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
Study period:
9 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:
2009
Report Date:
2009

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
Details on test material:
- Name of test material : FeMn slag
- Substance type: green/grey solid lumps
- Physical state: solid
- Composition of test material, percentage of components: MnO 34.62 %, SiO2 28.18 %, CaO 20.95 %, Al2O3 10.38 %, MgO 3.41 %, FeO 0.53 %, K2O 0.57 %, TiO2 0.24 %.
- Purity test date: 2 July 2008
- Storage condition of test material: 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
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.18 - 2.39 kg
- Housing: Animals were housed individually in suspended cages
- Diet: Free access to 2030 Teklad Global Rabbit diet (Harlan Teklad, Blackthorn, Bicester, Oxon, UK)
- Water: Free access to mains drinking water
- Acclimation period: A minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): At least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour cycle.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 100 mg
Duration of treatment / exposure:
Up to 72 hours
Observation period (in vivo):
Animals were assessed up to 72 hours after exposure (assessments were made at 1, 24, 48 and 72 hours post treatment).
Number of animals or in vitro replicates:
1 animal was initially treated, two further animals were treated thereafter
Details on study design:
APPLICATION OF TEST MATERIAL:
Initially a single rabbit was treated with 100 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 and 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: standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
80
Reversibility:
other: not applicable
Remarks on result:
other: No corneal effects observed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
10
Reversibility:
other: not applicable
Remarks on result:
other: No iridial effects observed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
4
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
The test material produced a maximum group mean score of 10.0

To calculate the maximum group mean score, encompassing all reactions, the following equations were used:
Cornea = (E x F) x 5
Where:
E = Degree of opacity
F = Area of Cornea Involved

Iris = (D x 5)

Conjunctivae = (A + B + C) x 2
Where:
A = Redness
B = Chemosis
C = Discharge

Any other information on results incl. tables

Measurement of pH

The pH of the test material was determined prior to commencement of the study and found to be as follows:

 

Preparation

pH Measurement

immediately

after 10 minutes

after 20 minutes

 10 % w/w aqueous preparation of the test material

8.9

9.6

9.6

 

 

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

Rabbit Number and Sex

68648 Male

68668 Male

68669 Male

IPR = 2

IPR = 2

IPR = 2

Time After Treatment

1 Hr

24 Hrs

48 Hrs

72 Hrs

1 Hr

24 Hrs

48 Hrs

72 Hrs

1 Hr

24 Hrs

48 Hrs

72 Hrs

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

1

0

0

0

1

0

0

0

1

0

0

0

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

 

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

68648 Male

10

4

0

0

68668 Male

10

4

0

0

68669 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

68648 Male

2.33

2.37

0.04

68668 Male

2.39

2.42

0.03

68669 Male

2.18

2.30

0.12

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Slight conjunctival redness and chemosis (score 1) was observed 24 hours following administration of the test material in the treated eyes of all three animals; all treated eyes appeared normal 48 hours after administration. 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 conjuctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. Under the conditions of the study the test material was determined to be not irritating to eyes.