Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP study. NO OECD and EU guidelines were followed.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
Method: according to Magnusson B. und Kligman A.M.: J. Invest. Derm. 52, 268-276
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

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, Darley Oaks, Newchurch, Burton upon Trent, Staffordshire
- Weight at study initiation: 300 - 450 g
- Housing: Animals were housed in groups of five in suspended metal cages.
- Diet: ad libitum, Guinea Pig Diet, J . Waring (Feeds) Limited, Shardlow, Derbyshire
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 + 3°C
- Photoperiod (hrs dark / hrs light): 14 hours light, 10 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
- Intradermal induction: 1% in water
- Topical induction: 10% in water
- Topical challenge: 2% in water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
- Intradermal induction: 1% in water
- Topical induction: 10% in water
- Topical challenge: 2% in water
No. of animals per dose:
10 (4 animals control group)
Details on study design:
RANGE FINDING TESTS:
a) intradermal injection: An area measuring 4 x 6 cm in the shoulder region of 2 guinea pigs was clipped free of hair using oster A5 electric animal clippers. Into these areas were injected simultaneously six 0 .1 mL intradermal injections as follows : 5% (animal 1) and 1% (animal 2). Animals were observed 24, 48 and 72 hours and 7 days following treatment and any evidence of localized necrosis or systemic toxicity was recorded. Using information obtained from this preliminary test the concentration of test material to be used for the Main Study was selected .
b) The test material at four concentrations (usually 100%, 50%, 25% and 10%) was topically applied under an occlusive patch to four sites on the shaved backs of each of a group of two guinea pigs. The degree of irritancy at the test sites were evaluated for erythema immediately after removal of the patches and then at 24 and 48 hours . The concentrations of the test material to be used on two further animals were chosen, applied and then evaluated after similar time intervats. Using the information obtained from this preliminary test the concentrations to be used for topical challenge in the Main Study were selected.

MAIN STUDY
A. INDUCTION EXPOSURE (indradermal)
- No. of exposures: 1
- Exposure period: single exposure
- Test groups: The treated animals were injected on three different sites of the shaved flank with either of three solutions (Freuds complete adjuvance (FCA) alone, test material alone, test material with FCA).
- Control group:The control animals were received similar treatment to the test group (FCA alone, sodium chloride alone, sodium chloride with FCA)
- Site: shoulder region
- Frequency of applications: single


If the test material was found to be non-irritating in the siting test, the area was pretreated with 10% sodium lauryl sulphate (SLS) in petrolatum 24 hours prior to topical application.

INDUCTION EXPOSURE (topical application)
- No. of exposures: 1
- Exposure period: at day 7
- Test groups: The treated animals were induced with the test substance.
- Control group:The control animals were treated with sodium chloride.
- Site: shoulder region
- Frequency of applications: single


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: two weeks after the topical induction
- Exposure period: 24, 48 h
- Test groups: The animals were treated with the test material.
- Control group: The control animals were treated with the vehicle (only).
- Site: shoulder region
- Concentrations: 2 %
- Evaluation (hr after challenge):24 and 48 hours

Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2 %
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 2 %. No with. + reactions: 0.0. Total no. in groups: 4.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2 %
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2 %. No with. + reactions: 4.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2 %
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2 %. No with. + reactions: 0.0. Total no. in groups: 4.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
2 %
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2 %. No with. + reactions: 2.0. Total no. in groups: 10.0.

Any other information on results incl. tables

As indicated in the above table 4/10 of the animals in the test group showed evidence of erythema at the challenge sites. As no evidence of erythema was observed in any of the control animals, these effects seen in the test group were attributed to contact sensitization.

The test material, therefore, produced a 40% sensitization rate and was classified as a moderate (GRADE III) contact sensitizer.

Applicant's summary and conclusion