Registration Dossier

Administrative data

Description of key information

Skin Irritation
Key (EC 613 -848 -7), Sanders, 2013, Skin irritation - not irritating
Supporting (EC 234-392-1), Clouzeau, 1990, Skin irritation – not irritating
Supporting (CAS 68424-31-7), Robinson, 1991 Skin irritation – not irritating

Eye Irritation
Key (EC 613 -848 -7), Sanders, 2013, Eye irritation - not irritating
Supporting (EC 234-392-1), Clouzeau, 1990, Eye irritation – not irritating
Supporting (CAS 68424-31-7), Robinson, 1991, Eye irritation – not irritating


Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-05-21 to 2013-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.26-2.33 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2013-05-21 To: 2013-05-24
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Test item was used as supplied (undiluted)
- pH of the undiluted test item: 6.0
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 h
Observation period:
Immediately following removal of the patches and approximately 1, 24, 48 and 72 h later, the sites were examined for evidence of primary irritation.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: On the day of the test a suitable site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch.
- Type of wrap if used: Treatment site was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing: Four hours after application the corset and patches were removed from animals and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize method
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 Hours
Score:
0.22
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Very slight erythema was noted at two treated skin sites 1 and 24 h after patch removal.
No evidence of skin irritation was noted at one treated skin site during the study.
Other effects:
All animals showed expected gain in body weight during the study.

Table 7.3.1/1: Individual Skin Reactions

Skin Reaction

Observation Time

(following patch

removal)

Individual Scores – Rabbit Number and Sex

73197 Male

73198 Male

73199 Male

Erythema/Eschar

Formation

Immediately

0

0

0

1 h

0

1

1

24 h

0

1

1

48 h

0

0

0

72 h

0

0

0

Mean (24, 48 and 72 h)

0.0

0.3

0.3

Oedema

Formation

Immediately

0

0

0

1 h

0

0

0

24 h

0

0

0

48 h

0

0

0

72 h

0

0

0

Mean (24, 48 and 72 h)

0.0

0.0

0.0

Individual body weights and body weight change:

Rabbit Number

Individual body weight (kg)

Body weight change (kg)

Day 0

Day 3

73197

2.33

2.40

0.07

73198

2.27

2.29

0.02

73199

2.26

2.29

0.03

Interpretation of results:
not irritating
Conclusions:
Under the test conditions the substance is not classified as irritating to skin according to the criteria of CLP Regulation (EC) No. 1272/2008.
Executive summary:

Test Guidance

OECD guideline 404 and EC Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion).

Method and materials

Three New Zealand White male rabbits were dermally exposed to 0.5 mL of the test material for 4 h under a semi-occlusive dressing. After removal of the residual test item, irritation was scored immediately following removal of the patches and approximately 1, 24, 48 and 72 h later, according to Draize method.

Results

Very slight erythema was noted at two treated skin sites 1 and 24 h after patch removal. No evidence of skin irritation was noted at one treated skin site during the study. All animals showed expected gain in body weight during the study. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.3, 0.3 for erythema and 0.0, 0.0, 0.0 for oedema score, respectively. The mean erythema and oedema scores at 24, 48 and 72 h were 0.22 and 0.0 respectively. The substance is not a skin irritant in male rabbits.

Conclusion

Under the test conditions the substance is not classified as irritating to skin according to CLP Regulation (EC) No. 1272/2008.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions Lack of details in study documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Lack of details in study documentation
Principles of method if other than guideline:
Application of 0.5 ml to an area of approx. 2.5 cm x 2.5 cm.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No Data
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
- Concentration (if solution): No Data
Duration of treatment / exposure:
4 h
Observation period:
12 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm² on the shorn left flank (dorso-lumbar region)
- Type of wrap if used: semi-occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water upon the removal of the dressing
- Time after start of exposure:4 h


SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of animal #15 and readings at
Time point:
other: 24 h, 48 h and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 12 d
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of animal #16 and readings at
Time point:
other: 24 h, 48 h and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 11 d
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of animal #17 and readings at
Time point:
other: 24 h, 48 h and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
mean
Remarks:
of animal #15 and readings at
Time point:
other: 24 h, 48 h and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
mean
Remarks:
of animal #16 and readings at
Time point:
other: 24 h, 48 h and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
mean
Remarks:
of animal #17 and readings at
Time point:
other: 24 h, 48 h and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
Following the single 4-hour application, a very slight to well-defined erythema and very slight to slight oedema were observed. This regressed and no signs of erythema or oedema were evident eleven or twelve days after application. Slight desquamation at the application site of one animal was observed seven days after application.

