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Toxicological information

Carcinogenicity

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Description of key information

The Carcinogenic NOEL value for the test substance 4-Chlororesorcinol is found to be 17 mg/Kg in mice. Thus 4-Chlororesorcinol is found to be 
non carcinogenc in nature.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal.
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
The carcinogenic potential following skin painting in mice was evaluated for oxidative dye (4-Chlororesorcinol) for 20 months.
GLP compliance:
not specified
Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Roscoe B. Jackson Memorial Laboratory (Bar Harbor, Me.)
- Age at study initiation: 6-8 wk old,
- Fasting period before study: No data available
- Housing: Individually housed, Mice were housed in plastic cages with granular cellulose bedding (Bed-O'-Cobs, Anderson Mills, Mony, Ohio). They were moved twice weekly to clean cages and bedding
- Diet (e.g. ad libitum): Commercial Wayne Lab-Blox pellets were available ad libitum.
- Water (e.g. ad libitum): Tap water was available ad libitum
- Acclimation period:14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Controlled
- Humidity (%):Controlled
Route of administration:
dermal
Type of inhalation exposure (if applicable):
other: not applicable
Vehicle:
other: 6% Hydrogen peroxide
Details on exposure:
TEST SITE
- Area of exposure: All animals were treated at a single site in the interscapular region
- Time intervals for shavings or clipplings: 24 h before dosing
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05-ml
- Concentration (if solution): 0.025 ml
VEHICLE
- Concentration (if solution): 6%
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
21 months
Frequency of treatment:
Once weekly
Remarks:
Doses / Concentrations:
0.05 ml/Kg (equivalent to 17 mg/kg)
Basis:
no data
No. of animals per sex per dose:
50/sex/dose
Control animals:
yes, concurrent vehicle
Positive control:
No data
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
DERMAL IRRITATION (if dermal study): Yes - Time schedule for examinations: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: monthly
Sacrifice and pathology:
GROSS PATHOLOGY: After 7 and 9 mo of treatment, 10 males and 10 females, randomly selected from each test and control group, were weighed and killed by ether inhalation and a gross necropsy was performed. For each animal the liver and kidney weights were recorded and the organ-to-body weight ratios calculated.

HISTOPATHOLOGY:
Yes , The following were preserved in 10% phosphate-buffered formalin and stained with hematoxylin and eosin for microscopic pathological evaluation: skin, neck (thyroid level), lung, gastrointestinal tract, spleen, pancreas, liver, skeletal muscle, pituitary, kidney, urinary bladder, ureters, bone marrow, lymph nodes, adrenals, gonads, brain, eyes, tumors, and other pathological lesions.
Statistics:
Fischer’s exact test, chi square values significant at p: 0.05
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
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 specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
Organ Weights: A considerable variation in the ratios, even among the controls was observed and none of the differences represent significant departures from control values.
Gross pathology: Gross examinations were performed on all mice found dead or sacrificed in moribund condition or at termination of the study.
No unusual tumor types developed in either treatment or control groups. A few skin tumors were diagnosed in both treatment and control groups; however, they occurred at low incidence and were not treatment-related. The predominant tumor types in the male and female mice of the Eppley colony are liver hemangioma, lung adenoma, and malignant lymphoma; the high spontaneous incidence of malignant lymphomas is characteristic of the Eppley Swiss colony
Histopathology: non-neoplastic: All mice were necropsied and examined thoroughly for neoplastic growth except one male mouse. Pathology of the skin was of special interest since the dyes were applied to a shaved area of skin in the interscapular region. A few skin tumors were diagnosed in both treatment and control groups;

Dose descriptor:
NOEL
Effect level:
17 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Lesions observed
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Conclusions:
The Carcinogenic NOEL value for the test substance 4-Chlororesorcinol is found to be 17 mg/Kg in mice.
Executive summary:

The chronic toxicological and carcinogenic potential following skin painting in mice was evaluated for 4-Chlororesorcinol.

Groups of 50 male and female Swiss mice were treated one time weekly for at least 20 month with one dose level of each dye.

The oxidative dyes were mixed 1:1 with 6% hydrogen peroxide before treatment. Control groups were shaved only and received no applications.

Body weights and survival rates did not differ between appropriate male and female treatment and control groups.

Absolute and relative liver and kidney weights were equivalent for treatment and control groups. After 7 and 9 month of treatment, 10 males and 10 females randomly selected from each group were necropsied and tissues taken for histopathological evaluation. Animals found dead or sacrificed in moribund condition or at termination of the study were necropsied and evaluated histopathologically.

 

Comparison of incidence of tumors and of non tumor pathology among the various treatment and control groups revealed no biologically significant differences. Toxicological and carcinogenic effects were not induced by the hair dye formulations.

 

Therefore NOEL was found to be 17 mg/Kg for 4-Chlororesorcinol formulations tested by skin painting procedures in this chronic study on male and female Swiss mice. Hence it is concluded that substance 4-Chlororesorcinol is likely to be non carcinogenic in nature.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
17 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
The data is of K2 level and is obtained from publication.

Justification for classification or non-classification

The avaialable study indicates that the substance 4-Chlororesorcinol is likely to be non carcinogenic in nature.

Additional information

The chronic toxicological and carcinogenic potential following skin painting in mice was evaluated for 4-Chlororesorcinol.

Groups of 50 male and female Swiss mice were treated one time weekly for at least 20 month with one dose level of each dye.The oxidative dyes were mixed 1:1 with 6% hydrogen peroxide before treatment. Control groups were shaved only and received no applications.

Body weights and survival rates did not differ between appropriate male and female treatment and control groups. Absolute and relative liver and kidney weights were equivalent for treatment and control groups. After 7 and 9 month of treatment, 10 males and 10 females randomly selected from each group were necropsied and tissues taken for histopathological evaluation. Animals found dead or sacrificed in moribund condition or at termination of the study were necropsied and evaluated histopathologically.

 

Comparison of incidence of tumors and of non tumor pathology among the various treatment and control groups revealed no biologically significant differences. Toxicological and carcinogenic effects were not induced by the hair dye formulations.

 

Therefore NOEL was found to be 17mg/Kg for 4-Chlororesorcinol formulations tested by skin painting procedures in this chronic study on male and female Swiss mice. Hence it is concluded that substance 4-Chlororesorcinol is likely to be non carcinogenic in nature.


Justification for selection of carcinogenicity via dermal route endpoint:
The Carcinogenic NOEL value for the test substance 4-Chlororesorcinol is found to be 0.05 mL/Kg in mice.