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EC number: 210-441-2 | CAS number: 615-66-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The substance 2-chloro-p-phenylenediamine (1,4–diamino-2-chlorbenzol) is non mutagenic to the bacterial tester strain E. coli 343/113.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Data is from peer-reviewed journal.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- In –vitro forward and reverse bacterial gene mutation assay for 2-chloro-p-phenylenediamine was studied in E. coli.
- GLP compliance:
- not specified
- Type of assay:
- bacterial gene mutation assay
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 1,4 –diamino-2-chlorbenzol
- Molecular formula: C6-H7-Cl-N2
- Molecular weight: 142.588 g/mol
- Substance type: Organic
- Physical state: Solid
- Purity: 99%
- Impurities (identity and concentrations): 1 % - Target gene:
- 343/113
- Species / strain / cell type:
- E. coli, other: E. coli 343/113
- Details on mammalian cell type (if applicable):
- No data available
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- not specified
- Test concentrations with justification for top dose:
- 1, 10 and 100 μg/ml
- Vehicle / solvent:
- Vehicle
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: No data available - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- Details on test system and conditions
METHOD OF APPLICATION: in agar (plate incorporation);
DURATION
- Preincubation period: No data available
- Exposure duration: 2 hours
- Expression time (cells in growth medium): 20 hours for standard medium, of 40 hours for gal+ mutants, and of 72 hours arg+ , nad+ and MTR mutants.
- Selection time (if incubation with a selection agent): 3 hours
- Fixation time (start of exposure up to fixation or harvest of cells): No data available
SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available
STAIN (for cytogenetic assays): No data available
NUMBER OF REPLICATIONS: Duplicate cultures per “mutant” type in one experiment
NUMBER OF CELLS EVALUATED: No data available
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available
OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other: No data available
OTHER: Both forward and reverse mutations in different genes: reverse mutations of arg- and nad- to prototrophy, forward mutations of 5-methyl-DL-tryptohan sensitivity (MTS) to MT resistance and forward (and reverse) mutations from Rs 18 to gal+. - Evaluation criteria:
- A biologically relevant increase in the number of revertants
- Statistics:
- No data available
- Species / strain:
- E. coli, other: E. coli 343/113
- Metabolic activation:
- not specified
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data available
- Effects of osmolality: No data available
- Evaporation from medium: No data available
- Water solubility: No data available
- Precipitation: No data available
- Other confounding effects: No data available
RANGE-FINDING/SCREENING STUDIES: Test concentrations were based on the basis of survival in a toxicity test with 3 h incubation with 1, 4–diamino-2-chlorbenzol in the dark.
COMPARISON WITH HISTORICAL CONTROL DATA: No data available
ADDITIONAL INFORMATION ON CYTOTOXICITY: No data available - Remarks on result:
- other: no mutagenic potential
- Conclusions:
- The substance 2-chloro-p-phenylenediamine (1,4–diamino-2-chlorbenzol) is non mutagenic to the bacterial tester strain E. coli 343/113.
- Executive summary:
In a in –vitro forward and reverse bacterial gene mutation assay, E. coli343/113 was treated with 2-chloro-p-phenylenediamine (1,4–diamino-2-chlorbenzol) in concentration of 1, 10 and 100 μg/ml. No effect were observed on survival of E. coli343/113 during 2 hours incubation and an expression period of 20 hours for standard medium, of 40 hours for gal+mutants, and of 72 hours arg+, nad+and MTR mutants for forward mutations of 5-methyl-DL-tryptohan sensitivity (MTS) to MT resistance and forward (and reverse) mutations from Rs18to gal+.
The substance 2-chloro-p-phenylenediamine (1,4–diamino-2-chlorbenzol) is non mutagenic to the bacterial tester strain E. coli 343/113.
According to the CLP classification, the test material does not classify as a gene mutant in vitro.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
The substance 2-chloro-p-phenylenediamine (1,4-diamino-2-chlorobenzene) failed to induce an increase in the number of polychromatic erythrocytes with micronuclei in the bone marrow cells and hence is negative for gene mutation in vivo.
Link to relevant study records
- Endpoint:
- genetic toxicity in vivo, other
- Remarks:
- Type of genotoxicity: Gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from SCCS report
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- In vivo Bone marrow micronucleus test for 2-chloro-p-phenylenediamine (1,4-diamino-2-chlorobenzene) was performed in rats.
