Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data available
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A GPMT was available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
See confidential details on test material section

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH - Wiga, Kisslegg, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 263 - 397 g
- Housing: 5 animals per cage
- Diet: ad libitum
- Water: ad libitum (tap water; about 2 g of ascorbic acid per 10 L water was added to the drinking water twice a week)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
intradermal induction: 0.5%
percutaneous induction: 50%
challenge: 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
intradermal induction: 0.5%
percutaneous induction: 50%
challenge: 25%
No. of animals per dose:
20 animals in the test group
10 animals in the control group
Details on study design:
RANGE FINDING TESTS: Two 24-hour percutaneous occlusive applications were performed within 96 hours. The minimum irritant concentration was found to be a 50% test substance preparation in aqua bidest. The maximum non-irritant concentration was found to be a 25% test substance preparation in aqua bidest.
It was possible to inject 5% and 1% test substance preparations in 0.9% aqueous NaCl-solution resp. in Freund's adjuvant / 0.9% aqueous NaCl-solution (1 : 1) with a syringe. These concentrations caused necrotic skin changes. Therefore, 0.5% test substance preparations were used in the main study for intradermal induction.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and after 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/0.9% aqueous NaCl-solution
Injection 2: 0.1 mL test substance in 0.9% aqueous NaCl-solution
Injection 3: test substance in a 1:1 mixture (v/v) FCA/0.9% aqueous NaCl-solution
Epicutaneous: test substance in 0.9% aqueous NaCl-solution
- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/0.9% aqueous NaCl-solution
Injection 2: 0.9% aqueous NaCl-solution
Injection 3: 0.9% aqueous NaCl-solution at a 1:1 mixture (v/v) FCA/0.9% aqueous NaCl-solution
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 0.1%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 2 (challenge and rechallenge)
- Day(s) of challenge: 14 (challenge) and 21 (rechallenge)
- Exposure period: 24 hours
- Test groups: test substance
- Control group: test substance
- Site: intact flank
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48
Challenge controls:
no data available
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldehyde

Results and discussion

Positive control results:
no data available

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
5
Total no. in group:
19
Clinical observations:
erythema and scaling
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 5.0. Total no. in groups: 19.0. Clinical observations: erythema and scaling.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
3
Total no. in group:
18
Clinical observations:
erythema and scaling
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 3.0. Total no. in groups: 18.0. Clinical observations: erythema and scaling.
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:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
17
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 17.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, the test item Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda is not classified as skin sensitizer according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).
Executive summary:

The test substance was tested for its sensitizing effect on the skin of the guinea pig in the Maximization Test based on the method of Magnusson and Kligman (BASF 1997, OECD 406). The intradermal induction with 0.5% test substance preparations caused slight to well-defined signs of skin irritation or necrotic skin changes in test group animals. After the percutaneous induction with a 50% test substance preparation incrustation, partially open (caused by the intradermal induction) could be observed in addition to well-defined erythema and slight edema or necrotic skin changes (caused by the intradermal induction) and slight edema in test group animals. Two challenges were performed 14 and 21 days after the percutaneous induction. After the first challenge with a 25% test substance preparation very slight to well-defined skin reactions could be observed after 24 hours in 5/19 (26%) animals and after 48 hours in 3/18 (16%) animals in the test group. The second challenge with a 25% test substance preparation did not cause any skin reaction. No skin reactions were found in all control groups. Based on the results of this study it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda is not classified as skin sensitizer according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).