Fatty acids, C16-18 and C18-unsatd., Et esters

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

09 Mar - 30 Apr 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no rationale for used concentrations given, limited details on test substance purity).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

analytical purity of test substance not specified, no range finding for irritation, thus no explanation for used concentrations of 5% for intra- and epidermal induction, 25% for challenge

Principles of method if other than guideline:

Magnusson and Kligman method in guinea pigs

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Züchter Winkelmann, Borchen
- Weight at study initiation: test group mean: 382 g; control group mean: 337 g
- Housing: 5 per cage
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23
- Humidity (%): 50 - 56
- Air changes (per hr): 11
- Photoperiod (hrs dark / hrs light): 12 / 12

Route:

intradermal and epicutaneous

Vehicle:

other: Carboxymethylcellulose, Cremophor

Concentration / amount:

5% for injection
5% for dermal induction
25% for dermal challenge

Route:

epicutaneous, occlusive

Vehicle:

other: Carboxymethylcellulose, Cremophor

Concentration / amount:

5% for injection
5% for dermal induction
25% for dermal challenge

No. of animals per dose:

15 for treatment, 19 as control

Details on study design:

RANGE FINDING TESTS: no data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: injection on day 1, epidermal application on day 7
- Test groups: 3 injections: 0.1 mL Freund's adjuvant, 0.1 mL 5% test substance in 2% Carboxymethylcellulose and 0.5% Cremophor, 0.1 mL Freund's adjuvant with test substance 1:1, concentration 5%; epidermal application: 5% in Vaseline
- Control group: the same than test group without test substance
- Site: two rows with 3 injections right and left of the scapular midline, dermal application on the injections sites
- Frequency of applications: 1
- Duration: single injections and 48 h dermal exposure under occlusive conditions
- Concentrations: 5%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after dermal induction (day 22)
- Exposure period: 24 h
- Test groups: 0.1 mL 25% test substance in 2% Carboxymethylcellulose and 0.5% Cremophor
- Control group: 0.1 mL 2% Carboxymethylcellulose and 0.5% Cremophor
- Site: test substance on the right flank, vehicle on the left
- Concentrations: 25% and vehicle only
- Evaluation (hr after challenge): 48 and 72 h

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

15

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: none.

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

25%

No. with + reactions:

0

Total no. in group:

19

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

15

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

25%

No. with + reactions:

0

Total no. in group:

19

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: none.

The test substance is not sensitising to the skin of guinea pigs, when used as 5% solution for induction and 25% solution for challenge.

Interpretation of results:

not sensitising

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 sensitising)

Additional information:

Justification for grouping of substances and read-across

There are no data available for the sensitisation potential of Fatty acids, C16-18 and C18-unsatd., ethyl esters (CAS 85049-36-1). In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, a 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 sensitisation

CAS#	Skin Sensitisation
85049-36-1 Target substance	RA: 110-27-0
110-27-0	Not sensitising

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 Fatty acids, C16-18 and C18-unsatd., ethyl esters (CAS 85049-36-1).

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

CAS 110-27-0

A Guinea pig maximisation test was performed with isopropyl myristate (CAS 110-27-0) according to a protocol similar to the OECD Guideline 406 (Potokar, 1984). No range-finding study was performed for dose selection. 15 female Pirbright-Hartley guinea pigs were treated with the test substance at 5% for intra- and epidermal induction on days 1 and 7, respectively. 20 animals served as negative controls (one control animal died during the study). A positive control group was not included in the study and no information is given on periodical testing of strain sensitivity, either. 14 days after the epidermal induction, epidermal challenging was performed with a 25% test material dilution in 2% Carboxymethylcellulose and 0.5% Cremophor. 48 and 72 hours after challenging skin examination revealed no irritation in the test group or in the control group. Thus, the test material was found to be not sensitising to the skin of guinea pigs, when used as 5% solution for induction and 25% solution for challenge.Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

Conclusion:

A GPMT has been conducted with the structure related substance isopropyl myristate (CAS 110-27-0). There is no evidence for a skin sensitising potential.

Migrated from Short description of key information:
The overall assessment of the available information gave no indication for sensitising properties of the structural analogues.

Justification for selection of skin sensitisation 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).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on read-across from the structurally similar substances, the available data on skin sensitisation 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.