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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:
other: GLP study in accordance with relevant guideline; selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Data source

Reference
Reference Type:
other: reference to body responsible for the test
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Remarks:
Study was conducted according to guideline in effect at time of study.
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4',4''-(ethan-1,1,1-triyl)triphenol
EC Number:
405-800-7
EC Name:
4,4',4''-(ethan-1,1,1-triyl)triphenol
Cas Number:
27955-94-8
Molecular formula:
C20H18O3
IUPAC Name:
4,4',4''-(ethan-1,1,1-triyl)triphenol
Details on test material:
- Purity: 99%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Not reported.
- Weight at study initiation: 459-546 g
- Housing: Suspended cages with wire mesh floors.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70%
- 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:
other: Intradermal injection vehicle: 5% acetone; Topical application, both induction and challenge: acetone
Concentration / amount:
Concentration of test material and vehicle used at induction:
a) Intradermal: 0.5% in 5% acetone in Alembicol D
b) Topical: 80 % in acetone
Concentration of test material and vehicle used for each challenge:
a) 80 % and 40 % in acetone, topically
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
other: Intradermal injection vehicle: 5% acetone; Topical application, both induction and challenge: acetone
Concentration / amount:
Concentration of test material and vehicle used at induction:
a) Intradermal: 0.5% in 5% acetone in Alembicol D
b) Topical: 80 % in acetone
Concentration of test material and vehicle used for each challenge:
a) 80 % and 40 % in acetone, topically
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 10
Details on study design:
RANGE FINDING TESTS: The intradermal and topical irritancy of a range of dilutions of the test substance was investigated to identify irritant concentrations suitable for the induction phase of the main study and non-irritant concentrations by the topical route for the challenge phase. A concentration of 0.5% was chosen for the intradermal injection as necrosis occurred at the injection site at all higher concentrations. There was no significant irritation at any concentration tested by the topical route. The maximum concentration chosen for topical application was 80% because this concentration of the test substance was the highest that could be prepared within acetone.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One exposure by intradermal injection and one by topical application
- Exposure period: 1 week after the injections, the topical dose was applied and left in place for 48 hours
- Test groups: One group of 20 animals.
- Control group: One group of 10 animals.
- Site: Interscapular area
- Frequency of applications: Once by injection and once topically to the same area.
- Duration: Topical application dressing was left in place for 48 hours.
- Concentrations: 0.5% by intradermal injection; 80% by topical application.

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: One
- Exposure period: 24 hours
- Test groups: One group of 20 animals were used. Each animal was challenged at two concentrations.
- Control group: One group of 10 animals.
- Site: Area on the left flank.
- Concentrations: 40% and 80%
- Evaluation (hr after challenge): 24, 48, and 72 hours after removal of the patches.
Challenge controls:
The sensitivity of the guinea-pig strain used was checked periodically. A check using apostive control substance was completed.
Positive control substance(s):
yes
Remarks:
Formalin

Study design: in vivo (LLNA)

Positive control substance(s):
other: Formalin
Statistics:
No analysis reported.

Results and discussion

Positive control results:
The positive control study (dated: February 10, 1990), induction with 0.1% intradermal injection and 10% topical application followed by topical challenge with 5 and 1% formalin concentrations resulted in a positive result in 10/10 female guinea-pigs.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
80 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 80 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
40 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 40 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
80 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 80 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
40 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 40 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
80 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 80 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
40 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 40 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
80 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 80 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
40 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 40 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Evidence of sensitisation of each challenge concentration: None.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability). The test substance did not produce any contact sensitivity during the observation in any test organism.
Executive summary:

The study assessed the skin sensitisation potential of the test substance. Twenty female guinea-pigs were given induction doses by intradermal injection of 0.5%w/w in 5% acetone in Alembicol D and 0.5% w/w in a 50:50 mixture of Freund's complete adjuvant and 5% acetone in Alembicol D. Test organisms were also given an injection of Freund's complete adjuvant diluted with equal volume of water into the same area at the same time. The area was clipped and shaved one week after exposure. Topical application of 80% w/w test substance in acetone was placed on the same area under a semiocclusive dressing for 48 hours. Two weeks later, the test organisms were challenged topically using 80% and 40% concentrations of test substance in acetone. The test substance was left in place for 24 hours. Challenge sites were evaluated at 24, 48, and 72 hours after removal. A vehicle control group of 10 female guinea-pigs was given the same treatments with acetone vehicle.

 

Reactions were scored on a scale from 0 to 4 for erythema, eschar formation and oedema formation. All test sites were scored 0 for both the test and control animals. The test substance did not produce evidence of contact hypersensitivity.