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Toxicological information

Genetic toxicity: in vivo

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Administrative data

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

Data source

Reference
Reference Type:
secondary source
Title:
OPINION ON 2-Chloro-p-phenylenediamine COLIPA n° A8
Author:
European Cosmetics Toiletry and Perfumery Association (COLIPA)
Year:
2013
Bibliographic source:
Scientific Committee on Consumer Safety (SCCS), SCCS/1510/13, 19 September 2013

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,4-diamino-2-chlorobenzene
- Molecular formula (if other than submission substance): C6-H7-Cl-N2
- Molecular weight (if other than submission substance): 142.588 g/mole
- Substance type: Organic
- Physical state: Solid
- Purity: 99%
- Impurities (identity and concentrations): 1 %
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 %

Test animals

Species:
rat
Strain:
other: CFY SPF
Sex:
male/female
Details on test animals and environmental conditions:
No data available

Administration / exposure

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
Doses / concentrations
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

Examinations

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

Results and discussion

Test results
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

Applicant's summary and conclusion

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.