Isodecyl pivalate

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating (based on read-across from CAS 10233-13-3)
Eye irritation: not irritating (based on read-across from CAS 59130-69-7 and CAS 110-27-0 and in vitro studies of the target substance in a weight of evidence approach)

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:

guideline study with acceptable restrictions

Remarks:

Limited information on test substance and test protocol, occlusive conditions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

limited information on test substance and test protocol, occlusive conditions

GLP compliance:

not specified

Species:

rabbit

Strain:

other: New Zealand

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Jegard
- Weight at study initiation: 1.84 kg
- Acclimation period: 4 days

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated sites served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): pure undiluted substance

Duration of treatment / exposure:

4 hours

Observation period:

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

Number of animals:

3 (male)

Details on study design:

Patch Method according to Selon J.O. R.F. ler Fevrier, 1982

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Directive 67/548/CEE

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

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:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

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 data available on the in vivo skin and eye irritation potential of isodecyl pivalate (CAS 60209-82-7). In order to fulfil the standard information requirements set out in Annex 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 of irritation / corrosion

CAS	Chemical name	Molecular weight	Skin irritation	Eye irritation
60209-82-7 (a)	Isodecyl pivalate	ca. 242	WoE: Experimental result: not irritating RA: CAS 10233-13-3	WoE: Experimental result: not irritating (in vitro) RA: CAS 110-27-0 RA: CAS 59130-69-7
10233-13-3 (b)	Isopropyl laurate	ca. 242	Experimental result: not irritating	--
110-27-0	Isopropyl myristate	270.46	Experimental result: not irritating	Experimental result: not irritating
59130-69-7	Hexadecyl 2-ethylhexanoate	368.63	Experimental result: not irritating	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 isodecyl pivalate (CAS 60209-82-7). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Skin irritation

CAS 60209-82-7

In a human skin patch test performed under GCP conditions, 0.02 mL isodecyl pivalate (CAS 60209-82-7) was applied to the skin of the arm or scapular area of 10 volunteers and covered with an occlusive dressing for 48 hours (Supporting, Stearinerie, 1997). The skin irritation reaction was scored 30 minutes and 24 hours after patch removal. No skin irritation reactions were seen in any volunteer at any time point.

CAS 10233-13-3

A primary dermal irritation study was performed with isopropyl laurate (CAS 10233-13-3) according to OECD Guideline 404 (Key, Stearinerie, 1991). The shaved skin of three rabbits was exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The rabbits were observed for 7 days. Slight oedema and erythema (score 1, respectively) was observed in 1/3 animals from the 1-hr reading time point until the 48-hr reading time point. The effects had cleared completely within 72 hours. 2/3 animals were free of any skin irritation.

Eye irritation

CAS 60209-82-7

Two in vitro eye irritation studies were performed using isodecyl pivalate (CAS 60209-82-7) (WoE, Stearinerie, 1997). The Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) assay was performed on 6 fertile, 10 days old, white Leghorn eggs. 6 eggs were exposed to the test substance for 20 seconds and the irritation was scored 30 sec, and 2 and 5 min after exposure ended. The IP-CAM score was 0, indicating that the test substance is not corrosive. The negative and positive controls were valid.

A cytotoxicity assay with rabbit cornea (SIRC) fibroblasts, following the MTT assay, was performed (WoE, Stearinerie, 1997). The SIRC cells were first seeded into Transwell inserts and then placed in tissue culture plate wells with culture medium. Following an incubation period of 48 hrs at 37 ⁰C, the Transwell inserts were transferred into second cluster plates and incubated with a 1% solution of the test substance for 30 min, 1 hr and 4 hrs. To measure the cell viability, the solution was incubated with MTT dye for 2-3 hrs. Finally, the absorbance of the solution was measured with a spectrophotometer at 570 nm. The cell viability was 96, 100 and 72% for the 30-min-, 1-hr- and 4-hr reading time points, respectively. The mean cytotoxicity index (MCI) was 2.4 and the ocular irritation index (IOeq) 6.0, indicating that the substance is slightly irritating.

CAS 110-27-0

An acute eye irritation study was performed with isopropyl myristate (CAS 110-27-0) according to a protocol similar to OECD 405, on 3 New Zealand White rabbits (WoE, Croda, 1977). 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. Conjunctival redness (score 1) was observed in 2/3 animals at the 24-h reading time point. The effect was fully reversible within 48 hours. No other eye irritation effects were observed.

CAS 59130-69-7

The potential of hexadecyl 2-ethylhexanoate (CAS 59130-69-7) to cause eye irritation was evaluated in a GLP study performed according to OECD guideline 405 (WoE, BASF, 1991). 0.1 mL hexadecyl 2-ethylhexanoate was instilled into the eyes of three Kleinrussen rabbits; the test substance was removed by washing with water after 24 hrs. 3/3 rabbits had slight conjunctiva (score 1) at the 1-hour reading time point. The mean scores after 24, 48 and 72 h for conjunctivae were 0.33, 0.33 and 0.67 respectively, while the mean scores for cornea, iris and chemosis were 0 for 3/3 rabbits. Therefore, hexadecyl 2-ethylhexanoate was found to be not irritating to eyes.

Conclusions for irritation / corrosion

The results of the skin irritation studies performed with the source and target substance (Key, Stearinerie, 1991; Supporting, Stearinerie, 1997) indicate that isodecyl pivalate (CAS 60209-82-7) will not cause skin irritation. The results of the in vitro studies of the target substance (WoE, Stearinerie, 1997) and in vivo eye irritation studies with the source substances (WoE, Croda, 1977;WoE, BASF, 1991) indicate that isodecyl pivalate will not cause eye irritation.

Justification for classification or non-classification

Based on substance-specific data and read-across from the structurally similar substances, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.