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Administrative data

Description of key information

N-phenyl-1-naphthylamine has been observed to be a skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-06-10 to 1987-07-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
A modified procedure from the maximization test of Magnusson and Kligman (J. invest. Dermatol. 52, 26 8-276, 1969; Contact Dermatitis 6, 46-50, 1980), recommended in the OECD guidelines 1981 and in the EEC directive 7 9/831, was performed. The method was selected on account of its suitability for final formulations or for compounds which are not injectable on account of their insolubility in standard vehicles.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
in vivo guinea pig studies were available.
Species:
guinea pig
Strain:
other: Pirbright White (Tif:DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 10 weeks old
- Weight at study initiation: 302 - 432 g
- Housing: individually in Macrolon cages (Type 3)
- Diet (e.g. ad libitum): standard guinea pig pellets - NAFAG No.846, Gossau SG
- Water (e.g. ad libitum): drinking water is examined periodically by the IWB (Industrielle Werke Basel)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: vaseline
Concentration / amount:
First induction: approx. 0.4 g of 10 % test material in vaseline
Second induction: approx. 0.4 g paste of 10 % test material in vaseline
Day(s)/duration:
24 h epicutaneous
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
approx. 0.2 g paste of 3 % test material in vaseline
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: The concentration of the test compound for the induction and challenge periods were determined on separate animals.

MAIN STUDY
INDUCTION EXPOSURE: first induction
0.1 mL of a freshly prepared adjuvant saline mixture (1:1) was injected intracutaneously at 4 sites into the animals neck skin. The test substance was incorporated in vaseline and applied on a filterpaper patch over the adjuvant injection sites (patch 2x4 cm; occluded adminstration for 24 hours); approx. 0.4 g of 10 % test material in vaseline.

INDUCTION EXPOSURE: second induction
One week later the test substance was again incorporated in vaseline and applied on the adjuvant injection sites of the first week. The filterpaper patches were administered occlusively for 48 hours; approx. 0.4 g paste of 10 % test material in vaseline.
CHALLENGE EXPOSURE
2 weeks after the epidermal induction application the animals were tested on the flank with the test substance in vaseline and the vehicle alone (patch 2x2 cm; occluded administration for 24 hours); approx. 0.2 g paste of 3 % test material in vaseline.

Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings.
Challenge controls:
A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test compound (at least 10 animals) to control the maximal subirritatant concentration of the test compound in adjuvant treated animals.
Separate animals were treated with the test item for the evaluation of the primary irritation threshold concentration. Concentrations of 1, 3, 10 and 30 % in vaseline were tested. Erythema reactions were observed at 10 and 30 %. No erythema was induced at the lower concentrations. Therefore, 3 % was used as the maximal subirritant concentration for the challenge application.
Positive control substance(s):
yes
Remarks:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-dichromate.
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3%
No. with + reactions:
18
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
not determinable because of methodological limitations
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3%
No. with + reactions:
18
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not determinable because of methodological limitations

Number of positive animals per group after occlusive epicutaneous application:

24 hours 48 hours
Control group vehicle control 0/20 0/20
test compound 0/10 0/10
test group vehicle control 0/20 0/20
test compound 18/20 18/20

Under the experimental test conditions employed, 90% of the animals showed skin reactions (erythema and edema) 24 and 48 hours after removing of the dressings.

Individual readings of the test group animals

DRAIZE Score 24 hours after removal of the dressing with the test compound:

Male animal  1 2 3 4 5 6 7 8 9 10
Erythema score 1 0 2 1 2 2 1 2 1 1
Edema score 2 0 3 1 3 2 2 3 2 1

Female animal 1 2 3 4 5 6 7 8 9 10
Erythema score 3 2 1 0 2 1 2 1 1 1
Edema score 3 2 0 0 3 1 2 1 1 1

DRAIZE Score 48 hours after removal of the dressing wih the test compound

Male animal  1 2 3 4 5 6 7 8 9 10
Erythema score 1 0 2s 1 2s 1 1 1 1 1
Edema score 1 0 2 1 3 1 1 2 1 1

