Registration Dossier

Administrative data

Description of key information

With an EC3 value of 1.3, 1-naphthol is a ‘strong’ sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 2001 - August 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot I 6694
- Expiration date of the lot/batch: No Data
- Purity test date: No data
- Purity : > 99%.
- Impurity : there was no evidence to suggest the presence of any significant impurities other than 2-Naphthol at 0.09% w/w and Iron at 2.5 ug/g.

RADIOLABELLING INFORMATION (if applicable)
- Specific activity: 3H
- Locations of the label : methyl Thymidine (Amersham TRA 310, aqueous solution, steriliez 74 GBq/mmol)
- Expiration date of radiochemical substance: No data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (17-20°C) away from direct sunlight
- Stability under test conditions:Yes
- Solubility and stability of the test substance in the solvent/vehicle: Yes
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING : No

FORM AS APPLIED IN THE TEST Suspension
Species:
mouse
Strain:
CBA:J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles Rivers Deutschland GmBh
- Females nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: No data
- Age at study initiation: 7 - 12 weeks
- Weight at study initiation: 14.6 - 25.4 g
- Housing: unique cage number
- Diet (ad libitum): Pelleted standard Kliba 3433
- Water (ad libitum): tap water from Itingen
- Acclimation period: Yes
- Indication of any skin lesions: only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0.1 ; 0.25 ; 0.5 ; 1 and 2.5%
No. of animals per dose:
3
Details on study design:
PRE-SCREEN TESTS:
- Compound solubility: Yes
- Irritation: No
- Systemic toxicity: No
- Ear thickness measurements: No
- Erythema scores: No

MAIN STUDY
12.5 μl 1-naphthol 0.1, 0.25, 0.5, 1 and 2.5% in 4:1 acetone:olive oil was applied on days 1, 2 and 3 by topical application to the ventral and dorsal surfaces of each ear. Five days after the first topical application, the mice were injected intravenously with 3H-methyl thymidine, five hours later killed and the draining lymph nodes excised and pooled. Single cell suspensions were prepared and the proliferation capacity determined.

ANIMAL ASSIGNMENT AND TREATMENT : No data

TREATMENT PREPARATION AND ADMINISTRATION:
Mice were treated by epidermal topical application to the dorsal surface of each ear lobe (left and right) with different test item concentration. The application volume, 25 µl, was spread over the entire dorsal surface of each ear lobe once daily for three consecutive days.
Five days after the first topical application, the mice were administrated with 250 µl of 87.55 µCi/ml 3HTdR by intravenou injection via a tail vein.
Approximately five hours after treatment with 3HTdR all mice were euthanized by intraperitoneal injection of Narcoren at a dose of at least 2ml/kgbw.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calcultaed in the body weight.
Positive control results:
The SI for the positive control was 2.4, 3.7, and 7.0 respectively for the 5, 10 and 25% dilutions
Parameter:
SI
Value:
ca. 1.4
Test group / Remarks:
0.1%
Parameter:
SI
Value:
ca. 1
Test group / Remarks:
0.25%
Parameter:
SI
Value:
ca. 1.2
Test group / Remarks:
0.5
Parameter:
SI
Value:
ca. 1.5
Test group / Remarks:
1%
Parameter:
SI
Value:
ca. 8.5
Test group / Remarks:
2.5%
Key result
Parameter:
EC3
Value:
1.3
Test group / Remarks:
2.5 %
Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION
See table 1 - Stimulation Index

EC3 CALCULATION No data

CLINICAL OBSERVATIONS: No clinical signs occured during the study period.

BODY WEIGHTS The body weight of the animals was within the range commonly recored for animals of this strain and age.

MORTALITY No death occured during the study period.

Table 1 - Stimulation Index

 Concentration (% w/v)  Stimulation Index
 0.1 1.4 
 0.25 1.0 
 0.5 1.2 
 1.0 1.5 
 2.5 8.5 
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
1-Naphthol produced evidence of allergic contact sensitisation in this study at when tested at 2.5%. The EC3 value was calculated to be 1.3. With an EC3 value of 1.3, 1-naphthol is a ‘strong’ sensitizer.
Executive summary:

12.5 μl 1-naphthol 0.1, 0.25, 0.5, 1 and 2.5% in 4:1 acetone:olive oil was applied on days 1, 2 and 3 by topical application to the ventral and dorsal surfaces of each ear. Five days after the first topical application, the mice were injected intravenously with 3H-methyl thymidine, five hours later killed and the draining lymph nodes excised and pooled. Single cell suspensions were prepared and the proliferation capacity determined.

The Mean stimulation indices was 1.4, 1.0, 1.2, 1.5 and 8.5 respectively for 0.1, 0.25, 0.5, 1.0 and 2.5% w/v concentration. The SI for the positive control was 2.4, 3.7, and 7.0 respectively for the 5, 10 and 25% dilutions.

1-Naphthol produced evidence of allergic contact sensitisation in this study at when tested at 2.5%. The EC3 value was calculated by the SCCS (The SCCP adopted this opinion in  April 2008: Opinion on 1 -naphthol SCCP/1123/07) to be 1.3.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

On the basis of the data, 1-naphthol is classified Skin Sens. Cat 1A, H317