Registration Dossier

Administrative data

Description of key information

SKIN
Not irritating, OECD 404, EU Method B.4, Pooles (2010)
EYE
Not irritating, OECD 405, EU Method B.5, Pooles (2010)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 October 2009 to 13 November 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Hillcrest, Belton, Loughborough, UK
- Weight at study initiation: 2.33 to 2.67 kg
- Housing: The animals were individually housed in suspended cages.
- Diet: Free access to food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study
- Water: Free access to mains drinking water was allowed throughout the study
- Acclimation period: an acclimatisation period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70% respectively
- Air changes (per hr): at least 15 air 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

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: tets material moistened with 0.5 mL distilled water to achieve a paste
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of test material
- Concentration: At each test site a quantity of 0.5 g of the test material, moistened sufficiently with 0.5 mL of distilled water to achieve a paste

Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 animals
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm cotton gauze
- Type of wrap if used: a strip of surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: four hours

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
erythema score
Remarks:
68623 Male
Basis:
mean
Time point:
other: mean score for 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
erythema score
Remarks:
68624 Male
Basis:
mean
Time point:
other: mean score for 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
erythema score
Remarks:
68663 Male
Basis:
mean
Time point:
other: mean score for 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
edema score
Remarks:
68623 male
Basis:
mean
Time point:
other: mean score for 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
edema score
Remarks:
68624 male
Basis:
mean
Time point:
other: mean score for 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
edema score
Remarks:
68663 Male
Basis:
mean
Time point:
other: mean score for 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritant / corrosive response data:
The individual scores for erythema/eschar and oedema are given in Table 1 (all tables are in the any other information on results section). Black staining of the fur was noted at all treated skin sites. No evidence of skin irritation was noted during the study.
Other effects:
Individual bodyweights and bodyweight changes are given in Table 2. All animals showed expected gain in bodyweight during the study.

Table 1: Individual Skin Reactions

Skin Reaction

Observation
(following patch removal)

Individual Scores – Rabbit Number and Sex

Total

68623Male

68624Male

68663Male

Erythema/Eschar Formation

Immediately

0STA

0STA

0STA

(0 )

1 Hour

0STA

0STA

0STA

( 0 )

24 Hours

0STA

0STA

0STA

0

48 Hours

0STA

0STA

0

( 0 )

72 Hours

0STA

0STA

0

0

Oedema Formation

Immediately

0

0

0

( 0 )

1 Hour

0

0

0

( 0 )

24 Hours

0

0

0

0

48 Hours

0

0

0

( 0 )

72 Hours

0

0

0

0

Sum of 24 and 72-hour Readings (S)       :          0

Primary Irritation Index (S/6)                   :          0/6 = 0.0

Classification                                        :          NON-IRRITANT

(   ) = Total values not used for calculation of primary irritation index

STA = Black staining of the fur

Table 2: Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 3

68623Male

2.33

2.43

0.10

68624Male

2.33

2.45

0.12

68663Male

2.67

2.84

0.17

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was not considered to be an irritant under the conditions of the study.
Executive summary:

The skin irritation potential of the test material was investigated in vivo in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 404 and EU Method B.4.

During the study no signs of skin irritation were noted at any of the observation points. The test material was therefore concluded to be a non-irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 November 2009 to 19 November 2009.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
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 (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Limited, Hillcrest, Belton, Loughborough, UK
- Weight at study initiation: 2.31 to 2.82 kg
- Housing: The animals were individually housed in suspended cages
- Diet: Free access to mains drinking water and food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water:Free access to mains drinking water was allowed throughout the study.
- Acclimation period: of at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70% respectively
- 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

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
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 32 mg
- Concentration (if solution): A volume of 0.1 mL of the test material, which was found to weigh approximately 32 mg

VEHICLE
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:
APPLICATION OF TEST SUBSTANCE:
Initially a single rabbit was treated with 0.1 mL (32 mg) of test material. The test material was administered 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 test material and then released. The left eye served as a control and remained untreated. Immediately after administration of the test material an assessment of the initial pain reaction was made. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

SCORING SYSTEM:
Assessment of ocular damage/irritation was made 1, 24, 48 and 72 hours post dosing using the scoring system from Draize JH (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 at this point along with any clinical signs of toxicity if present. Individual bodyweights were recorded on day 0 and 3. The numerical values corresponding to each animal, tissue and observation time were recorded. These scores were then assessed using a modified version of the system described by Kay JH and Calandra JC (1962), J. Soc. Cosmet. Chem. 13, 281-289. If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.

