Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Final Report on the Safety Assessment of Acid Violet 43

Author:

Fiume MZ

Year:

2001

Bibliographic source:

International Journal of Toxicology, 20(Suppl. 3):1–6, 2001

Materials and methods

Principles of method if other than guideline:

Carcinogenic potential of the test compound Acid Violet 43 was evaluated on mice in 107 weeks study period

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Acid violet 43

IUPAC Name:

Acid violet 43

Constituent 2

Reference substance name:

Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate

EC Number:

224-618-7

EC Name:

Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate

Cas Number:

4430-18-6

Molecular formula:

C21H15NO6S.Na

IUPAC Name:

sodium 2-[(4-hydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yl)amino]-5-methylbenzenesulfonate

Details on test material:

- Name of test material (as cited in study report): Ext. D & C Violet No. 2- Molecular formula (if other than submission substance): C21H15NO6S.Na- Molecular weight (if other than submission substance): 431.399 g/mol- Substance type: organic- Physical state: No data availablePurity No data available- Impurities (identity and concentrations): Ext. D & C Violet No. 2 must be free of impurities except for the following: ≤ 18% volatile matter (at 135±C) and chlorides and sulfates (calculated as sodium salts); ≤ 0.4%water-insoluble matter; ≤ 0.2% 1-hydroxy-9,10-anthracenedione ; ≤ 0.2% 1,4-dihydroxy-9,10-anthracenedione; ≤ 0.1% p-toluidine; ≤ 0.2% p-toluidine sulfonic acids, sodium salts; ≤ 1% subsidiary colors;≤ 20 ppm lead (as Pb); ≤ 3 ppm arsenic (as As); ≤ 1 ppm mercury (as Hg); and ≥ 80% total color (FDA 1976).

Test animals

Species:

mouse

Strain:

other: Swiss-Millerton mice

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: American Cyanamid Company 1967- Age at study initiation: 6 weeks- Weight at study initiation: No data available- Fasting period before study: No data available- Housing: 10/cage- Diet (e.g. ad libitum): No data available- Water (e.g. ad libitum): No data available- Acclimation period: No data availableENVIRONMENTAL CONDITIONS- Temperature (°C): No data available- Humidity (%):No data available- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): No data availableIN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:

dermal

Vehicle:

propylene glycol

Details on exposure:

DIET PREPARATION- Rate of preparation of diet (frequency): No data available- Mixing appropriate amounts with (Type of food): No data available- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): No data available- Concentration in vehicle: 0, 1 or 2%(1428.5 or 2857.1 mg/Kg bw)- Amount of vehicle (if gavage): No data available- Lot/batch no. (if required): No data available- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data available

Duration of treatment / exposure:

107 weeks

Frequency of treatment:

Daily

Post exposure period:

No data available

Doses / concentrations

Remarks:

Doses / Concentrations:0, 1 or 2% (1428.5 or 2857.1 mg/Kg bw)Basis:

No. of animals per sex per dose:

Total: 4001%: 1002%: 100Control: 200

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes- Time schedule: Daily- Cage side observations checked in table [No.?] were included. MortalityDETAILED CLINICAL OBSERVATIONS: No data available - Time schedule: No data availableDERMAL IRRITATION (if dermal study): No data available- Time schedule for examinations: No data availableBODY WEIGHT: Yes- Time schedule for examinations: 6 months intervalFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data availableFOOD 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 availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available- Time schedule for examinations: No data availableOPHTHALMOSCOPIC EXAMINATION: No data available - Time schedule for examinations: No data available- Dose groups that were examined: No data availableHAEMATOLOGY: No data available- Time schedule for collection of blood: No data available- Anaesthetic used for blood collection: No data available- Animals fasted: No data available- How many animals: No data available- Parameters checked in table [No.?] were examined. No data availableCLINICAL CHEMISTRY: No data available - Time schedule for collection of blood: No data available- Animals fasted: No data available- How many animals: No data available- Parameters checked in table [No.?] were examined. No data availableURINALYSIS: No data available- Time schedule for collection of urine: No data available- Metabolism cages used for collection of urine: No data available- Animals fasted: No data available- Parameters checked in table [No.?] were examined. No data availableNEUROBEHAVIOURAL EXAMINATION: No data available- Time schedule for examinations: No data available- Dose groups that were examined: No data available- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data availableOTHER: No data available