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 1,4-diamino-2-chlorobenzene
- Molecular formula: C6-H7-Cl-N2
- Molecular weight: 142.588 g/mole
- Substance type: Organic
- Physical state: Solid
- Purity: 99%
- Impurities (identity and concentrations): 1 % - Species:
- rat
- Strain:
- other: CFY SPF
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: unspecified
- Vehicle:
- - Vehicle(s)/solvent(s) used: 0.5% gum tragacanth
- Justification for choice of solvent/vehicle: No data available
- Concentration of test material in vehicle: 0 and 900 mg/kg bw/day
- Amount of vehicle (if gavage or dermal): No data available
- Type and concentration of dispersant aid (if powder): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on exposure:
- No data available
- Duration of treatment / exposure:
- 30 hours
- Frequency of treatment:
- Twice in 24h interval
- Post exposure period:
- 6 hours
- Remarks:
- Doses / Concentrations:
0 and 900 mg/kg bw/day
Basis:
no data - No. of animals per sex per dose:
- 5/sex/dose
Total: 20
0 mg/kg bw/day: 5 male, 5 female
900 mg/kg bw/day: 5 male, 5 female - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- No data available
- Tissues and cell types examined:
- Bone marrow cells
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Test doses were based on the results of a preliminary toxicity study with doses between 800 and 900 mg/kg bw/day on a group of 5 male and 5 female rats recording clinical signs and mortality for a period of 30 h performed under identical conditions.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): No data available
DETAILS OF SLIDE PREPARATION: No data available
METHOD OF ANALYSIS: No data available
OTHER: No data available - Evaluation criteria:
- Increase in the number of bone marrow cells with micronuclei
- Statistics:
- No data available
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: between 800- 900 mg/kg bw/day
- Solubility: No data available
- Clinical signs of toxicity in test animals: Orange pigmented urine was observed.
- Evidence of cytotoxicity in tissue analyzed: No data available
- Rationale for exposure: No data available
- Harvest times: 30 hours
- High dose with and without activation: 900 mg/kg bw/day
- Other: No data available
RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels (for Cytogenetic or SCE assay): No data available
- Induction of micronuclei (for Micronucleus assay): Biologically relevant increases in the number of polychromatic erythrocytes with micronuclei compared to the concurrent vehicle controls were not found in either males or females.
- Ratio of PCE/NCE (for Micronucleus assay): No data available
- Appropriateness of dose levels and route: No data available
- Statistical evaluation: No data available - Conclusions:
- The substance 2-chloro-p-phenylenediamine (1,4-diamino-2-chlorobenzene) failed to induce an increase in the number of polychromatic erythrocytes with micronuclei in the bone marrow cells and hence is negative for gene mutation in vivo.
- Executive summary:
In a in -vivo gene toxicity test, CFY SPF male and female rats were treated with 2-chloro-p-phenylenediamine (1,4-diamino-2-chlorobenzene) in the concentration of 0 and 900 mg/kg bw/day. Bone marrow cells were collected 6 h after the last treatment. For each rat the percentage of polychromatic erythrocytes with a micronucleus was counted in 2000 polychromatic erythrocytes. Negative and positive controls were included.
2-chloro-p-phenylenediamine (1,4-diamino-2-chlorobenzene) failed to induce an increase in the number of polychromatic erythrocytes with micronuclei in the bone marrow cells and hence is negative for gene mutation in vivo.
According to the CLP classification, the test material does not classify as a gene mutant in vivo.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
The potential genotoxicity of 2-chloro-p-phenylenediamine (CAS No. 615-66-7) was evaluated using in vitro and in vivo assays. Various peer reviewed publications and prediction model based estimation for target substance and read across substances have been reviewed and summarized to determine the mutagenic potential of 2-chloro-p-phenylenediamine:
In Vitro
2-chloro-p-phenylenediamine was investigated for the induction of gene mutations in E. coli strain 343/113 according to Mohn et al. (Mutation Research 25, 187-196, 1974). In a in –vitro forward and reverse bacterial gene mutation assay, E. coli343/113 was treated with 2-chloro-p-phenylenediamine (1,4–diamino-2-chlorbenzol) in concentration of 1, 10 and 100 μg/ml. No effect were observed on survival of E. coli343/113 during 2 hours incubation and an expression period of 20 hours for standard medium, of 40 hours for gal+mutants, and of 72 hours arg+, nad+and MTR mutants for forward mutations of 5-methyl-DL-tryptohan sensitivity (MTS) to MT resistance and forward (and reverse) mutations from Rs18to gal+. The substance 2-chloro-p-phenylenediamine (1,4–diamino-2-chlorbenzol) is non mutagenic to the bacterial tester strain E. coli 343/113.
