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Toxicological information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The in vivo skin sensitisation study that was carried out before 10 May 2017, and that meets the requirements set out in Article 13(3), first subparagraph, and Article 13(4) shall be considered appropriate to address this standard information requirement.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular
Specific details on test material used for the study:
Tribromophenol was supplied by the sponsor, Bromine Compounds Ltd.
Batch number: 950225
Date received: 18 July 1996
Physical description: pink to white flakes
Purity: 99.9%
Storage conditions: ambient temperature (< 25°C), shielded from light

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd, Burton-on-Trent, Staffordshire UK
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 319 - 438 grams
- Housing: singly or in pairs on solid floor propylene cages with woodflakes
- Diet: Guinea Pig FD1 Diet (Special Diet Services Limited, Witham, Essex, UK) ad libitum
- Water: tap water ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 50 - 66
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and dark

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
10% w/v in arachis oil in Freund's Complete Adjuvant/distilled water 1:1 for induction using intradermal injection
50% w/w in arachis oil for topical induction (occluded)
Day(s)/duration:
9
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Topical challenge 75 % and 50 % w/w in arachis oil bp.
Day(s)/duration:
1
No. of animals per dose:
20 test animals (one dose in main study), and ten controls
Details on study design:
RANGE FINDING TESTS
Four concentrations of test material were investigated (1%, 5%, 10% and 25% w/v in arachis oil) for intradermal injection in four guinea pigs (four injections of the same dose per animal). Four concentrations were investigated (10%, 25%, 50%, 75% w/w in arachis oil) for occluded topical induction. The degree of erythema and edema was evaluated at 24, 48, 72 hours, and 7 days after injections acording to the Draize scale (1977). The reactions were evaluated at 1, 24, and 48 hours after dressing removal for topical induction. The highest concentration producing only mild to moderate dermal irritation was selected for the induction stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 (10% w/v in arachis oil and 10% in Freund's Complete Adjuvant 1:1 in distilled water one injection of each); subsequent topical application of 50% test material w/w in arachis oil with occlusion bandage for all animals.
- Exposure period: 7 days between intradermal injections and topical treatment, 48 hours of topical occlusion.
- Test groups: 1 (20 animals)
- Control group: 1 (10 animals)
- Site: shoulder
- Frequency of applications: one intradermal injection per site on day 1; one topical application beginning on day 7
- Duration: Time between first injection and removal of topical occlusion bandage was 9 days
- Concentrations: 10% w/v for injection, 50% w/w for topical application

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 days after first dose
- Exposure period: 24 hours
- Test groups: 1 (20 animals)
- Control group: 1 (10 animals)
- Site: right flank
- Concentrations: 50% w/w in arachis oil
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Procedures as for the test animals except without test compound
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Topical challenge 75 % w/w in arachis oil bp.
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
Very slight to well-difined erythema - grades 1 or 2 and incidents of very slight to slight oedema
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Topical challenge 75 % w/w in arachis oil bp.
No. with + reactions:
10
Total no. in group:
20
Clinical observations:
very slight to well-difined erythema - grades 1 or 2 and incidents of very slight to slight oedema
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Topical challenge 50 % w/w in arachis oil bp.
No. with + reactions:
15
Total no. in group:
20
Clinical observations:
very slight to moderate to severe erythema - grades 1 or 3 and incidents of very slight to slight oedema
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Topical challenge 50 % w/w in arachis oil bp.
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
very slight to moderate to severe erythema - grades 1 or 3 and incidents of very slight to slight oedema
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions were noted at the challenge sites of control group animals at 24 and 48-hour observations.
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Under the conditions of this study tribromophenol produced 75% (15/20 animals) sensitization rate and is therefore categorized as a strong skin sensitizer to guinea pigs according to EU regulations based on the proportion of animals that reacted to the test compound.