:
other: no effect
Irritation parameter:
iris score
Basis:
animal: 68650 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
10
Reversibility:
other: no effect
Irritation parameter:
iris score
Basis:
animal: 68672 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
10
Reversibility:
other: no effect
Irritation parameter:
conjunctivae score
Basis:
animal: 68633 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal: 68650 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal: 68672 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 (all tables are in the any other information on results section).
Black staining of the fur was noted around all treated eyes throughout the study.
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation.
Other effects:
Individual bodyweights and bodyweight changes are given in Table 3. All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1: Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex

68633 Male

68650 Male

68672 Male

IPR= 2

IPR= 2

IPR= 2

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

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

0

0

0

0

F = Area of Cornea Involved

0

0

0

0

0

0

0

0

0

0

0

0

Score (E x F) x 5

0

0

0

0

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

 

 

 

 

D

0

0

0

0

0

0

0

0

0

0

0

0

Score (D x 5)

0

0

0

0

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

 

 

 

 

A = Redness

2

1

0

0

2

1

0

0

2

1

0

0

B = Chemosis

2

1

0

0

2

1

0

0

2

1

0

0

C = Discharge

1Sf

0Sf

0Sf

0Sf

1Sf

0Sf

0Sf

0Sf

1Sf

0Sf

0Sf

0Sf

Score (A + B + C) x 2

10

4

0

0

10

4

0

0

10

4

0

0

Total Score

10

4

0

0

10

4

0

0

10

4

0

0


IPR= Initial pain reaction

Sf = Black staining of the fur around treated eye

Table 2: Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number

and Sex

Individual Total Scores At:

1 Hour

24 Hours

48 Hours

72 Hours

68633 Male

10

4

0

0

68650 Male

10

4

0

0

68672 Male

10

4

0

0

Group Total

30

12

0

0

Group Mean Score

10.0

4.0

0.0

0.0

Table 3: Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 3

68633Male

2.31

2.37

0.06

68650Male

2.82

2.85

0.03

68672Male

2.55

2.57

0.02

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study the test material was determined to be not irritating to eyes.
Executive summary:

The eye irritation potential of the test material was investigated in vivo in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 405 and EU Method B.5.

No corneal or iridial effects was noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation.

Therefore, under the conditions of the study the test material was determined to be not irritating to eyes.