Sacrifice and pathology:

GROSS PATHOLOGY:Yes, The animals were necropsied over weeks 102 to 107 and neoplasms were observedHISTOPATHOLOGY: YesMicroscopic examination was performed on tissues of 10 animals of the test and control groups; animals with the “greatest array of grossly evident lesions” were chosen for microscopic examination. Neoplasms from other animals, with the exception of some “obvious leukemias,” were also examined microscopically.

Other examinations:

No data available

Statistics:

No data available

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not specified

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:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Details on results:

Details on Result:CLINICAL SIGNS AND MORTALITYMortality: Survival of test animals was similar to or slightly greater than that of controls.BODY WEIGHT AND WEIGHT GAIN No data availableFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study) No data availableFOOD EFFICIENCY No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study) No data availableOPHTHALMOSCOPIC EXAMINATION No data availableHAEMATOLOGY No data availableCLINICAL CHEMISTRY No data availableURINALYSIS No data availableNEUROBEHAVIOUR No data availableORGAN WEIGHTS No data availableGROSS PATHOLOGY No data availableHISTOPATHOLOGY: NON-NEOPLASTIC No data availableHISTOPATHOLOGY: NEOPLASTIC (if applicable) The probability of occurrences of neoplasms or of leukemia in the test mice was no different than, or significantly lower than, that of controls.HISTORICAL CONTROL DATA (if applicable) No data availableOTHER FINDINGS No data available

Effect levels

Dose descriptor:

NOAEL

Effect level:

2 857.1 mg/kg bw (total dose)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Lesions observed were same in the treated and control group

Remarks on result:

other:

Remarks:

Effect type: other: Not carcinogenic (migrated information)

Applicant's summary and conclusion

Conclusions:

Ext. D & C Violet No. 2–induced gross or microscopic lesions were not observed and hence the carcinogenic No Observed Adverse Effect Level (NOAEL) for the test compound is 2% (2857.1 mg/Kg bw).

Executive summary:

Carcinogenic potential of the test compound Acid Violet 43 was evaluated on mice in 107 weeks study period.

 

One hundred female Swiss-Millerton mice, grouped 10 per cage, received weekly dermal applications of Ext. D & C Violet No. 2 to a shaved scapular area of the back. A control group of 200 mice received weekly applications of vehicle.

For thefirst dose, 0.1 ml of a 1%aqueous solution of Ext. D & C Violet No. 2 was applied witha syringe; this method of dosing was unsatisfactory because thesolution did not wet the skin of the animals. Doses 2 through6 were applied with a “camel’s hair” brush as 2% dispersionsin propylene glycol, and doses 7 through 103 were applied as1% dispersions in propylene glycol. The applications were madeover a 107-week period. The test and control animals were killedwhen test group survival approached 30%of the original 100 animalsof the group. The animals were necropsied over weeks 102to 107. Observations were made daily for dead animals and, afterdosing, for presence of papillomas or other neoplasms. Bodyweights were determined at 6-month intervals. Microscopic examinationwas performed on tissues of 10 animals of the test

and control groups; animals with the “greatest array of grossly evident lesions” were chosen for microscopic examination. Neoplasms from other animals, with the exception of some “obvious leukemias,” were also examined microscopically.

 

It was estimated that the test animals received approximately 27 mg/kg of Ext. D & C Violet No. 2 each week. Survival of test animals was similar to or slightly greater than that of controls. The probability of occurrences of neoplasms or of leukemia in the test mice was no different than, or significantly lower than,that of controls.

 

Ext. D & C Violet No. 2–induced gross or microscopic lesions were not observed and hence the carcinogenic No Observed Adverse Effect Level (NOAEL) for the test compound is2% (2857.1 mg/Kg bw).