Isononanoic acid, C16-18 (even numbered)-alkyl esters

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): 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:

experimental study

Adequacy of study:

key study

Study period:

11 - 18 Mar 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Occlusive exposure, analytical purity of test substance not specified.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive exposure

GLP compliance:

no

Species:

rabbit

Strain:

other: New Zealand

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Jègard
- Weight at study initiation: 2.868 kg (mean)

Type of coverage:

occlusive

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:

7 days
Reading time points: 1, 24, 48 and 72 h and 7 days

Number of animals:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test site was not washed after the 4-hour exposure period

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

Very slight erythema (score 1) was observed in 2/3 rabbits 1 hour after exposure ended, and persisted in 1/3 rabbits up to and including the 72-hour reading time point (see Table 1). 1/3 animals had very slight oedema from the 1-hour reading time point up to and including the 48-hour reading time point. All irritiation effects had cleared completely within 7 days.

Other effects:

At the 72-hour reading time point, dry skin was noted at the test site in the rabbit that also showed very slight erythema.

Table 1: Individual skin irritation scores

 

Observation time	Rabbit No.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	0	0	1	1	1	0
24 h	0	0	0	1	1	0
48 h	0	0	0	1	1	0
72 h	0	0	0	0	1	0
7 days	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	0	0	0	0.66	1	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)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given. Limited documentation was available, 48-hour observation period, an unknown volume was applied, 1-2 animals per group, no chemosis scores were given, the analytical purity of the test substance was not specified.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no information on actual amount applied, 48-hour observation period, 1-2 animals per group, no chemosis scores

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

other: oil; type not specified

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3 drops
- Concentration (if solution): 5%, 10% and undiluted

VEHICLE
- Concentration (if solution): 90% and 95%

Duration of treatment / exposure:

Single application without washing

Observation period (in vivo):

48 h
Reading time points: 24 and 48 h

Number of animals or in vitro replicates:

5% solution: 1 male
10% solution: 1 male
undiluted: 2 males

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of 2 animals

Time point:

other: mean over 24 and 48h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: undiluted test substance

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of 2 animals

Time point:

other: mean over 24 and 48h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Remarks on result:

other: undiluted test substance

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of 2 animals

Time point:

other: mean over 24 and 48h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Remarks on result:

other: undiluted test substance

Irritant / corrosive response data:

No eye irritation effects were observed at any time point in animals in the 5%, 10% and undiluted group.

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

CAS 111937-03-2

An acute skin irritation study was performed (similar to OECD 404) with isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) (Dufour, 1991). 0.5 mL undiluted test substance was applied to the shaved skin of 3 rabbits and covered with an occlusive dressing for 4 hours. The test substance caused very slight erythema in 2/3 rabbits at the 1-hour reading time point; the effect persisted in 1/3 rabbits until 72 hours after exposure ended. 1/3 animals had very slight edema from the 1-hour reading time point until the 4-hour reading time point. All skin irritation effects were completely reversible within 7 days.

In a study performed by Potokar (1970), an unknown amount of the test substance was applied to the dorsal skin of a group of 5 hairless mice twice a day for 7 days. No irritation effects were noted. 

In a human epicutaneous patch test performed according to the COLIPA protocol and under GCP conditions, isononanoic acid, C16 -18 alkyl esters was applied to the intact skin of the back of 20 volunteers (Häntschel, 1999). A single exposure to 75 µL of the test substance diluted to 20% in ethanol or of the undiluted test substance for 24 hours under occlusive conditions did not result in skin irritation reactions. As the test protocol was comparable to national standards, the study was judged to be valid for assessment. 

 

Justification for grouping of substances and read-across

There are no data available on the in vivo eye irritation potential of isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). 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
111937-03-2 (a)	Isononanoic acid, C16-18 alkyl esters	382.66; 410.72	WoE: Experimental result: not irritating RA: CAS 59219-71-5
59219-71-5 (b)	3,5,5-trimethylhexyl 3,5,5 -trimethylhexanoate	284.48	Experimental result: not irritating

(a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 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 isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Eye irritation

CAS 111937-03-2

An acute eye irritation study was performed with isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) according to a non-guideline protocol (Potokar, 1970). 3 drops of a 5% solution in oil, 10% solution in oil or undiluted test substance, was instilled into the eye of 1, 1, and 2 rabbits, respectively. The irritation effects were assessed 24 and 48 hours after instillation. No irritation effects were observed in any rabbit at any time point.

59219-71-5

An acute eye irritation study was performed with 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate (CAS 59219-71-5) according to a protocol similar to OECD 405, on 3 New Zealand White rabbits (Dufour, 1990). One eye of the rabbits was exposed to 0.1 mL of the undiluted test substance and scored for eye reactions. The animals were observed for 7 days and scoring was performed 24, 48 and 72 h and 4 and 7 days after application. 3/3 rabbits had slight to moderate chemosis and severe redness (conjunctivae, score 3 of 3) at the 1-hour reading time point. The mean chemosis scores after 24-72 h were 0, 0, 0.33, respectively and the effect was completely reversible within 48 hours. The severity of the conjunctivae decreased gradually and cleared completely within 72 hours, with individual mean scores after 24-72 h of 1.67, 0.67, and 1.00, respectively. No effects on the cornea or iris were noted at any time point.

Conclusions for irritation / corrosion

The results of the skin irritation studies (Dufour, 1991; Häntschel, 1999) indicate that isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) will not cause skin irritation. The results of the eye irritation studies of the source substance and the read-across substance (Dufour, 1990; Potokar, 1970) indicate that isononanoic acid, C16-18 alkyl esters will not cause eye irritation.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.

Justification for selection of skin irritation / corrosion endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (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.