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Diss Factsheets

Administrative data

Description of key information

Skin, rabbit (read-across OECD 404): not irritating

Eye, rabbit (read-across OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
25 Feb - 04 Mar 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
lack of test material details, occlusive dressing
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
RL 79/831/EWG
Deviations:
yes
Remarks:
lack of test material details, occlusive dressing
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Council Regulation (EC) No 440/2008 of 30 May 2008
Deviations:
yes
Remarks:
lack of test material details, occlusive dressing
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Weight at study initiation: 3738 g
- Housing: animals were housed individually in cages (Heinkel, Kuchen, Germany)
- Diet: Altromin-Haltungsdiät 2023 (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 month

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 45-50
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:
4 h
Observation period:
14 days
Reading time points: 1, 24, 48 and 72 h and 6 days
Number of animals:
5
Details on study design:
TEST SITE
- Area of exposure: 6.25 cm² on the dorsal area of the trunk
- Type of wrap if used: The treated skin was covered with a gauze patch and covered with plastic strip and hold in place with an adhesive plaster and an acrylastic bandage.

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema 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:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 5 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No edema formation was observed in any animal at any reading time point during the study period. 1/5 animals showed a slight erythema at the 24 h reading time point and one animal at the 48 h reading time point which were both fully reversible within 48 and 72 h, respectively. 1/5 animals showed a well defined erythema at the 24 h reading time point, after 48 h only a slight erythema was visible and was fully reversible within 6 days.
Other effects:
No effects on bodywheight were observed.

Table 1. Results of skin irritation study.

Observation time

Rabbit no.
1 2 3 4 5
Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema
1 h 0 0 0 0 0 0 0 0 0 0
24 h 0 0 0 0 1 0 2 0 0 0
48 h 1 0 0 0 0 0 1 0 0 0
72 h 0 0 0 0 0 0 1 0 0 0

Mean value 24 + 48 + 72 h

 0.33 0.00 0.00 0.00 0.33 0.00 1.33 0.00 0.00 0.00
Mean value 24 + 48 + 72 h all animals 0.40 0.00                
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Limited data on test material and test animals.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted: 17 Jul 1992
Deviations:
yes
Remarks:
limited data on test material and test animals
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted: 28 Jul 2015
Deviations:
yes
Remarks:
limited data on test material and test animals
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not required
Duration of treatment / exposure:
Not reported
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3
Details on study design:
SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
At the 1 h reading time point, very slight erythema (score 1) and no edema were observed in all 3 animals.
No skin reactions were observed at the 24, 48 and 72 h readings.
Other effects:
No further local or systemic effects were reported.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
7 Jun - 10 Jun 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Purity of test substance is not specified.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
purity of test substance not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.24-2.42 kg
- Housing: individually in suspended metal cages
- Diet: rabbit diet (Preston Farmers Ltd., Lincolnshire, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-20
- Humidity (%): 64-68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated sites of the same animals served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 24, 48 and 72 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm gauze patch on the back of each rabbit
- Type of wrap if used: the treated skin was covered with surgical adhesive tape (BLENDERM), the trunk of rabbits was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing: residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No skin reactions were observed during the study period in any animal.
Other effects:
No other local or systemic effects were observed in the study.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
National guideline study
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology", FDA, according to Draize (1959)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.4-2.6 kg
- Housing: individually caged
- Diet: standard diet (Höing 222), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 days
Reading time points: 1, 2, 8, 24, 48 and 72 h and 4, 5, 6 and 7 days
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 4 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritant / corrosive response data:
Within the first 1, 2 and 8 h post-instillation, no corneal opacity and no iritis were observed. At this time points, slight to moderate conjunctival redness and moderate to strong chemosis and discharge were seen in all animals.
Corneal opacity was observed in 2/6 animals and was fully reversible within 48 h and 72 h, respectively.
No effects on the iris were observed in any animal at any time point.
Slight to moderate conjunctival redness was observed in all animals 24 h post-instillation. Effects were fully reversible within 48 h (2 animals), 72 h (1 animal) or 5 days (3 animals).
Slight to strong discharge was observed in all animals 24 h post-instillation. Effects were fully reversible within 72 h (5 animals) or 4 days (1 animal).
Other effects:
No further local or systemic effects were reported.

Table 1. Results of eye irritation study.

