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Diss Factsheets

Administrative data

Description of key information

According to OECD 406: non sensitizing

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: Comparable to guideline study.
Justification for type of information:
LLNA was not available/validated at that time point of conducting the GPMT
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
LLNA was not available/validated at that time point of conducting the GPMT
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 chemical
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 chemical
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.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
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.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
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.
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.
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.
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 chemical
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 chemical
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 chemical
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 chemical
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:

Ethylparaben was examined in a Guinea Pig Maximization Test equivalent to OECD 406 (Anonymous, 1981). The intradermal induction was conducted using 1% of the test substance in propylene glycol in a 1:1 mixture with Freund's complete adjuvant and 5% test substance in propylene glycol, respectively. The epicutaneous induction was conducted with 50% test substance in petrolatum.

At challenge with 1% and 2% test substance in petrolatum, neither the test group nor the control group showed any skin reactions. The positive control animals, treated with induction doses of 5% and challenge doses of 1% or 2% phenylacetaldehyde in petrolatum, showed positive reactions at the first (7/8 and 8/8, respectively) and the second reading time point (8/8 at both concentrations).

Under the test conditions, the test substance was not considered to be a skin sensitizer.

 

A further study on skin sensitization in male guinea pigs was conducted similar to Maurer optimization test (Sokol, 1952). A solution of 0.1% test substance in physiological saline was intradermally injected for induction and challenge. No allergic response was observed in any animal.


Migrated from Short description of key information:
Skin (Guinea pig maximisation test, OECD 406): not sensitizing

Justification for selection of skin sensitisation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation of the test substance does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.