Registration Dossier

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: Guideline study (OECD)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Remarks:
Department of Toxicology, BASF AG
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,6-Hexandiol
- Number of test substance : 91/38
- Physical state: crystalline, white
- Lot/batch No.: continuous production from tank 20
- Date of manufacturing: January 18, 1991
- Analytical purity: 95.9%; verified by Analytical laboratory of BASF AG
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co . KG, D-W4923 Extertal 1, Germany
- Age at study initiation: young adult
- Identification: ear tag numbering
- Weight at study initiation: 308 - 344 g
- Housing: in groups of 5 in Makrolon type V cages
- Bedding: Typ 3/4 (staubfrei); SSNIFF
- Diet (e.g. ad libitum): Kliba 341.4 mm (Kaninchen - Meerschweinchen - Haltungsdiät), Firma Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland; ad libitum
- Water (e.g. ad libitum): 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 d


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

OTHER:
- Feed analysis:
The feed used in the study was assayed for chemical and microbiological contaminants.

- Drinking water analysis:
The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the Technical Services o f BASF Aktiengesellschaft as well as for the presence of germs by a contract laboratory.

- Analysis of the bedding:
The bedding is regularly assayed for contaminants (chlorinated hydrocarbons, heavy metals)

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: saline and water
Concentration / amount:
- intradermal induction: 5% in 0.9% aqueous NaCl-solution resp. in Freunds adjuvant/0.9 % aqueous NaCl-solution (1:1) resp. 0.9 % a aqueous NaCl-solution
- percutaneous induction: 50% in aqua bidest.
- challange: 25% in aqua bidest.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: saline and water
Concentration / amount:
- intradermal induction: 5% in 0.9% aqueous NaCl-solution resp. in Freunds adjuvant/0.9 % aqueous NaCl-solution (1:1) resp. 0.9 % a aqueous NaCl-solution
- percutaneous induction: 50% in aqua bidest.
- challange: 25% in aqua bidest.
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS:
- Amount applied:
2 x 2 cm filter paper strips were applied to the skin of the flanks under an occlusive dressing (the bandage consists of rubberized linenpatches 4 x 4 cm from Russka and Fixomull Stretch (adhesive fleece) from Beiersdorf AG). In the case of liquids the test filter paper strip was
soaked in the test substance formulation; thus the animals were exposed to about 0,15 g of the test substance formulation.

- Exposure period :
The test substance was applied 2 times for 24 hours within a period of 96 hours in order to detect non-specific phenomena that are not caused by a sensitization reaction but could possibly be attributed to a shift in the irritation threshold .

- Site of application: flank, respective on the same area
- Number of test animals 4 per test concentration
- Readings: about 24 and 48 h after the beginning of application
- Assessment of skin findings: according to Draize JH (1959)


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6 intradermal injections in groups of tw o per animal (2 injections each of 0.1 ml Freund's adjuvant without test substance emulsified with 0.9 % aqueous NaCl-solution in a ratio of 1:1; 2 injections each of 0.1 ml of the test substance formulation; 2 injections each of 0.1 ml Freund's adjuvant/0.9% aqueous NaCl-solution (1:1) with test substance);
- Exposure period:
- Test groups: 10 animals
- Control group: 5 animals
- Site: shoulder
- Frequency of applications: Percutaneous induction was carried out one week after intradermal induction
- Duration: 48 h
- Concentrations: 2 x 4 cm filter paper strips were applied to the skin of the shoulder under an occlusive dressing (the bandage consists of gubberized linenpatches 4 x 4 cm from Russka and Fixomull Stretch (adhesive fleece) from Beiersdorf AG) . The filter paper strip was soaked in the test substance formulation; thus the animals were exposed to about 0.3 g of the test substance formulation. The control animals were not treated since the distilled water used as formulating agent was not expected to influence the result of the study.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 days after induction
- Exposure period: 24 h
- Test groups: 10 animals
- Control group: 5 animals
- Site: in t act clipped flank
- Concentrations: 2 x 2 cm filter paper strips were applied to the skin of the flank under an occlusive dressing (the bandage consists oferubberized linenpatches 4 x 4 cm from Russka and Fixomull Stretch (adhesive fleece) from Beiersdorf AG). The test filter paper strip was soaked in the test substance formulation; thus the animals were exposed to about 0.15 g of the test substance formulation.
- Evaluation (hr after challenge): 24 h and 48 h after the removal of the patch; according to Draize JH (1959)
Challenge controls:
A positive control (reliability check) with a known sensitizer is not included in this study however a separate study was performed twice a year in the laboratory (Study No. 0H0038/912125, BASF AG)
Positive control substance(s):
yes
Remarks:
1-chlor-2,4-dinitro-benzol; BASF AG, 0H0038/912125

Results and discussion

Positive control results:
After the challenge (24 hours after the removal of the test patch) with the 1% 1-chlor-2,4-dinitro-benzol preparation in ethanol well-defined erythema and slight edema could be observed in 6 out of 8 test group animals. Two animals showed very slight erythema, one of them additionally had very slight edema .

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
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: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
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: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
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: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
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: 5.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Classification: not sensitizing