Registration Dossier

Administrative data

Description of key information

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%. Thus, 2-ethoxynaphthalene was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).

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:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed journal
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical Ethyl 2-naphthyl ether (CAS No. 93-18-5).
GLP compliance:
not specified
Type of study:
open epicutaneous test
Justification for non-LLNA method:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): Naphthalene, 2-ethoxy-
- Molecular formula : C12H12O
- Molecular weight: 172.226 g/mol
- Substance type: Organic
- SMILES : c12c(ccc(c1)OCC)cccc2
- InChI: 1S/C12H12O/c1-2-13-12-8-7-10-5-3-4-6-11(10)9-12/h3-9H,2H2,1H3
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation: 300-450g
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Concentration / amount:
Concentration:100%, 30%, 10%, 3%, 1%, or 0.3%
Amount: 0.1ml
Day(s)/duration:
3 weeks (0-21 days)
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Concentration / amount:
Concentration:2%
Amount: 0.025ml
Day(s)/duration:
72 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
6-8 guinea pigs
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups:6-8 guinea pigs
- Control group:3 guinea pigs
- Site: an area measuring 8 cm2 on the clipped flank skin of the guinea pigs
- Frequency of applications: The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks
- Duration: 21 days (3 weeks)
- Concentrations: 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle.
Amount: 0.1ml

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: on days 21 and 35
- Exposure period:24 hours
- Test groups: 6-8 guinea pigs
- Control group: 3 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:2%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.
Challenge controls:
Yes concurrent vehicle.
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
2% (0.025ml)
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
No known signs of skin sensitization were observed.
Remarks on result:
no indication of skin sensitisation
Remarks:
at 24,48 and/or 72h.
Cellular proliferation data / Observations:
No known signs of skin sensitization were observed.
Interpretation of results:
other: Not sensitizing
Conclusions:
It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%. Thus, 2-ethoxynaphthalene was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).
Executive summary:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of 2-ethoxynaphthalene. The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100, 30, 10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 8 %.

On day 1 during induction, 0.1 ml of 8% test chemical was applied to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

 

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%. Thus, 2-ethoxynaphthalene was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).

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

Various studies have been summarized to ascertain the extent of dermal sensitization caused by 2-Ethoxynaphthalene in living organisms. These studies include in vivo experimental results on guinea pigs and humans for the target and its structurally similar chemicals. The experimental results have also been compared with estimated results.

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of 2-ethoxynaphthalene. The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100, 30, 10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 8 %.

On day 1 during induction, 0.1 ml of 8% test chemical was applied to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

 

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%. Thus, 2-ethoxynaphthalene was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).

This is supported by the results of a human maximization test carried out to assess the dermal sensitization potential of 2-Ethoxynaphthalene. 2-Ethoxynaphthalene 2% in petrolatum was applied to the skin of 25 human volunteers and observed for signs of dermal sensitization (duration of exposure, observation period not specified). 2-Ethoxynaphthalene 2% in petrolatum did not induce any sensitization reactions on the skin of 25 human volunteers.

Hence, 2-Ethoxynaphthalene was considered to be not sensitizing to skin.

These results are supported by Repeat insult Patch test (Shelanski & Shelanski) performed to assess the dermal sensitization potential of 2-Ethoxynaphthalene. 2% 2 -Ethoxynaphthalene was applied to the skin of 50 human volunteers using 15 24-hours exposure and observed for effects.

2-Ethoxynaphthalene 2% did not induce any sensitization reactions on the skin of 50 human volunteers. Hence, 2-Ethoxynaphthalene was considered to be not sensitizing to skin.

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 2 -Ethoxynaphthalene. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, 2 -Ethoxynaphthalene was considered to be not sensitizing.

The experimental and estimated results are in mutual agreement with each other, indicating a very strong possibility of 2-Ethoxynaphthalene being not sensitizing to skin.

The above results are further supported by a human maximization test carried out to assess the dermal sensitization potential of the structurally similar chemical. The test chemical 4% in petrolatum was applied to the skin of 25 human volunteers and observed for signs of dermal sensitization (duration of exposure, observation period not specified).

The test chemical 4% in petrolatum did not induce any sensitization reactions on the skin of 25 human volunteers. Hence, the test chemical was considered to be not sensitizing to skin.

These results are also lended support by a maximisation test performed in guinea pigs following the Magnusson and Kligman method to determine the dermal sensitization potential of other structurally similar test chemical.

Bor:DHPW guinea-pigs were induced by intradermal injections of Freund's Complete Adjuvant (FCA), a 10% dilution of the test substance in maize oil, and a 10% dilution of the test substance in a mixture (1:1) of FCA and maize oil, followed one week later by topical application of a 50% dilution of the test substance in demineralised water for 24 hours.

Fourteen days following the last induction, animals were challenged with a 50% dilution of the test substance in demineralised water for 48 hours. A group of control animals were similarly treated but without the test substance. The challenge treatment induced very slight erythema in 5/20 of the test animals and in 1/10 of the controls. On the basis of similarities between the type of skin reactions occurring in test and control groups, the results of a preliminary skin irritation study in which a 50% test dilution produced irritation in 1/3 animals tested, and the nature and degree of the skin reactions normally observed after challenging with standard allergens, the skin reactions in this study were considered to be consistent with signs of skin irritation rather than sensitisation.

Therefore the test chemical was considered to be not sensitizing to skin.

Based on the available data for the target and structurally similar read across substances, it can be concluded that 2-Ethoxynaphthalene can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, 2-Ethoxynaphthalene can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Available studies for 2-ethoxynaphthalene indicates that it is not likely to cause any dermal sensitization to humans and guinea pigs.

Hence, 2-ethoxynaphthalene can be considered to be not sensitizing to skin. It can be further classified under the category “Not Classified” as per CLP Regulation.