Registration Dossier

Administrative data

Description of key information

Skin irritation:
according to OECD 404, in compliance with GLP, RL1 (Steiling, 1991): not irritating
Eye irritation:
according to OECD 405, in compliance with GLP, RL1 (Steiling, 1991): not irritating

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:
15 Oct 1991 - 29 Oct 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance Cetyl-2-Ethylhexanoate. According 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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb: HM
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany.
- Age at study initiation: approx. 9 months
- Weight at study initiation: approx. 2540 g
- Housing: individual
- Diet: Ssniff rabbit diet K4, Ssniff GmbH, Soest, Germany; ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 75
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
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 (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
14 days
Reading time points: 1, 24, 48, 72 h and 7 and 14 days after exposure
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm² on the left or right flank
- Type of wrap if used: gauze patch covered with an adhesive air- and vapor-permeable patch and fixed by using a hypoallergenic adhesive gauze-bandage.

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3 showed the same mean value for the 3 readings
Time point:
other: mean over 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days

Table 1: Evaluation of the dermal reaction

Skin effect

Erythema

Edema

 

1h

24h

48h

72h

Meana

1h

24h

48h

72h

Meana

Animal No.

#1

 

1

 

1

 

1

 

2

 

1.3

 

1

 

1

 

1

 

2

 

1.3

#2

1

1

2

2

1.7

1

1

1

2

1.3

#3

1

1

2

3

2.0

1

1

1

2

1.3

amean of readings at 24, 48 and 72 hours

 

Skin effect

days after exposure

 

7

14

Animal No.

#1

 

i b S

 

+

#2

i b S

+

#3

i b S

+

i = irreversible

b = brownish

S = eschar

+ = reversible

Interpretation of results:
not classified
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)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Sep 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
limited data
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
not specified
Controls:
other: the untreated eye served as control
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:
3 animals
Irritation parameter:
cornea opacity score
Basis:
mean
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
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:
1
Max. score:
3
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable

Results:

 

 

Cornea

Iris

Conjunctiva

Reading time

Animal No.

Opacity

Area of opacity

Redness

Chemosis

Discharge

1 h

6599

0

0

1

2

0

2

6600

0

0

0

2

1

2

6601

0

0

1

2

1

2

24 h

6599

0

0

0

1

0

0

6600

0

0

0

1

0

0

6601

0

0

0

1

0

0

48 h

6599

0

0

0

1

0

0

6600

0

0

0

0

0

0

6601

0

0

0

1

0

0

72 h

6599

0

0

0

1

0

0

6600

0

0

0

0

0

0

6601

0

0

0

0

0

 

mean 24-48-72 h

6599

0.0

0.0

0.0

1.0

0.0

0.0

6600

0.0

0.0

0.0

0.3

0.0

0.0

6601

0.0

0.0

0.0

0.7

0.0

0.0

mean

0.0

0.0

0.0

0.7

0.0

0.0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
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

Justification for grouping of substances and read-across

There are no sufficient data available regarding skin and eye irritation/corrosion of Hexanoic acid, 2-ethyl, C16-18 alkyl esters (CAS No. 90411-68-0). 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 irritation/corrosion

CAS

90411-68-0

95912-86-0

59130-69-7

Chemical name

Hexanoic acid, 2-ethyl, C16-18 alkyl esters

Fatty acids, C8-10, C12-18-alkyl esters

Hexadecyl 2-ethylhexanoate

MW

368.6-396.7 g/mol

312.53-424.74 g/mol

368.6 g/mol

Skin irritation

RA: CAS 59130-69-7

Experimental result: not irritating

Experimental result: not irritating

Eye irritation

RA: CAS 59130-69-7

-

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 Hexanoic acid, 2-ethyl, C16-18 alkyl esters (CAS No. 90411-68-0).

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

Discussion

Skin irritation

A study conducted in accordance with OECD guideline 404 on skin irritation is available for Hexanoic acid, 2-ethyl, C16-18 alkyl esters, but only limited data from the report are available (Dufour, 1997). Skin sites of three New Zealand White rabbits was treated with substance and were assessed for effects 1, 24, 48 and 72 h after removal of the patch. While no edema was seen in any animals, erythema was noted in any animals leading to mean score between 1 and 1.7. However, since no data on later assessment of the erythema later given, the result of this study has to be regarded as inconclusive.

Irritation to skin by the structural analogue hexadecyl 2-ethylhexanoate was evaluated in a GLP study performed in accordance with OECD guideline 404 (Steiling, 1991). The flank skin of three Kleinrussen rabbits were treated with 0.5 mL of the test substance under semiocclusive conditions for 4 h. The readings 24, 48 and 72 hours later revealed mean erythema scores from 1.3 to 2 in the three animals and a mean edema score of 1.3 in any animals, respectively. All skin effects were fully reversible within the 14 days observation period. Based on these results, no skin irritation potential by hexadecyl 2-ethylhexanoate was observed.

Another structural analogue fatty acids, C8-10, C12-18-alkyl esters was tested in a study similar to OECD guideline 404 (no data on GLP compliance), where 0.5 mL of the test substance was applied with an occlusive patch for 4 h to the skin of three male New Zealand White rabbits (Dufour, 1991). 1, 24, 48 and 72 h after the patch removal the treated skin sites were graded according the Draize scoring system. While the mean erythema scores after 24, 48 and 72 h was 0 in two animals, a score of 0.33 was found in the third animal, where the effect was fully reversible within 48 h. The third animal also showed slight edema, but these fully reversed within 72 h leading to a mean score of 1. The two other animals developed no edema. These data show that fatty acids, C8-10, C12-18-alkyl esters is not irritating to skin.

Eye irritation

An eye irritation study was performed with Hexanoic acid, 2-ethyl, C16-18 alkyl estersaccording to OECD 405 (Dufour, 1997). The undiluted test substance was instilled into the conjunctival sac of one eye of 3 New Zealand White rabbits. The eyes were examined and scored 1, 24, 48 and 72 h after application. No effects on cornea and iris and no chemosis was observed in any animals at any time point. Conjunctiva mean scores of 1.0, 0.7, and 0.3 (mean over 24, 48, and 72 h) were observed for the three animals, respectively. These were fully reversible within 72 h in 2/3 animals. In one animal a conjunctiva score of 1 was still observed after 72 h. No further reading at a later time point was reported.

Conclusion

In conclusion, the available data on the skin and eye irritation potential ofHexanoic acid, 2-ethyl, C16-18 alkyl esters and structural analogue substances indicate that Hexanoic acid, 2-ethyl, C16-18 alkyl esters 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 structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
There is only one study available.

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.