Registration Dossier

Administrative data

Description of key information

Several read across substances were tested in three skin irritating studies and in three eye irritating studies. The read across substance was not found to be a skin irritating or an eye damaging.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Method: Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
abraded
Remarks:
and intact skin
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 mL of the undiluted test substance
Duration of treatment / exposure:
24 hour(s)
Observation period:
7 days
Number of animals:
12 (6 animals were treated on intact skin)
Details on study design:
TEST PROCEDURE
- Primary irritation to the skin was measured by a patch-test technique on the abraded and intact skin of albino rabbits. Twelve healthy adult New Zealand White albino rabbits were used for the test substance.
- Pretreatment: 24 hours prior to applying the material, the hair was removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions
- Application procedure: The test substance was brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches were fixed to the application site by means of adhesive tape and the entire trunk of the rabbits was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.
- Abrasions: The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.
- Exposure: After an exposure period of 24 hours the patches and the material applied were removed.
- Readings of skin reactions: Readings were performed after 24 and 72 hours. If, at the second reading, distinct irritation was observed a third reading was performed after seven days. After the final reading all rabbits were killed and, in the case of eschar formation, the scab was removed to examine the nature of the underlying tissue damage.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 h
Score:
2.4
Max. score:
8
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
1.42
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
0.6
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other:
Remarks:
intact skin
Irritant / corrosive response data:
After 24 hours, intact skin : very slight or well-defined erythema and very slight edema .
After 24 hours, abraded skin: very slight or well-defined erythema, slight ischemia and slight edema.
After 72 hours, intact skin: very slight or well-defined erythema, slight scaliness and very slight edema.
After 72 hours, abraded skin: very slight erythema, slight scaliness and very slight edema.
On the abraded skin the test compound caused edema to a slightly higher degree than on the intact skin .
As to the other dermal effects observed there were no differences between reactions of the intact skin and those of the abraded skin .
Generally, the following dermal effects were observed:
After 24 hours, intact skin: very slight or well-defined erythema and very slight edema.
After 72 hours, intact skin: very slight or well-defined erythema, slight scaliness and very slight edema.
On the abraded skin the test compound caused edema to a slightly higher degree than on the intact skin.
As to the other dermal effects observed, there were no differences between reactions of the intact skin and those of the abraded skin.


I
ndividual and average skin irritation scores:

 

Intact skin

 

Abraded skin

No. Animal

24 h

72 h

No. animal

24 h

72 h

 

A

B

A

B

 

A

B

A

B

1

2

1

1

0

 

2

2

1

1

2

2

1

1

0

 

4

2

1

0

3

1

0

1

0

 

2

2

1

0

4

1

1

1

0

 

2

2

1

1

5

2

1

2

1

 

2

2

1

0

6

2

1

1

1

 

1

1

1

0

average

1.7

0.8

1.2

0.3

 

2.1

1.8

1.0

0.3

Sum

2.5

1.5

 

4.0

1.3


A: erythema
B: edema


Mean values over 24 and 72 hours (intact skin):

No. Rabbit

Erythema

Edema

1

1.5

0.5

2

1.5

0.5

3

1.0

0.0

4

1.0

0.5

5

2.0

1.0

6

1.5

1.0

 average  1.42  0.6
Interpretation of results:
GHS criteria not met
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Acceptable, well documented study report which meets basic scientific principles Read across was performed with Laurylacrylate 1214 (mixture of laurylacrylate (CAS No.: 2156-97-0) and tetradecylacrylate (CAS No.: 21643-42-5) . Please refer to IUCLID section 13 for read across justification.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Method: Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
undiluted
Amount applied: 0.1 mL
Duration of treatment / exposure:
168 hour(s)
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
- Comment: not rinsed
- In general, the techniques of tests as published by the FDA of the United States (Fed. Reg. 28 (119): 5582, 1963) and Draize and Kelley (Drug Cosmet. Industr. 71: 36, 1952) were followed.
- Pretest: The eyes of the animals were examined before testing and only those animals without observable eye defects are used.
- Total dose: 0.1 mL of the undiluted test material
- Instillation procedure: 0.1 mL of the undiluted test substance was allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid were then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye remaining untreated, served as a control. The eyes were not washed following instillation.
- Readings of eye reactions: The eyes were examined at one hour, 24, 48, 72 hours and 7 days after instillation of the test material.
- Evaluation of eye reactions: Eye reactions were evaluated by the method published by Draize and Kelley (1952). Drug. Cosmet. Industr. 71: 36
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
The test compound caused slight lesions of the conjunctivae in all  rabbits. After 24 hours these lesions had subsided completely.

Individual eye irritation scores:
---------------------------------

rabbit cornea iris conjunctivae Total score
opacity area redness chemosis discharge
-------------------------------------------------------------------------- -----------------
after 1 hour
1 0 0 0 1 0 0 2
2 0 0 0 1 1 0 4
3 0 0 0 1 0 0 2
4 0 0 0 1 0 0 2
5 0 0 0 1 0 0 2
6 0 0 0 1 0 0 2

after 24 hours
1 0 0 0 0 0 0 0
2 0 0 0 0 0 0 0
3 0 0 0 0 0 0 0
4 0 0 0 0 0 0 0
5 0 0 0 0 0 0 0
6 0 0 0 0 0 0 0

After 48, 72 hours and 7 days all scores were recorded as 0.
-------------------------------------------------------------------------- ------------------