Female animal 1 2 3 4 5 6 7 8 9 10
Erythema score 2s 2s 1 0 1s 1s 2s 1s 1 1
Edema score 2 2 0 0 2 1 2 1 1 1

s = scaling

Interpretation of results:
other: Category 1B (indication of skin sensitising potential) based on EU GHS criteria
Conclusions:
90 % of the animals were sensitized under the experimental conditions employed.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
The guinea pig maximisation test was performed (Magnusson and Kligman, 1970) with phenyl-alpha-napthylamine.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
intradermal and epicutaneous
Vehicle:
other: intradermally: olive oil, epicutaneously: petrolatum
Concentration / amount:
intradermal injection: 10 % test substance in olive oil (w/w)
topical application: 25 % test substance in pet (w/w), with sodium lauryl sulphate pretreatment
Adequacy of induction:
other: pretreated with SLS
Route:
other: epicutaneous
Vehicle:
petrolatum
Concentration / amount:
0.5, 2.5, 5 % test substance in pet. (w/w)
No. of animals per dose:
20 exposed animals
19 control animals
Details on study design:
no information given
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 %
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2.5 %
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5 %
No. with + reactions:
14
Total no. in group:
20
Clinical observations:
no data
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 %
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
no data
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2.5 %
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
no data
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5 %
No. with + reactions:
15
Total no. in group:
20
Clinical observations:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2.5 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no data
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no data
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2.5 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no data
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no data

Summary of results:

Challenge concentration (%) 5 2.5 0.5 vehicle

controls
n=10

 24h 0 0 0 0
48h 0 0 0 0

test group
n=20

 24h 14 13 9 0
48h 15 12 9 1

Chi-aquare

 24h p<0.001 p<0.001 p<0.001
48h p<0.001 p<0.001 p<0.001 p>0.2
Interpretation of results:
other: Category 1B (indication of skin sensitising potential) based on EU GHS criteria
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2003-03-17 to 2003-05-01
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Repeatedly positive findings in the control group, positive findings not discussed or explained, no definition on evaluation criteria
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
No LLNA was performed because sensitization studies with guinea pigs were available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre de Production Animale (F-45160 Olivet)
- Weight at study initiation: mean 449.8 g (males), 428.4 g (females)
- Diet (e.g. ad libitum): Guinea Pig Breeding Diet, Cobayes-Elevage
- Acclimation period: 5 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 26 - 61
Route:
intradermal and epicutaneous
Vehicle:
other: olive oil for intradermal injections; paraffin oil for topical application
Concentration / amount:
- intradermal induction: 15%
- topical induction: 100%
Day(s)/duration:
topical: 24 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: olive oil for intradermal injections; paraffin oil for topical application
Concentration / amount:
- 1st challenge: 12.5%, 25%
- 2nd challenge: 6.25%, 12.5%
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Preliminary studies:
Maximum Non Necrotizing Concentration (M.N.N.C.) determination: 2 males
Pre-Maximum Non Irritant Concentration (M.N.I.C.) determination: 2 males
Maximum Non Irritant Concentration (M.N.I.C.) determination: 3 females

Main study:
- main group: 10 males
- control group: 5 males
Details on study design:
RANGE FINDING TESTS:
- Maximum Non Necrotizing Concentration (M.N.N.C.) determination: test substance was injected by intradermal route at 15%, 7.5%, 3.75%, 1.875%, 0.938% and 0.469% diluted in olive oil.
- Pre-Maximum Non Irritant Concentration (M.N.I.C.) determination: test substance was applied under an occlusive dressing during 24 hours, at 100%, 50%, 25% and 12.5% diluted in paraffin oil.
- Maximum Non Irritant Concentration (M.N.I.C.) determination: after induction by intradermal injection with olive oil and by topical application with parafin oil and a 17-days rest phase, the challenge phase under occlusive dressing for 24 hours consists in a single topical application of the test substance at 50%, 25%, 12.5%, 6.25% diluted in parafin oil.

MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL INDUCTION
- No. of exposures: 6 topical injections (2 intradermal injections of the test substance diluted at 15% in olive oil; 2 intradermal injections of Freund's Complete Adjuvant diluted at 50% in a physiological saline solution; 2 intradermal injections of a mixture with equal volumes - Freund's Complete Adjuvant at 50% and the test substance diluted at 15% in olive oil
- Exposure period: 7 days
- Test groups: 10 animals
- Control group: 5 animals
- Frequency of applications: single application

B. INDUCTION EXPOSURE: INTRADERMAL INDUCTION
- No. of exposures: topical application with the test substance at 100%, 24 hours after brushing with 0.5 ml of a solution of Sodium lauryl
- Exposure period: 24 hours
- Test groups: 10 animals
- Control group: 5 animals
- Site: the same test site as for intradermal induction
- Frequency of applications: single application
- Concentrations: 100%

C. CHALLENGE EXPOSURE
- No. of exposures: 2 (1st and 2nd challenge) under occlusive dressing
- Day(s) of challenge: 28 (1st challenge); 36 (2nd challenge)
- Exposure period: 24 h
- Test groups: 10 animals
- Control group: 5 animals
- Concentrations: 12.5%, 25% (1st challenge), 6.25% 12.5% (2nd challenge)
- Evaluation (hr after challenge): 24, 48 h

D. WEIGHING:
- Time schedule: animals were weighed on da of topical inductionand on day od 48 hours readings (1st and 2nd challenge)
Positive control substance(s):
yes
Remarks:
benzocaine and neomycin sulfate (historical controls)
Positive control results:
Bezocaine and neomycin sulfate are found to be skin sensitizers in albino guinea pigs according to the grading of Magnusson and Kligman.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
12.5 %
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
12.5%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
erythema, but no edema noted
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
erythema, but no edema noted
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
12.5%
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
erythema, but no edema noted
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
12.5%
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
12.5%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
12.5%
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
6.25%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
6.25%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
12.5%
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
1
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
6.25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
erythema, but no edema noted
Reading:
other: rechallenge: 2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
6.25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
erythema, but no edema noted

Preliminary studies:

- Maximum Non Necrotizing Concentration (M.N.N.C.) determination:

No necrosis has been observed at the concentrations of 15%, the first induction has been carried out by intradermal injection at the same concentration.

Macroscopic evaluation of cutanous reaction:

Animal Concentration (%)
15 7.5 3.75 1.875 0.938 0.469
1 2 2 2 1 0 0
2 2 2 1 1 0 0

- Pre-Maximum Non Irritant Concentration (M.N.I.C.) determination:

24 hours after the removal of the occlusive dressings, it was noted a slight erythema on the treated area at 100%. In view of these results, the concentrations selected were 100% for the 2nd induction of the main study and the MNIC began at the concentration of 50%.

Macroscopic evaluation of cutanous reaction:

Application Animal Concentration (%) 
100 50 25 12.5
Topical application under occlusive dressing 1 1 0 0 0
2 1 0 0 0

-Maximum Non Irritant Concentration (M.N.I.C.) determination:

24 hours after removal of the occlusive dressings, it was noted a slight erythema in 2 animals, on the treated area at 50%. In view of this result, the concentrations selected were 25% (MNIC) and 12.5% (1/2 MNIC) for the challenge phase of the main study.

