Fatty acids, safflower-oil, Et esters

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

May - July 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP and guideline compliant study with minor deviations. Methyl linoleate (CAS# 112-63-0) was used as a structural analogue read-across substance for skin sensitization hazard identification of ethyl linoleate, which is the main component of the test substance. It can be expected that methyl linoleate would exert similar characteristics in pathophysiological mechanism of skin sensitization. Upon activity of dermal esterases, methyl linoleate would be cleaved into linoleic acid and methanol, representing sufficient similarity to the metabolites linoleic acid and ethanol, resulting from cleavage of ethyl linoleate.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

only 10 test animals are used

GLP compliance:

yes

Type of study:

Buehler test

Test material

Test material information

Constituent 1

Reference substance name:

Methyl linoleate

EC Number:

203-993-0

EC Name:

Methyl linoleate

Cas Number:

112-63-0

IUPAC Name:

methyl octadeca-9,12-dienoate

Constituent 2

Reference substance name:

Octadecadienoic acid methyl ester

IUPAC Name:

Octadecadienoic acid methyl ester

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): octadecadienoic acid methyl ester
- Physical state: liquid
- Lot/batch No.: 89F0928
- Storage condition of test material: cool and dark

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Crl:(HA)BR
- Source: Charles River, D-Sulzfeld
- Age at study initiation:approx. 6 weeks
- Weight at study initiation: approx. 340 g (main study)
- Housing: air-conditioned, groups of 2-3 animals in Makrolon Type IV cages with standard softwood bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -25°C
- Humidity (%): 45 - 70%
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12h dark / 12h

IN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

olive oil

Induction 2

Concentration / amount:

Preliminary study: 10, 20, 30, 40, 50, 70, 90%
Main Study:
Induction: minimal irritating concentration (solution of 40%)
Challenge: maximally non-irritating concentration (solution of 20%)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

olive oil

Challenge 2

Concentration / amount:

Preliminary study: 10, 20, 30, 40, 50, 70, 90%
Main Study:
Induction: minimal irritating concentration (solution of 40%)
Challenge: maximally non-irritating concentration (solution of 20%)

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS:
- left flank: 30 - 50 - 70 - 90%
- right flank: 10 - 20 - 30 - 40%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6h
- Test groups: 10 animals
- Control group: 2 x 10 animals
- Site: left cranial sheared flank
- Frequency of applications: once a week
- Concentrations: 40%

B. CHALLENGE EXPOSURE
- Exposure period: 6 h
- Site: bilaterally to sheared flanks of test animals and control group 1 animals
- Concentrations: 20%
- Evaluation (hr after challenge): 24, 48 h

Challenge controls:

The control group 2 was treated with olive oil in the first and second week after the challenge of the other groups in order to estimate the influence of the vehicle.

Positive control substance(s):

no

Results and discussion

Positive control results:

No results available.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20%

No. with + reactions:

5

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20%. No with. + reactions: 5.0. Total no. in groups: 10.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

20%

No. with + reactions:

2

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20%. No with. + reactions: 2.0. Total no. in groups: 10.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Olive oil

No. with + reactions:

3

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Olive oil. No with. + reactions: 3.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

olive oil

No. with + reactions:

1

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: olive oil. No with. + reactions: 1.0. Total no. in groups: 10.0.

Any other information on results incl. tables

	24 hours		48 hours
	control animals (10)left / right	Test animals (10)left / right	Control animals (10)left / right	Test animals (10)left / right
none	4 / 7	5 / 5	6 / 9	7 / 7
weak	5 / 3	5 / 5	2 / 1	3 / 2
moderate	1 / 0	0 / 0	0 / 0	0 / 0
strong	0 / 0	0 / 0	0 / 0	0 / 0

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Since no increased dermal alterations (incidence and severity) were observed in the animals of the treatment group compared with the animals of the control group after the challenge, the test substance is proved to be a "non-sensitizer" on the skin of guinea pigs.

Executive summary:

The purpose of the study was to assess the sensitizing potential of the test substance on the skin of guinea pigs by epicutaneous application under an occlusive patch following an induction period.

The test substance was tested on the skin using a "non-adjuvans-methos" (Buehler test). In total 30 guinea pigs of the strain "Crl:(HA)BR" were used as the test sytem.

According to the results of the preliminary studies, a 40 % dilution of the test substance was the minimally irritating, a 20 % dilution of the test substance was the maximally non-irritating concentration.

After triple (once a week) epicutaneous application (occlusive/6h) of the minimally irritating concentration to induce sensitization, a challenge of the animals was performed with the maximally non-irritating concentration (occlusive/6h).

The treatment animals and the control animals as well were without any distinct dermal effects after challenge. The challenge reactions after exposure to olive oil in the experimental animals of the control group 2 were weak to moderate dermal reactions. Since no increased dermal alterations (incidence and severity) were observed in the animals of the treatment group compared with the animals of the control group after the challenge, the test substance is proved to be a "non-sensitizer" on the skin of guinea pigs.