Registration Dossier

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

Study conducted to recognised training guidelines with GLP. In vitro study waived as in vivo data available

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:
1987-05-04, 1987-06-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
yes
Remarks:
The intradermal induction was performed with Freund´s Complete Adjuvant (FCA)/saline (1:1) only. Test article was applied dermal (occlusive) for 24 h. Modifications of the intradermal induction were performed since the test article was not injectable.
Principles of method if other than guideline:
Intradermal induction according to guideline requires injection of (1) FCA/saline 1:1, (2) test article at a selected concentration and (3) test article/FCA saline 1:1.
However, in the present study the intradermal induction was performed with Freund´s Complete Adjuvant (FCA)/saline (1:1) only. Subsequently, test article was applied dermal (occlusive) for 24 h.
Modifications of the intradermal induction were done by the author since the test article was not injectable. Validation of this modification with six known sensitisers was published by the author 1998 (Fd. Chem. Toxic. Vol. 27, No. 12, pp. 807-811, 1998).
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was performed in 1987, pre-dating LLNA guideline adoption.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain as cited in the report: Pirbright White Strain (Tif: DHP)
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: Approx. 10 weeks
- Weight at study initiation: 319 - 424 g
- Housing: Individually in Macrolon cages (Type 3)
- Diet: Ad libitum, standard guinea pig pellets (NAFAG No.846, Gossau SG)
- Water: Ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: FCA/saline 1:1 (intradermal) Petrolatum (epicutanious)
Concentration / amount:
0% test material
0.1 ml
Day(s)/duration:
Day 1
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
30 % test material


Day(s)/duration:
Day 7 (24 hours)
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
10% test material
Day(s)/duration:
Day 22 (48 hours)
Adequacy of challenge:
not specified
No. of animals per dose:
10 males and 10 females
Details on study design:
RANGE FINDING TESTS
Separate animals were treated with test article for evaluation of the primary irritation threshold concentration.
Concentrations of 10 and 30 % of test article in vaseline were tested. Erythema reactions were observed at 30 %. No erythema was induced at the lower concentrations. Therefore, 10 % was used as the maximal subirritant concentration for the challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
Induction was performed in two steps. First, FCA/saline (1:1) was injected intradermally (0.1 ml) followed by epidermal application of test article in the neck region under occlusive conditions for 24 h. One week later, the second induction was performed by epidermal application under occlusive conditions for 48 h.
- Control group: During the induction period the control group was treated with FCA/saline (1:1) and the vehicle.
- Concentrations: 0.4 g paste of 30 % test article in vaseline.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
Two weeks after epidermal induction the animals were challenged on the flank with test article (0.2 g paste of 10 % test article in vaseline) and the vehicle alone (patch 2 x 2 cm; occluded application for 24 h).
- Control group: The control group was challenged with the vehicle as well as with the test article (at least 10 animals/group) to control the maximal subirritant concentration of the test compound in FCA/saline (1:1) treated animals.
- Evaluation (hr after challenge): 24 and 48 h

Challenge controls:
10 control males were challenged with 0.2 g of 10 % test article in vaseline and with vaseline, respectively.
Positive control substance(s):
yes
Remarks:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-dichromate
Positive control results:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-dichromate.
(s. Th. Maurer, R. Hess, Toxicology 31 (1984) pp. 217-222)
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
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: 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:
10 %
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: negative control. Dose level: 10 % . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Vehicle
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: Vehicle. 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:
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: 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:
10 %
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: negative control. Dose level: 10 % . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Vehicle
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: Vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

Number of positive animals per group after occlusive epicutaneous challenge

Control group

Time after challenge

24 h

48 h

Vehicle control

0/20

0/20

Test compound

0/10

0/10

Test group

Time after challenge

24 h

48 h

Vehicle control

0/20

0/20

Test compound

0/20

0/20

Interpretation of results:
GHS criteria not met
Conclusions:
The test material failed to induce skin sensitisation in the Guinea pig under the conditions of the test. The test material is not considered a skin sensitiser.
Executive summary:

In this guideline (OECD 406) study conducted to GLP standards, the test material (EC 404-360-3) was determined to be not sensitising to skin. Two groups of 20 male/female guinea pigs were divided into a test group and a control group. For the induction phase FCA/saline (1:1) was injected intradermally (0.1 ml) followed by epidermal application of test article (0.4 g paste of 30 % test article in vaseline) in the neck region under occlusive conditions for 24 h. The control group was treated with FCA/saline (1:1) and vaseline. One week later, the second induction was performed on the test group by epidermal application under occlusive conditions for 48 h.

For the challenge phase, two weeks after epidermal induction the test group animals were challenged on the flank with test article (0.2 g paste of 10 % test article in vaseline) followed by the vehicle alone (occlusive application for 24 h). The control group was challenged with the vehicle as well as with the test article (at least 10 animals/group) to control the maximal subirritant concentration of the test compound in FCA/saline (1:1) treated animals. Both test and control groups were evaluated after 24 and 48 hours. As none of the animals of the test group scored positive for any effects, the test material is not classified as a skin sensitiser under CLP regulation 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The sensitising potential of test article was assessed using a modified Guinea Pig Maximisation Test similar to OECD 406 (1981). Induction was conducted with 30 % test article in vaseline and the challenge was performed with 10 % test article in vaseline. None of twenty animals of the test group was scored positive after 24 and 48 h following challenge. Thus, under the conditions used in this study, the test article was not sensitising in guinea pigs.


Migrated from Short description of key information:
A valid study on the skin sensitisation potential is available. A Guinea Pig Maximisation Test was conducted, which was similar to OECD 406 (1981). Under the conditions used in this study, the test article is not sensitising (Ciba-Geigy 874073).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.