Macroscopic evaluation of cutanous reaction:

Application Animal Concentration (%)
50 25 12.5 6.25
Topical application under occlusive dressing 1 1 0 0 0
2 0 0 0 0
3 1 0 0 0

Main Study:

Macroscopic evaluation of cutanous reaction of challenge:

Animal Concentration: 25% Concentration: 12.5%
24 h 48 h 24 h 48 h
Erythema Edema Erythema Edema Erythema Edema Erythema Edema
Negative control group 1 0 0 0 0 0 0 0 0
2 0 0 0 0 1 0 0 0
3 2 0 2 0 2 0 2 0
4 1 0 0 0 0 0 0 0
5 1 0 0 0 1 0 0 0
Test group 1 2 0 2 0 2 0 2 0
2 2 0 2 0 2 0 2 0
3 2 0 1 0 2 0 1 0
4 1 0 1 0 1 0 1 0
5 0 0 0 0 0 0 0 0
6 2 0 1 0 2 0 1 0
7 2 0 2 0 2 0 2 0
8 1 0 2 0 2 0 2 0
9 1 0 2 0 0 0 1 0
10 1 0 2 0 0 0 0 0

Overall evaluation of the challenge:

Only animals with a reactions of >2 were regarded as positive.

The % of positve animals in the control group were subtracted from the % of positive animals in the test group to yield the sensitization rate.

Groups Reading Time Concentration number of animals with grade % of positive response sensitization rate (%)
0 1 2 >3
negative control group 24h 25% 2 2 1 0 20% -
48h 25% 4 0 1 0 20% -
24h 12.50% 2 2 1 0 20% -
48h 12.50% 4 0 1 0 20% -
treated group 24h 25% 1 4 5 0 50% 30%
48h 25% 1 3 6 0 60% 40%
24h 12.50% 3 1 6 0 60% 40%
48h 12.50% 2 4 4 0 40% 20%

Macroscopic evaluation of cutanous reaction of re-challenge:

Animal Concentration: 12.5% Concentration: 6.25%
24 h 48 h 24 h 48 h
Erythema Edema Erythema Edema Erythema Edema Erythema Edema
Negative control group 1 1 0 1 0 0 0 0 0
2 2 0 1 0 1 0 1 0
3 1 0 1 0 1 0 1 0
4 1 0 0 0 0 0 0 0
5 0 0 1 0 0 0 0 0
Test group 1 1 0 1 0 0 0 0 0
2 2 0 2 0 0 0 0 0
3 1 0 1 0 0 0 1 0
4 1 0 0 0 0 0 0 0
5 2 0 2 0 2 0 0 0
6 1 0 0 0 0 0 0 0
7 2 0 1 0 1 0 1 0
8 2 0 1 0 2 0 2 0
9 2 0 2 0 1 0 0 0
10 0 0 1 0 0 0 0 0

Overall evaluation of the re-challenge:

Only animals with a reactions of >2 were regarded as positive.

The % of positve animals in the control group were subtracted from the % of positive animals in the test group to yield the sensitization rate.

Groups Reading Time Concentration number of animals with grade % of positive response sensitizatin rate (%)
0 1 2 >3
negative control group 24h 12.50% 1 3 1 0 20% -
48h 12.50% 1 4 0 0 0% -
24h 6.25% 3 2 0 0 0% -
48h 6.25% 3 2 0 0 0% -
treated group 24h 12.50% 1 4 5 0 50% 30%
48h 12.50% 2 5 3 0 30% 30%
24h 6.25% 6 2 2 0 20% 20%
48h 6.25% 7 2 1 0 10% 10%

Body Weight:

Not any abnormality was recorded in the weight growth of both groups.

Mean weight +/- SD (g) at begining and end of test:

- Males: 449.8 +/- 6.6; 667.2 +/- 71.6

- Females: 428.4 +/- 35.2; 691.9 +/- 70.7

Interpretation of results:
other: Category 1B (indication of skin sensitising potential) based on EU GHS criteria
Conclusions:
24 hours after the challenge a moderate erythema was observed in 30% and 40% of treated animals at a challenge concentration of 25% and 12.5%, respectively. After 48 hours, 40% and 20% of treated animals were observed at 25% and 12.5%, respectively.
24 hours after the re-challenge a moderate erythema was observed in 30% and 20% of treated animals at a challenge concentration of 12.5% and 6.25%, respectively. After 48 hours, 30% and 10% of treated animals were observed at 12.5% and 6.25%, respectively.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Animal Studies

