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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1998-04-07 to 1998-05-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted with a structural analogous read-across substance in compliance to GLP and according to current guidelines. Please refer to IUCLID section 13 for read-across justification.
Qualifier:
according to
Guideline:
other: method of BUEHLER, E.V. (1965): Delayed Contact Hypersensitivity in the Guinea Pigs, Arch. Dermat. Vol. 91, pp. 171 -177
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted July 17, 1992
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Version / remarks:
revised edition November 1984
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Commission Directive 96/54/EC of July 30,1996
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
BASF AG
Type of study:
Buehler test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Age at study initiation: Young adult animals
- Weight at study initiation: 305 - 396 g
- Housing: 5 animals per cage, stainless steel wire mesh cages with plastic-coated grating
- Diet: Kliba Labordiät (Kaninchen-Meerschweinchen-Haltungsdiät) ad libitum
- Water: Tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 25°C
- Humidity: 30 - 70%.
- Air changes: Fully air-conditioned
- Photoperiod: 12 h light/ 12 h darkness
Route:
epicutaneous, occlusive
Vehicle:
other: 1 % Tylose CB 30.000 in aqua bidest.
Concentration / amount:
The following concentrations for induction and challenge were selected on the basis of the pretests:

1st until 9th induction:
Test substance 60% in 1% Tylose CB 30.000 in aqua bidest.

Challenge:
Test substance 50% in 1% Tylose CB 30.000 in aqua bidest.
Route:
epicutaneous, occlusive
Vehicle:
other: 1 % Tylose CB 30.000 in aqua bidest.
Concentration / amount:
The following concentrations for induction and challenge were selected on the basis of the pretests:

1st until 9th induction:
Test substance 60% in 1% Tylose CB 30.000 in aqua bidest.

Challenge:
Test substance 50% in 1% Tylose CB 30.000 in aqua bidest.
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS: Pretest
Three 6-hour percutaneous occlusive applications were performed (three applications per week).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 6 hours // 24 hours (reading), epicutaneous
- Test groups: All
- Control group: Yes control group 1+2 (vehicle - left flank anterior)
- Site: Anterior left flank
- Frequency of applications: Three applications per week; days 0 - 2, 7 -9 and 14 -16 on the same application area
- Duration: 3 weeks
- Concentrations: 60% in 1% Tylose CB 30.000 in aqua bidest.

B. CHALLENGE EXPOSURE
- No. of exposures: 1, epicutaneous
- Day(s) of challenge: 13 days after the ninth induction
- Exposure period: 6 hours
- Test groups: All
- Control group: Yes, (control group 1: formualtion - anterior right flank; vehicle - posterior right flank); control group 2 (vehicle- right flank posterior)
- Site: Anterior right flank
- Concentrations: 50% in 1% Tylose CB 30.000 in aqua bidest.
- Evaluation (hr after challenge): 24 and 48 h after the removal of the patch
Challenge controls:
Yes, treated with the test substance formulation, additionally 1% Tylose CB 30.000 in aqua bidest. was applied as a vehicle control.
Positive control substance(s):
yes
Remarks:
Alpha-Hexylcinnamaldehyde techn. 85 %
Positive control results:
A positive control (reliability check) with a known sensitizer is not included in this study. However, a separate study is performed twice a year in the laboratory.
The positive control with Alpha-Hexylcinnamaldehyde techn. 85% showed that the chosen guinea pig strain was able to detect sensitizing compounds under the laboratory conditions chosen.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 % w/v
No. with + reactions:
0
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: 50 % w/v. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50 % w/v
No. with + reactions:
0
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: 50 % w/v. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group 1
Dose level:
50 % w/v
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: other: control group 1. Dose level: 50 % w/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group 1
Dose level:
50 % w/v
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: other: control group 1. Dose level: 50 % w/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group 2 (vehicle)
Dose level:
0 %
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: other: control group 2 (vehicle). Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group 2 (vehicle)
Dose level:
0 %
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: other: control group 2 (vehicle). Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

BODY WEIGHTS

The expected body weight gain was generally observed in the course of the study.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Key study

 

A study was performed to assess the skin sensitisation potential of SAN 836H 86 SP 401 DP Formulation using the guinea pig. The method followed was that described in:

EPA Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animals 81-6 Dermal sensitization study (Revised Edition November 1984).

Based on the results of a preliminary study and in compliance with the guideline, the following dose levels were selected:

Induction (epicutaneous): 50% w/v in Alembicol D

Challenge (epicutaneous): 50% w/v in Alembicol D

Twenty test and ten control guinea-pigs were used in this study.

In this study, SAN 836H 86 SP 401 DP Formulation did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in eighteen of the twenty test animals. A further one animal gave an inconclusive response and the remaining test animal gave a positive response.

 

Supporting study

 

The read-across test substance (free acid) was tested for its sensitizing effect on the skin of the guinea pig in the Modified BUEHLER Test with 9 induction treatments according to the method of BUEHLER, E.V. (1965).

The application of the main test was performed over three weeks.

All inductions (epicutaneous) were performed with 60% test substance preparations (highest applicable concentration). The first, second and third induction caused discrete or patchy erythema in 2 test group animals.

After the fourth until ninth induction no signs of skin irritation were observed in all test group animals. A challenge (epicutaneous) was performed 13 days after the last induction.

The animals showed no clinical signs and skin sensitizing effect.

The expected body weight gain was generally observed in the course of the study.

The control group animals, which were applied with 1% Tylose CB 30.000 in aqua bidest., did not show any skin reactions.

 

Based on the results of this study and applying the evaluation criteria it was concluded that the read- across test substance (free acid) does not have a sensitizing effect on the skin of the guinea pig in the Modified BUEHLER Test under the test conditions chosen.

 

In a further supporting study with the read across test substance (free acid) conducted according the EPA guideline the test substance did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in any of the twenty test animals tested.

Thus, the substance was judged non-sensitizing.

 

 

 


Migrated from Short description of key information:
The test item and the read- across test substance (free acid of the registered substance) do not have a sensitizing effect on the skin of the guinea pigs in the BUEHLER Test under the test conditions chosen.

Justification for selection of skin sensitisation endpoint:
GLP and guideline compliant study

Justification for classification or non-classification

Based on the data of the test substance and read-across substance Diflufenzopyr (free acid), the substance Diflufenzopyr sodium salt needs not be classified as a skin sensitiser according to the criteria of Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).