Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
LONG-TERM TOXICITY STUDY OF BLACK PN IN MICE
Author:
J. J.-P. DRAKE, K. R. BUTrERWORTH, I. F. GAUNT and P. GRASSO
Year:
1977
Bibliographic source:
Fd (Cosmet. Toxicol. Vol 15, pp. 503-508), 1977

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Carcinogen toxicity was performed on maouse via oral route using test substance BLACK PN.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): BLACK PN- Molecular formula (if other than submission substance): Not applicable- Molecular weight (if other than submission substance): Not applicable- Substance type: Organic- Physical state: Solid (powder)-Purity: No data available- Impurities (identity and concentrations): No data available

Test animals

Species:
mouse
Strain:
other: CFW strain
Sex:
male/female
Details on test animals and environmental conditions:
Details on test animalTEST ANIMALS- Source: No data available- Age at study initiation: No data available- Weight at study initiation: yes (weight not mention)- Fasting period before study: No data available- Housing: They were caged in groups of 15 in a room maintained- Diet (e.g. ad libitum): Breeding diet - Water (e.g. ad libitum): water ad libitum- Acclimation period: No data availableENVIRONMENTAL CONDITIONS- Temperature (°C): No data- Humidity (%):50-60%- Air changes (per hr): No data- Photoperiod (hrs dark / hrs light): 21 ± 1°CIN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:
oral: unspecified
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
Details on oral exposurePREPARATION OF DOSING SOLUTIONS: No dataDIET PREPARATION- Rate of preparation of diet (frequency): No data- Mixing appropriate amounts with (Type of food): No data- Storage temperature of food: No dataVEHICLE- Justification for use and choice of vehicle (if other than water): No data- Concentration in vehicle: No data- Amount of vehicle (if gavage): No data- Lot/batch no. (if required): No data- Purity: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available
Duration of treatment / exposure:
80 wk
Frequency of treatment:
Daily
Post exposure period:
No data available
Doses / concentrations
Remarks:
Doses / Concentrations:0.1, 0.25,0.5 or 1.0%Basis:no data
No. of animals per sex per dose:
30 male and 30 female mice
Control animals:
yes
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: No data- Cage side observations checked in table [No.?] were included.: No dataDETAILED CLINICAL OBSERVATIONS: No data- Time schedule: No dataBODY WEIGHT: Yes - Time schedule for examinations: start of the experiment, at wk 3 and then at intervals of 2 wk until wk 73 of the experimentFOOD 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: No data- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD 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 dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data- Time schedule for examinations: No dataOPHTHALMOSCOPIC EXAMINATION: No data - Time schedule for examinations: No data- Dose groups that were examined: No dataHAEMATOLOGY: Yes - Time schedule for collection of blood:At wk 28 and 55 from the caudal vein of ten males and ten females from the control group and from the groups of 0.5 and 1.0% dietary levels.At 80 wk, blood samples were collected from the aorta of all surviving mice during the autopsy.- Anaesthetic used for blood collection: No data- Animals fasted: No data- How many animals: 20 animals (10 male and 10 female)- Parameters were examined: counting the reticulocyte and leucocytes.CLINICAL CHEMISTRY: No data- Time schedule for collection of blood: No data- Animals fasted: No data- How many animals: No data- Parameters were examined: No dataURINALYSIS: Yes - Time schedule for collection of urine: At 28 wks at 6-hr period from three groups of five mice of each sex from the controls and the groups on the two highest dietary levels (0.5 and 1.0%) of Black PN.- Metabolism cages used for collection of urine: No data- Animals fasted: No data- Parameters were examined: reducing substances, bile salts and blood as well as for colour, pH and microscopic constituentsNEUROBEHAVIOURAL EXAMINATION: No data - Time schedule for examinations: No data- Dose groups that were examined: No data- Battery of functions tested: sensory activity / grip strength / motor activity / other: No dataOTHER: No data
Sacrifice and pathology:
Sacrifice and pathologyGROSS PATHOLOGY: No dataHISTOPATHOLOGY: Yes
Other examinations:
No data available
Statistics:
chi-square test, Student's t test

