Fatty acids, C8-10, Me esters

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1998-04-28 to 1998-05-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

lack of data on reliability test, analytical purity of test substance not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Methyl laurate

EC Number:

203-911-3

EC Name:

Methyl laurate

Cas Number:

111-82-0

Molecular formula:

C13H26O2

IUPAC Name:

methyl laurate

Details on test material:

- Name of test material (as cited in study report): methyl laurate
- Physical state: colourless liquid
- Content of active substance: Not indicated, treated as 100% pure
- Storage: at room temperature in the dark

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: approx. 5 weeks
- Weight at study initiation: <500 g
- Housing: 5 animals in metal cages with wire mesh floors
- Diet (e.g. ad libitum): free access to standard guinea pig diet, including ascorbic acid (1600 mg/kg); LC 23-B (Hope farms, The Netherlands), in addition, hay was provided once a week (B.M.I., The Netherlands)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Induction 2

Concentration / amount:

- Induction: three pairs of intradermal injections (One of each pair was injected on each side of the midline and from cranial (1) to Caudal (3))
1. 1:1 mixture of Freuds´complete adjuvant with water
2. Test substance (50%) in corn oil
3. 1:1 mixture of the undiluted test substance with Freuds´complete adjuvant
- The epidermal induction was done with the undiluted test substance
- Challenge: 20% test substance in corn oil

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Challenge 2

Concentration / amount:

- Induction: three pairs of intradermal injections (One of each pair was injected on each side of the midline and from cranial (1) to Caudal (3))
1. 1:1 mixture of Freuds´complete adjuvant with water
2. Test substance (50%) in corn oil
3. 1:1 mixture of the undiluted test substance with Freuds´complete adjuvant
- The epidermal induction was done with the undiluted test substance
- Challenge: 20% test substance in corn oil

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: Based on the results of a preliminary studie a 50% dilution of the test substance in corn oil was used for intradermal induction and the undiluted substance was used for the epidermal induction exposure. A 20% test substance concentration was selected for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Intradermal induction on day 1 and epidermal induction at day 8 (for 24 h)
- Test groups: 10 animals, TS in FCA
- Control group: 5 animals treated with vehicle only
- Site: the scapular region of both flanks
- Frequency of applications: once
- Duration: 3 weeks
- Concentrations: 50% dilution of the test substance in corn oil was used for intradermal induction and 100% used for epidermal induction


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after epidermal induction (day 22)
- Exposure period: 24 h
- Test groups: 10 animals, TS
- Control group: 5, TS
- Site: One sheared flanks
- Concentrations: 20% solution in corn oil
- Evaluation (hr after challenge): 24 and 48 h

Positive control substance(s):

no

Results and discussion

Positive control results:

Data not reported

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20% . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

20%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

20%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20% . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

20%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Any other information on results incl. tables

Induction readings:

 

Animal number	Intradermal injection (reading at day 3)			Epidermal exposure (reading at day 10)
	A	B	C	100%
Control				Erythema	Edema
31	E2	NA	E3	0	0
32	N2	NA	E4	0	0
33	E4	NA	E4	0	0
34	E2	NA	E3	0	0
35	E3	E1	E2	0	0
Experimental
36	E2	E1	E2	3	2
37	E3	NA	E3	3	2
38	E3	E2	E4a	4	3
39	E2	E1	E3a	3	1
40	E3	E1	E4a	4n	1
41	E3	E2	E3	4	1
42	E4	E3	E4	4	3
43	E4	E4	E4	4	3
44	E4	E3	E4a	4	3
45	E3	E2	E3a	4	1

A: 1:1 mixture of Freuds´complete adjuvant with water

B: Test substance (50%) in corn oil

C: 1:1 mixture of the undiluted test substance with Freuds´complete adjuvant

a: Moderate erythema visible approx. 2 cm caudally of the injection sites

n: Signs of necrosis

 

Skin effects intradermal injections:

NA: No abnormalities

E(.): Erythema (grade)

N(.): Signs of necrosis (mm in diameter)

Challenge readings

 

Animal No.	Day 24		Day 25			Comments
	20%	Vehicle	20%		Vehicle
Control
31	0	0	0	0
32	0	0	0	0
33	0	0	0	0
34	0	0	0	0
35	0	0	0	0
Experimental
36	0	0	0	0		Not sensitized
37	0	0	0	0		Not sensitized
38	0	0	0	0		Not sensitized
39	0	0	0	0		Not sensitized
40	0	0	0	0		Not sensitized
41	0a	0a	0	0		Not sensitized
42	0	0	0	0		Not sensitized
43	0	0	0	0		Not sensitized
44	0	0a	0	0		Not sensitized
45	0	0	0	0		Not sensitized

 a: Skin reactions grade 1 noted at the edges of the application area are considered non-specificpossibly provoked by the edges of the patches.

No deaths occured. No significant differences in the gain of body weight was observed between treatment and control group.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information According to DSD and CLP classification criteria for skin sensitisation, the test substance has not to be classified.