2-ethylhexyl nonanoate

Endpoint summary

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP, analogue approach)
Eye irritation: not irritating (OECD 405, GLP, analogue approach)

Key value for chemical safety assessment

Skin irritation / corrosion

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:

key study

Study period:

15 May - 16 Jul 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study, tested with the source substance CAS 92044-87-6. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, 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)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 2693 - 2894 g
- Housing: individually in plastic cages with perforated floors
- Diet: standard animal diet (100 g per day), obtained from Hope Farms, Woerden (LK-01, pellet diameter 4 mm)
- Water: tap-water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 60 - 70
- 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 eye instillation

Observation period (in vivo):

72 hours (in the absence of any persistent sign of irritation)

Reading time points: 1, 24, 48 and 72 hours after instillation

Number of animals or in vitro replicates:

3 females

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

2 out of 3 animals showed only slight swelling of the blood-vessels in the conjunctivae 1 hour after instillation. The effects were fully reversible 24 hours after instillation. The fluorescein analysis 24 hours after instillation did not reveal any epithelial damage.

Other effects:

Signs of systemic intoxication were not observed.

Table 1: Results of eye irritation test

Rabbit No. / sex	Scoring [h]	Cornea	Iris	Conjunctiva
				Redness	Chemosis
1 / f	1	0	0	1	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0	0	0	0
2 / f	1	0	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0	0	0	0
3 / f	1	0	0	1	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0	0	0	0
Group mean		0	0	0	0

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

There are no data available on the skin and eye irritation potential of 2 -ethylhexyl nonanoate (CAS 59587 -44 -9). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.1 and 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 for Skin and Eye Irritation

CAS	Skin Irritation/Corrosion	Eye Irritation/Corrosion
59587-44-9 Target substance	RA: 92044-87-6 RA: 135800-37-2	RA: 92044-87-6
92044-87-6	Not irritating	Not irritating
135800-37-2	Not irritating	--

The above mentioned substance is considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2-ethylhexyl nonanoate (CAS 59587-44-9).

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

Skin irritation:

CAS 92044 -87 -6

The skin irritation/corrosion potential of Fatty acids, coco, 2-Ethylhexyl Esters (CAS 92044-87-6) was tested in a primary dermal irritation study according to OECD Guideline 404 under GLP conditions (Weterings 1987). The clipped skin of three New Zealand White rabbits was exposed to 0.5 mL unchanged test material (approx. 100% pure) for 4 hours under semi-occlusive conditions. Then, test substance residues were wiped off with a dry and a water-moistened tissue. The rabbits were observed for 7 days. Skin reactions were assessed using the Draize scheme 45 min, 24, 48, 72 hours, and 7 days after patch removal. Slight erythema (mean scores = 1.0, 1.0, and 0.67) and slight oedema (mean scores = 1.0, 0.67, and 0.67) were observed in all animals. All effects were fully reversible within 72 h to 7 days. Thus, the test substance was is not irritating in this study.

CAS 135800 -37 -2

Another acute skin irritation study was performed with Fatty acids, C8-16, 2-Ethylhexyl Esters (CAS 135800-37-2) according to OECD Guideline 404 (Steiling, 1990). The shaved skin of four adult Kleinrussen rabbits was exposed to 0.5 mL test substance (no data on purity) for 4 hours under occlusive conditions. The animals were observed for 7 days. Skin examinations according to Draize revealed only slight erythema (mean scores = 1.33, 0.67, 0.67, and 0.33) in four animals which was fully reversible within 7 days and slight oedema (mean score = 0.33) in one animal which was fully reversible in 48 hours. Based on this study result, the test substance has no skin irritating potential.

Eye irritation:

CAS 92044 -87 -6

One study with Fatty acids, coco, 2-Ethylhexyl Esters (CAS 92044-87-6) for the assessment of the acute eye irritation/corrosion potential is available (Weterings, 1987). The study was performed according to OECD Guideline 405 under GLP conditions. 0.1 mL of the test substance (approx. 100% pure) was instilled into the eyes of three female New Zealand White rabbits. The animals were observed for 72 hours and scoring according to Draize was performed 1, 24, 48, and 72 hours after application. 2/3 animals showed only slight swelling of the blood-vessels in the conjunctivae 1 hour after instillation. The effects were fully reversible within 24 hours. The fluorescein analysis 24 hours after instillation did not reveal any epithelial damage. Based on the results of the study, the test substance is not considered irritating to the eyes.

Conclusion for skin and eye irritation

There are two skin irritation studies available with the structural related substances Fatty acids, coco, 2-Ethylhexyl Esters (CAS 92044-87-6) and Fatty acids, C8-16, 2-Ethylhexyl Esters (CAS 135800-37-2). All studies revealed no indication for skin irritation.

Eye irritation potential has been investigated based on an analogue read-across approach with Fatty acids, coco, 2-Ethylhexyl Esters (CAS 92044-87-6) in in vivo assay. There was no indication of eye irritating potential.

Therefore, 2-ethylhexyl nonanoate is not considered to be skin or eye irritating.

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:
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

Based on read-across from the structurally similar substances, the available data for skin and eye irritation 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.