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Administrative data

Description of key information

Repeated dose toxicity: Oral

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.

Repeated dose toxicity: Inhalation

2-chlorobenzene-1,4-diammonium sulphate has very low vapor pressure (2.12E-012 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated inhalation toxicity was considered for waiver

Repeated dose toxicity: Dermal

The acute dermal toxicity value for 2-chlorobenzene-1,4-diammonium sulphate (as provided in section 7.2.3) is >2000 mg/kg body weight. The substance was also found to be not irritating and not sensitizing to the skin. Based on these considerations, the end point for repeated dermal toxicity is considered as waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
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
Qualifier:
according to
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
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
Species:
rat
Strain:
Fischer 344
Details on species / strain selection:
No data
Sex:
male
Details on test animals 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
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
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
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
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
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
Critical effects observed:
not specified
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Data is from K2 review article from handbook

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation, other
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: Oral

Data available for the target chemical was reviewed to determine the toxic nature of 2-chlorobenzene-1,4-diammonium sulphate. The study summary is as mentioned below:

Combined repeated dose & carcinogenicity study was performed by Matsumoto et al (Cancer Informatics, 2009) 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.

Repeated dose toxicity: Inhalation

2-chlorobenzene-1,4-diammonium sulphate has very low vapor pressure (2.12E-012 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated inhalation toxicity was considered for waiver

Repeated dose toxicity: Dermal

The acute dermal toxicity value for 2-chlorobenzene-1,4-diammonium sulphate (as provided in section 7.2.3) is >2000 mg/kg body weight. The substance was also found to be not irritating and not sensitizing to the skin. Based on these considerations, the end point for repeated dermal toxicity is considered as waiver.

Based on the data available for the target chemical, 2-Chloro-p-phenylenediamine sulphate does not exhibit toxic effects upon repeated exposure by oral route and hence the test chemical is considered to be non toxic as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical, 2-Chloro-p-phenylenediamine sulphate (CAS no 6219 -71 -2) does not exhibit toxic effects upon repeated exposure by oral route and hence the test chemical is considered to be non toxic as per the criteria mentioned in CLP regulation.