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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(May, 1981)
GLP compliance:
yes
Remarks:
Research & Consulting Company AG CH-4452 Itingen and BRL, Biological Research Laboratories Ltd. CH-4414 Fullinsdorf
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
EC Number:
248-421-0
EC Name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
Cas Number:
27344-41-8
Molecular formula:
C28H22O6S2.2Na
IUPAC Name:
disodium 2,2'-(biphenyl-4,4'-diyldiethene-2,1-diyl)dibenzenesulfonate
Details on test material:
- Name of test material (as cited in study report): FAT 65029/G
- Physical state: powder
- Analytical purity: about 90%
- Impurities (identity and concentrations): 7 % NaCl, 3 % H2O
- Lot/batch No.: EN 372980, Op. 247/248
- Storage condition of test material: room temperature, light protected

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Himalayan spotted
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wolferstrasse 4, CH-4414 Fullinsdorf
- Age at study initiation: 8 weeks
- Weight at study initiation: 321 - 479 g
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 40-70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: physiol. saline for intracutaneous application and vaselium album for epicutaneous application
Concentration / amount:
intradermal application: 5%
epidermal application: 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: physiol. saline for intracutaneous application and vaselium album for epicutaneous application
Concentration / amount:
intradermal application: 5%
epidermal application: 25%
No. of animals per dose:
10 for control group
20 for test group
Details on study design:
RANGE FINDING TESTS: intradermal application: 1, 3, 5 % and epidermal application: 5, 10, 15, 25 %

MAIN STUDY
A. INDUCTION EXPOSURE
An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped free of hair. Three pairs of Intradermal injections (0.1 ml/site) were made at the border of a 4 x 6 cm area in the clipped region as follows:
Test group:
1) Freund's complete adjuvant 50:50 with physiological saline.
2) The test article, diluted to 5% with physiological saline.
3) The test article at the concentration used in (2), emulsified in a 50:50 mixture of Freund's complete adjuvant and the vehicle used in (2)
Control Group:
1) Freund's complete adjuvant 50:50 with physiological saline.
2) Vehicle used in (2) for test group.
3) Freund's complete adjuvant 50:50 with physiological saline
At day 7 of the test and approximately 24 hours prior to the epidermal application the scapular area (approximately 6 x 8 cm) was clipped, shaved free of hair and the test area were pretreated with 10 % Sodium-Lauryl-Sulfate (SLS) in petrolatum-oil, because no primary irritation concentration could be determined in the corresponding pretest. The SLS was massaged into the skin with a glass rod without bandaging. This SLS-concentration enhances sensitization by provoking a mild inflammatory reaction. At day 8 of the test a 2 x 4 cm patch of filter paper was saturated with the test article (25% in vaselinum album) and placed over the injection sites of the test animals. The dressings were left in place for approximately 48 hours. The epidermal application procedure described ensured intensive contact of the test article. The guinea-pigs of the control group were treated as described above with the omission of test article.


B. CHALLENGE EXPOSURE
The test and control guinea-pigs were challenged two weeks after the epidermal induction application. Hair was clipped and shaved from a 5 x 5 cm area on the left and right flank of each guinea-pig. Two patches (2 x 2 cm) of filter paper were saturated with a) non-irritant concentration (25% in vaselinum album) of the test article and b) with the vehicle only and applied to the (a) left flank and (b) right flank using the same method as for the epidermal application. The dressings were removed approximately 24 hours later. The sites were assessed for erythema and edema immediately, 24 and 48 hours after removal of the dressing, using the numerical scoring system as described under preliminary study. The control animals were treated in the same way as described above.

Study design: in vivo (LLNA)

Statistics:
Mean values with standard deviations.
Fisher-Test (The Exact Fisher Test for comparison of the basic probability of two binomial distributions).
For calculation of p-values the 24-hour reading of the animals from the control and test group was used.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

No toxic symptoms were evident in the guinea pigs of the control or test group. No death occurred.

CONTROL GROUP:

Application area around the injection sites 1 and 3 was found to show erythema and edema from day 2 to 8; necrosis was observed from day 10 to 12; encrustations from day 13 to 19 and exfoliations from day 20 to 25 (termination of test). No local symptoms were observed in the injection site 2 treated with physiological saline alone.

TEST GROUP:

Application area around the injection sites 1, 2 and 3 was found to show the same local symptoms as described above for the injection sites 1 and 3 of control group.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
From the results described above no allergenic potency of the test article was concluded. The results were interpreted according to the rating
of Magnusson and Kligman (1969).