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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:
23 October 2012 to 26 October 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
In-Vivo study carried out as substance is intended for global registration where In-Vivo data is required

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
See other information on method section for details
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
See other information on method section for details
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
Remarks:
See other information on method section for details
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction products of 1,4-Benzenedimethanol and 1-naphthol
EC Number:
834-894-6
Cas Number:
113601-85-7
Molecular formula:
C10H8O to C82H64O5
IUPAC Name:
Reaction products of 1,4-Benzenedimethanol and 1-naphthol
Test material form:
solid
Details on test material:
Name: CAS 113601-85-7
Chemical name: 1,4-Benzenedimethanol, polymer with 1-naphthalenol
Batch/Lot number: 0950986
Description: Brown, solid
Purity: 100%
Expiry date: 08 February 2020
Storage conditions: Controlled room temperature (15-25°C ≤ 70% relative humidity)
Safety precautions: Routine safety precautions (gloves, goggles, face mask, lab coat) for unknown materials were applied to ensure personnel health and safety. Causes skin irritation and serious eye irritation.
Specific details on test material used for the study:
No further details specified in the study report

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
EXPERIMENTAL ANIMALS
Species and strain: New Zealand White rabbit
Source: S&K-LAP Kft.
2173 Kartal, Császár út 135, Hungary
Justification of strain: The New Zealand White rabbit is one of the standard strains used for acute irritation toxicity studies.
Animal health: Only animal in acceptable health condition was used for the test. Both eyes of animal provisionally selected for testing were examined prior to starting the study.
Number of animals: 3 animals
Age of animals at treatment: ~14-15 weeks old (young adult)
Sex: Male
Body weight at the
beginning of the in-life phase: 3756-3828 g
end of the in-life phase: 3822-3897 g
Date of receipt: 13 and 19 September 2012

Acclimatization time: At least 34 days
Animal identification: The individual identification was by engraved ear tag. The cage was marked with individual identity card with information about study code, sex, dosage, cage number and individual animal number.

HUSBANDRY
Animal health: Only healthy animals were used for the test. The veterinarian certified health status.
Number of animal room: 609
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature
during the in-life phase: 17.5 – 22.2°C
Relative humidity
during the in-life phase: 40 – 82 %
Housing/Enrichment: Rabbit was individually housed in AAALAC approved metal wire rabbit cages. Cage was of an open wire structure and cage was placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour.
The temperature and relative humidity values were measured continuously. The measured range was checked at least daily during the acclimatisation and experimental phases.
Variations from the target relative humidity (max. 82 %) were observed during the acclimation period. These deviations were considered to have no impact on the animal health, as certified by the Clinical Veterinarian, or on the outcome of the study and interpretation of the results.

FOOD AND FEEDING
Animals received diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum (Batch number: 0140 07 12 Expiry date: 25 October 2012,). The details of diets used will be archived with the raw data and are not reported.

WATER SUPPLY AND QUALITY CONTROL OF WATER
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system. The quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201
Veszprém, József A.u.36., Hungary). The quality control results are retained in the archives of CiToxLAB Hungary Ltd.

Test system

Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
A single volume of 0.1g of the solid test item SN-475N was administered to the animals.
Duration of treatment / exposure:
The treated eye was rinsed with physiological saline solution at 1 hour observation.
Observation period (in vivo):
72 hours
Duration of post- treatment incubation (in vitro):
Not applicable
Number of animals or in vitro replicates:
3 animals
Details on study design:
ADMINISTRATION OF THE TEST ITEM
Dosage
A single volume of 0.1g of the solid test item SN-475N was administered to the animals.

Application of the Test Item
Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals that had a normal eye condition and any with ocular lesions were rejected.
An initial test was performed using one animal. The test item was instilled into the conjunctival sac of the left eye. The eyelids were held closed for a few seconds to prevent the loss of the test item. The contra lateral eye served as the control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made according to the six point scale.
After consideration of the ocular responses produced in the first animal, one hour after the treatment of the first animal, two additional animals were treated.

Duration of Exposure
The treated eye was rinsed with physiological saline solution at 1 hour observation.

OBSERVATIONS AND SCORING
Clinical Observations
The eyes were examined at 1, 24, 48 and 72 hours after the application. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of ill-health during the study were recorded. At the end of the observation period, the animals were sacrificed by intramuscular injections of CP-Ketamin 10% and CP-Xylazin 2% followed by iv. Euthasol® 40% anaesthesia. Death was verified by checking pupil and corneal reflex and the absence of respiration.

Scoring and Assessment of Local Reaction
The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002)

Classification of the Test Items
Individual reactions of the animal were recorded at each observation time. The nature, severity and duration of all lesions observed were described.
Results were presented and interpreted according to Regulation (EC) No 1272/2008 and UN Globally Harmonised System of Classification and Labelling of Chemicals.

