Registration Dossier

Administrative data

Description of key information

According to the results of valid GLP OECD Guideline studies,the source substance of this read across approach,  2-ethylhexanoic acid, is slightly irritating to the skin and the eyes (for read across justification please refer to the attached document, IUCLID Chapter 13). Based on these results it is concluded that 2-ethylhexanoic acid vapor is non to slightly irritating to the repiratory tract as well.

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:
key study
Study period:
May 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG Kastengrund
- Age at study initiation: 3 -5 month
- Weight at study initiation: 2.8 - 2.9 kg
- Housing: single housing
- Diet (e.g. ad libitum): Altromin 2123 Haltungsdiät - Kaninchen; Altromin GmbH Lage/Lippe
- Water (e.g. ad libitum): Tab water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 50 +/- 20 %
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 h, test substance was removed by washing with warm tab water at the end of the exposure period
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, lukewarm tap water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72
Score:
0.66
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: eshar formation was still visible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Remarks:
7 days
Irritant / corrosive response data:
Edema score was 0 at day 7 but raised to a grade 1 in one animal and grade 2 in another animal at day 14. Erythema and eshar formaton was still visible after 14 days. Because edema was gone at day 7 and returned afterwards it may concluded that scratching occurred. The over all assumption is that ethylhexanoic acid is only slightly irritating.
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
With reference to the reported edema score (0) on day 7 after application and the conclusion that scratching may have caused its return on day 14 and with reference to the overall mean scores 24 to 72 h after application 2-ethylhexanoic acid was judged to be slightly irritant to the skin and does not have to be classified as irritant to the skin according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be a skin irritant and is therefore not subjected for labelling and classification requirements according to regulatory requirements.
Executive summary:

A read across was performed from the source substance 2 -ethylhexanoic acid to the target substance sodium 2 -ethylhexanoate (for read across justification please refer to attached document, IUCLID Chapter 13).

2 -Ethylhexanoic acid was tested for its skin irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 404. Effects skin (mean erythema grade 0.66 and mean edema scores 0.33) were observed 24 - 72 hours after application. Edema score was 0 at day 7 but raised to a grade 1 in one animal and grade 2 in another animal at day 14. Erythema and eshar formaton was still visible after 14 days. Because edema was gone at day 7 and returned afterwards it may concluded that scratching occurred.

With reference to the reported edema score (0) on day 7 after application and the conclusion that scratching may have caused its return on day 14 and with reference to the overall mean scores 24 to 72 h after application 2-ethylhexanoic acid was judged to be slightly irritant to the skin and does not have to be classified as irritant to the skin according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be a skin irritant and is therefore not subjected for labelling and classification requirements according to regulatory requirements.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
key study
Study period:
Oct 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conforme GLP Study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG Kastengrund
- Age at study initiation: 3 - 5 month
- Weight at study initiation: 3.0 - 3.6 kg
- Housing: single housing
- Diet (e.g. ad libitum): Altromin 2123 Haltungsdiät - Kaninchen; Altromin GmbH Lage/Lippe
- Water (e.g. ad libitum): Tab water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 50 +/- 20 %
- Photoperiod (hrs dark / hrs light): 12h/12h
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 µL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
no

SCORING SYSTEM:
Draize

TOOL USED TO ASSESS SCORE:
fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.56
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 -72 h
Score:
1.2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.89
Max. score:
4
Reversibility:
fully reversible within: 7 days
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
With reference the reported scores and the reversibility of the observed effects 2-ethylhexanoic acid does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC) and in the EU Dangerous Substances Directive (67/548/EEC).
Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be a eye irritant and is therefore not subjected for labelling and classification requirements according to regulatory requirements.
Executive summary:

A read across was performed from the source substance 2 -ethylhexanoic acid to the target substance sodium 2 -ethylhexanoate (for read across justification please refer to attached document, IUCLID Chapter 13).

2 -Ethylhexanoic acid was tested for its eye irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 405.

Effects on conjunctivae (mean redness score: 1.2 and mean swelling score: 0.89), cornea (mean score: 0.44) and iris (mean score: 0.56) were observed 24 - 72 h after application. These signs were fully reversible within 72 h (corneal effects) and 7 days (all other observed effects).

With reference the reported scores and the reversibility of the observed effects 2-ethylhexanoic acid does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC) and in the EU Dangerous Substances Directive (67/548/EEC).

Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be a eye irritant and is therefore not subjected for labelling and classification requirements according to regulatory requirements.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A read across was performed from the source substance 2 -ethylhexanoic acid to the target substance sodium 2 -ethylhexanoate (for read across justification please refer to attached document, IUCLID Chapter 13).

Valid animal studies concerning irritating properties are available for 2-ethylhexanoic acid.

 

0.5 ml 2-ethylhexanoic acid was applied to the shaved flank of 3 New Zeeland white rabbits in a GLP OECD 404 guideline conform skin irritation study. The test substance was washed off after 4 h exposure with lukewarm tap water. The 24 – 72 h mean values are 0.66 (erythema) and 0.33 (edema). Edema score was 0 at day 7 but raised to a grade 1 in one animal and grade 2 in another animal at day 14. Erythema and eshar formation was still visible after 14 days. Because edema was gone at day 7 and returned afterwards it may concluded that scratching occurred. The overall assumption is that 2-ethylhexanoic acid is only slightly irritating.

 

In a GLP OECD 405 guideline study 100 µl 2-ethylhexanoic acid was applied to one eye of 3 New Zeeland white rabbits. The other eye served as control. The average score (24 to 72 hours) for irritation was calculated to be 0.44 for corneal opacity, 0.56 for iris, 1.2 for conjunctival redness and 0.89 for chemosis . The findings were reversible in all animals within 7 days after application. Considering the described findings, 2-ethylhexanoic acid is slightly irritant to the eye.


Justification for selection of skin irritation / corrosion endpoint:
Guideline conform GLP study.

Justification for selection of eye irritation endpoint:
Guideline conform GLP study.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

With reference to the reported edema score (0) on day 7 after application and the conclusion that scratching may have caused its return on day 14 and with reference to the overall mean scores 24 to 72 h after application 2-ethylhexanoic acid was judged to be slightly irritant to the skin and does not have to be classified as irritant to the skin according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

With reference the reported scores and the reversibility of the observed effects 2-ethylhexanoic acid does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC) and in the EU Dangerous Substances Directive (67/548/EEC).

Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be a eye irritant and is therefore not subjected for labelling and classification requirements according to regulatory requirements.