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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
Study period:
Dec 26, 1996 - May 8, 1997
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 guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted before LLNA was established.

Test material

Constituent 1
Chemical structure
Reference substance name:
Diisopropylbiphenyl and triisopropylbiphenyl
EC Number:
915-589-8
Molecular formula:
not applicable for UVCB substance
IUPAC Name:
Diisopropylbiphenyl and triisopropylbiphenyl
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Sure Sol-300
= compound of diisopropyl-1,1'-biphenyl [CAS no. 69009-90-1] and tris(1-methylethyl)-1,1'-biphenyl [CAS no. 29225-91-0],
~60% and ~35%, resp., plus other alkylbiphenyls (not specified: ~5% (acronym: di-IPB/tri-IPB, not specified in the report)
- Reference: Koch Chem. Comp USA 1999: Sure Sol 300 - MSDS 10 Feb. 1999

- Substance type: organic
- Physical state: clear liquid
- Analytical purity: 100 % aromatics
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Lot/batch No.: #TK1903-96-3
- Stability under test conditions: no measured data; based on chemical structure assumed to be stable
- Storage condition of test material: in a cabinet at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: albino Crl:(HA)BR
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc.; Portage, Michigan, USA)
- Age at study initiation: young adult (age not precisely specified)
- Weight at study initiation: 350g - 550g
- Housing: individually in suspended screen-bottom stainless steel cages (during acclimation and throughout the study)
- Diet: Certified Guinea Pig Diet #5026 (PMI Feeds, Inc.) ad libitum
- Water: ad libitum
- Acclimation period: 7 days after receipt

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): relative humidity 50% (+/-20%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted (since the test item was non-irritating based on the results of the range finding test).
Challenge
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted (since the test item was non-irritating based on the results of the range finding test).
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
total 34 of any sex
- Irritation screen study: 4
- Main study: 20 (test group)
10 (Irritation control group)
Identification by individual numbered ear tag
Details on study design:
RANGE FINDING TESTS: Irritation screening study
- Four animals were treated with test item: undiluted, 25%, 50%, 75% (w/v in mineral oil). Each animal received two different concentrations.
- The test item was was applied to saturation to filter papers (Whatman No. 3, 2 cm x 2 cm), which were applied to both sides of each animal
(right and left side of the shaved back) and covered with overlapping strips of Blenderm™ tape and overwrapped with Elastoplast® tape.
- After 24 hours the patches were removed, and the application sites were wiped with wet disposable paper towels.
- The application sites were opserved at 24 and 48 hours after removal for dermal reactions.

MAIN STUDY

A. INDUCTION EXPOSURE
Intradermal injections (Day 1):
2 pairs of intradermal injections within a 2 cm x 4 cm-area (3 injections on each side of the midline of the shoulder region)
- Test group: anterior sites: 0.1 mL of Freund's Complete Adjuvant (FCA; 1:1 dilution with sterile water)
medial sites: 0.1 mL suspension of test material (5% w/v in mineral oil)
posterior sites: 0.1 mL suspension of test material in Freund's Complete Adjuvant (5% w/v in 1:1 FCA in sterile water)
- Control group: anterior sites: 0.1 mL of Freund's Complete Adjuvant (1:1 dilution with sterile water)
medial sites: 0.1 mL of mineral oil
posterior sites: 0.1 mL mineral oil in Freund's Complete Adjuvant
Topical application
- Pretreatment with 10% w/w sodium lauryl sulfate (SLS) (Day 7)
- The test item or control item was was applied to saturation to filter papers (Whatman No. 3, 2 cm x 2 cm), which were placed over the injection site
and covered with overlapping strips of Blenderm™ tape and overwrapped with Elastoplast® tape (Day 8).
- After48 hours the patches were removed and the application sites were wiped with wet disposable paper towels.
- Test groups: Test item, FCA
- Control group: vehicle control (mineral oil), FCA
- Site: shoulder
- Frequency of applications: 2 (intradermal injection and topical application)
- Duration: 48 h (topical application)
- Concentrations: undiluted test item

B. CHALLENGE EXPOSURE (Day 22; two weeks after topical application)
- No. of exposures: 1
- Day of challenge: test day 22
- Exposure period: 24 h
- Test groups: Test item, vehicle
- Control group: Test item, vehicle
- Site: flanks
- Concentrations: undiluted test item(right side) and vehicle (left side)
- Application sites were covered with overlapping strips of Blenderm™ tape and overwrapped with Elastoplast® tape.
- Evaluation (hr after challenge): 24 h and 48 h

Clinical observation: daily until experimental termination
Challenge controls:
A positive control study using the same maximisation method was conducted within six month of the conduct of the main study.
Control group: 5 animals
Test group: 10 animals
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene (0.1% w/v in acetone)

Results and discussion

Positive control results:
1st reading (24 hrs after challenge): All animals of the test group challenged with 4-dinitrochlorobenzene (0.1% w/v in acetone) exhibited dermal
reactions in the range between 2 and 3 at the treated areas;
2nd reading (48 hrs after challenge): All animals of the test group challenged with 4-dinitrochlorobenzene (0.1% w/v in acetone) exhibited
desquamation, one in combination with subcutaneous hemorrhaging.
Control application of the test group did not result in any reactions.
All animals in the vehicle control group kept healthy after challenging.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
undiluted test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
mineral oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
undiluted test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
mineral oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
induction: 0.1% (w/v) intradermal, 0.3 % (w/v) epictuaneous, challenge: 0.1% (w/v)
No. with + reactions:
9
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
induction: 0.1% (w/v) intradermal, 0.3 % (w/v) epictuaneous, challenge: 0.1% (w/v)
No. with + reactions:
9
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

In the preliminary irritation screening study the test material caused no dermal reaction in any animal at any concentration. Therefore it was administered undiluted for topical induction and for the challenge phase in the main study.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
Under the conditions of the conducted GPMT test, the test substance did not exhibit sensitising properties.
CLP: not classified