Naphthalene

Skin sensitisation

Administrative data

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 with acceptable restrictions (limited documentation, low dosing), acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1985

Reference 2

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

as of 12 May 1981

Deviations:

yes

Remarks:

non-occlusive challenge treatment; FCA-water mixture not applied

Principles of method if other than guideline:

Guinea pig maximization test reported by Magnusson and Kligman 1969:
Comparative study including naphthalene, Naphthol AS [CAS No. 92-77-3], 2-naphthol [CAS No. 135-19-3] and 2-hydroxy-3-naphthoic acid [CAS No. 92-70-6]

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Naphthalene

EC Number:

202-049-5

EC Name:

Naphthalene

Cas Number:

91-20-3

Molecular formula:

C10H8

IUPAC Name:

naphthalene

Details on test material:

- Name of test material (as cited in study report): naphthalene
- Supplier: Katayama Chemical Co., Ltd.
- Molecular formula (if other than submission substance): C10H8
- Molecular weight (if other than submission substance): 128.18
- Substance type: organic
- Physical state: solid
- Analytical purity: no data

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
body weight 300 - 350 g

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: paraffin oil and white vaseline (induction) / acetone (challenge)

Induction 2

Concentration / amount:

1 % (i.d induction); 10 % (epicutaneous induction) / 0.1 and 1 % (epicutaneous challenge)

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other: paraffin oil and white vaseline (induction) / acetone (challenge)

Challenge 2

Concentration / amount:

1 % (i.d induction); 10 % (epicutaneous induction) / 0.1 and 1 % (epicutaneous challenge)

No. of animals per dose:

12 treated animals each;
12 in the untreated control group (only the vehicle)

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 (i.d.); 1 (topical)
- Exposure period: 48 h topical
- Test groups: test substance
- Control group: no data (2-naphthol as surrogate)
- Site: shoulder
- Frequency of applications: day 0 (i.d.); day 7 (topical)
- Duration: 7 + 2 days
- Concentrations: First induction:
50 µL i.d. injected in 1 % of test substance in liquid paraffin
50 µL i.d. injected in 1 % of test substance in Freund´s complete adjuvants (FCA)
(Dose: 500 µg each)
Second induction: after 7 d: topically 10 % of test substance in vaseline (volume: no data) for 48 h (closed patch)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24 h
- Test groups: test substance
- Control group: no data (2-naphthol as surrogate)
- Site: flank
- Concentrations: 0.1 and 1 % in acetone
- Dosage volume: 20 µL/cm2
- Dose: 20 and 200 µg/cm2
- Evaluation (hr after challenge): 24 and 48 h

Challenge controls:

no data

Positive control substance(s):

not specified

Remarks:

No accepted standard mentioned: 2-naphthol proved the responsiveness of the test system.

Results and discussion

Positive control results:

2-Naphthol: 8/8 animals clearly positive

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 and 1 %

No. with + reactions:

0

Total no. in group:

24

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 and 1 %. No with. + reactions: 0.0. Total no. in groups: 24.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1 and 1 %

No. with + reactions:

0

Total no. in group:

24

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1 and 1 %. No with. + reactions: 0.0. Total no. in groups: 24.0.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Considering the quality of the reporting and the low challenge concentrations of naphthalene used, no firm conclusions can be drawn from this study (ECB 2003).

Executive summary:

In a poorly reported skin sensitisation study based on the guinea pig maximisation method, a 24-hour open application dermal challenge, with 0.1% or 1% naphthalene in acetone, did not produce any sign of a sensitisation reaction in any of the 24 animals. However no information was provided on the use of positive controls, and at the induction stage no signs of naphthalene-induced irritation were reported at the concentrations examined. However, 2-naphthol was also tested and was positive in all 16 animals tested.