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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 conducted according to internationally accepted testing guidelines and according to the GLP procedures.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland.
- Age at study initiation: males: 7 weeks, females: 8 weeks.
- Weight at study initiation: males: 336 - 461 g, females: 332 - 428 g.
- Housing: single.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: one week.

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: distilled water and petrolatum oil
Concentration / amount:
Intradermal induction: 5 %
Cutaneaous induction: 25 %
Challenge: 10 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: distilled water and petrolatum oil
Concentration / amount:
Intradermal induction: 5 %
Cutaneaous induction: 25 %
Challenge: 10 %
No. of animals per dose:
Control group: 5 male and 5 female
Test group: 10 male and 10 female
Details on study design:
RANGE FINDING TESTS
The objective of this investigation was to identify irritant test article concentrations suitable for the induction phase of the main study. In addition, a suitable non-irritant concentration of the test article, by the topical route of administration, was identified for the challenge application.
The procedure applied for these investigations was as follows:
_Intradermal injections: intradermal injections (0.1 ml/site) were made into the clipped flank of two guinea-pigs at concentrations of 1, 3 and 5 % of the test article in distilled water. The resulting dermal reactions were assessed 24 hours later.
_Epidermal applications: patches of filter paper ( 2 x 2 cm) were saturated with concentrations of 3, 5, 10 and 25 % of the test article in petrolatum oil and applied to the clipped and shaved flanks of each of four guinea-pigs. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wound round the trunk and covered with impervious adhesive tape. This procedure ensured the intensive contact of the test article. The dressings were removed after an exposure period of 24 hours and the reaction sites were assessed for erythema and edema on a numerical basis according to the scale described above. Further examination of the sites were performed 24 and 48 hours after removal of the dressings.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (one intradermal, one epidermal).
- Exposure period: 1 week after intradermal, 48 hours epidermal application.
- Test groups: 5% intradermal application, 25% epidermal application.
- Control group: intradermal with distilled water, epdermal with petrolatum oil.
- Site: scapular region.

B. CHALLENGE EXPOSURE
- No. of exposures: 1 epidermal application.
- Day(s) of challenge: two weeks after epidermal induction.
- Exposure period: 24 hours.
- Test groups: 10 % test article in petrolatum oil, and vehicle alone.
- Control group: 10 % test article in petrolatum oil, and vehicle alone.
- Site: right and left flank.
- Concentrations: 10 %
- Evaluation (hr after challenge): 24 and 48 hours after challenge.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitro-benzol (DNCB)

Results and discussion

Positive control results:
For the induction period a 0.5 % dilution of DNCB in ethanol, and for the challenge procedure a 0.3 % dilution of DNCB was used.
Positive erythema reaction after first challenge procedure after 24 hours:
postive: 6 animals; negative: 3 animals
67 % with positive reaction
According to the results observed it is considered that DNCB possess a strong skin sensitizing (contact allergenic) potential in the guinea pig strain used (Dunkin-Hartley albino guinea pigs; DUHA KFM. Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: none.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Not sensitising.
Executive summary:

Method

A sensitization test in guinea pigs was performed to determine the contact allergenic potency of the test compound. The test was performed according to the OECD Guideline No. 406.

Results

According to the results a weak allergenic potency of the test article was observed in this test when followed the rating of allergenicity described by Magnusson B. and Kligman A.M. (1969).

Conclusion

According to the CLP Regulation, the results showed that test articol is not a skin sensitizer.