Amines, N-(C18-unsatd. alkyl)trimethylenedi-, ethoxylated

Skin sensitisation

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

Test material information

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)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

arachis oil

Induction 2

Concentration / amount:

Induction intra dermal: 0.1%; epicutaneous: 5%
challenge: 1% & 2%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

arachis oil

Challenge 2

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)

Results

Results 1

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.

Results 2

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.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

1% and 2%

No. with + reactions:

0

Total no. in group:

5

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

1% and 2%

No. with + reactions:

0

Total no. in group:

5

Results 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.