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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:
other: Study according/similar to OECD TG und GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
The method used followed closely the procedure of the Guinea Pig Maximisation Test of OECD TG 406.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time when the GPMT) study was conducted (1993), the LLNA had not been established.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Sure Sol-250, monoisopropylbiphenyl
- Physical state: colorless liquid
- Analytical purity: no data
- Lot/batch No.: 4194-01
- Stability under test conditions: no data
- Storage condition of test material: at room temperature in a brown glass bottle under nitrogen

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 Limited, Burton-on-Trent, Staffordshire, U.K.
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 349 - 442 g
- Housing: in groups of up to three in solid floor polypropylene cages furnished with sofftwood shavings
- Diet (e.g. ad libitum): Guine Pig FD1 Diet, Special Diet Services Limited, Witham Essex, U.K.; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: 5 days at minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 25
- Humidity (%): 54 - 67
- 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:
arachis oil
Concentration / amount:
Intradermal induction: 25% (w/v) TS in arachis oil B.P.
25% (w/v) TS in an 1:1 mixture of Freund's Complete Adjuvants and arachis oil
Topical induction: undiluted TS as supplied from sponsor
Topical challenge: undiluted TS (0.1 - 0.2 mL) and 75% (w/v) TS in arachis oil B.P.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Intradermal induction: 25% (w/v) TS in arachis oil B.P.
25% (w/v) TS in an 1:1 mixture of Freund's Complete Adjuvants and arachis oil
Topical induction: undiluted TS as supplied from sponsor
Topical challenge: undiluted TS (0.1 - 0.2 mL) and 75% (w/v) TS in arachis oil B.P.
No. of animals per dose:
Test animals: 20
Control animals: 10
Details on study design:
RANGE FINDING TESTS:
A. INDUCTION EXPOSURE
- Intradermal induction
4 guinea pigs were intradermally injected with preparations of 1, 5, 10, and 25% of TS in arachis oil B.P. The highest concentration that died not cause local necrosis, ulceration, or systemic toxicity was selected for intradermal induction (25% TM in arachis oil).
- Topical induction
2 guinea pigs - intradermally injected with Freund's Complete Adjuvants 10 days earlier - were treated with the undiluted test material and three preparations of the test material (75, 50, and 25% v/v in arachis oil B.P). The highest concentration producing only mild to moderate dermal irritation after a 48 h occlusive exposure was selected for topical induction (neat test material).
B. CHALLENGE EXPOSURE
- Topical challenge
2 guinea pigs, treated for induction like control animals, were occlusively exposed to neat test material and to 75% v/v test material in arachis oil B.P for 24 h. The highest non-irritant and one lower concentration were selected for topical challenge (both concentrations tested were selected).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: two (intradermal and topical induction)
- Exposure period: topical induction 48 h (occlusive wrapping)
- Test groups: intradermal induction - application of FCA and distilled water 1:1, 25% TS in arachis oil, and 25% TS in an 1:1 mixture of FCA and arachis oil, topical induction - pure TS applied on filter paper 40 x 20 mm
- Control group: intradermal induction - application of FCA and distilled water 1:1, pure arachis oil, and FCA and arachis oil 1:1, topical induction - only application of filter paper
- Site: shoulder region, for intradermal induction three injections on both sides of the mid-line
- Frequency of applications: intradermal induction at day 0, topical induction at day 7
- Duration: 7 days followed by 14 days induction period
- Concentrations: see above

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21 of test
- Exposure period: 24 h (occlusive wrapping)
- Test groups: neat TS, 75% TS in arachis oil (right flank), and pure arachis oil (left flank)
- Control group: same as test group
- Site: right and left flank
- Concentrations: see above
- Evaluation (hr after challenge): 24 and 48 h after after challeng dressing removal
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
neat test substance
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: neat test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
neat test substance
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: neat test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

No skin reactions were noted at the challenge sites and vehicle control sites of the test or control group animals at the 24 and 48 h observations. The test material SURE SOL-250 (monoisopropylbiphenyl, MIPB) produced a 0% (0/20) sensitisation rate and was classified as non-sensitiser to guinea pig skin.

 

Body weight gains of guinea pigs in the test group over the test period were comparable to those observed in the control group animals.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guinea pig maximisation test according to OECD test guideline 406 performed under GLP conditions, test animals did not show any skin reactions at the challenge site 24 and 48 h after challenge (0/20 animals - sensitisation rate 0% ). The test sbstance Sure Sol-250 (monoisopropylbiphenyl, MIPB) is assessed to be not sensitising.