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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 April 2001 - 19 May 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recent guideline study under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An in vivo GPMT study was available pre-REACh.

Test material

Constituent 1
Reference substance name:
Tris(hydroxyethyl) oleyl diaminopropane
IUPAC Name:
Tris(hydroxyethyl) oleyl diaminopropane
Test material form:
liquid: viscous
Details on test material:
Ethoduomeen OV/13
Amber coloured. slightly viscous liquid
Batch number: p-1001
Date received: 05 February 2001
Storage conditions: room temperature, in darkness
Analytical results on chainlength distribution ayttached
C16, C18:1, C18:0 with 3EO): 82 %;
C16, C18:1, C18:0 with 2EO: 12.6%;
C16, C18:1, C18:0 with 4EO: 4.4%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 300 - 45Og
- Housing: n pairs in solid-floor polypropylene cages furnished with woodflake
- Diet: ad libitum (Guinea pig FDl Diet, Special Diets Services Limited, Witham, Essex, UK)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- 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:
arachis oil
Concentration / amount:
Induction intra dermal: 0.1%; epicutaneous: 5%
challenge: 1% & 2%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Induction intra dermal: 0.1%; epicutaneous: 5%
challenge: 1% & 2%
No. of animals per dose:
10 test, 5 control
Details on study design:
RANGE FINDING TESTS:
intra dermal: 4 animals: 5%, 1%, 0.5%, 0.1% (1 animal per dose)
epicutaneous dose (48hr):
2 animals: 100%, 75%, 50%, 25% (all levels in each animal)
2 animals: 10%, 5%, 2%, 1% (all levels in each animal)
Challenge (24 hr): 2 animals: 10%, 5%, 2%, 1% (all levels in each animal)

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 i.d., 1 epicutaneous
- Exposure period: 48 hr
- Test groups: 10 animals: 0.1 ml of: A: FCA/water 1:1; B: 0.1% test metarial in arachis oil; C: 0.1% test in a 1:1 preparation FCA/water;
saturated with 5% test susbatnce filter paper 40x20 mm for 48 hrs under occlusion
- Control group: 5 animals similar, except only vehicle instead of test substance.
- Site: A row of three injections (0.1 ml each) was made on each side of the mid-line into a 20 mm x 40 mm area on the shoulder region
- Frequency of applications: day 0: i.d., day 7 epicutaneous
- Concentrations: Induction intra dermal: 0.1%; epicutaneous: 5%; challenge: 1% & 2%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 hrs exposure
- Test groups & Control group: saturated filter paper 20x20 mm with 1% & 2% test substance in arachis oil, for 24 hrs under occlusion. After 24 hr removal patches, and sites were wabbed with cotton wool soaked in diethyl ether
- Site: 2% on shorn right flank; 1% on left flank
- Evaluation (hr after challenge): 24 and 48 hr after removal
Positive control substance(s):
yes
Remarks:
historic list with 2-Mercaptobenzothiazole and alpha-Hexylcinnamaldehyde

Results and discussion

Positive control results:
Positive control performed run 3 month earlier showed adequate reactions: alpha-Hexylcinnamaldehyde: Induction intradermal: 5% in arachis oil, topical 100%; challenge 100% and 75% in arachis oil: results 40% (4/10) sensistisation.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1% and 2%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% and 2%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1% and 2%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% and 2%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1% and 2%
No. with + reactions:
0
Total no. in group:
5
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1% and 2%
No. with + reactions:
0
Total no. in group:
5
Reading:
other:
Group:
positive control
Dose level:
100% & 75%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
a-Hexylcmnamaldehyde: Induction: intradermal 5% in arachis oil BP; topical: 100%. Challenge: 100% and 75% in arachis oil BP

Any other information on results incl. tables

Individual Skin Reactions at Challenge

 

 

 24 Hours

48 Hours

 

 

1%

2%

1%

2%

 Group 

Animal

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

 TEST 

1

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

2

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

3

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

4

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

5

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

6

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

7

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

8

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

9

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

10

0

0

 -

0

0

 -

0

0

 -

0

0

 -

CONTROL

11

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

12

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

13

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

14

0

0

 -

0

0

 -

0

0

 -

0

0

 -

 

15

0

0

 -

0

0

 -

0

0

 -

0

0

 -

Intradermal Induction - Individual Skin Reactions

Grade of Erythema at Observation Site

 

 

 24 Hours 

 48 Hours 

 Group 

Animal

 Left Side 

 Right Side 

 Left Side 

 Right Side 

TEST 

1

2

2

2

2

 

2

2

2

2

2

 

3

2

2

2

2

 

4

2

2

2

2

 

5

2

2

2

2

 

6

2

2

2

2

 

7

2

2

2

2

 

8

2

2

2

2

 

9

2

2

2

2

 

10

2

2

2

2

 

11

2

1

1

0

 

12

1

2

0

0

CONTROL

13

1

1

0

0

 

14

1

1

0

0

 

15

1

2

0

0

 

Topical Induction - Individual Skin Reactions

Skin Reactions (Hours After Removal of Dressing)

 

 

 

1 Hour 

 24 Hours 

 Group 

Animal

Er

Oe

Other

Er

 Oe

Other

 TEST 

1

2

0

 -

2

0

 -

 

2

1

0

 -

1

0

 -

 

3

2

0

 Bs 

?e

?od

 St 

 

4

2

0

 Bs 

?e

?od

 St 

 

5

2

0

 Bs 

?e

?od

 St 

 

6

1

0

 -

1

0

 -

 

7

2

0

 Bs 

2

0

 Bs 

 

8

2

0

 Bs 

?e

?od

 St 

 

9

2

0

 Bs 

?e

?od

 St 

 

10

2

0

 Bs 

?e

?od

 St 

CONTROL

11

1

0

 -

0

0

 -

 

12

1

0

 Bs 

0

0

 -

 

13

1

0

 -

0

0

 -

 

14

1

0

 -

0

0

 -

 

15

2

0

 Bs 

0

0

 -

 

Er = Erythema Oe = Oedema

Bs = Bleeding from intradermal injection sites

?e = Adverse reactions prevent evaluation of erythema

- = No other reactions noted

St = Hardened dark brown/black-coloured scabs

?od = adverse reactions prevent evaluation of oedema

 

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a 0% (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin under the conditions of the test.
Executive summary:

Introduction.

The study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. The method was designed to meet the requirements of the following:

• GECD Guidelines for the Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992)

• Commission Directive96/54/ECMethod B6 Acute Toxicity (Skin Sensitisation)

 

Method.

Ten test and five control animals were used for the study. Two phases were involved in the main study; an induction of a response by intradermal injection and topical application and a topical challenge of that response.

 

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as:

Intradermal Induction    0.1% v/v in arachis oil BP

Topical Induction          5% v/v in arachis oil BP

Topical Challenge         2% and 1% v/v in arachis oil BP

 

Conclusion.

Under the conditions of the test, the test material produced a 0% (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

The test material did not meet the criteria for classification as a sensitiser according to EU labelling regulations Commission Directive 93/211EEC. No symbol and risk phrase are required.