Registration Dossier

Administrative data

Description of key information

Skin irritation:
according to OECD 404, in compliance with GLP, RL2: not irritating
Eye irritation:
according to OECD 405, in compliance with GLP, RL2: 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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
04 Mar - 10 Mar 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study with acceptable restrictions (analytical purity is not reported, occlusive dressing, residual test substance was not removed)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1983
Deviations:
yes
Remarks:
Analytical purity is not reported, occlusive dressing, residual test substance was not removed.
GLP compliance:
yes
Species:
rabbit
Strain:
other: Chbb: HM
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Fa. Thomae, Biberach, Germany- Weight at study initiation: 2.5 kg- Housing: individual - Diet: Zucht- / Haltungsdiät - Water: tap water, ad libitum- Acclimation period: at least 7 daysENVIRONMENTAL 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: untreated sites of the same animal served as control
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 daysReading time points: 1, 24, 48 and 72 h
Number of animals:
4 males
Details on study design:
TEST SITE- Area of exposure: back - Type of wrap if used: the treated skin was covered with a linen patch (2.5 cm x 2.5 cm). This was then covered with a large plastic foil, which was held in place with tape. Finally, by mean of a bond a secure fixation was achieved. SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 4 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 4 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No skin irritations were observed.
Other effects:
No further effects were observed.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only abstract available
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Abstract, only results given
GLP compliance:
yes
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
other: not required, untreated sites of the same animal served as control
Duration of treatment / exposure:
4 h
Observation period:
72 hReading time points: 24, 48 and 72 h
Number of animals:
3
Details on study design:
SCORING SYSTEM:Draize scoring system
Irritation parameter:
erythema 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:
erythema 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:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
There were no signs of irritations observed in two animals. Slight erythema and transient slight oedema were observed in the third rabbit with complete regression 2 days after removal of the test substance.

Reading scores:

Time Animal Erythema Edema
24 h 1 0 0
2 0 0
3 1 0
48 h 1 0 0
2 0 0
3 0 0
72 h 1 0 0
2 0 0
3 0 0
mean 24 - 72 h 1 0.0 0.0
2 0.0 0.0
3 0.3 0.0
mean 0.1 0.0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
29 May 1996 - 31 May 1996
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only abstract avilable
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: Only basic data on test substance and procedure given
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:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
No data
Duration of treatment / exposure:
No data
Observation period:
7 days Reading time points: 4, 24, 48 and 72 h and 7 days
Number of animals:
3
Details on study design:
SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 28 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
ot all three animals
Time point:
other: mean out of 24 h, 48 h and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No effects were seen in any animals at any reading time points.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
01 Jul - 08 Jul 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study with acceptable restrictions (analytical purity not reported)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1984
Deviations:
yes
Remarks:
analytical purity not reported; single application without washing.
GLP compliance:
yes
Species:
rabbit
Strain:
other: Chbb: HM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Thomae, Biberach, Germany- Weight at study initiation: 2.7 kg- Housing: individual housing- Diet: Altromin-Haltungsdiät, ad libitum- Water: tap water, ad libitum- Acclimation period: at least 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20-21- Humidity (%): 45-55- 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:
Single application without washing
Observation period (in vivo):
3 daysReading time points: 1, 6, 24, 48, and 72 h
Number of animals or in vitro replicates:
4 males
Details on study design:
SCORING SYSTEM: Draize scoring systemTOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
mean out of all 4 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:
mean out of all 4 animals
Time point:
other: mean over 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
mean out of all 4 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
mean out of all 4 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
Slight conjuctival reactions were observed between 1-6 hours after treatment. They consisted in redness (4/4 animals within the first hour after treatment, 3/4 within 6 hours after treatment) and exudation (4/4 animals within the first hour after treatment). However, these reactions were fully reversible within 24 hours after treatment.
Interpretation of results:
not irritating
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only abstract available
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
limited data
GLP compliance:
yes
Species:
rabbit
Strain:
not specified
Vehicle:
not specified
Controls:
other: the untreated eye served as control
Duration of treatment / exposure:
single application
Observation period (in vivo):
3 daysReading time points: 1 h and 1, 2 and 3 days
Number of animals or in vitro replicates:
3 females
Details on study design:
SCORING SYSTEM:Draize scoring system
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
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks:
reversibility: not applicable
Irritation parameter:
chemosis 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
Irritant / corrosive response data:
Slight erythema were noted in all animals 1 h after instillation. While this reaction was absent in two animals at the following reading time points, it last in the third animal until the 2 day reading time point. Erythema was seen in one animal and discharge in all three animals. However this were only seen 1 h after instillation.

Reading Scores:

Reading time point Animal No. Cornea Iris Conjunctiva
Opacity Area of opacity Redness Chemosis Discharge
1 h 1100 0 0 0 1 0 3
1101 0 0 0 1 1 1
1102 0 0 0 1 0 4
Day 1 1100 0 0 0 0 0 0
1101 0 0 0 1 0 0
1102 0 0 0 0 0 0
Day 2 1100 0 0 0 0 0 0
1101 0 0 0 1 0 0
1102 0 0 0 0 0 0
Day 3 1100 0 0 0 0 0 0
1101 0 0 0 0 0 0
1102 0 0 0 0 0 0
mean days 1-3 1100 0.0   0.0 0.0 0  
1101 0.0   0.0 0.7 0  
1102 0.0   0.0 0.0 0  
mean 0.0   0.0 0.2 0  
Interpretation of results:
not irritating
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
28 May 1996 - 30 May 1996
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only abstract available
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: Only basic data on test substance and procedure given.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
No data
Duration of treatment / exposure:
No data
Observation period (in vivo):
7 daysReading time points: 4, 24, 48, 72 h and 7 days
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize scoring system
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:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
mean 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:
mean 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
Irritant / corrosive response data:
Conjunctival reactions were observed in all three animals after 4 hours. These reactions disappeared within 24 hours in one animal, while in the other two animals the effects were completely reversed after 48 hours.

