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

Endpoint summary

Description of key information

A recent GLP Maximisation has shown Oleyl-diamine3EO not to be sensitising to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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.

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.

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

Route:

intradermal and epicutaneous

Vehicle:

arachis oil

Concentration / amount:

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

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

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.

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

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There is one study available in which Oleyl-diamine3EO has been evaluated for skin sensitising properties. The study was performed in Guinea pigs according to OECD 406 Maximisation test method, and in compliance to GLP, using ten test and five control animals. 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

Topical Induction          5% v/v in arachis oil 

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

Under the conditions of the test, the test material produced a 0% (0/10) sensitisation rate.

Consequently, Oleyl-diamine3EO is considered not to possess sensitising properties.

 

Further information that should be considered:

- These substances are corrosive to skin.

- The profiling of these substances do not indicate reactivity to protein; No alerts for sensitisation are given by QSARs on these structures (Derek Nexus: 6.0.1: non-sensitiser; No misclassified or unclassified features)

- No concerns from structural analogues

- No concerns have been raised from the use/application of these products with respect to the occurrence of sensitisation (or contact dermatitis).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There is no information on respiratory sensitisation. However, no concerns are expected.

As chemical respiratory sensitisers also elicit positive results in predictive tests for contact sensitisation, a negative outcome for dermal sensitisation is also predictive for non respiratory sensitisation of the substance.

Additionally, the likelihood for exposure via inhalation and thus becoming sensitised to Oleyl-diamine3EO, is very low, based on the high boiling point (> 300 °C) and very low vapour pressure (< 0.0015 Pa at 20°C) and use that is limited to industrial and professional users and which does not involve the forming of aerosols, particles or droplets of an inhalable size.

Justification for classification or non-classification

Oleyl-diamine3EO has shown to be non-sensitising in a adequately performed Guinea pig study following the Magnusson and Kligman Maximisation Method. Consequently, the substance does not need to be classified for sensitisation.

These negative results for skin sensitisation can also be regarded as indicating the lack of the potential to cause allergic sensitisation of the respiratory tract.