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Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 07 December 2009 to 17 December 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 April 2002
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
No. 440/2008
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-benzylidenedianiline
EC Number:
210-038-1
EC Name:
4,4'-benzylidenedianiline
Cas Number:
603-40-7
Molecular formula:
C19H18N2
IUPAC Name:
4-[(4-aminophenyl)(phenyl)methyl]aniline
Test material form:
solid
Details on test material:
Identification: DATIPH
Physical form: Solid
Solubility in water: < 1 g/L
Colour: yellow brown
CAS no.: 603-40-7
Chemical name: 4,4’-Benzylidenedianiline
Molecular formula: C19H18N2
Test substance storage: At room temperature protected from light
Stability: Stable under storage conditions
Expiry date: 31 October 2010
Specific details on test material used for the study:
- Source: Sponsor's identification DATIPH
- Description: brown solid lumps
- Date received: 09 November 2009
- Storage conditions: approximately 4°C in the dark

The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility of the Sponsor.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For the purpose of the study the test material was ground to a powder prior to application.
- The pH of the test material was determined prior to commencement of the study and found to be as follows:
Preparation: 10% w/w aqueous preparation of the test material
pH Measurement: immediately - 8.9; after 10 minutes - 9.4; after 20 minutes - 9.5

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Remarks:
Sex: Male
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: twelve to twenty weeks old
- Weight at study initiation: 2.38 or 2.81 kg
- Housing: individual housing in suspended cages
- Diet (e.g. ad libitum): Free access throughout the study (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK)
- Water (e.g. ad libitum): Free access throughout the study (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 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:
water
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml of the test material (approximately 67 mg)
Observation period (in vivo):
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 Table 2 (below), (from Draize J H (1977) "Dermal and Eye Toxicity Tests" ln: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).
Number of animals or in vitro replicates:
2
Details on study design:
A volume of 0.1 ml of the test material, which was found to weigh approximately 67 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 material, and then released. The left eye remained untreated and was used for control purposes.

SCORING SYSTEM: lmmediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale (see Table 1 below).
TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

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 = Dx5
Score for cornea = (Ex F) x 5

Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C (1962), J. Soc. Cosmet. Chem. 13, 281-289 was used to classify the ocular irritancy potential of the test material (see Table 3 below). 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 material.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 1h, 24h, 48h, 72h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1h
Score:
8
Max. score:
20
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
20
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1h
Score:
8
Max. score:
20
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
20
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 1h
Score:
8
Max. score:
110
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
110
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
110
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
110
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
other: 1h
Score:
8
Max. score:
110
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
110
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
110
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
110
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in the treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. Treated eyes appeared normal at the 48-hour observation.
Other effects:
All animals showed expected gain in bodyweight during the study (see Table 4 below).

Any other information on results incl. tables

Table 4. Individual bodyweights and bodyweight changes

Rabbit Number and Sex

lndividual Bodyweight (kg)

 

Bodyweight Change (kg)

Day 0

Day 3

 

68712 Male

 

2.81

 

2.89

 

0.08

 

68730 Male

 

2.38

 

2.42

 

0.04

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
The test material did not meet the criteria for classification as eye irritant according to EU labelling regulations (EC) No 440/2008.
Executive summary:

The study was performed ta assess the irritancy potential of the test material to the eye of the New Zealand White rabbit following the OECD guideline 405 and the Method B5 of (EC) No.440/2008 regulation.

A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Treated eyes appeared normal at the 48-hour observation. The test material produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as eye irritant according to EU labelling regulations (EC) No 440/2008.