Measurement of Body Weight
Individual body weight was recorded at the beginning (the day of treatment) and end of the experiment.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Examination of eye-irritancy
The eyes were examined at 1, 24, 48 and 72 hours after the application.
Initial Pain Reaction (IPR) (score 2) was observed in two animals and (score 1) in one animal.
One hour after the application, conjunctival redness (score 2) was seen in all animals, conjuctival chemosis (score 2) was observed in one animal and (score 1) in two animals, discharge (score 2) was seen in all rabbits.
At 24 hours after treatment, conjunctival redness (score 2) was seen in all animals, discharge (score 1) was seen in one rabbit.
At 48 hours after treatment, conjunctival redness (score 1) was seen in all animals.
At 72 hours after treatment, no signs of eye irritation or other clinical signs were observed.
Other effects:
MORTALITY
There was no mortality observed during the study.

BODY WEIGHTS
The body weight and body weight change were considered to be normal with no indication of a treatment related effect.

CLINICAL OBSERVATION
General daily examination
There were no clinical signs observed that could be related to treatment.

Any other information on results incl. tables

Study Code: 12/356-005N

Species: NZW Rabbit

Dose: 0.1 g

Sex: Male

Start of Exposure: 23 October 2012

Test Item: SN-475N

 

Abbreviations:

R = Redness, OD = Opacity degree of density,

CH = Chemosis, OE = Extent of opaque area,

D = Discharge, IPR = Initial pain reaction

 

Time of Observation: Day 0

Time

Animal No.

Score of irritation

 

IPR

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

1 hour

2639

2

2

2

0

0

0

0

0

1

2646

2

1

2

0

0

0

0

0

2

2601

2

1

2

0

0

0

0

0

2

 

 Time of Observation: Day 1

Time

Animal No.

Score pf irritation

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

24 hours

2639

2

0

1

0

0

0

0

0

2646

2

0

0

0

0

0

0

0

2601

2

0

0

0

0

0

0

0

 

 Time of Observation: Day 2

Time

Animal No.

Score pf irritation

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

48 hours

2639

1

0

0

0

0

0

0

0

2646

1

0

0

0

0

0

0

0

2601

1

0

0

0

0

0

0

0

Time of Observation: Day 3

Time

Animal No.

Score pf irritation

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

72 hours

2639

0

0

0

0

0

0

0

0

2646

0

0

0

0

0

0

0

0

2601

0

0

0

0

0

0

0

0

 

 Mean Values of Eye Irritation (24, 48, 72 hour reading)

 

Study Code: 12/356-005N

Species: NZW Rabbit

Dose: 0.1 g

Sex: Male

Start of Exposure: 23 October 2012

Test Item: SN-475N

 

Animal Number

Sex

Cornea Opacity

Iris

Conjunctivae

Redness

Chemosis

Discharge

2639

Male

0.00

0.00

1.00

0.00

0.33

2646

Male

0.00

0.00

1.00

0.00

0.00

2601

Male

0.00

0.00

1.00

0.00

0.00

 

 Body Weight Data

 

Animal Number

At the beginning of experiment (Day of treatment) (g)

At the end of experiment (72 hours after treatment) (g)

Body weight gain (g)

2639

3787

3846

59

2646

3756

3822

66

2601

3828

3897

69

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item SN-475N (Batch No.: 90603), applied to rabbit eye mucosa, caused conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 72 hours. Not classified as eye irritant.
Executive summary:

An acute eye irritation study of the test item SN-475N was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A single volume of 0.1 g of the test item was administered as a single dose.

Individual body weight was recorded at the beginning (the day of treatment) and end of the experiment. Morbidity and clinical signs of toxicity were checked daily. The eyes were examined at 1, 24, 48 and 72 hours after the application.

Initial Pain Reaction (IPR) (score 2) was observed in two animals and (score 1) in one animal.

One hour after the application, conjunctival redness (score 2) was seen in all animals, conjuctival chemosis (score 2) was observed in one animal and (score 1) in two animals, discharge (score 2) was seen in all rabbits.

At 24 hours after treatment, conjunctival redness (score 2) was seen in all animals, discharge (score 1) was seen in one rabbit.

At 48 hours after treatment, conjunctival redness (score 1) was seen in all animals.

At 72 hours after treatment, no signs of eye irritation or other clinical signs were observed.

As all signs of eye irritation had fully reversed the study was terminated after a period of 72 hours observation.

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

The body weight of the treated rabbits was considered to be within the normal range of variability.

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

chemosis : 0.00, 0.00, 0.00

discharge : 0.33, 0.00, 0.00

redness : 1.00, 1.00, 1.00

cornea opacity : 0.00, 0.00, 0.00

iris : 0.00, 0.00, 0.00

The test item SN-475N (Batch No.: 90603), applied to rabbit eye mucosa, caused conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 72 hours.

According to Regulation (EC) No 1272/2008, SN-475N does not require classification as an eye irritant.

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, SN-475N does not require classification as an eye irritant.