Erythema score

Animal Number

1 h

24 h

48 h

72 h

7 days

11 days

12 days

Mean Score

15

2

-

1

1

1

 

0

1.0

16

2

2

1

1

1

0

 

1.3

17

1

2

1

1

0

 

 

1.3

 

Edema Score

Animal Number

1 h

24 h

48 h

72 h

7 days

11 days

12 days

Mean Score

15

1

-

1

1

0

 

0

1.0

16

2

2

2

1

0

0

 

1.7

17

1

2

2

1

0

 

 

1.7

Conclusion: The test substance does not have to be classified as irritant to the skin according to the criteria of the DSD and CLP regulations under the conditions of this study.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
November 13th, 1990 - November 16th, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: Lack of details on test substance
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elvage Cunicole du Val de Selle, France
- Weight at study initiation: 2.3 kg
- Diet: ad libitum; Rabbit substance ref. 112 C
- Water: ad libitum
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 h
Observation period:
3 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm², flanks were clipped a day before treatment
- Type of wrap if used: adhesive hypoallergic aerated semi-occlusive dressing (Laboratories de Pansements et d´Hygiène, France)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No


SCORING SYSTEM:According to Draize
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: no cutaneous effects observed
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: no cutaneous effects observed

Erythema score

Animal Number

1 h

24 h

48 h

72 h

O1

0

0

0

0

O2

0

0

0

0

O3

0

0

0

0

 

Edema Score

Animal Number

1 h

24 h

48 h

72 h

O1

0

0

0

0

O2

0

0

0

0

O3

0

0

0

0

 

No cutaneous reactions were observed in all the animals.

Interpretation of results:
not irritating
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: analogue substance
Justification for type of information:
Skin irritation in vivo does not need to be investigated because available data indicate that structural variation does not influence test results or adverse effect profile (see read-across and category justifications attached in Section 13).
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-05-28 to 2013-06-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Principles of method if other than guideline:
Not applicable
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 UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.37-2.70 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2013-05-28 To: 2013-06-20
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Test item was used as supplied (undiluted)
- pH of undiluted test item: 6.0
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:
Eyes were not rinsed throughout study
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 h following treatment.
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Draize method

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:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
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 h observation.
- All treated eyes appeared normal at the 48 h observation.
Other effects:
One animal showed body weight loss, one animal showed no gain in body weight and the remaining animal showed expected gain in body weight during the study.

Results table is attached.

Interpretation of results:
not irritating
Conclusions:
Under the test conditions the substance is not classified as irritating to eyes according to the criteria of CLP Regulation (EC) No. 1272/2008.
Executive summary:

Test Guidance

OECD guideline 405 and EC Method B.5 (Acute Toxicity: Eye Irritation / Corrosion).

Method and materials

Three New Zealand White male rabbits were exposed to 0.1 mL of test item in the right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for one second before releasing. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method.

Results

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 h observation. All treated eyes appeared normal at the 48 h observation. One animal showed body weight loss, one animal showed no gain in body weight and the remaining animal showed expected gain in body weight during the study. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.0, 0.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 0.3, 0.3, 0.3 for conjunctivae score and 0.3, 0.3, 0.3 for chemosis score. In this study, the test substance is not an eye irritant in male rabbits.

Conclusion

Under the test conditions, the substance is not classified as irritating to eyes according to CLP Regulation (EC) No. 1272/2008.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation Basic data given
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: Only basic data given
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 3556-4556 g

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): pure

Duration of treatment / exposure:
No Data
Observation period (in vivo):
3 d
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
2
Reversibility:
other: No effects
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
3
Reversibility:
other: No effects
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all three animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects

No corneal or iridial effects were observed. Conjunctival effects included slight redness (one animal) and slight discharge (one animal) were transiently seen approx. one hour after dosing.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
November 20th, 1990 - November 23th, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD) Limited details on test substance
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: Limited details on test substance
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole du Val de Selle
- Weight at study initiation: 2.6 kg
- Housing: individually
- Diet: ad libitum; Rabbits substance ref. 112 C
- Water: ad libitum
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:
single dose, no rinsing
Observation period (in vivo):
3 d
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: according to 84/499/EEC appendix V B5