The sensitization potential of N-phenyl-1-naphthylamine was investigated in a modified procedure from the maximization test of Magnusson and Kligman following OECD guideline 406 using guinea-pigs. The induction was a two-stage operation. First, 0.1 ml of a freshly prepared adjuvant saline mixture (1:1) was injected intracutaneously at 4 sites into the animals neck skin. The test item (0.4g of a 10% solution) was incorporated in vaseline and applied on a filterpaper patch over the adjuvant injection sites (patch 2x4 cm; occluded administration for 24 hours). Secondly, one week later the test item was again incorporated in vaseline in 10% and applied on the adjuvant injection sites of the first week. The filterpaper patches were administered occlusively for 48 hours. Two weeks after the epidermal induction application the animals were tested on the flank with the test item in vaseline (3% = maximal subirritant concentration) and the vehicle alone (patch 2 x 2 cm; occluded administration for 24 hours). The concentration of the test compound for the induction and challenge periods were determined on separate animals. A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test compound (at least 10 animals) to control the maximal subirritant concentration of the test compound in adjuvant treated animals. Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings. Under the experimental conditions employed, 90 % of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings (Ciba-Geigy, 1987).

In a second guinea-pig maximization study following the procedures of Magnusson and Kligman, the animals were induced intradermally with N-phenyl-1-naphthylamine at a concentration of 10% followed by an epidermal induction at a concentration of 25% in petrolatum after pretreatment with SLS. The challenge occurred epidermally with concentrations of 5, 2.5 and 0.5 % test material. As a result, positive reactions were reported in 15 of 20 animals with the highest challenge concentrations. Therefore, the test article is considered a moderate skin sensitizer (Boman et al., 1980).

In a third guinea-pig maximization study following OECD guideline 406, groups of guinea-pigs were induced with intradermally and topically with the test item at 15% and 100%, respectively. 24 hours after the challenge a moderate erythema was observed in 30% and 40% of treated animals at a challenge concentration of 25% and 12.5%, respectively. After 48 hours, 40% and 20% of treated animals were observed at 25% and 12.5%, respectively. 24 hours after the re-challenge a moderate erythema was observed in 30% and 20% of treated animals at a challenge concentration of 12.5% and 6.25%, respectively. After 48 hours, 30% and 10% of treated animals were observed at 12.5% and 6.25%, respectively. Based on this result, the test article is considered a moderate sensitizer. This assay has methodical short-comings (repeatedly positive findings in the control group, positive findings not discussed or explained, no definition on evaluation criteria), therefore its reliability is only assessed as Klimisch 3. However, since the result is supporting the findings of the above described studies, it is kept in the dossier as suporting information (Phycher, 2003).

In a modified Landsteiner´guinea-pig sensitisation test (no further information available), which is not a standard method, N-phenyl-1-naphthylamine did not exhibit a sensitizing potential (MacEwen and Vernot, 1974).

Overall, N-phenyl-1-naphthylamine is considered to be a moderate skin sensitizer.

Studies in humans

N-phenyl-1-naphthylamine was reported to have sensitizing properties in humans. Case studies on patients with contact dermatitis, potentially associated with occupational exposure to N-phenyl-1-naphthylamine in greases or oils, have been identified. The majority of these patients also had positive reactions to other substances. Lower incidences were reported in patients with past exposure to rubber materials. Because of the incorporation into the polymer matrix, exposure to N-phenyl-1-naphthylamine in rubber materials is assumed to be lower than exposure from greases or oil. At the workplace, there is a risk of dermal sensitisation from exposure to greases and antirust oil containing N-phenyl-1-naphthylamine. The risk from exposure to rubber materials may be much lower, owing to the low concentrations of N-phenyl-1-naphthylamine in such materials; a risk to the general population from exposure to products containing N-phenyl-1-naphthylamine can not be excluded.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The epicutaneous sensitisation study indicates a potential for skin sensitisation. As a result the substance is considered to be classified as skin sensitizer category 1B (H317: "May cause an allergic skin reaction") under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.