Also, the gene mutation study of 2-chloro-p-phenylenediamine (CAS No. 615-66-7) was predicted using OECD QSAR toolbox version 3.3 (2017) with respect to the descriptor log Kow and considering the ten closest read across substances. This is specifically designed to assess the ability of a chemical to cause point mutations in the DNA of the bacterium Salmonella typhimurium strains. The prediction assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with the presence of S9 mix. The substance 2-chloro-p-phenylenediamine was predicted to be non mutagenic in S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system.
Similarly, the gene mutation study of 2-chloro-p-phenylenediamine (CAS No. 615-66-7) was predicted using OECD QSAR toolbox version 3.3 (2017) with respect to the descriptor log Kow and considering the ten closest read across substances. The prediction assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the absence of of S9 mix. The substance 2-chloro-p-phenylenediamine was predicted to be non mutagenic in S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the absence of S9 metabolic activation system.
In addition to these studies, Zeiger,E et al (Environ. Mutagen. Vol. 9 (Suppl 9) (1987) 1-109) conducted gene mutation study for read across substance 3-chloroaniline. In an Ames test , 3-chloroaniline, in dimethyl sulfoxide from doses 33 - 2000 µg/plate was not mutagenic in Salmonella typhimurium strains TA100 , TA 1535, TA1537 , TA 97 and TA 98 with and without addition of S9 liver microsome fractions from Aroclor induced rats.The same has been obtained for hamsters as well.
Moreover,Loveday et al (Environ. Mol. Mutagen. 16(9):272-303,1990) conducted mammalian chromosome aberration test . In mammalian chromosome aberration test , 4-chlorobenzene-1,3-diamine, in dimethyl sulfoxide from doses 148; 494; 14800 µg/ml was not mutagenic in CHO-LB CELLS with addition of S9 liver microsome fractions from Aroclor induced rats.
Based on the key study and its supporting data summarized,the test material does not classify as a gene mutant in vitro.
In Vivo
2-chloro-p-phenylenediamine has been investigated for induction of micronuclei in bone marrow cells of rats. The study was published in a Scientific Committee on Consumer Safety report (OPINION ON 2-Chloro-p-phenylenediamine COLIPA n° A8). In this in -vivo gene toxicity test, CFY SPF male and female rats were treated with 2-chloro-p-phenylenediamine (1,4-diamino-2-chlorobenzene) in the concentration of 0 and 900 mg/kg bw/day. Bone marrow cells were collected 6 h after the last treatment. For each rat the percentage of polychromatic erythrocytes with a micronucleus was counted in 2000 polychromatic erythrocytes. Negative and positive controls were included. 2-chloro-p-phenylenediamine (1,4-diamino-2-chlorobenzene) failed to induce an increase in the number of polychromatic erythrocytes with micronuclei in the bone marrow cells and hence is negative for gene mutation in vivo.
Moreover, gene toxicity in vivo study was conducted by W. Suter et al. (Environmental and Molecular Mutagenesis 28:354-362 (1996)) on male and female Big BlueTMmice. The test compound 4-chloro-o-phenylenediamine (4-C-o-PD) was used at a concentration of 0 and 200 mg/kg/day for 10 days orally. The results showed that there was no cellular proliferation in the liver of male mice however in female mice 1.73 cellular proliferations in the liver were observed as compare to control. Therefore, it is considered that 4 -chloro-o-phenylenediamine (4-C-o-PD) in 200 mg/kg/day is negative for male mice and positive for female mice when mice are exposed to the test chemical for 10 days. However, In accordance with the CLP classification, the test material 4-chloro-o-phenylenediamine (4-C-o-PD) does not classify as a mutagen.
Based on the above mentioned in vitro and in vivo studies for target and read across substance and according to CLP criteria, it can be concluded that 2-chloro-p-phenylenediamine (CAS No. 615-66-7) is non genotoxic.
Justification for classification or non-classification
The results of several mutagenicity studies in vitro and in vivo shows that no classification for mutagenicity according to CLP regulation is warranted for 2-chloro-p-phenylenediamine (CAS No. 615-66-7).
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