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects

Animal

Hours after application

1

24

48

72

A

B

C

D

E

A

B

C

D

E

A

B

C

D

E

A

B

C

D

E

01

0

0

0

0

1

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

02

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

03

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

A = Cornea Score

B = Iris Score

C = Erythema Score

D = Chemosis Score

E = Exsudation Score

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: analogue substance
Justification for type of information:
Eye irritation in vivo does not need to be investigated because available data indicate that structural variation does not influence test results or adverse effect profile (see read-across and category justifications attached in Section 13).
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no specific data on the substance. Read-across to the properties of Hexanoic acid, 3,5,5-trimethyl-, 1,1'-[2-ethyl-2-[[(3,5,5-trimethyl-1-oxohexyl)oxy]methyl]-1,3-propanediyl] ester (EC 613-848-7, CAS65870-94-2),Fatty acid polyols (Fatty acids, C5-9, esters with pentaerythritol (EC 270-290-3, CAS 68424-30-6) and Decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate (EC 234-392-1, CAS 11138-60-6)) and their analogues is applicable based on the similarity in structure and physico-chemical properties. The justification for read-across is presented in Section 13 Assessment reports- Read-across justification.

Skin Irritation

One reliable study is available. In this study (Sanders, 2013) performed under GLP according to OECD TG 404 and EC Method B.4, three male New Zealand White rabbits were exposed to 0.5 mL of the analogue substance (EC 613 -848 -7) for 4 hours under semi-occlusive conditions. After removal of the residual test item, irritation was scored immediately following removal of the patches and approximately 1, 24, 48 and 72 h later, according to Draize method. Very slight erythema was noted at two treated skin sites 1 and 24 h after patch removal. No evidence of skin irritation was noted at one treated skin site during the study. All animals showed expected gain in body weight during the study. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.3, 0.3 for erythema and 0.0, 0.0, 0.0 for oedema score, respectively. The mean erythema and oedema scores at 24, 48 and 72 h were 0.22 and 0.0 respectively. The substance is not a skin irritant in male rabbits.

 

In a supporting study, 2,2-bis[(octanoyloxy)methyl]butyl decanoate (EC 234 -392 -1) was tested for its skin irritation potential according to OECD Guideline 404 (Clouzeau, 1990): The shaved back of three New Zealand White rabbits was exposed to 0.5 mL test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 3 d after exposure and skin reactions were assessed using the Draize scheme periodically (24, 48 and 72 hours) after removal of the test substance. No cutaneous reactions were observed in any of the tested animals at any observation interval.

Furthermore, the result of an acute dermal toxicity study on CAS 131459-39-7 which was conducted according to OECD 402 (Allen, 1999) can be used for risk evaluation of the irritation potential and supports the view that a non-classification of fatty acid polyol esters with short chain length of the fatty acids is warranted for skin irritation. This fatty acid polyol is composed of C5 -C9 fatty acids with pentaerythritol. A single dose of 2000 mg/kg bw of the test material was applied on the shaved skin of five Sprague-Dawley rats for 24 h under semiocclusive conditions and, in addition to mortality and systemic effects, the skin reactions were observed for up to 14 days after exposure. None of the animals showed any signs of skin reaction (erythema/edema/scale) after exposure to this limit dose.

Eye Irritation

One reliable study is available. In this study (Sanders, 2013) performed under GLP according to OCED TG 405 and EC Method B.5, three male New Zealand White rabbits were exposed to 0.1 mL of the analogue substance (EC 613 -848 -7) in the right eye while the left eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method. 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 h observation. All treated eyes appeared normal at the 48 h observation. One animal showed body weight loss, one animal showed no gain in body weight and the remaining animal showed expected gain in body weight during the study. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.0, 0.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 0.3, 0.3, 0.3 for conjunctivae score and 0.3, 0.3, 0.3 for chemosis score. In this study, the substance is not an eye irritant in male rabbits.

 

In a supporting study, 2,2-bis[(octanoyloxy)methyl]butyl decanoate (EC 234 -392 -1) was tested for its eye irritation potential according to OECD Guideline 405 (Clouzeau, 1990): 0.1 mL of the test material were instilled into the conjunctival sac of one eye of three New Zealand White rabbits. Animals were observed for 72 hours and observed effects were scored 24, 48 and 72 hours after instillation according to 84/499/EEC appendix V B5 (Draize). No effects, except for one animal with a very slight exudation reaction at the 24 h time point, were observed in any of the tested animals at any relevant observation interval.

Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7) were tested for eye irritation potential according to OECD Guideline 405 (Robinson, 1991): 0.1 mL of the test material was instilled into the conjunctival sac of one eye of three New Zealand White rabbits. Animals were observed for 72 hours. Irritation was scored 24, 48 and 72 hours after instillation according to the method of Draize. No corneal or iridial effects were observed. Conjunctival effects included slight redness (one animal) and slight discharge (one animal) were transiently seen approx. one hour after dosing but were completely reversible within the first 24 h.


Justification for classification or non-classification

According to the CLP criteria for classification and labelling the analogue test items are not classified as skin or eye irritants.