Registration Dossier

Administrative data

Description of key information

WoE:
Dibutyl sebacate (CAS No. 109-43-3) used as a Read Across substance was found to be not irritating to the rabbit skin.
Diisopropyl sebacate (CAS No. 7491 -02-3) used as a Read Across substance was found to be not irritating to the rabbit skin.
WoE:
Dibutyl sebacate (CAS No. 109-43-3) used as a Read Across substance was found to be not irritating to the rabbit eye.
Diisopropyl sebacate (CAS No. 7491-02-3) used as a Read Across substance was found to be not irritating to the rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline Study with acceptable restrictions.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
24 hours exposure instead of 4 hours, occlusive instead of semi-occlusive dressing, skin examinations only at 24 and 72 hours, not at 48 hours after patch removal. Lack of details on test substance and test animals.
Principles of method if other than guideline:
Federal Hazardous Substances Labeling Act (FHSA)
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
other: clipped back skin
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Unchanged test substance
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: back skin
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used:
The patches consisted of two layers of light gauze cut in squares (2.5 cm x 2.5 cm). The patches were secured to the area by thin bands of adhesive tape. The material to be tested (0.5 mL) was introduced beneath the patch. The entire trunks of the animals were then wrapped in clear plastic trunk bands. The trunk bands helped to hold the patches in position an retarded evaporation of volatile substances during the 24 h exposure.
The animals were immobilized in a special holder during the 24 h exposure period.

SCORING SYSTEM: Draize system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: average 24 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 24 hours exposure of intact skin under occlusive coonditions.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: average 24 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 24 hours exposure of intact skin under occlusive coonditions.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: average 24 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 24 hours exposure of intact skin under occlusive coonditions.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: average 24 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 24 hours exposure of intact skin under occlusive coonditions.
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: 24 hours exposure of intact skin under occlusive coonditions.
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: average 24 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 24 hours exposure of intact skin under occlusive coonditions.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: average 24 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 24 hours exposure of intact skin under occlusive conditions.

The test substance was not skin irritating, as no edema and only light erythema in 1 out of 6 animals occured which was fully reversible within 72 hours, although the testing was performed according to FHSA, and therefore under more critical conditions than those required for OECD Guideline 404.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
25 - 28 Mar 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance decan di acid, dibutyl ester (CAS 109-43-3). In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(adopted in 1990)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(adopted in 1984)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 31 months
- Weight at study initiation: mean 2.86 kg
- Housing: individually
- Diet: ad libitum, Altromin-Haltungsdiät 2023, Altromin GmbH, Lage, Germany
- Water: ad libitum, tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Air changes (per hr):
- 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(s) applied (volume or weight with unit): 0.1 mL


Duration of treatment / exposure:
24 h
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was rinsed with warm water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp, fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
Strong exudation was seen in the treated eyes of all three animals 1 h after application of the test substance. The observed conjunctival reactions (erythema and edema) were only mild and disappeared completely within 48 h. The treated eyes were without any lesion on their cornea and no effects on the iris were observed at any time during the test.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Justification for grouping of substances and read-across

There are no data available on the in vivo skin irritation potential of diisodecyl azelate (CAS 28472-97-1). In order to fulfil the standard information requirements set out in Annex VIII, 8.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of skin Irritation / corrosion

CAS

Chemical name

Molecular weight

Skin irritation

28472-97-1 (a)

Diisodecyl azelate

468.75

WoE:

RA: CAS 7491-02-3

RA: CAS 109-43-3

7491-02-3 (b)

Diisopropyl sebacate

286.41

Experimental result:
not irritating

109-43-3

Dibutyl sebacate

314.47

Experimental result:
not irritating

(a) The substance subject to registration is indicated in bold font.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for diisodecyl azelate (CAS 28472-97-1). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Skin irritation

CAS 7491-02-3

The skin irritation potential of Diisopropyl sebacate was investigated in a study similar to OECD guideline 404 (Wallace, 1976). The undiluted test substance (0.5 mL) was applied to the clipped dorsal skin of 3 male and 3 female rabbits for 24 h under occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24 and 72 h after removal of the dressing. No edema and only slight erythema occurred in 2 of 6 animals, which were fully reversible within 72 h after test substance application. For calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Thus, the mean erythema and edema scores after 24, 48 and 72 h were 0.22 and 0 for all 6 animals.

 

CAS 109-43-3

The skin irritation potential of Dibutyl sebacate (CAS 109-43-3) was investigated in a study similar to OECD guideline 404 (Wallace, 1976).

