Isobutyl laurate

Endpoint summary

Description of key information

Skin irritation (OECD 404), rabbit: not irritating (RA CAS 10233-13-3 and RA CAS 123-95-5)
Eye irritation (OECD 405), rabbit: not irritating (RA CAS 110-27-0)

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (limited documentation on test substance purity and test protocol).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

limited documentation on test substance purity and test protocol

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1800 - 2400 g

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 instillation without washout

Observation period (in vivo):

7 days in the absence of any irritation reaction
Reading time points: 24h, 48h, 72h, 4 days and 7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE: No

SCORING SYSTEM: according to Draize scale for scoring ocular lesions

TOOL USED TO ASSESS SCORE: hand-held lenses

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

After instillation of the test substance into rabbit eyes there was slight conjunctival irritation observed, that was reversible after 48h.

Table 1: Individual irritation scores

Animal Number	Hours after Application
	24				48				72
	A	B	C	D	A	B	C	D	A	B	C	D
1	0	0	1	0	0	0	0	0	0	0	0	0
2	0	0	1	0	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0	0	0	0	0

A = Cornea Score

B = Iris Score

C = Conjunctiva Score

D = Chemosis Score

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: 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 only limited data available on skin and eye irritation of isobutyl laurate (CAS 37811-72-6). 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 of skin and eye irritation

CAS	Chemical name	Molecular weight [g/mol]	Skin irritation	Eye irritation
37811-72-6 (a)	Isobutyl laurate	256.42	WoE: RA: CAS 10233-13-3 RA: CAS 123-95-5	RA: CAS 110-27-0
110-27-0 (b)	Isopropyl myristate	270.45	Experimental result: not irritating	Experimental result: not irritating
10233-13-3 (b)	Isopropyl laurate	242.40	Experimental result: not irritating	--
123-95-5 (b)	Butyl stearate	340.59	Experimental result: not irritating	Experimental result: not irritating

(a) The substance subject to registration is indicated in bold font.

(b) Reference (read-across) substances 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 isobutyl laurate (CAS 37811-72-6). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

No data on skin and eye irritation is available with isobutyl laurate (CAS 37811-72-6). Therefore, read across from the structurally analogue substances isopropyl myristate (CAS 110-27-0), isopropyl laurate (CAS 10233-13-3) and butyl stearate (CAS 123-95-5) was applied.

 

Skin irritation

CAS 10233-13-3

In the reliable skin irritation study performed according to OECD TG 404 three male New Zealand rabbits were exposed to 0.5 mL of the neat test material (CAS 10233-13-3) for 4 hours applied onto the shaved skin via occlusive dressing (Dufour, 1991). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48 and 72 hours and 7 days post-application. No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study. Very slight erythema and edema formation (grade 1) were observed for 1/3 animals 24 and 24 hours post-application which were fully reversible within 72 hours. The mean value for erythema and edema were calculated to be 0.67.

CAS 123-95-5

In the reliable skin irritation study performed according to OECD TG 404 three Albino rabbits of each sex were exposed to 0.5 mL of the neat test material (CAS 123-95-5) for 24 hours applied onto the shaved intact and abraded skin via occlusive dressing (Wallace, 1976). Skin reactions were evaluated according to the Draize scoring system 24 and 72 hours post-application. No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study. Very slight erythema (grade 1) were observed in 2/6 (intact skin) and 3/6 (abraded skin) animals 24 hours post application which were fully reversible within 72 hours. The mean values for erythema were calculated to be 0.22 (intact skin) and 0.33 (abraded skin), respectively. No edema formation (neither intact nor abraded skin) was observed in any animal during the entire study period.

Taken together, the available data on skin irritation from structural analogue substances do not indicate any irritating potential. Therefore, according to EU classification criteria, the target substance isobutyl laurate (CAS 37811-72-6) is not to be classified.

Eye irritation

CAS 110-27-0

In the reliable eye irritation study with isopropyl myristate (CAS 110-27-0) performed equivalent or similar to OECD TG 405 (Palanker, 1977) 0.1 mL of the neat test material was instilled in the eye of three New Zealand White rabbits. The eyes were examined and the changes were graded according to the Draize scoring system 24, 48 and 72 hours and 4 and 7 days post-application. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred during the course of the study. Neither iridial irritation nor corneal opacity and chemosis were observed in any animal during the course of the study. 2/3 animals showed slight conjunctivae irritation (grade 0.33) which was fully reversible within 48 hours.

Therefore, according to EU classification criteria, the target substance isobutyl laurate (CAS 37811-72-6) is not to be classified.

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.

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.

References:

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

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to isobutyl laurate (CAS 37811-72-6), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, 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.