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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from National Cancer Institute Technical report

Data source

Reference
Reference Type:
review article or handbook
Title:
BIOASSAY OF 2·NITRO-p·PHENYLENEDIAMINE FOR POSSIBLE CARCINOGENICITY
Author:
National Cancer Institute
Year:
1979
Bibliographic source:
National Cancer Institute, CARCINOGENESIS, Technical Report Series No. 169, 1979

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Subchronic toxicity tests were conducted with rats
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2 nitro p phenylene diamine- Substance type: Organic - Physical state: Solid

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
- Source: A. R. Schmidt, Madison, Wisconsin, and Laboratory Supply Company, Inc., Indianapolis, Indiana.- Age at study initiation: 4 weeks old- Weight at study initiation: No data- Fasting period before study: Housing: polycarbonate cages suspended from aluminum racks. Ab-sorb-dri® hardwood chip bedding- Diet (e.g. ad libitum): Wayne Lab-Blox meal, ad libitum - Water (e.g. ad libitum): Acidulated water (pH 2.5) was supplied to animals in water bottles filled by an automated metering device, ad libitum- Acclimation period: quarantined for 2 weeks prior to initiationENVIRONMENTAL CONDITIONS- Temperature (°C): 22° to 26°C- Humidity (%): 45 and 55 percent- Air changes (per hr): Incoming air was filtered through HEPA filters, at a rate of 12 to 15 complete changes of room air per hour.- Photoperiod (hrs dark / hrs light): Fluorescent lighting was provided 8 hours per day (9:00 a.m. to 5:00 p.m.).IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: basal laboratory diet
Details on oral exposure:
DIET PREPARATIONThe chemical was removed from its container and a proper amount was blended with an aliquot of the ground feed using a mortar and pestle. Once visual homogeneity was attained, the mixture was placed in a 6 kg capacity Patterson-Kelley standard model twin-shell stainless steel V-blender along with the remainder of the feed to be prepared. After 20 minutes of blending, the mixtures were placed in double plastic bags and stored in the dark at 4°C. The mixture was prepared once weekly.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Doses were analysed spectrophotometrically
Duration of treatment / exposure:
4 weeks followed by 2 weeks observation
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:31.5, 68.0, 146.5,315.5 and 680.0 mg/kgbwBasis:no data
No. of animals per sex per dose:
five males and five females in six dose groups
Control animals:
yes
Details on study design:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes / No / No data: No dataTime schedule: No data- Cage side observations checked in table [No.?] were included. No dataDETAILED CLINICAL OBSERVATIONS: Yes / No / No data: No data Time schedule: No dataBODY WEIGHT: Yes / No / No data: YesTime schedule for examinations: No dataFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No dataFood consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data: No dataCompound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No 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: Yes / No / No data: No dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data: No dataTime schedule for examinations: No dataOPHTHALMOSCOPIC EXAMINATION: Yes / No / No data: No dataTime schedule for examinations: No dataDose groups that were examined:No dataHAEMATOLOGY: Yes / No / No data: No dataTime schedule for collection of blood: No dataAnaesthetic used for blood collection: Yes (identity) / No / No data: No dataAnimals fasted: Yes / No / No data: No dataHow many animals:- Parameters checked in table [No.?] were examined.: No dataCLINICAL CHEMISTRY: Yes / No / No dataTime schedule for collection of blood: No dataAnimals fasted: Yes / No / No data: No dataHow many animals: No dataParameters checked in table [No.?] were examined.: No dataURINALYSIS: Yes / No / No dataTime schedule for collection of urine: No dataMetabolism cages used for collection of urine: Yes / No / No data: No dataAnimals fasted: Yes / No / No data: No dataParameters checked in table [No.?] were examined.: No dataNEUROBEHAVIOURAL EXAMINATION: Yes / No / No data: No data
Sacrifice and pathology:
No data
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No abnormal clinical signs were recorded for any rat group.
Mortality:
no mortality observed
Description (incidence):
No abnormal clinical signs were recorded for any rat group.
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:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
680 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Sub-chronic toxicity tests were conducted with both rats and mice. Rats were distributed among six groups, each consisting of five males and five females. 2-Nitro-p-phenylenediamine was incorporated into the basal laboratory diet and supplied ad libitum to five of the six rat groups in concentrations of 31.5, 68.0, 146.5,315.5 and 680.0 mg/kgbw. The remaining rat group served as a control group, receiving only the basal laboratory diet. No abnormal clinical signs were recorded for any rat group.The NOAEL for 2 nitro p phenylenediamine is 680.0mg/kgbw
Executive summary:

Subchronic toxicity tests were conducted with both rats and mice. Rats were distributed among six groups, each consisting of five males and five females. 2-Nitro-p-phenylenediamine was incorporated into the basal laboratory diet and supplied ad libitum to five of the six rat groups in concentrations of 31.5, 68.0, 146.5,315.5 and 680.0 mg/kg bw. The remaining rat group served as a control group, receiving only the basal laboratory diet.

The dosed dietary preparations were administered for a period of 4 weeks, followed by a 2-week observation period during which all animals were fed the basal laboratory diet. Individual body weights and food consumption data were recorded twice weekly throughout the study. Upon termination of the study all survivors were sacrificed and necropsied.

 

No abnormal clinical signs were recorded for any rat group. The NOAEL for 2 nitro p phenylenediamine is 680 mg/ kg bw.