The undiluted test substance (0.5 mL) was applied for 24 h to the shaved or abraded skin of 3 male and 3 female 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 24 and 72 h after removal of the dressing. No edema was observed after test substance application on intact skin and only slight erythema occurred in 1/6 animals, which was fully reversible within 72 h. Erythema were also observed in 2/6 animals on abraded skin, but also disappeared within 72 h. For calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Thus, the mean erythema and edema scores after 24, 48 and 72 h were 0.11 and 0 for all 6 animals.

Based on the results of this study, Dibutyl sebacate is not irritating to the skin.

 

Eye irritation

Justification for grouping of substances and read-across

There are no data available on the in vivo eye irritation potential of diisodecyl azelate (CAS 28472-97-1). In order to fulfil the standard information requirements set out in Annex VIII, 8.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of eye Irritation / corrosion

CAS

Chemical name

Molecular weight

Eye irritation

28472-97-1 (a)

Diisodecyl azelate

468.75

WoE:

RA: CAS 7491-02-3

RA: CAS 109-43-3

7491-02-3 (b)

Diisopropyl sebacate

286.41

Experimental result:
not irritating

109-43-3 (b)

Dibutyl sebacate

314.47

Experimental result:
not irritating

(a) The substance subject to registration is indicated in bold font.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for diisodecyl azelate (CAS 28472-97-1). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Eye irritation

CAS 7491-02-3

An eye irritation study was performed with Diisopropyl sebacate according to the Federal Hazardous Substances Labeling Act (FHSLA, 1964) and similar to OECD guideline 405 (Prince, 1971). The undiluted test substance (0.1 mL) was placed into the conjunctival sac of one eye of 6 rabbits. 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 and 7 days after application. No corneal, iridial or conjunctival effects were noted in the animals at any of the reading time points. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0 for all 6 animals, respectively.

In summary, Diisopropyl sebacate is not eye irritating.

 

CAS 109-43-3

The eye irritation potential of Dibutyl sebacate was investigated according to OECD guideline 405 and in compliance with GLP (Steiling, 1991). The undiluted test substance (0.1 mL) was placed into the conjunctival sac of one eye of 3 male Kleinrussen, Chbb:HM. The other eye remained untreated and served as control. 24 h after test substance application, test substance was removed by rinsing with warm water. The eyes were examined and scored 1, 24, 48 and 72 h after application. Strong exudation was observed in the treated eyes of all three animals at the 1 h reading. The observed conjunctival reactions (erythema and edema) were only mild and disappeared completely within 48 h. No effects on cornea and iris were observed at any reading time point. The mean cornea and iris scores after 24, 48, and 72 h were 0 for all 3 animals. The mean score for conjunctivae and chemosis after 24, 48, and 72 h were 0.33/0/0.33 and 0/0/0.33 for the 3 animals, respectively

In a further study similar to OECD guideline 405, the eye irritation potential of the test substance was investigated in 6 albino rabbits (Wallace, 1976). The undiluted test substance (0.1 mL) was placed into the conjunctival sac of one eye of the animals. The other eye remained untreated and served as control. The eyes were examined and scored 24, 48 and 72 h after application. Four out of six animals showed mild (3/6) to moderate (1/6) conjunctival redness after 24 h exposure. However, this effect was fully reversible within 48 to 72 h. No effects on cornea and iris and no chemosis were noted in any animal during the study period. The mean cornea, iris and chemosis scores after 24, 48, and 72 h were 0 for all 6 animals, respectively. The mean score for conjunctivae after 24, 48, and 72 h was 0.33 for all 6 animals.

In summary, Dibutyl sebacate is not eye irritating.

 

Conclusions for irritation / corrosion

No data on skin and eye irritation is available for diisodecyl azelate (CAS 28472-97-1).

However, the results of the skin irritation studies of the structurally related substances diisopropyl sebacate (CAS 7491-02-3) and dibutyl sebacate (CAS 109-43-3) (Wallace, 1976) indicate that diisodecyl azelate (CAS 28472-97-1) will not cause skin irritation. The results of the eye irritation studies using the same structural analogues for read-across (Prince, 1971; Steiling, 1991; Wallace, 1976) indicate that diisodecyl azelate (CAS 28472-97-1) will not cause eye irritation.


Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substances and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substances and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on substance specific studies and read-across following an analogue approach, the available data on the skin and eye irritation potential do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available on respiratory irritation.