Animal Number

4 h

1 day

2 days

3 days

7 days

CO

COR

IR

CO

COR

IR

CO

COR

IR

CO

COR

IR

CO

COR

IR

446

3

0

0

1

0

0

0

0

0

0

0

0

0

0

0

447

3

0

0

1

0

0

0

0

0

0

0

0

0

0

0

448

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

CO: Conjunctivae Score

COR: Cornea Score

IR: Iris Score

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classifedDSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no sufficient data available for skin and eye irritation of 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS 28510-23-8). In order to fulfil the standard information requirements set out in Annex IX, 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, 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.

Skin and eye irritation/corrosion

CAS

28510-23-8

97281-24-8

Chemical name

2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate

Fatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropane

MW

356.55 g/mol

256.54-596.94 g/mol

Skin irritation

RA: CAS 97281-24-8

Experimental result: not irritating

Eye irritation

RA: CAS 97281-24-8

Experimental result: not irritating

 

The above mentioned substances are considered to be similar on the basis of the structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS 28510-23-8).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

Skin irritation

Skin irritation was evaluated in a study performed with three New Zealand White rabbits in accordance with OECD guideline 404 (Bouffechoux, 1996a). The animals were treated with 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate.The readings of the treated skin sites after 4, 24, 48 and 72 h and 7 days revealed no noticeable irritation effects. As a consequence, the mean scores for erythema and edema were 0 in all animals, respectively. Thus, no skin irritating potential of the test substance was supposed. No final decision on classification was possible as important information as test material purity, amount of substance applied, coverage, and duration of treatment were not specified in detail.

Further supporting data on the skin irritation of 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoateare available (Duerden, 1994a). In another rabbit study performed according to GLP and similar to OECD guideline 404 with2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate no irritating effects were observed. The mean scores for erythema were 0.33 in one animal and 0 in the two other animals, while the edema scores were 0 for all animals, respectively. No final decision on classification was possible as only limited data on test material purity, amount of substance applied, and coverage, were available.

As the two studies that were performed with the test substance did not allow a final decision on classification due to limited data, an appropriate read-across was performed from the analogue substanceFatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropane (CAS 97281-24-8). Fatty acids, C8-10, mixed esters with neopentylglycoland trimethylolpropanewas tested for skin irritation in a study with rabbits in compliance with GLP and similar to OECD guideline 404 (Kästner, 1988a). 0.5 mL of the test substance was applied to the skin of four male Chbb: HM rabbits for 4 h being kept under an occlusive dressing. 1, 24, 48 and 72 h after the patch removal the treated skin sites were evaluated for erythema and edema. The mean cores were 0, both for erythema and edema, in all animals. In conclusion, Fatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropane was not irritating to the skin.

Based on the fact that neither in the two studies with 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate nor in the study with the analogue substance Fatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropane skin irritation was observed, 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is not to be classified for skin irritation.

Eye irritation

An eye irritation study was performed with2,2-dimethylpropane-1,3-diyl 2-ethylhexanoateaccording to OECD 405 (Bouffechoux, 1996b). After treatment with the test substance, no effects on cornea and iris were observed. Conjunctiva mean scores (over 24, 48, and 72 h) of 0.0, 0.3, and 0.3 were observed in animal 1, 2, and 3, respectively. The effects on conjunctiva were fully reversible within 48 h.No final decision on classification was possible as important information as test material purity, amount of substance applied, and duration of treatment were not specified in detail.

A further eye irritation study was performed with2,2-dimethylpropane-1,3-diyl 2-ethylhexanoateequivalent or similar to OECD 405 (Duerden, 1994b). After treatment with the test substance, no effects on cornea and iris and no chemosis were observed. Conjunctivae mean scores (over 24, 48, and 72 h) of 0, 0, and 0.67 were observed in animal 1, 2, and 3, respectively. The effects on conjunctiva were fully reversible within 72 h. Againno final decision on classification was possible as important information as test material purity and amount of substance applied were not specified in detail.

As the two studies that were performed with the test substance did not allow a final decision on classification due to limited data, an appropriate read-across was performed from the analogue substanceFatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropane (CAS 97281-24-8).Theeye irritation potential of the structural analogueFatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropanewas evaluated in a GLP study performed equivalent or similar to OECD guideline 405 (Kästner, 1988b). 0.1 mL ofFatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropanewas instilled into the eyes of fourChbb: HM rabbits. The eyes were observed 1, 6, 24, 48, and 72 h after application. Slight conjunctival reactions (grade 1) were observed up to 6 h after treatment in 4/4 animals. These were fully reversible within 24 h. No effects on cornea and iris and no chemosis were observed throughout the study period.

Based on the fact that neither in the two studies with 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate nor in the study with the analogue substance Fatty acids, C8-10, mixed esters with neopentylglycol and trimethylolpropane eye irritation was observed, 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is not to be classified for skin irritation.

Conclusion

In conclusion, the available data on the skin and eye irritation potential of 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate and a structural analogue substance indicate that 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is not irritating to the skin and eye.


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

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.