Ferrate(4-), hexakis(cyano-C)-, methylated 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]benzenamine copper(2+) salts

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

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 publication.

Data source

Reference

Reference Type:

publication

Title:

Chronic effects of test chemical after intra-gastric administration

Author:

Ketkar et.al

Year:

1982

Bibliographic source:

Cancer Letters, 1982

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the toxic nature of the test chemical in male and female Sprague-Dawley rats by oral gavage for life.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride

EC Number:

211-189-6

EC Name:

(4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride

Cas Number:

632-99-5

Molecular formula:

C20H19N3.ClH

IUPAC Name:

(4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Basic Violet 14
- Molecular formula (if other than submission substance): C20H19N3.ClH
- Molecular weight (if other than submission substance): 337.8 g/mol
- Physical State: Solid
- Substance type: organic

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wiga Company, Sulzfeld, F.R.G.)
- Females (if applicable) nulliparous and non-pregnant: [yes/no] : not specified
- Age at study initiation: 12 weeks
- Weight at study initiation: no data available
- Fasting period before study: no data available
- Housing: housed, sex segregated, 3 to a Makrolon cage (Type III, E. Becker & Co. GmbH, Castrop- Rauxel, F.R.G.).
- Diet (e.g. ad libitum): pelleted diet (RMH-B, Hope Farms, Woerden,Netherlands), ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: no data available

DETAILS OF FOOD AND WATER QUALITY: no data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature 22 * 2”C,
- Humidity (%): relative humidity 50 + 5%
- Air changes (per hr): air change 20 times per hour
- Photoperiod (hrs dark / hrs light): no data available

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: NaCl solution.

Details on oral exposure:

Details on oral exposure
VEHICLE
- Justification for use and choice of vehicle (if other than water): Since the test chemical dissolve only a little in water and may not be reabsorbed by the intestinal tract, the effect which was seen in the subcutaneous tissue of rats could well be associated with the physical properties of the compounds
- Concentration in vehicle: 200 and 300 mg/kgbw/day
- Amount of vehicle (if gavage): 0.9%

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

20 weeks

Frequency of treatment:

Twice weekly for life

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: mg/kgbw

Remarks:

vehicle

Doses / concentrations 2

Dose / conc.:

200 other: mg/kgbw

Doses / concentrations 3

Dose / conc.:

300 other: mg/kgbw

No. of animals per sex per dose:

Total number of animals 240 animals
0 mg/kgbw/week,40 male and 40 females
200 mg/kgbw/week,40 male and 40 females
300 mg/kgbw/week ,40 male and 40 females

Control animals:

yes

yes, concurrent vehicle

Details on study design:

Not specified

Positive control:

Not specified

Examinations

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:Twice daily
- Cage side observations checked in table [No.?] were included.: Animals weer observed twice daily for mortality and morbidity

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified

- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

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: Not specified


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified


OPHTHALMOSCOPIC EXAMINATION: Not specified


HAEMATOLOGY: Not specified


CLINICAL CHEMISTRY ; Not specified


URINALYSIS: Not specified


NEUROBEHAVIOURAL EXAMINATION: Not specified


OTHER:

Sacrifice and pathology:

Sacrifice and pathology
GROSS PATHOLOGY: Yes, Complete autopsies were performed on all animals and the organs were fixed in 10% buffered formalin.
HISTOPATHOLOGY: Yes , Paraplast sections from the liver, kidneys and urinary bladder and macroscopically observed abnormal tissue were routinely stained with haematoxylin and eosin.

Statistics:

For statistical evaluation, only those animals were considered which had been histologically examined (effective number of animals). Survival data are from the beginning of treatment.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Dose levels of 600 and 400 mg/kg body wt. of test chemical were toxic and not well tolerated by the rats which showed rapid weight loss, diarrhoea and short average survival.

Mortality:

mortality observed, treatment-related

Description (incidence):

Dose levels of 600 and 400 mg/kg body wt. of test chemical were toxic and not well tolerated by the rats which showed short average survival.Therefore, after 2 and 12 weeks, respectively, treatment was discontinued for 1 week.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Dose levels of 600 and 400 mg/kg body wt. of test chemical were toxic and not well tolerated by the rats which showed rapid weight loss.

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

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Description (incidence and severity):

No significant effects were observed at the 200 and 300mg/kgbw/week of treated group compare to control.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No significant effects were observed at the 200 and 300mg/kgbw/week of treated group compare to control.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

Macroscopic alterations and microscopic observations were similar in experimental and control rats and were unrelated to the treatment. Age dependent alterations included amyloidosis of the kidneys and liver. Tumours found in the treated groups and not seen in controls were either isolated observations or were within the incidence of tumours commonly known to occur spontaneously in these animals

Other effects:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

300 other: mg/kg bw/week

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effects were observed at this dose.

Remarks on result:

other: No toxic effect were observed

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 300 mg/kg bw/week for the test chemical in male and female Sprague-Dawley rats by oral gavage for chronic study.

Executive summary:

Sprague-Dawley rats received intragastric administration of  the test chemical for their lifetime.The animals were exposed at the 600 and 400 mg/kg body weight/week.The dose levels of 600 and 400 mg/kg body wt. of the test chemical was not well tolerated by the rats which showed rapid weight loss, diarrhoea and short average survival. Therefore, after 2 and 12 weeks, respectively, treatment was discontinued for 1 week. As no improvement in the general health of the rats was found after a further 6 weeks, half of the original dose levels was used for the remaining treatment. Macroscopic alterations and microscopic observations were similar in experimental and control rats and were unrelated to the treatment. Age dependent alterations included amyloidosis of the kidneys and liver. Tumours found in the treated groups and not seen in controls were either isolated observations or were within the incidence of tumours commonly known to occur spontaneously in these animals. The urinary bladder and kidneys were free of neoplastic growth in the test chemical treated rats. Therefore NOAEL was considered to be 300mg/kg bw/week for the test chemical in male and female Sprague-Dawley rats by oral gavage for chronic study.