Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FAT 66 031/B
- Physical state: powder
- Analytical purity: 88.1% of active ingredient
- Lot/batch No.: Mg. 636
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: between 313 to 422 g
- Housing: Individually housed in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets NAFAG No. 846, Gossau SG; ad libitum
- Water: fresh water; ad libitum
- Acclimation period: Guinea pigs were reported to be acclimatized, but number of days was not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: physiological saline or vaseline
Concentration / amount:
Concentration of the test substance in physiological saline and adjuvant mixture: 1% (intradermal induction)
Approximately 0.4 g paste of 30% test substance in vaseline (epidermal induction)
Approximately 0.2 g paste of 10% test substance in vaseline (epidermal challenge)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: physiological saline or vaseline
Concentration / amount:
Concentration of the test substance in physiological saline and adjuvant mixture: 1% (intradermal induction)
Approximately 0.4 g paste of 30% test substance in vaseline (epidermal induction)
Approximately 0.2 g paste of 10% test substance in vaseline (epidermal challenge)
No. of animals per dose:
10 animals/sex/group
Details on study design:
Methods:
The test was carried out according to the maximization test of Magnusson and Kligman (J. invest. Dermatol. 52, 268-276, 1969, Cont. Dermatitis 6, 46-50, 1980), recommended in the OECD guideline 406, adopted May 12, 1981 and in the EEC directive 79/831.

Induction Procedure:
The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.

First Induction, intradermal application:
Three pairs of intradermal injections (0.1 mL per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant and saline (1:1)
- test compound in physiological saline
- test compound in the adjuvant saline mixture
Concentration of in physiological saline and adjuvant mixture: 1 %

Second Induction, epidermal application:
One week later the test substance was incorporated in vaseline and applied on a filter paper patch to the neck of the animals (patch 2 x 4 cm; occlusive treatment, 48 hours). The application sites were pretreated the day before with 10 % sodium lauryl sulfate (open application). Dose of application: approx. 0.4 g paste of 30 % test substance in vaseline

Challenge:
Two weeks after the epidermal induction application the animals were tested on the flank with test substance in vaseline and the vehicle alone (patch 2 x 2 cm; occlusive treatment, 24 hours). Dose of application: approx. 0.2 g paste of 10 % test substance in vaseline. The concentrations of the test compound for the induction and challenge periods were determined on separate animals.

Control group:
A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test compound (at least 10 animals) to control the maximal sub-irritant concentration of the test compound in adjuvant treatedanimals. Separate animals were treated with FAT 66 031/B for the evaluation of the primary irritation threshold concentration. The tested concentrations of 10 and 30 % FAT 66 031/B in vaseline did not induce erythema reactions. 10 % was used as a sub-irritant concentration for the challenge application, to exclude nonspecific reactions in the adjuvant treated animals (s. Magnussen, 1980).

Observations and records:
24 hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings. The sensitizing potential of FAT 66 031/B was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.
Challenge controls:
A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test compound (at least 10 animals) to control the maximal sub-irritant concentration of the test compound in adjuvant treated animals. Separate animals were treated with the test substance for the evaluation of the primary irritation threshold concentration. The tested concentrations of 10 and 30 % test substance in vaseline did not induce erythema reactions. 10 % was used as a sub-irritant concentration for the challenge application, to exclude nonspecific reactions in the adjuvant treated animals (s. Magnussen, 1980).
Positive control substance(s):
yes
Remarks:
Paraphenylene-diamine or Potassium-dichromate

Results and discussion

Positive control results:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-dichromate. The results of the latest reliability check were not provided in the report.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 10%
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: negative control. Dose level: induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 10%
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: negative control. Dose level: induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 0%
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: negative control. Dose level: induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 0%
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: negative control. Dose level: induction, intradermal: 0%, epidermal: 0%; challenge, epidermal: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 10%
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: induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 10%. 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:
induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 10%
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: induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 0%
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: induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 0%. 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:
induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 0%
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: induction, intradermal: 1%, epidermal: 30%; challenge, epidermal: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No animal of the test group was sensitized by the test substance under the experimental condition employed. According t o the maximization grading the test substance has not to be classified for skin sensitisation.