Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
1976
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Major deficiences : unknow purity and specification of 1-naphthol (commercial product), no information on test animals and environmental conditions/ type of coverage/ observations. And there is only one concentration of exposition.

Data source

Reference
Reference Type:
publication
Title:
Teratology and Percutaneous Toxicity Studies on Hair Dyes
Author:
Burnett, C., Goldenthal, E. I., Harris, S. B., Wazeter, F. X., Strausberg, J., Kapp, R., and Voelker, R.
Year:
1976
Bibliographic source:
J. Toxicol. Environ. Health, 1: 1027-1040

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: a hair dye formulation containing 1-naphthol was tested for systemic effects following application to groups of 12 New Zealand White Rabbits
- Short description of test conditions: 1-naphthol was tested by topical application twice weekly for 13 weeks to group of 12 New Zealand White Rabbits.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
No data
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: No data (commercial product)
- Expiration date of the lot/batch: No data
- Purity test date: No data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: No data
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/vehicle: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING No

FORM AS APPLIED IN THE TEST Solution

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

DETAILS OF FOOD AND WATER QUALITY: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light):No data

Administration / exposure

Type of coverage:
not specified
Vehicle:
other: 6% hydrogen peroxide
Details on exposure:
TEST SITE
- Area of exposure: thoracic-lumbar
- % coverage: No data
- Type of wrap if used: No (the rabbit were restrained in holding stocks)
- Time intervals for shavings or clipplings: the hair at the site of application on the back and sides of each rabbit was clipped short throughout the study

REMOVAL OF TEST SUBSTANCE
- Washing (if done): shampooed, rinsed, dried
- Time after start of exposure:1 hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 ml/kg
- Concentration (if solution): 0.25%
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Amount(s) applied (volume or weight with unit): volume 1:1
- Concentration (if solution): 6%
- Lot/batch no. (if required): No data
- Purity: No data

USE OF RESTRAINERS FOR PREVENTING INGESTION: No data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Twice weekly
Doses / concentrations
Dose / conc.:
0.5 other: %
No. of animals per sex per dose:
12
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION (if dermal study): No data

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: No data

FOOD EFFICIENCY:No data

WATER CONSUMPTION:No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood:0, 3, 7 and 13 weeks
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals:No data
- Parameters checked : blood count, methemoglobin, fasting blood sugar, blood urea nitrogen, alkaline phosphatase and serum glutamic oxaloacetic transminase.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 0, 3, 7 and 13 weeks
- Animals fasted: No data
- How many animals:No data
- Parameters checked :

URINALYSIS: Yes
- Time schedule for collection of urine: 0, 3, 7 and 13 weeks
- Metabolism cages used for collection of urine: No data
- Animals fasted:No data
- Parameters checked : color, pH, albumin, glucose, occult blood and microscopic elements

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (organ-body weight ratios were determined for liver, kidneys, adrenals, heart, thyroid, spleen and brain)

HISTOPATHOLOGY: Yes (spleen, stomach, duodenum, colon, liver, gall, bladder, adrenals, nerve, eyes, pancreas, kidneys, urinary bladder, ovaries, testes, bone, bone marrow, hearth, lung, thyroid, brain and skeletal muscle)
Statistics:
Analysis of variance F test and Student's test.

Results and discussion

Results of examinations

Clinical signs:
not examined
Dermal irritation:
not specified
Mortality:
not examined
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 0.5 other: %
Based on:
test mat.
Sex:
male/female

Applicant's summary and conclusion

Conclusions:
Hair dye formulation containing 0.5% of 1 -naphthol was applied to rabbits twice weekly for 13 weeks. There was no evidence of systemic toxicity
Executive summary:

Hair dye formulation containing 0.5% of 1 -naphthol was applied to rabbits twice weekly for 13 weeks. There was no evidence of systemic toxicity