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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:
Between 07 July 2015 and 16 July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
(3S,6E)-3,7,11-trimethyldodeca-6,10-dienal
EC Number:
810-298-1
Cas Number:
194934-66-2
Molecular formula:
C15H26O
IUPAC Name:
(3S,6E)-3,7,11-trimethyldodeca-6,10-dienal
Test material form:
liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Envigo RMS (UK) Limited, Leicestershire, UK. At the start of the study the animals weighed 2.93 or 3.59 kg and were 12 to 20 weeks old. After an acclimatization period of at least 5 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 (2930C Teklad Global Rabbit diet supplied by Envigo RMS (UK) Limited, Leicestershire, 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. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 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:
0.1 mL of the test item was placed into the conjunctival sac of the right eye
Duration of treatment / exposure:
Up to 1 hour
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
2
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 subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre dose anesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.

A volume of 0.1 mL of the test item 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.

Eight hours after test item application, a subcutaneous injection of post dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.

After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated.

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977) given in Appendix 2.

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 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: 75136 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal: 75140 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: 75136 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: 75140 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 75136 Male
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 75140 Male
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: 75136 Male
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: 75140 Male
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Ocular Reactions
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2. Individual mean scores for ocular irritation required for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals are given in Table 3.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in both treated eyes 1 hour after treatment with minimal conjunctival irritation noted at the 24 and 48 Hour observations.

Both treated eyes appeared normal at the 72-Hour observation.
Other effects:
Body weight
Individual body weights and body weight change are given in Table 4.

Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Individual mean scores for ocular irritation required for classification are as follows:

 

Rabbit Number and Sex

Time After Treatment

Corneal Opacity

Iridial Inflammation

Conjunctival Redness

Conjunctival Chemosis

75136Male

24 Hours

0

0

1

1

48 Hours

0

0

1

0

72 Hours

0

0

0

0

Total

0

0

2

1

Mean

0.0

0.0

0.7

0.3

75140Male

24 Hours

0

0

1

1

48 Hours

0

0

1

0

72 Hours

0

0

0

0

Total

0

0

2

1

Mean

0.0

0.0

0.7

0.3

Table 1     Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex

75136Male

75140Male

IPR= 0

IPR = 0

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

Score (E x F) x 5

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

D

0

0

0

0

0

0

0

0

Score (D x 5)

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

A = Redness

2

1

1

0

2

1

1

0

B = Chemosis

1

1

0

0

2

1

0

0

C = Discharge

2

0

0

0

2

1

0

0

Score (A + B + C) x 2

10

4

2

0

12

6

2

0

Total Score

10

4

2

0

12

6

2

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

75136Male

10

4

2

0

75140Male

12

6

2

0

Group Total

22

10

4

0

Group Mean Score

11.0

5.0

2.0

0.0

Table 3     Individual and Mean Scores for Cornea, Iris and Conjunctivae- According to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals

Rabbit Number and Sex

Time After Treatment

Corneal Opacity

Iridial Inflammation

Conjunctival Redness

Conjunctival Chemosis

75136Male

24 Hours

0

0

1

1

48 Hours

0

0

1

0

72 Hours

0

0

0

0

Total

0

0

2

1

Mean

0.0

0.0

0.7

0.3

75140Male

24 Hours

0

0

1

1

48 Hours

0

0

1

0

72 Hours

0

0

0

0

Total

0

0

2

1

Mean

0.0

0.0

0.7

0.3

Table 4     Individual Body Weights and Body Weight Change

Rabbit Number
and Sex

Individual Body Weight (kg)

Body Weight Change (kg)

Day 0

Day 3

75136Male

2.93

3.02

0.09

75140Male

3.59

3.63

0.04

Interpretation of Results

The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:

 

Score for conjunctivae      =      (A + B + C) x 2

Score for iris                     =      D x 5

Score for cornea               =      (E x F) x 5

 

Using the numerical data obtained a modified version of the system described by Kay J.H. and Calandra J.C. (1962)(seeAppendix 3) was used to classify the ocular irritancy potential of the test item. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test item.

 

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

 

The results were also interpreted according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a maximum group mean score of 11.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

 

Results

A single application of the test item to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Both treated eyes appeared normal at the 72‑Hour observation.

 

Individual mean scores for ocular irritation required for classification are as follows:

 

Rabbit Number and Sex

Time After Treatment

Corneal Opacity

Iridial Inflammation

Conjunctival Redness

Conjunctival Chemosis

75136Male

24 Hours

0

0

1

1

48 Hours

0

0

1

0

72 Hours

0

0

0

0

Total

0

0

2

1

Mean

0.0

0.0

0.7

0.3

75140Male

24 Hours

0

0

1

1

48 Hours

0

0

1

0

72 Hours

0

0

0

0

Total

0

0

2

1

Mean

0.0

0.0

0.7

0.3

 

 Conclusion

The test item produced a maximum group mean score of 11.0 and was classified as a mild irritant (Class4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

 

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals.

 

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