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. Based on the evaluation criteria of Annex VI of the Commission Directive 67/548/EEC, the evaluation "sensitizing" is warranted when at least 30 % of the test animals exhibit positive skin reactions in an adjuvant test. Therefore, in line with the above argument, the test article is considered not sensitizing after skin contact.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without GLP
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted in 1981)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
Carried out according to the maximization test of Magnusson and Kligman (J. Invest. Dermatol. 52, 268-276, 1969).
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
When this test was performed, the LLNA did not yet exist.
Specific details on test material used for the study:
- Batch No.: EN 24705
- Purity: techn. qual.
- Appearance: white powder
- Validity: 12/1984
- Stability under the condition of administration: not determined
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba Geigy AG
- Age at study initiation: ca. 10 wks
- Weight at study initiation: 328 - 468 g
- Housing: individually in macrolon cages (type 3)
- Diet: ad libitum; guinea pig pellets (NAFAG No. 846, Gossau SG), feed was supplemented with fresh carrots
- Water: ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 14/10

Route:
intradermal and epicutaneous
Vehicle:
other: Sesame oil (intradermal induction), vaseline (epicutaneous induction and challenge)
Concentration / amount:
Intradermal induction: 1 %
Epicutaneous induction: 30 %
Challenge: 30 %
Route:
epicutaneous, occlusive
Vehicle:
other: Sesame oil (intradermal induction), vaseline (epicutaneous induction and challenge)
Concentration / amount:
Intradermal induction: 1 %
Epicutaneous induction: 30 %
Challenge: 30 %
No. of animals per dose:
20 (10 males + 10 females)
Details on study design:
PRELIMINARY TEST: The concentrations of the test compound for the induction and challenge period were determined on separate animals.

MAIN STUDY
A. INDUCTION EXPOSURE
A1. Intradermal Injection
- Site of injection: neck
- Number of injections: 2/ formulation
- Formulations: 1). mixture of adjuvant and saline, 2). test compound in sesame oil (test group) or sesame oil (control group), 3). test compound in the adjuvant saline mixture (test group) or adjuvant saline mixture without test compound (control)
- Volume per injection: 0.1 mL/ formulation
- Evaluation (hr after injection): no data

A2. Epicutaneous induction exposure:
- Time schedule: one week after intradermal inductions
- Site: same as intradermal injections (site was pretreated the day before with 10% sodium lauryl sulphate: open application)
- Concentrations: 30 % (test group), and vehicle (control group)
- Volume applied: no data
- Type of coverage: occlusive
- Duration: 48 hours
- Evaluation (hr after challenge): no data

B. CHALLENGE EXPOSURE (identical treatment for treated and control animals)
- Time schedule: two weeks after topical induction
- Site: flank (one flank: test substance) other flank (vehicle)
- Vehicle: vaseline
- Concentrations: 30 %
- Volume applied: no data
- Type of coverage: occlusive
- Duration: 24 hours
- Evaluation (hr after challenge): 24 and 48 hours after termination of exposure.
- Evaluation method: Draize scoring
Positive control substance(s):
yes
Remarks:
The sensitivity of the strain is controlled every six months with p - phenylenediamine
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30 % in vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 30 % in vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
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.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30 % in vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 30 % in vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
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.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30 % in vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30 % in vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
30 % in vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30 % in vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.

Body weights were taken before the start of the treatment and at termination.

Control animals

- At start: Mean (n = 20) = 380.7 +/- 36.66 g

- At termination: Mean (n = 20) = 528.4 +/- 68.74 g

Test group animals

- At start: Mean (n = 20) = 383.3 +/- 31.65 g

- At termination: Mean (n = 20) = 532.1 +/- 54.17 g

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

In the key study, the potential of the test article (technical grade) to cause "delayed contact hypersensitivity" after dermal contact was appraised in Pirbright-Hartley Guinea Pigs pursuant to OECD TG 406 (Skin Sensitisation, GPMT). Intradermal inductions were performed with 1% of the test substance in sesame oil. Topical induction (occlusive; 48 hours) and as well as challenge exposures (epicutaneous occlusive; 24 hours) were performed with 30% of the test substance in vaseline. The control and test groups consisted of 20 animals each. Evaluation of the skin reactions were performed 24 and 48 hours after challenge according to the Draize method. After challenge, 0 out of 20 guinea pigs exhibited evidence of "delayed contact hypersensitivity". All animals of the control group did not show evidence of "delayed contact hypersentisation" (0/20). The sensitivity and reliability of the experimental technique was ascertained every 6 months using p - phenylenediamine.


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 are reliable and suitable for the purpose of classification under Regulation 1272/2008. 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.