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Toxicological information

Skin sensitisation

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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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
lack of data on reliability test, analytical purity of test substance not specified
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
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)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
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
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
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)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
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.
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.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
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.
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.