TOOL USED TO ASSESS SCORE:
Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
animal: 68633 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
80
Reversibility:
other: no effect
Irritation parameter:
cornea opacity score
Basis:
animal: 68650 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
80
Reversibility:
other: no effect
Irritation parameter:
cornea opacity score
Basis:
animal: 68672 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
80
Reversibility:
other: no effect
Irritation parameter:
iris score
Basis:
animal: 68633 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
10
Reversibility:
other: no effect
Irritation parameter:
iris score
Basis:
animal: 68650 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
10
Reversibility:
other: no effect
Irritation parameter:
iris score
Basis:
animal: 68672 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
10
Reversibility:
other: no effect
Irritation parameter:
conjunctivae score
Basis:
animal: 68633 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal: 68650 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal: 68672 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
20
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 (all tables are in the any other information on results section).
Black staining of the fur was noted around all treated eyes throughout the study.
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-hour observation. All treated eyes appeared normal at the 48-hour observation.
Other effects:
Individual bodyweights and bodyweight changes are given in Table 3. All animals showed expected gain in bodyweight during the study.

Table 1: Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex

68633 Male

68650 Male

68672 Male

IPR= 2

IPR= 2

IPR= 2

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

2

1

0

0

2

1

0

0

2

1

0

0

B = Chemosis

2

1

0

0

2

1

0

0

2

1

0

0

C = Discharge

1Sf

0Sf

0Sf

0Sf

1Sf

0Sf

0Sf

0Sf

1Sf

0Sf

0Sf

0Sf

Score (A + B + C) x 2

10

4

0

0

10

4

0

0

10

4

0

0

Total Score

10

4

0

0

10

4

0

0

10

4

0

0


IPR= Initial pain reaction

Sf = Black staining of the fur around treated eye

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

68633 Male

10

4

0

0

68650 Male

10

4

0

0

68672 Male

10

4

0

0

Group Total

30

12

0

0

Group Mean Score

10.0

4.0

0.0

0.0

Table 3: Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 3

68633Male

2.31

2.37

0.06

68650Male

2.82

2.85

0.03

68672Male

2.55

2.57

0.02

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study the test material was determined to be not irritating to eyes.
Executive summary:

The eye irritation potential of the test material was investigated in vivo in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 405 and EU Method B.5.

No corneal or iridial effects was 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-hour observation. All treated eyes appeared normal at the 48-hour observation.

Therefore, under the conditions of the study the test material was determined to be not irritating to eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

In vitro testing concluded that the test material was unlikely to be either corrosive to skin, or irritating to skin, following exposure. An in vivo test was subsequently performed to confirm findings of the in vitro studies.

The skin irritation potential of the test material was therefore investigated in vivo in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 404 and EU Method B.4.

During the study no signs of skin irritation were noted at any of the observation points. The test material was therefore concluded to be a non-irritant.

Eye

In vitro testing concluded that the test material was unlikely to be an eye irritant. An in vivo test was subsequently performed to confirm findings of the in vitro study.

The eye irritation potential of the test material was therefore investigated in vivo in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 405 and EU Method B.5.

No corneal or iridial effects was 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-hour observation. All treated eyes appeared normal at the 48-hour observation. Therefore, under the conditions of the study the test material was determined to be not irritating to eyes.

 


Justification for selection of skin irritation / corrosion endpoint:
The key study was selected as such because it represents the only available in vivo study.

Justification for selection of eye irritation endpoint:
The key study was selected as such because it represents the only available in vivo study.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to either skin or eye irritation.