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
no effect on the condition or behaviour of the animals. : There were no statistically significant differences between the number of deaths in the control mice and those given Black PN.
Mortality:
no mortality observed
Description (incidence):
no effect on the condition or behaviour of the animals. : There were no statistically significant differences between the number of deaths in the control mice and those given Black PN.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
the body weights of mice of both sexes were similar in all groups . Weight gain : No dose related effects on weight gain
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:
effects observed, treatment-related
Description (incidence and severity):
: No abnormal constituents were detected in the urine from the control or treated mice.
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
ORGAN WEIGHTS: Scattered differences in mean organ weights between treated and control animals.A lower brain weight in females, compared with the control value, was the only difference affecting animals fed 1% Black PN.The relative brain weight of females fed 0.25% Black PN was higher than the control. Liver weights of female but not of male mice fed 0.25% Black PN were lower than control values, but again this was an isolated finding and there were no significant differences in relative liver weights. Kidney weights of male animals only were significantly lower than control values at the two lowest levels of treatment (0.1 and 0.25%), but a significant difference in relative kidney weights of males occurred only at the 0.5% level, at which a higher value was recorded for the treated mice. The only other significant differences occurred in the relative heart weights, which were raised in male mice fed 0.5% and in females fed 0.25% Black PN.The changes in organ weight showed no dose related effects. Moreover the isolated changes seen at the lower levels were not found in both sexes and were not evident when expressed relative to body weight. It is considered that these random findings were not associated with Black PN treatment.HISTOPATHOLOGY: NON-NEOPLASTIC: Most of the tumours in the study occurred with either a comparable or a greater incidence in the control groups than in the treated mice. Several isolated tumours were identified in mice given the lower levels of Black PN, without comparable findings in the controls or in the highest dose group. They were a mammary fibroadenoma (in a female on 0.1%), a uterine fibromyoma (0.19%) and a squamous-cell carcinoma of the skin (female, 0.5%). The only tumour found at the highest dietary level without comparable control findings was a squamous-cell carcinoma of the skin in a male mouse fed 1% Black PN.The frequency of histopathological findings in the treated animals did not differ significantly from those in the controls. Hence, no relationship was obvious between these findings and treatment with Black PN. Only in the case of adenomas of the lung and of the mammary tissue did more than one tumour of a given type occur among the treated animals of any group.

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 300 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Body weight, weight gain, organ weight and histopathology.
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

Applicant's summary and conclusion

Conclusions:
The Black PN was found to be non-carcinogenic at 1% (1300 mg/kg/day) concentration when treated to mice.
Executive summary:

Carcinogenicity test were performed on mice with different concentrations from 0.1, 0.25, 0.5 or 1.0% Black PN for 80 wk. 30 males and 30 females was used for the treatment and group of 60 mice of each sex as control. The general condition and behaviour of the animals were observed frequently and any mouse that showed signs of ill-health was isolated, to be returned to its cage on recovery or to be killed if its condition deteriorated. The mice were weighed at the start of the experiment, at wk 3 and then at intervals of 2 wk until wk 73 of the experiment. Blood sample were taken at wk 28 and 55.At 80 wk, blood samples were collected from the aorta of all surviving mice during the autopsy. For haematology blood samples were collected and for urine sample from 6-hr period from three groups of five mice of each sex from the controls and the groups on the two highest dietary levels of Black PN. Histopathology was also conducted

There were no dose-related effects on body-weight gain, haematology or organ weights. The incidence of histopathological findings, including tumours, was not altered by the feeding of Black PN.These results provide no evidence of a carcinogenic or toxic effect on the part of Black PN when given at dietary levels up to 1% (providing an intake of 1300 mg/kg/day).

Therefore,the Black PN was found to be non-carcinogenic at 1% (1300 mg/kg/day) concentration when treated to mice.