Mean values over 24, 48, and 72 hours for the single animals for cornea, iris and conjunctivae were without exception zero.
Thus, the eye irritation score was calculated to be zero.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In the key study, a read across substance (mixture of laurylacrylate (CAS No.: 2156-97-0) and tetradecylacrylate (CAS No.: 21643-42-5)) was examined for primary skin irritating properties with 6 albino rabbits. Primary irritation to the skin was measured by a patch-test technique on the abraded and intact skin of albino rabbits. Healthy adult New Zealand White albino rabbits were used for the test substance. The total dose is 0.5 mL of the undiluted test material. The test substance was brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches were fixed to the application site by means of adhesive tape and the entire trunk of the rabbits was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances. Readings were performed after 24 and 72 hours. After the final reading all rabbits were killed and, in the case of eschar formation, the scab was removed to examine the nature of the underlying tissue damage. After 24 hours, intact skin: very slight or well-defined erythema and very slight edema. After 72 hours, intact skin: very slight or well- defined erythema, slight scaliness and very slight edema. On the abraded skin the test compound caused edema to a slightly higher degree than on the intact skin. As to other dermal effects observed, there were no differences between reactions of the intact skin and those of the abraded skin. Based on the results of this study, the scores were smaller than the threshold value (the erythema score (mean, intact skin, 24, 72 h) was 1.42 and the edema score (mean, intact skin, 24, 72 h) was 0.6). There were no data for the recovery. Therefore, the read across substance is not considered to be skin irritating in this study.

 

In the first supporting study, a read across substance (mixture of laurylacrylate (CAS No.: 2156 -97 -0) and tetradecylacrylate (CAS No.: 21643 -42 -5)) was tested for skin irritation potential using an internal method (BASF test). Two animals were treated for 1, 5 and 15 minutes on the right site of their backs and for 20 hours on the left site using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance. In addition, skin tissue from the ear was tested by wrapping the ear. These results from the ear, however, were not taken into account for evaluation as they do not represent testing of the dorsal / lateral flank of the back. After the application time, the skin was washed with water which contained a mild detergent (Lutrol conc./Lutrol 50 %, 1/1). The animals were observed for 8 days and skin changes were recorded on working days. The report describes findings after 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 72 hours from the raw data were taken into account. The mean edema scores after 24, 48 and 72 h for 2 animals were 0 and 0.7 (for exposure time: 1, 5, 15 min) and 2 and 1 (for the exposure time: 20 h). The read across substances is skin irritating.

  

In the second supporting study, a read across substance (mixture of laurylacrylate (CAS No.: 2156-97-0) and tetradecylacrylate (CAS No.: 21643-42-5)) was tested for the skin irritating potential using the internal method (BASF test). Two animals were treated for 1, 5 and 15 minutes on the right site of their backs and for 20 hours on the left site using occlusive conditions.  An application site of 2.5 x 2.5 cm was covered with the liquid test substance. In addition, skin tissue from the ear was tested by wrapping the ear.  These results from the ear, however, were not taken into account for evaluation as they do not represent testing of the dorsal / lateral flank of the back. After the application time, the skin was washed with water which contained a mild detergent (Lutrol conc./Lutrol 50 %, 1/1). The animals were observed for 8 days and skin changes were recorded on working days. The report describes findings after 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 72 hours from the raw data were taken into account. The mean edema scores after 24, 48 and 72 h for 2 animals were 0 and 0 (for exposure time: 1, 5, 15 min) and 2 and 0 (for the exposure time: 20 h). The read across substances is skin irritating.

 

Eye irritation: 

In the key study, a read across substance (mixture of laurylacrylate (CAS No.: 2156 -97 -0) and tetradecylacrylate (CAS No.: 21643 -42 -5)) was tested according to Draize test. Six healthy adult New Zealand White albino rabbits were used for the test substance. The total dose was 0.1 mL of the undiluted test material. 0.1 mL of the undiluted test substance was allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid were then carefully closed and subsequently held together for at least one second before releasing, to preventloss of material. The other eye remaining untreated, served as a control. The eyes were not washed following instillation. The eyes were examined at one hour, 24, 48, 72 hours and 7 days after instillation of the test material. The cornea, iris, conjunctivae and chemosis scores (mean, 24, 48, 72 h) were 0. The read across substance was not eye damaging.

 

In the first supproting study, a read across (mixture of laurylacrylate (CAS No.: 2156 -97 -0) and tetradecylate (CAS No.: 21643 -42 -5) was tested for the eye irritating potential using an internal method (BASF test). 50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The saline-treated adjacent eye served as control. The animals were observed several times on the day of treatment and up to 7 days afterwards. Findings were recorded on working days. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. The report describes findings after 1 and 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 72 hours from the raw data were taken into account. The iris score (mean, 24, 48) were 0. The read across substance was not eye irritating.

 

In the supporting study, a read across substance (mixture of acrylic esters of saturated unbranched alcohols with C10- C16 carbon chain lengths) was tested for an eye irritating potential using an internal method (BASF test). 50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The saline-treated adjacent eye served as control. The animals were observed several times on the day of treatment and up to 7 days afterwards. Findings were recorded on working days. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. The report describes findings after 1 and 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and72 hours from the raw data were taken into account. The iris score (mean, 24, 48) were 0. The read across substance was not eye irritating.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. One key and two supporting studies with an adequate read-across substance are available for skin (similar to OECD 404) and eye irritation (similar to OECD 405), respectively. For both endpoints, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No. 2017/776.

Nevertheless, for the group of substances (monoalkyl or monoaryl or monoalkylaryl esters of acrylic acid) an entry in Table 3.1 and 3.2 of Annex VI of Regulation (EC) No. 1272/2008 exists which has to be adopted for dodecyl acrylate although obtained data show the opposite. Thus, the substance is classified as Skin Irrit. 2 (H315), Eye Irrit. 2 (H319) and as STOT SE 3 (H335) according to Regulation (EC) No. 1272/2008 .