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Description of key information

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:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study equivalent to guideline, tested with the source substance Ethylparaben. 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.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study performed before implementation of LLNA method
Test material information:
Composition 1
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratories, Inc. (Denver, PA, USA)
- Weight at study initiation: 301 - 350 g
- Housing: Animals were housed in groups of 5 per cage in stainless steel wire floored cages.
- Diet: Licket, ad libitum
- Acclimation period: 14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1
- Humidity (%): 50 ± 5
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: Induction: Propylene glycol, Petrolatum and Freund's complete adjuvant (FCA); Challenge: Petrolatum
Concentration / amount:
Induction: 1 and 50%
Challenge: 1 and 2%
Route:
epicutaneous, occlusive
Vehicle:
other: Induction: Propylene glycol, Petrolatum and Freund's complete adjuvant (FCA); Challenge: Petrolatum
Concentration / amount:
Induction: 1 and 50%
Challenge: 1 and 2%
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
To find an appropriate concentration for epicutaneous induction and challenge phase, 20 additional guinea pigs were treated with 5, 10 and 50% of the test substance in Petrolatum under occlusive conditions for 24 h. 3 h after removal of the occlusive dressing, the patch sites were graded for erythema response. Based on the outcome of this investigation, concentrations of 50 and 1 or 2% test substance were chosen for epicutaneous induction and challenge, respectively.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single intradermal injection and 48 h epicutaneous treatment
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: 0.05 mL of a 1:1 mixture (v/v) FCA/water
Injection 2: 0.05 mL of 5% test substance in Propylene glycol
Injection 3: 0.05 mL of 1% test substance in a 1:1 mixture (v/v) FCA/water

Epicutaneous: 50% test substance in Petrolatum
The day before the epicutaneous induction, 0.5 mL of 10% Sodium lauryl sulfate (SLS) was applied on the treatment site.

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: Propylene glycol
Injection 3: a 1:1 mixture (v/v) of aqueous FCA and Propylene glycol

Epicutaneous: 100% Petrolatum
The day before the epicutaneous induction, 0.5 mL of 10% Sodium lauryl sulfate (SLS) was applied on the treatment site.

- Site: upper back (intradermal and epicutaneous)

- Frequency of applications: intradermal injection on Day 1 and epicutaneous application on Day 8
- Duration: single intradermal injections; epicutaneous treatment for 48 h
- Concentrations: intradermal 1% of the test substance (with FCA) or 5% of the test substance (without FCA), epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: Day 21
- Exposure period: 24 h
- Test groups: 0.4 mL 1 and 2% test substance in Petrolatum
- Control group: 0.4 mL 1 and 2% test substance in Petrolatum
- Site: left flank
- Concentrations: 1 and 2%
- Evaluation (hr after challenge): 24 and 48 h after patch removal
Positive control substance(s):
yes
Remarks:
Phenylacetaldehyde
Positive control results:
The positive control substance (Phenylacetaldehyde in Petrolatum; induction dose 5%, challenge doses 1 and 2% ) induced positive reactions in 7/8 and 8/8 animals (88 and 100%), respectively, thus meeting the reliability criteria for the Guinea Pig Maximization Test (≥ 30% positive response).
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; Challenge: 1%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Induction: 0%; Challenge: 1%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; Challenge: 2%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Induction: 0%; Challenge: 2%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 1%; Challenge: 1%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 1%; Challenge: 1%. No with. + reactions: 0.0. Total no. in groups: 6.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 1%; Challenge: 2%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 1%; Challenge: 2%. No with. + reactions: 0.0. Total no. in groups: 6.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 5%; Challenge: 1%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 5%; Challenge: 1%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 5%; Challenge: 2%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 5%; Challenge: 2%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction: 5%; Challenge: 1%
No. with + reactions:
7
Total no. in group:
8
Clinical observations:
desquamation in 2/8 animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: Induction: 5%; Challenge: 1%. No with. + reactions: 7.0. Total no. in groups: 8.0. Clinical observations: desquamation in 2/8 animals.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction: 5%; Challenge: 2%
No. with + reactions:
8
Total no. in group:
8
Clinical observations:
desquamation in 7/8 animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: Induction: 5%; Challenge: 2%. No with. + reactions: 8.0. Total no. in groups: 8.0. Clinical observations: desquamation in 7/8 animals.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; Challenge: 1%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Induction: 0%; Challenge: 1%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; Challenge: 2%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Induction: 0%; Challenge: 2%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 1%; Challenge: 1%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 1%; Challenge: 1%. No with. + reactions: 0.0. Total no. in groups: 6.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 1%; Challenge: 2%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 1%; Challenge: 2%. No with. + reactions: 0.0. Total no. in groups: 6.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 5%; Challenge: 1%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 5%; Challenge: 1%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 5%; Challenge: 2%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 5%; Challenge: 2%. No with. + reactions: 0.0. Total no. in groups: 9.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction: 5%; Challenge: 1%
No. with + reactions:
8
Total no. in group:
8
Clinical observations:
desquamation in 4/8 animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Induction: 5%; Challenge: 1%. No with. + reactions: 8.0. Total no. in groups: 8.0. Clinical observations: desquamation in 4/8 animals.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction: 5%; Challenge: 2%
No. with + reactions:
8
Total no. in group:
8
Clinical observations:
desquamation in 7/8 animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Induction: 5%; Challenge: 2%. No with. + reactions: 8.0. Total no. in groups: 8.0. Clinical observations: desquamation in 7/8 animals.

During the study period, mortality was observed in 1/10 animals of the negative control, 1/10 animals of the 5% test substance induction group, 4/10 animals of the 1% test substance induction group and 2/10 animals of the positive control group. All deaths noted during the study period resulted from excessively tight occlusive wrapping during the epicutaneous induction phase and were not considered to be related to the test substance.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Migrated from Short description of key information:
The source substance ethyl paraben proved to be not sensitising in course of an OECD 406 study in guinea pigs.

Justification for selection of skin sensitisation endpoint:
Study equivalent to guideline, tested with the source substance Ethylparaben. 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.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

With reference the reported results of an OECD 406 study performed with the structural surogate ethyl paraben test substance does not have to be classified as sesnsitising according to the criteria laid down in theEU Classification Labelling and Packaging Regulation (1272/2008/EC).