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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
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 publication

Data source

Reference
Reference Type:
publication
Title:
Teratology and percutaneous toxicity studies on hair dyes
Author:
C. Burnett , E. I. Goldenthal , S. B. Harris , F. X. Wazeter , J. Strausburg , R. Kapp & R. Voelker
Year:
1976
Bibliographic source:
Journal of Toxicology and Environmental Health,1, 1027-1040, 1976

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Repeated dose dermal toxicity study was performed to determine the dermal toxic nature of Gentian violet using Charles River CD female rats
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report):Gentian violet
- IUPAC name: N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride
- Molecular formula : C25H30N3.Cl
Molecular weight : 407.986 g/mol
- Smiles notation: C(\c1ccc(N(C)C)cc1)(c1ccc(N(C)C)cc1)=C1\C=C\C(=[N+](/C)C)C=C1.[ClH-]
- InChl:1S/C25H30N3.ClH/c1-26(2)22-13-7-19(8-14-22)25(20-9-15-23(16-10-20)27(3)4)21-11-17-24(18-12-21)28(5)6;/h7-18H,1-6H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid
Specific details on test material used for the study:
- Name of test material : Basic violet 3
- Molecular formula : C25H30ClN3
- Molecular weight : 407.986 g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): No data

Test animals

Species:
rat
Strain:
other: Charles River CD
Details on species / strain selection:
No data
Sex:
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
- Fasting period before study: No data
- Housing: the mated female animals were housed individually in temperature- and
humidity-controlled rooms
- Diet (e.g. ad libitum): Ralston Purina Laboratory Chow ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: No data

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

IN-LIFE DATES: From: To: No data

Administration / exposure

Type of coverage:
not specified
Vehicle:
not specified
Details on exposure:
TEST SITE
- Area of exposure: The dorso-scapular area
- % coverage: No data
- Type of wrap if used: No data
- Time intervals for shavings or clipplings: The hair at the site of application on the dorso-scapular area was shaved closely the day prior to application

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg of the P-23 dye formulation
- Concentration (if solution): 0.002% (2.0 mg/Kg)
- Constant volume or concentration used: No data
- For solids, paste formed: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): No data
- 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
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
Duration of treatment: 19 days
Duration of exposure: 1, 4, 7, 10, 13, 16 and 19 day of gestation
Frequency of treatment:
Once on days 1, 4, 7, 10, 13, 16 and 19 of gestation
Doses / concentrations
Remarks:
0.002% (0.00942 mg/Kg)
No. of animals per sex per dose:
Total: 100
0 mg/Kg: 60 female rats
2.0 mg/Kg: 20 female rats
Positive control: 20 female rats
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
Acetylsalicylic acid

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: No data

BODY WEIGHT: Yes
- Time schedule for examinations: 1, 4, 7, 10, 13, 16 and 19 day of gestation

FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY:
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data - Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY:
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: No data sensory activity / grip strength / motor activity / other: No data

OTHER: No data
Sacrifice and pathology:
No data
Other examinations:
No data
Statistics:
All statistical analyses compared the treatment groups with the control groups. Statistically significant differences between groups were judged valid only when there were significant differences between any one of the dye treated groups and each of the three untreated control groups.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
no effects observed
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Clinical signs and mortality
Clinical signs: No signs of toxicity were noted during the study period
Mortality: No data

Dermal irritation: No irritation or other changes in appearance were noted except for changes in skin and hair color at the site of topical application of the dye formulation

Body weight and weight gain: Changes in female body weights were similar for rats in the untreated controls and all dye-treated groups at 0.00942 mg/Kg.

Food consumption and compound intake: Mean food consumption for all groups throughout gestation was similar

Food efficiency: No data

Water consumption and compound intake: No data

Opthalmoscopic examination: No data

Haematology: No data

Clinical chemistry: No data

Urinanalysis: No data

Neurobehaviour: No data

Organ weights: No data

Gross pathology: No data

Histopathology: No data

Effect levels

Dose descriptor:
NOAEL
Effect level:
0.009 other: mg/Kg
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No evidence of compound-induced toxicity was observed
Remarks on result:
other: No adverse effects were observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No Observed Adverse Effect Level (NOAEL) for gentian violet in female Charles River CD rats is considered to be 0.00942 mg/Kg.
Executive summary:

Repeated dose dermal toxicity study was performed to determine the dermal toxic nature of Gentian violet. The study was performed using female Charles River CD rats. 2 mL/Kg dye formulation P-23 containing 0.002% ( 0.00942 mg/Kg) test compound was applied to the dorso-scapular area. The application was made during the gestation days 1, 4, 7, 10, 13, 16 and 19. The animals were observed for clinical signs, body weight changes, dermal irritation if any and food consumption. No dye formulation related toxicity was noted. Changes in female body weights and food consumption were similar for rats in the untreated controls and all dye-treated groups. No irritation or other changes in appearance were noted except for changes in skin and hair color at the site of topical application of the dye formulation. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for gentian violet in female Charles River CD rats is considered to be 0.00942 mg/Kg.