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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:
4th July to 8th August 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
1-bromohexadecane
EC Number:
204-008-7
EC Name:
1-bromohexadecane
Cas Number:
112-82-3
Molecular formula:
C16H33Br
IUPAC Name:
1-bromohexadecane
Details on test material:
- Substance type: White semi-solid block on arrival which melts into a clear colourless viscous liquid.
- Date received: 12th April 2002
- Storage condition of test material: Room temperature in a dark room

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 Ltd, UK and Harlan UK Ltd (used in intradermal induction sighting study).
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 364 to 512 g
- Housing: Individually or in pairs in a solid floor polypropylene cage.
- Diet (e.g. ad libitum): Certified Guinea Pig Diet (Code 5026) supplied by IPS Product Supplies Ltd. UK, permitted ad libitum.
- Water (e.g. ad libitum): Mains tap water ad libitum
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 17 - 23°C
- Humidity: 30-70%
- Air changes (per hr): 15 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours of light 06:00 to 18:00, followed by 12 hrs of dark.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Remarks:
BP
Concentration / amount:
Concentrations were determined by a sighting test.

Intradermal induction application: 5% v/v in arachis oil BP
Epicutaneous induction application: 75% v/v in arachis oil BP
Epicutaneous challange: 50 and 25% v/v in arachis oil BP
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Remarks:
BP
Concentration / amount:
Concentrations were determined by a sighting test.

Intradermal induction application: 5% v/v in arachis oil BP
Epicutaneous induction application: 75% v/v in arachis oil BP
Epicutaneous challange: 50 and 25% v/v in arachis oil BP
No. of animals per dose:
Total of 15 animals were used in the main test; 10 for the test and 5 for the control

Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
Day 0 - Hair was removed on the shoulder region of the test animals. Three injections of volume 0.1 ml, were made in a row on each side of the mid-line:
Injection 1: Freund's Complete Adjuvant plus distilled water in the ratio 1:1
Injection 2: 5% v/v formulation of the test material
Injection 3: 5% v/v formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.

Observations made at 24 and 48 hours post intradermal injection.

Day 7, epicutaneous application of 75% v/v formulation of the test material formulation at the same application site. This was covered occlusively and strapped with an elastic bandage. The animals were exposed to the test material for 48 hours.

Observations were made at 1 and 24 hours following removal of the patches.

B. CONTROL
Intradermal injections were administered in the same manner as described above, except the test material was omitted and injections were as follows:
Injection 1: Freund's Complete Adjuvant plus distilled water in the ratio 1:1
Injection 2: Vehicle
Injection 3: 50% of the vehicle in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.

Epicutaneous application was identical to as described above, except the test material was omitted.

C. CHALLENGE EXPOSURE
On day 21, epicutaneous application of the test material was applied to the flanks of each animal. 50% v/v test material in arachis oil was applied to the right flank of the animal was 25% v/v test material applied to the left flank. The sites were covered occlusively and strapped with an elastic bandage. The animals were exposed to the test material for 24 hours and diethyl ether was used to remove residual material after the 24 hour exposure time.

Observations made at 24 and 48 hours post exposure.

All erythema and oedema observations were recorded according and scored according to the scale shown in table 1 in the field "Any other information on materials and methods incl. tables". Any other reactions were also recorded.
Challenge controls:
Challenge control performed.
Positive control substance(s):
not specified

Study design: in vivo (LLNA)

Statistics:
The senitisation potential of the test material was classified according to the scale in table 2 which can be seen in the field "Any other information on materials and method incl. tables".

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: Challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25 % v/v and 50% v/v
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no other observations
Remarks on result:
other: Reading: other: Challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25 % v/v and 50% v/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no other observations.
Reading:
other: Challenge
Hours after challenge:
48
Group:
other: control
Dose level:
25% v/v and 50% v/v
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no other observations
Remarks on result:
other: Reading: other: Challenge. . Hours after challenge: 48.0. Group: other: control. Dose level: 25% v/v and 50% v/v. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no other observations.

Any other information on results incl. tables

One animal was found dead on day 17. The cause of death was not determined, however it was determined that this did not result from treatment and its absence from the test did not affect the integrity of the study.

Intradermal Induction

Discrete and patch erythema were noted at the induction site of the test and control test animals.

Epicutaneous Induction

Discrete or patchy to moderate and confluent erythema and very slight oedema were noted at the topical induction sites in both test animals. No reaction was noted for the control animals. Bleeding from intradermal injections was noted in five test animals and one control animal. Small superficial scabs were also noted.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test the test material was determined to have a 0% sensitisation rate and is therefore classified as a non-sensitiser.
Executive summary:

The skin sensitising potential of the test material to guinea pigs was determined by performing a maximisation test, in accordance with standardised guidelines OECD 406 and EU Method B.6. Ten test animals and five control animals were exposed to 25% v/v and 50% v/v concentrations of the test material in arachis oil BP. No signs of skin sensitisation were observed at either 24 or 48 hours post exposure.

The test material is determined to be non-sensitising and is unclassified according to Regulation 1272/2008.

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