Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 06 September 2005 and 29 September 2005.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

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)
Remarks:
Date of Inspection: 02/12/2002. Date of signature: 13/02/2003

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification : Barium di(bistridecylsulfosuccinate) in mixture with barium hydrogen phosphate
Description : colourless waxy solid block
Batch number : Y-T-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:
TEST ANIMALS
- Source: Three New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: At the start of the study the animals were in the weight range of 2.0 to 3.5 kg.
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water 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.
- Acclimation period: At least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature was set to achieve limits of 17 to 23°C
- Humidity (%): The relative humidity was set to achieve limits of 30 to 70%
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


IN-LIFE DATES: From: Day 1 To: Day 3

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):A volume of 0.1 ml of the test material, which was found to weigh approximately 96 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.
- Concentration (if solution): Not applicable.


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable.
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of treatment / exposure:
72 hours.
Observation period (in vivo):
72 hours.
Number of animals or in vitro replicates:
3.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not appicable.
- Time after start of exposure: Not applicable.

SCORING SYSTEM:
Immediately after administration of the test material, 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.


TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
: Redness
Basis:
mean
Remarks:
: Animal 105 (male)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Max score at 1 hour observation.
Irritation parameter:
conjunctivae score
Remarks:
: Redness
Basis:
mean
Remarks:
: Animal 59 (Female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
: Redness
Basis:
mean
Remarks:
: Animal 60 (Female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
: Chemosis
Basis:
mean
Remarks:
: Animal 105 (Male)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
: Chemosis
Basis:
mean
Remarks:
: Animal 59 (Female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
: Chemosis
Basis:
mean
Remarks:
: Animal 60 (Female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
: Animal 105 (male)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
: Animal 59 (Female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
: Animal 60 (Female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Remarks:
: Animal 105 (male)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Remarks:
: Animal 59 (female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Remarks:
: Animal 60 (Female)
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
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.
Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and in two treated eyes at the 24-hour observation.
One treated eye appeared normal at the 24-hour observation and the remaining two treated eyes appeared normal at the 48-hour observation.
Other effects:
None.

Any other information on results incl. tables

Table 1               Individual Scores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex

105 Male

59 Female

60 Female

IPR= 1

IPR = 1

IPR = 1

Time After Treatment

1

Hour

24

Hours

48

Hours

72

Hours

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

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

1

0

0

0

1

1

0

0

1

1

0

0

B = Chemosis

0

0

0

0

0

0

0

0

0

0

0

0

C = Discharge

0

0

0

0

0

0

0

0

0

0

0

0

Score (A + B + C) x 2

2

0

0

0

2

2

0

0

2

2

0

0

Total Score

2

0

0

0

2

2

0

0

2

2

0

0


IPR= Initial pain reaction

Table 2               Individual Total Scores and Group Mean Scoresfor Ocular Irritation

Rabbit Number

and Sex

Individual Total Scores At:

1 Hour

24 Hours

48 Hours

72 Hours

105 Male

2

0

0

0

59 Female

2

2

0

0

60 Female

2

2

0

0

Group Total

6

4

0

0

Group Mean Score

2.0

1.3

0.0

0.0

The test material did not meet the criteria for classification as an eye irritant according to EU classification and labelling regulations (Council Directive 67/548/EEC - Dangerous Substances Directive).

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material did not meet the criteria for classification as an eye irritant according toEU classification and labelling regulations (Council Directive 67/548/EEC - Dangerous Substances Directive).
Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

§        Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 2004/73/EC

Result. 

A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. One treated eye appeared normal at the 24-hour observation and the remaining two treated eyes appeared normal at the 48-hour observation.

Conclusion. 

The test material produced a maximum group mean score of 2.0 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 an eye irritant according to EU classification and labelling regulations (Council Directive 67/548/EEC - Dangerous Substances Directive).