Rabbit #

Time [h]

conjunctivae

iris

cornea

redness

swelling

1

1

1

2

0

0

24

2

1

0

0

48

2

1

0

0

72

1

1

0

0

average

1.7

1.0

0.0

0.0

2

1

1

2

0

0

24

2

1

0

0

48

1

1

0

0

72

1

1

0

0

average

1.3

1.0

0.0

0.0

3

1

1

2

0

0

24

2

2

0

0

48

1

1

0

0

72

0

0

0

0

average

1.0

1.0

0.0

0.0

4

1

1

3

0

0

24

1

1

0

0

48

0

0

0

0

72

0

0

0

0

average

0.3

0.3

0.0

0.0

5

1

1

2

0

0

24

2

1

0

1

48

2

1

0

1

72

2

1

0

1

average

2.0

1.0

0.0

1.0

6

1

2

2

0

0

24

2

2

0

1

48

2

2

0

1

72

1

1

0

0

average

1.7

1.7

0.0

0.7

 

 

Time [h]

conjunctivae

iris 

cornea

redness

swelling

average
score

1

1.17

2.17

0.00

0.00

24

1.83

1.33

0.00

0.33

48

1.33

1.00

0.00

0.33

72

0.83

0.67

0.00

0.17

24+48+72

1.33

1.00

0.00

0.28
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Basic data given. Limited data on test material and test animals.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted: 24 Feb 1987
Deviations:
yes
Remarks:
limited data on test material and test animals
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted: 9 Oct 2017
Deviations:
yes
Remarks:
limited data on test material and test animals
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
not specified
Controls:
not specified
Duration of treatment / exposure:
Not reported
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
No corneal opacity, iritis or chemosis were observed at any reading time point in any animal.
Very slight discharge was observed on 2 animals at the 1 h reading.
Moderate conjunctival redness was observed in all 3 animals at the 1 h reading, decreasing to slight in 2 animals at 24 h and to very slight in all 3 animals at 48 h. No effects were observed at 72 h.
Other effects:
No further local or systemic effects were reported.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
5 Jul - 9 Jul 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Lack on test material details.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
yes
Remarks:
lack on test material details.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.76-3.34 kg
- Housing: individually in suspended metal cages
- Diet: Rabbit Diet (Preston Farmers Ltd., Lincolnshire, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18
- Humidity (%): 65-75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
4 females and 2 males
Details on study design:
SCORING SYSTEM: Draize scoring system modified version by Kay and Calandra

TOOL USED TO ASSESS SCORE: standard ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all 6 animals
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:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
- Cornea: no adverse corneal effects were noted in any animal.
- Iris: 1 h after treatment iridial inflammation in 1/6 animals were observed. 24, 48 and 72 h no iridial effects were observed in any animal.
- Conjunctivae: mild to moderate conjunctivae effects were apparent in 6/6 animals 1 h after instillation. In 1/6 animals mild conjunctivae redness and chemosis was still apparent after 24 h being reversible after 48 h. In the remaining 5/6 animals conjunctivae irritation was fully reversible within 24 h.
Other effects:
No further local or system effects were reported.

Table 1. Results of eye irritation study

Rabbit #

Time [h]

conjunctivae

 

iris

cornea

redness

chemosis

1

1

2

2

1

0

24

1

1

0

0

48

0

0

0

0

72

0

0

0

0

average

0.33

0.33

0

0

2

1

1

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

3

1

1

1

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

4

1

1

1

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

5

1

2

1

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

6

1

2

1

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

 

 

Time [h]

conjunctivae

 

iris

cornea

 

redness

swelling

 

 

average
score

1

1.50

1.00

0

0

24

0.17

0.17

0

0

48

0

0

0

0

72

0

0

0

0

24+48+72

0.06

0.06

0

0
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

No data on the skin and eye irritation of Dodecanoic acid, ester with 1,2,3-propanetriol (CAS 37318-95-9) are available. The assessment was therefore based on studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation in animals

CAS 91845-19-1

A skin irritation study was conducted with Glycerides, C16-18 and C18-hydroxy mono- and di- according to EU method B.4 and in compliance with GLP (WoE, 1985). The undiluted test substance (0.5 g) was applied for 4 h to the shaved skin of 5 New Zealand White rabbits under occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h as well as 6 days after removal of the dressing. At the 24 and 48 h reading time points, 1/5 animals showed a slight erythema (score 1), which was fully reversible within 48 and 72 h, respectively. In 1/5 animals, well-defined erythema (score 2) was observed at the 24-h reading time point, which decreased to slight erythema (score 1) at the 48-h reading time point and was fully reversible within the 6-day observation period. No edema formation was observed in the animals at any reading time point during the study period. No signs of systemic toxicity and no effects on body weights were observed in the animals. The mean erythema scores over the 24, 48 and 72 h reading time points were 0.33, 0, 0.33, 1.33 and 0 for the 5 animals, respectively. Edema scores were 0 for all reading time points in all animals. Therefore, the test substance is considered to be non-irritating to the skin.

CAS 538-24-9

The skin irritation potential of Glycerol trilaurate was investigated in a study performed according to OECD guideline 404 (WoE, 1998). The test substance was applied to the skin of 3 New Zealand White rabbits and the scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. Very slight erythema (score 1) was observed in all 3 animals 1 h after patch removal, which were fully reversible at the 24-h reading time point. No further skin reactions were noted in any animal at any other reading time point. No further local or systemic effects were reported. The mean erythema and edema scores after over the 24, 48 and 72 h reading time points were 0 for the 3 animals, respectively. Therefore, the test substance is considered to be non-irritating to the skin.

