Registration Dossier

Administrative data

Description of key information

The test substance was not sensitising in a skin sensitisation study in the guinea pig similar to the OECD guideline 406.

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:
1982-06-14 to 1982-07-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
(no pos. control in study (pos. controls regularly tested in facility), no data on test material purity, vehicle not specified, first induction is epidermal, only one reading 24 hours after challenge, application sites chemically depilated before reading)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT is available, therefore an LLNA is not required.
Species:
guinea pig
Strain:
other: Pirbright White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ivanovas, Germany
- Age at study initiation: 10 weeks
- Weight at study initiation: 310 - 425 g
- Housing: Individually in Macrolon cages (type 3)
- Diet: Standard guinea pig pellets, NAFAG No. 830, Gossau SG, ad libitum
- Water: ad libitum, supplemented with fresh carrots
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 10/14
Route:
epicutaneous, occlusive
Vehicle:
other: not specified
Concentration / amount:
10%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: not specified
Concentration / amount:
30%
No. of animals per dose:
10 males and 10 females
Details on study design:
RANGE FINDING TESTS:
The concentrations of the test compound for induction and challenge periods were determined on seperate animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 exposures: Intracutanous injection of adjuvant at 4 sites of the animal's neck prior to induction. First induction: Occlusive epidermal application of the test substance and second induction again as occlusive epidermal application of the test substance.
- Exposure period: Day 1: Epidermal exposure to test substance for 24 hours at first induction and one week later second epidermal induction application for 48 hours.
- Test groups: 0.1 ml of a freshly prepared adjuvant saline mixture was injected intracutanously at 4 sites on the animal's neck. The test compound was applied on filter patches (2 x 4 cm) to the epidermis over the injection sites under an occlusive dressing. One day before second induction the animals were pretreated with 10 % sodium laurylsulphate (open application).
- Control group: A control group was treated with adjuvant and the vehicle.
- Site: Neck
- Frequency of applications: 2 occlusive epidermal applications (see above)
- Duration: Day 1 epidermal application for 24 hours, after one week epidermal application for 48 hours.
- Concentrations: 10 % test substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after induction
- Exposure period: 24 hours
- Test groups: The compound was applied on filter paper patches (2 x 2 cm) to an untreated flank skin of the animals for 24 hours epidermal occlusively.
- Control group: The control group was treated with the vehicle as well as with the test substance to control the maximal subirritant concentration of the test compound in adjuvant treated animals.
- Site: Flank
- Concentrations: 30 % test substance
- Evaluation (hr after challenge): 24 hours after patch removal
- The application sites were chemically depilated before examination (Veet, 5 minutes)
Challenge controls:
20 animals (vehicle control)
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
other: vehicle control
Dose level:
30 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30 %
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30 %. No with. + reactions: 3.0. Total no. in groups: 20.0.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitisation property of the test substance was determined using a modified version of the Maximisation Test in the guinea pig. The study was conducted similar to the OECD-Guideline 406. 20 guinea pigs (Pirbright White Strain, 10 males and 10 females) were intradermally treated with 4 injections of 0.1 ml freshly prepared adjuvant saline mixture. At first induction, the test compound (10 %) was occlusively applied on filter patches (2 x 4 cm) to the epidermis over the injection sites for 24 hours. One week later, the test substance was occlusively applied in the same way for 48 hours. The application sites were pretreated the day before with 10 % sodium laurylsulphate (open application). The challenge was performed 14 days later, when the test compound (30 %) was applied epidermal on filter paper patches (2 x 2 cm) to an untreated flank skin of the animals for 24 hours (occlusive application). A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period thecontrol animals were treated with the test substance to control the maximal subirritant concentration of the test compound in adjuvant treated animals. 24 hours after removal of the dressings the challenge reactions were graded according to the Draize scale. The application sites were chemically depilated before examination. 15 % of the animals in the test substance group showed skin reactions 24 hours after removal of the dressings. Concluding, the test substance did not reveal skin sensitising properties in the guinea pig maximization test under the test conditions chosen (Ciba-Geigy, 1982).

The results are supported by the findings from a human insult patch study (Hill Top Research Institute Inc, No. K-141E, 1960; no guideline followed). 59 subjects (12 men, 47 women) received 24 h patch exposures to the test substance three times weekly for three weeks, followed by a similar challenge exposure in the sixth week. The test substance did not reveal skin sensitising properties in the human insult patch test under the test conditions chosen.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data is reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for skin sensitisation is not warranted.