Registration Dossier

Administrative data

Description of key information

No irritant effects to rabbit skin were observed in a study conducted according to current OECD guideline and under GLP (BSL Bioservice, 2013a).

No irritant effects to rabbit eyes were observed in a study conducted according to current OECD guideline and under GLP (BSL Bioservice, 2013b).

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:
2012-10-21 to 2012-10-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: 21-22 weeks old
- Weight at study initiation: >2kg
- Housing: plastic rabbit cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: left side on the dorsal area
- Type of wrap if used: the test item was applied to a gauze patch, which was applied to the skin and held in place with non-irritating tape. The patch was fixed with semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not stated


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Initial test in animal no. 1: no signs of irritation were seen immediately after the patch removal. Examination of the test site 1 hour after patch removal revealed erythema grade 1 which was fully reversible within 24 hours after the patch removal. No irritant or corrosive effects were observed on the intact skin of the two further female rabbits (strain NZW) of the main test after a contact time of 4 hours.

Under the conditions of the present study, the single dermal application of the test item F-D3 to three rabbits at a dose of 0.5 g showed irritant but no corrosive effects in animal no.1 which were fully reversible within 24 hours. Neither mortalities nor significant clinical signs of toxicity were observed.

Table: Dermal Irritation Evaluation

Animal
No.

Application
Site

Irritation (hours after patch removal)

1 hour

24 hours

48 hours

72 hours

T

C

T

C

T

C

T

C

1

Erythema

1

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

2

Erythema

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

3

Erythema

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

T = test item;       C = control;        0 – 3 = grade

Table: Individual Data

Individual Systemic and Local Findings - Animal No. 1

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

nsf

-

48 hours

nsf

nsf

-

72 hours

nsf

nsf

-

Individual Systemic and Local Findings - Animal No. 2

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

nsf

-

48 hours

nsf

nsf

-

72 hours

nsf

nsf

-

Individual Systemic and Local Findings - Animal No. 3

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

nsf

-

48 hours

nsf

nsf

-

72 hours

nsf

nsf

-

nsf = no specific findings

Table: Absolute Body Weights in kg

 

Animal No. 1

Animal No. 2

Animal No. 3

Start of Study
(weight in kg)

4.4

4.2

3.1

End of Study
(weight in kg)

4.4

4.2

3.2

Interpretation of results:
GHS criteria not met
Conclusions:
No irritant effects to rabbit skin were observed in a study conducted according to current OECD guideline and under GLP.
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:
2012-10-29 to 2012-11-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: ca. 14 weeks old
- Weight at study initiation: >2kg
- Housing: plastic rabbit cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml


The test item was gently warmed in a water bath at 32 °C for liquid application.

Duration of treatment / exposure:
single instillation,
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
The test item was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second in order to prevent loss of the material. The untreated contralateral eye served as control.
The treated eye was not rinsed 24 hours after the application.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
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
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
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
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
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
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
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
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
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
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
After the application into the eyes of three female NZW rabbits the test item produced slightly irritant but no corrosive effects.
Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal.
Conjunctival redness and discharge were observed in all animals.
Other effects:
Neither mortalities nor significant clinical signs of toxicity were observed.

Table:  Eye Irritation Scores – Animal No. 1

Animal No. 1

Single Data

 

Time Post-Application

Average Score
(24, 48 and 72 hours)

1 hour

24 hours

48 hours

72 hours

T/C

T/C

T/C

T/C

Conjunctival Redness

1/0

1/0

1/0

0/0

0.67

Conjunctival Chemosis

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Cornea

0/0

0/0

0/0

0/0

0

T =test item,     C = control

Table:  Eye Irritation Scores – Animal No. 2

Animal No. 2

Single Data

 

Time Post-Application

Average Score
(24, 48 and 72 hours)

1 hour

24 hours

48 hours

72 hours

T/C

T/C

T/C

T/C

Conjunctival Redness

1/0

1/0

1/0

0/0

0.67

Conjunctival Chemosis

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Cornea

0/0

0/0

0/0

0/0

0

T =test item,     C = control

 

Table:  Eye Irritation Scores – Animal No. 3

Animal No. 3

Single Data

 

Time Post-Application

Average Score

(24, 48 and 72 hours)

1 hour

24 hours

48 hours

72 hours

T/C

T/C

T/C

T/C

Conjunctival Redness

1/0

1/0

1/0

0/0

0.67

Conjunctival Chemosis

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Cornea

0/0

0/0

0/0

0/0

0

T =test item,     C = control

Table:  Clinical Signs of Toxicity

Animal No. 1

Time after
Test Item Application

Systemic Findings

Local Findings
(apart from findings in Table 3)

1 hour

nsf

discharge grade 1

24 hours

nsf

nsf

48 hours

nsf

nsf

72 hours

nsf

nsf

Animal No. 2

Time after
Test Item Application

Systemic Findings

Local Findings
(apart from findings in Table 4)

1 hour

nsf

discharge grade 2

24 hours

nsf

discharge grade 1

48 hours

nsf

nsf

72 hours

nsf

nsf

Animal No. 3

Time after
Test Item Application

Systemic Findings

Local Findings
(apart from findings in Table 5)

1 hour

nsf

discharge grade 2

24 hours

nsf

nsf

48 hours

nsf

nsf

72 hours

nsf

nsf

nsf: no specific findings

Table:  Absolute Body Weights in kg

 

Animal No. 1

Animal No. 2

Animal No. 3

Start of Study
(weight in kg)

3.1

3.1

3.0

End of Study
(weight in kg)

3.2

3.2

3.1

Interpretation of results:
GHS criteria not met
Conclusions:
No irritant effects to rabbit eyes were observed in a study conducted according to current OECD guideline and under GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for skin irritation found the test material not irritating to the skin of rabbits, conducted according to OECD guideline and under GLP (BSL Biosevice 2013a). Mild irritant effects were present in one animal, which were fully reversible within 24 hours. Neither mortalities nor significant clinical signs of toxicity were observed.

The key study for eye irritation, conducted according to OECD guideline and under GLP, found the test material not irritating to the eyes of rabbits (BSL Bioservice 2013b). There were no ocular symptoms following application.

Justification for classification or non-classification

Based on the available information, no classification is proposed for skin or eye irritation in accordance with Regulation (EC) No 1272/2008.