CAS 73398-61-5

The skin irritation potential of Triglycerides, mixed decanoyl and octanoyl was investigated in a study according to OECD guideline 404 (WoE, 1988). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved skin of 6 New Zealand White rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24, 48 and 72 h after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation time points. No signs of systemic toxicity were seen. The mean erythema and edema scores over the 24-, 48- and 72-h reading time points were 0 for all 6 animals. Therefore, the test substance is considered to be non-irritating to the skin.

Skin irritation in human

CAS 620-67-7

A human patch test was performed in 15 male and 35 female volunteers to assess the skin irritating potential of Propane-1,2,3-triyl trisheptanoate in humans (WoE, 2003). The undiluted test substance was applied once at 2 mg test substance/cm² to healthy skin on the back area of the test subjects using a commercial test patch for 48 h. After patch removal, skin reactions were evaluated immediately (48 h post-application) and 24 h later (72 h post-application). No primary skin irritation was observed 48 or 72 h after test substance application. Furthermore, no skin reactions were induced in this test. Based on these results, the test substance was not considered to be a skin irritant in humans.

 

Eye irritation

CAS 142-18-7

An eye irritation study was conducted with 2,3-dihydroxypropyl laurate according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics" (WoE, 1977). The solid test material (0.1 g) was placed into the conjunctival sac of the left eye of 6 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h as well as 4, 5, 6 and 7 days after application. At the 1, 2 and 8 h reading time points, no corneal opacity and iritis were observed. At this time points, slight to moderate conjunctival redness and moderate to strong chemosis and discharge were seen in all animals. 24 h post-application, corneal opacity was observed in 2/6 animals which was fully reversible within 72 h and 96 h, respectively. Slight to moderate conjunctival redness was observed in all animals 24 h post-application. These effects were fully reversible within 48 h (1/6 animals), 72 h (1/6 animals) or 5 days (4/6 animals). Slight to strong discharge was observed in all animals 24 h post-application. These effects were fully reversible within 72 h (5/6 animals) or 4 days (1/6 animals). Test substance application into the rabbit eye induced no iridial effects at any observation time point; scores were all 0. Over 24, 48 and 72 h the mean cornea scores were 0, 0, 0, 0, 1 and 0.7, chemosis scores were 1, 1, 1, 0.3, 1 and 1.7 and conjunctivae scores were 1.7, 1.3, 1, 0.3, 2 and 1.7 for the 6 animals respectively. No further local or systemic toxic effects were observed. Therefore, the test substance was not considered as eye irritant.

CAS 538-24-9

An eye irritation study was performed with Glycerol trilaurate according to OECD guideline 405 and in compliance with GLP (WoE, 1998). The test substance was instilled into the eyes of 3 New Zealand White rabbits each. The eyes were examined and scored 1, 24, 48 and 72 h after application. No corneal opacity, iritis or chemosis were observed at any reading time point in any animal. Very slight discharge was observed in 2 animals at the 1-h reading time point. Moderate conjunctival redness (score 3) was observed in all 3 animals at the 1-h reading time point, decreasing to slight (score 2) in 2/3 animals at 24 h after installation and to very slight (score 1) in 3/3 animals at 48 h after installation. No effects were observed at the 72-h reading time point. The mean scores for conjunctivae after 24, 48, and 72 h were 1.3, 1 and 1. The mean scores for cornea, iris and chemosis over 24, 48, and 72 h were 0 for all 3 animals. Therefore, the test substance was not considered as eye irritant.

CAS 73398-61-5

An eye irritation study was performed with Triglycerides, mixed decanoyl and octanoyl according to EPA OPP guideline 81-4 and in compliance with GLP (WoE, 1988). The undiluted test substance (0.1 mL) was instilled into the conjunctival sac of one eye of 6 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. At the 1 h reading, iridial inflammation (score 1) was observed in 1/6 animals. 24, 48 and 72 h no iridial effects were observed in any animal. Mild to moderate (score 1-2) conjunctivae effects were apparent in all animals at 1 h reading. In 1/6 animals, mild conjunctivae redness (score 1) and chemosis was still apparent after 24 h, but was fully reversible at the 48 h reading. In the remaining 5/6 animals, conjunctivae irritation was fully reversible within 24 h. No adverse corneal effects were noted in any animal at any observation time point. No further local or systemic toxic effects were observed. After 24, 48, and 72 h the mean scores for chemosis and conjunctivae were 0.33, 0, 0, 0, 0 and 0 for all 6 animals, respectively. The mean scores for cornea and iris over 24, 48, and 72 h were 0 for all 6 animals. Therefore, the test substance was not considered as eye irritant.

Overall conclusion for skin and eye irritation

The available data on source substances did not show any skin or eye irritation effects. Therefore, the target substance Dodecanoic acid, ester with 1,2,3-propanetriolis not expected to be a skin irritant or an eye irritant.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Dodecanoic acid, ester with 1,2,3-propanetriol (CAS 37318-95-9), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

 

Therefore, based on an analogue read-across approach, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.