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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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well performed OECD study with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2012

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identification: Amino-C-Dion trocken
Description : yellow brown powder
Purity : 97.35% (w/w) comp.1
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:
Three New Zealand White (Hsdlf:NZW) strain rabbits were used.
At the start of the study the animals weighed 2.65 to 2.88 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 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 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:
A volume of 0.1 ml of the test item, which was found to weigh approximately 60 mg.
Duration of treatment / exposure:
Up to 1 hour
Observation period (in vivo):
Approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3 (After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.)
Details on study design:
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 item, which was found to weigh approximately 60 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 item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1.

After consideration of the ocular responses produced in the first treated animal, two additional animals were 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 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.

Any clinical signs of toxicity, if present, were also recorded.
Individual bodyweights 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: 71540 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal: 71574 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal: 71575 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal: 71540 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal: 71574 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal: 71575 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
other: redness
Basis:
animal: 71540 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: redness
Basis:
animal: 71574 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: redness
Basis:
animal: 71575 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal: 71540 Male
Time point:
other: Score at 1, 24, 48 and 72
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 71574 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 71575 Male
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
2
Max. score:
4
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.
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 and 48-Hour observations.
All treated eyes appeared normal at the 72-Hour observation.
Other effects:
Body weight
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              Eye Irritation Scores

Individual Scores for Eye Irritation

Rabbit Number and Sex

IPR

Evaluation interval*

Corneal Opacity

Area of CorneaI Opacity

Iris

Conjunctivae

Redness

Chemosis

Discharge

71540Male

2

1 Hour

0

0

0

2

2

1

71574Male

2

0

0

0

2

2

1

71575Male

2

0

0

0

2

2

1

71540Male

 

24 Hour

0

0

0

2

1

0

71574Male

 

0

0

0

2

1

0

71575Male

 

0

0

0

2

1

0

71540Male

 

48 Hour

0

0

0

1

0

0

71574Male

 

0

0

0

1

0

0

71575Male

 

0

0

0

1

0

0

71540Male

 

72 Hour

0

0

0

0

0

0

71574Male

 

0

0

0

0

0

0

71575Male

 

0

0

0

0

0

0


IPR=  Initial pain reaction

*=      Examinations were performed at the specified times aft instillation of the test item

Table 1 (continued)           Eye Irritation Scores

Mean Values after 24, 48 and 72 Hours

Rabbit Number
and Sex

Number of available data points

Corneal Opacity

Iris

Conjunctivae

Redness

Chemosis

71540Male

3

0.00

0.00

1.00

0.33

71574Male

3

0.00

0.00

1.00

0.33

71575Male

3

0.00

0.00

1.00

0.33

Assessment According to EC Classification Guidelines

Evaluated Intervals

Corneal Opacity

Iris

Conjunctivae

Redness

Chemosis

24 Hours

Not classified

Not classified

Not classified

Not classified

48 Hours

72 Hours

Table 2              Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 3

71540Male

2.79

2.84

0.05

71574Male

2.88

2.96

0.08

71575Male

2.65

2.72

0.07

Interpretation of Results

Data was summarised in tabular form, showing for each animal the irritation scores for the designated observation time, a description of the degree and nature of irritation, the presence of serious lesions and non-ocular effects. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

If evidence of irreversible ocular damage is noted, the test item will be classified as corrosive to the eye.

The results were interpreted according to the Regulation (EC) No 1272/2008of the European Parliament and of the Council of 16 December 2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria (Regulation (EC) No. 1272/2008 of the European Parliament and of the Council of 16 December 2008), Amino-C-Dion trocken does not have to be classified with respect to eye irritation in rabbits.
Executive summary:

Introduction

The primary eye irritation potential of Amino-C-Dion trocken was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. 

The mean score was calculated separately for each animal across three scoring times (24, 48 and 72 hours after instillation) for corneal opacity, iritis, redness and chemosis of the conjunctivae, respectively. The individual mean scores for corneal opacity, iritis were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 1.00 and 1.00 for reddening and 0.33, 0.33 and 0.33 for chemosis.

Results

The instillation of Amino-C-Dion trocken into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae, ocular discharge and chemosis. These effects were reversible and were no longer evident 72 hours after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea of any animals at any of the examinations. No corrosion was observed at any of the measuring intervals. No clinical signs were observed.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.