Registration Dossier

Administrative data

Description of key information

In the key study, 0 out of 20 guinea pigs gave positive results after challenge exposures with the test article.Therefore, the test article is considered not sensitizing after skin contact (reliability score: 1).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
When this study was performed, the LLNA did yet exist as an OECD guideline.
Specific details on test material used for the study:
- Name of test substance (as cited in study report): Tinuvin 329
- Analytical purity: >99%
- Batch No.: EN 171744.92
- Physical state: solid
- Storage conditions: room temperature
- Validity: November 1993
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., Animal Production, 4332 Stein, Switzerland
- Weight at study initiation (range): 351 g - 433 g
- Housing: individually in Makrolon cages (type 3)
- Diet: standard guinea pig pellets (NAFAG No. 845, Gosau SG); ad libitum
- Water: ad libitum
- Acclimation period: 5-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: oleum arachidis (intradermal) and vaseline (epidermal)
Concentration / amount:
Induction, intradermal: 5% in oleum arachidis
Induction, epidermal: 30% in vaseline
Challenge, epidermal: 10% in vaseline
Route:
epicutaneous, occlusive
Vehicle:
other: oleum arachidis (intradermal) and vaseline (epidermal)
Concentration / amount:
Induction, intradermal: 5% in oleum arachidis
Induction, epidermal: 30% in vaseline
Challenge, epidermal: 10% in vaseline
No. of animals per dose:
- Test group: 10 males and 10 females
- Control group: 5 males and 5 females
Details on study design:
RANGE FINDING TESTS:
To identify irritant concentrations of the test substance a preliminary study was performed to select suitable, non-irritant concetration for the main study.
- Intradermal: 1% and 5% were tested and both were well tolerated
- Epidermal: 1, 5, 10 and 30% were tested and none of them induced erythema reactions

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal:
- No. of exposures: one intradermal application (3 pairs of intradermal injections (each 0.1 mL) were made simultaneously into the shaved neck of the guinea pigs)
- Test groups: intradermal: 1) adjuvant/saline mixture 1:1 (v/v), 2) test article in oleum arachidis (w/v), 3) test article in the adjuvant saline mixture (w/v);
- Control group: same treatment as test group only with adjuvant and vehicle
- Site: neck region
- Concentrations: intradermal: 5%

Epidermal:
- Test group: epidermal: closed patch exposure over the injection sites (test substance in vaseline, 2 x 4 cm², ca. 0.4 g paste per patch)
- Control groups: same treatment as test group only with adjuvant and vehicle
- Concentrations: 30% in vaseline
- Duration of exposure: 48 h
- Schedule: one week after intradermal induction (week 2)
week 3 and 4: no treatment

B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day of challenge: day 29 (4 weeks after study initiation)
- Exposure period:24 h
- Test groups: the animals were tested with the test article in vaseline and the vehicle alone (patch 2 x 2 cm², 0.2 g paste per patch, occluded administration).
- Control group: The control group was treated with the vehicle as well as with the test article to check the maximum subirritant concentration of the test article in adjuvant treated animals.
- Site: flank
- Concentrations: 10%
- Evaluation (hr after challenge): 24 h and 48 h after removing the dressings, the challenge reactions were graded according to the Draize scoring scale.

OTHER:
The sesitivity of the strain is checked every six months with a known sensitiser, such as 2,4-dinitrochlorobenzene, para-phenylene-diamine or potasium-dichromate.
The body weight was recorded at start and end of the test.
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene, para-phenylene-diamine or potassium-dichromate.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
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: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
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: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
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: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
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: 20.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.

Mean body weight (study initiation; study termination):

- Test group: males: 382 g; 602 g; females: 375 g; 564 g

- Control group: males: 383 g; 629 g; females: 377 g; 569 g

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a dermal sensitisation study with the test substance (> 99% pure) in oleum arachidis or vaseline, Pirbright White Strain (Tif: DHP) guinea pigs (10 males and 10 females) were tested using the method of the guinea pig maximisation test according to the OECD TG 406. Intradermal and epicutaneous induction (occlusive, 48 h) was performed with 5% (in oleum arachidis) and 30% (in vaseline) of the test substance, respectively. Epicutaneous challenge exposure (occlusive, 24 h) was performed with 10% (in vaseline) of the test substance. 2,4-dinitrochlorobenzene and para-phenylene-diamine or potassium-dichromate were used as positive control substances. Evaluation of the skin reactions were performed 24 and 48 hours after challenge according to the Draize method. No deaths occurred and no clinical signs of toxicity or irritation were seen in any animal. In this study, the test substance is not a dermal sensitizer. 0/20 animals had positive skin responses at either observation time points (24 and 48 h) after end of challenge exposure.

 

The study is suitable for assessment of sensitizing potential as it was performed according to OECD 406 and GLP standards.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Dangerous substance Directive (67/548/EEC)

The available experimental test data are considered reliable and suitable for the purpose of classification. Based on the criteria for classification of Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC, classification as a skin sensitizer is not warranted.

 

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

The available experimental test data are reliable and suitable for the purpose of classification. Based on the criteria laid down in Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013, classification as a skin sensitizer is not warranted.