2-nitro-p-phenylenediamine

Repeated dose toxicity: oral

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

Guideline:

other: as below

Principles of method if other than guideline:

Subchronic toxicity tests were conducted with rats

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-nitro-p-phenylenediamine

EC Number:

226-164-5

EC Name:

2-nitro-p-phenylenediamine

Cas Number:

5307-14-2

Molecular formula:

C6H7N3O2

IUPAC Name:

2-nitrobenzene-1,4-diamine

Constituent 2

Reference substance name:

2 nitro p phenylene diamine

IUPAC Name:

2 nitro p phenylene diamine

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 or test system 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.