Registration Dossier

Administrative data

Description of key information

Diisopropanol-p-Toluidin was not sensitising in the guinea pig maximisation test.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11.09.2001-12.10.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
other: MAFF Testing Guideline of 12 Nosan No. 1847
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
testing lab.
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was conducted before LLNA guideline was published.
Species:
guinea pig
Strain:
other: Hsd Poc: DH
Sex:
female
Details on test animals and environmental conditions:
The animals were identified via ear tattoo.
Age of the animals at start of the study: ca. 6 weeks
Body weight range at start of the study: 323 - 385 g
The guinea pigs were housed in fully air-conditioned rooms with a temperature in the range of 20 - 24°C
Relative humidity of 30 - 70 %
The day/night rhythm was 12 h dark and 12 h light
Five animals per cage (type stainless steel wire mesh cages with plastic-coated grating)
A standardized laboratory diet and tap water were available ad libitum
Source Harlan Winkelmann GmbH, Borchen, FRG
Route:
intradermal and epicutaneous
Vehicle:
other: Lutrol E 400 or olive oil
Concentration / amount:
intradermal induction: 0.1 % in olive oil
epicutaneous induction: 50 % test substance preparation in Lutrol E 400
challenge: 25 % test substance preparation in Lutrol E 400
Route:
epicutaneous, occlusive
Vehicle:
other: Lutrol E 400 or olive oil
Concentration / amount:
intradermal induction: 0.1 % in olive oil
epicutaneous induction: 50 % test substance preparation in Lutrol E 400
challenge: 25 % test substance preparation in Lutrol E 400
No. of animals per dose:
5 control group
10 test group
Details on study design:
Induction
Intradermal induction:

6 intradermal injections in groups of two per animal were applied to each animal
side of application: neck region
Injections for the control groups:
A) front row: 2 injections each of 0.1 mL Freund's adjuvant without test substance
emulsified with 0.9 % aqueous NaCI-solution in a ratio of 1 : 1

B) middle row: 2 injections each of 0.1 mL of the undiluted vehicle

C) back row: 2 injections each of 0.1 mL of a 50 % formulation of the vehicle without
test substance emulsified with Freund's adjuvant* / 0.9 % aqueous NaCI-solution 1 :1

Injection for the test group:
A) front row: 2 injections each of 0.1 mL Freund's adjuvant* without test substance
emulsified with 0.9 % aqueous NaCI-solution in a ratio of 1 : 1

B) middle row: 2 injections each of 0.1 mL of a test substance formulation in an
appropriate vehicle at the selected concentration

C) back row: 2 injections each of 0.1 mL Freund's adjuvant* / 0.9 % aqueous
NaCI-solution 1 : 1 with test substance at the selected concentration.

Reading: 24 h after the beginning of application

Epicutaneous induction:
one week after intradermal induction
test group: 1 mL of the test substance formulation/animal
control group: treated analogously to the test group but only with the vehicle without the test substance
Duration of exposure: 48 hours
Side of application: neck region, same area as in the case of the previous intradermal application
Reading: 48 h after the beginning of application

Challenge:
14 days after the epicutaneous induction
0.5 mL of the test substance formulation was applied to each animal
test group and control group 1 were treated with the substance formulation. Additionally, Lutrol E 400 was applied as a vehicle control. Control group 2 only received Lutrol E 400.
Duration of exposure: 24 hours
Site of application: intact flank
Reading: 24 h and 48 h after the removal of the patch
Positive control substance(s):
yes
Remarks:
A positive control with a known sensitizer was not included in this study. However, a separate study was performed twice a year in the Iaboratory using Alpha-Hexylcinnamaldehyde.
Positive control results:
The positive controls with Alpha-Hexylcinnamaldehyde techn. 85% showed that the test system was able to detect sensitizing compounds under the Iaboratory conditions chosen.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25 %
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 %. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy erythema.
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:
negative control
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: negative control. 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.

The intradermal induction caused moderate and confluent erythema and swelling or intense erythema and swelling at the injection sites of the test substance preparation in all test group animals. After the epicutaneous induction incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test group animals.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a dermal sensitisation study with diisopropanol-p-toluidin (BASF AG, 2002) guinea pigs were tested using the maximisation test of Magnusson and Kligman according to the OECD Guideline 406. The test substance concentrations for the main test were selected based on the results of the pretest. The intradermal induction was performed with a 0.1 % test substance preparation in olive oil and the epicutaneous induction with a 50 % test substance preparation in Lutral® E 400. For the challenge a 25 % test substance preparation in Lutral® E 400 was chosen. The study was initiated with 2 control groups and 1 test group. The intradermal induction was performed on day 0 and the epicutaneous induction on day 7. A challenge was carried out 14 days after the epicutaneous induction. The intradermal induction caused moderate and confluent erythema and swelling or intense erythema and swelling at the injection sites of the test substance preparation in all test group animals. After the epicutaneous induction incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test group animals. After the challenge discrete or patchy erythema was observed in one out of 10 animal of the test group. Based on the results of this study it was concluded that diisopropanol-p-toluidin does not have a sensitising effect on the skin of the guinea pig in the maximization test under the test conditions chosen.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, diisopropanol-p-toluidin is not subject to C&L according to Regulation 1272/2008/EC.