2-chlorobenzene-1,4-diammonium sulphate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

Combined repeated dose & carcinogenicity

Type of information:

experimental study

Adequacy of study:

key study

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 peer reviewed publication

Data source

Reference

Reference Type:

review article or handbook

Title:

Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats Following 28-day administration

Author:

Hiroshi Matsumoto, Yoshikuni Yakabe, Koichi Saito, Kayo Sumida, Masaru Sekijima, Koji Nakayama, Hideki Miyaura, Fumiyo Saito, Masanori Otsuka and Tomoyuki Shirai

Year:

2009

Bibliographic source:

Cancer Informatics 2009:7 253–269

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Combined repeated dose & carcinogenicity study was performed to determine the toxic nature of 2-Chloro-p-phenylenediamine SO4

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-chlorobenzene-1,4-diammonium sulphate

EC Number:

228-291-1

EC Name:

2-chlorobenzene-1,4-diammonium sulphate

Cas Number:

6219-71-2

Molecular formula:

C6H7ClN2.xH2O4S

IUPAC Name:

2-chlorobenzene-1,4-diammonium sulphate

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: 2-chlorobenzene-1,4-diammonium sulphate
- IUPAC name: 2-chlorobenzene-1,4-diammonium sulphate
- Molecular formula: C6H7ClN2.xH2O4S
- Molecular weight: 240.6661 g/mole
- Smiles : S(=O)(=O)(O)O.c1(c(ccc(c1)N)N)Cl
- Inchl: 1S/C6H7ClN2.H2O4S/c7-5-3-4(8)1-2-6(5)9;1-5(2,3)4/h1-3H,8-9H2;(H2,1,2,3,4)
- Substance type: Organic
- Physical state: Solid (Light grey powder)

Specific details on test material used for the study:

- Name of test material : 2-Chloro-p-phenylenediamine SO4
- Molecular formula : C6H7ClN2xH2O4S
- Molecular weight : 240.6661 g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

rat

Strain:

Fischer 344

Details on species / strain selection:

No data

Sex:

male

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
(Atsugi, Japan)
- Age at study initiation: 6 weeks
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): pelleted chow food (CRF-1, Oriental Yeast, Co., Ltd) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%):No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: No data

Oral: gavage
1% CMC
Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with No data at dose levels of 0 or 100 mg/Kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: 0 or 100 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

No data

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1%

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with No data at dose levels of 0 or 100 mg/Kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: 0 or 100 mg/Kg/day
- 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

Duration of treatment / exposure:

28 days

Frequency of treatment:

Once a day

Doses / concentrations

Remarks:

0 or 100 mg/Kg/day

No. of animals per sex per dose:

Total: 8
0 mg/Kg/day: 4 male rats
100 mg/Kg/day: 4 male rats

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The administration dose for each chemical was set around their minimum carcinogenic doses for carcinogens or maximum tolerable doses based on the information in NTP and CCRIS database as well as other literatures for non-carcinogens.
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: No data
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- 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 data

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: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL 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 data

OTHER: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, Rats were humanly sacrificed with CO2-O2 (4:1) gas inhalation at 3, 14 or 28 days after administration. The livers were immediately excised and weighed

HISTOPATHOLOGY: Yes, A portion of the left lateral lobe was also taken for histopathology. Tissues were fixed in 10% neutral-buffered formalin, and subsequently sectioned and stained with hematoxylin and eosin.

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

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

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

No histological abnormalities were noted

Other effects:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

100 other: mg/Kg/day

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant alterations were noted at the mentioned dose level

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for 2-Chloro-p-phenylenediamine SO4 is considered to be 100 mg/kg/day.

Executive summary:

Combined repeated dose & carcinogenicity study was performed to determine the toxic nature of 2-Chloro-p-phenylenediamine SO4. The study was performed using 6 week old male F344 rats in a 28 days study. The test chemical was mixed with 1% CMC and used at dose level of 0 or 100 mg/Kg/day.Rats were humanly sacrificed with CO2-O2 (4:1) gas inhalation at 3, 14 or 28 days after administration. The livers were immediately excised and weighed. Tissues were fixed in 10% neutral-buffered formalin, and subsequently sectioned and stained with hematoxylin and eosin.No histological abnormalities were noted due to test chemical treatment. The No Observed Adverse Effect Level (NOAEL) for 2-Chloro-p-phenylenediamine SO4 is considered to be 100 mg/kg/day.