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EC number: 222-695-1 | CAS number: 3576-88-3
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February - September 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: "the Guidelines for the Testing of Chemicals (2004)" in China 474
- Deviations:
- not specified
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- 2,2'-iminobis[4,6-diamino-1,3,5-triazine]
- EC Number:
- 222-695-1
- EC Name:
- 2,2'-iminobis[4,6-diamino-1,3,5-triazine]
- Cas Number:
- 3576-88-3
- Molecular formula:
- C6H9N11
- IUPAC Name:
- N~2~-(4,6-diamino-1,3,5-triazin-2-yl)-1,3,5-triazine-2,4,6-triamine
- Details on test material:
- - Name of test material (as cited in study report): 2,2'-iminobis[4,6-diamino-1,3,5-triazine]
CAS No.: 3576-88-3
Supplier: DSM Engineering Plastics
Physical state: Off-white Powder
Sample storage: At normal room temperature and in a dry place
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shanghai SILAIKE Experimental Animal Co. Ltd.
- Weight at study initiation: 25-30g
- Assigned to test groups randomly: yes, under following basis: by body weight, half of each sex.
- Housing: plastic feeding cages (L46 xW31 xH20cm) and Cages were replaced twice weekly.
- Diet: ad libitum; Commercial diet was provided by Suzhou Shuangshi Laboratory Animal Feed Science and Technology LTD.
- Water: ad libitum; Commercial water
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): Lighting was artificial, and a 12h light/dark cycle.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: 1 % CMC (carboxymethyl cellulose)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Sample preparation was following the dosage design to weigh the test sample of all groups. Then
5000mg, 2500mg and 1250mg of the test sample were weighed and 1% sodium carboxymethylcellulose
were added to 20ml and mixed extensively as the test sample. - Duration of treatment / exposure:
- Double oral gavages (24h's interval).
Dose volume 0.4mL/20g bw.
20h after the 2nd gavage, mice were executed by cervical dislocation. - Frequency of treatment:
- double oral gavages
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
5000 mg/kg
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
2500 mg/kg
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
1250 mg/kg
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0 mg/kg
Basis:
- No. of animals per sex per dose:
- 5 groups by body weight, 10 for each group, half of each sex
- Control animals:
- yes
- Positive control(s):
- cyclophosphamide
Examinations
- Tissues and cell types examined:
- Femur marrow
polychromatic erythrocytes (PCE)
normal chromatic erythrocytes (NCE) - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: acute oral LD50 of male and female mice
DETAILS OF SLIDE PREPARATION: Femur marrow was fetched out and mixed with bovine serum.
Slides were smeared, fixed and stained by Giemsa's solution.
METHOD OF ANALYSIS: rate of cell containing micronucleus of the dosage groups was
analysed by U-test of Poisson distribution - Evaluation criteria:
- Observed under the microscope, 2000 polychromatic erythrocytes (PCE) of each mouse were counted and number
of PCE containing micronucleus was recorded, and then rate of cell containing micronucleus
was calculated as per mil. As 200 polychromatic erythrocytes (PCE) were counted, normal
chromatic erythrocytes (NCE) were also counted to obtain the value of PCE/RBC. - Statistics:
- U test of Poisson distribution
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
Any other information on results incl. tables
For the Table "Result of the Mice Erythrocyte Micronucleus Test of 2,2' -iminobis[4,6-diamino-1,3,5-triazine] (CAS No.:3576-88-3)" see attachment.
Historical Data:
Historical data of this lab: the ratio of negative control was 0 per mil - 4per mil, the ratio of positive control was 21 per mil - 34 per mil.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Mammalian Erythrocyte Micronucleus Test of 2,2'-iminobis[4,6-diamino-1,3,5-triazine] is negative. - Executive summary:
Summary
According to the test protocol of the Guidelines for the Testing of Chemicals (2004) 474 of National
Environment Protection Agency, Mammalian Erythrocyte Micronucleus Test of
2,2'-iminobis[4,6-diamino-1,3,5-triazine] (CAS No.: 3576-88-3) has been performed.
Mice were divided randomly into 5 groups by body weights, 10 for each group, half of each sex.
The acute oral LD50 of male and female mice were all greater than 5000mg/kg. Then 5000mg/kg was set as
the highest dose group for this test, 1/2 LD50 and 1/4 LD50 were middle dosage group and low dosage
group respectively, namely 5000mg/kg, 2500 mg/kg, 1250mg/kg, a negative control group (1% sodium
carboxymethylcellulose), and a positive control group of cyclophosphamide.
The test sample of various doses, the positive control and the negative control was administered to the mice by oral gavages twice
daily (24h's interval). All mice were weighed and gavage volume was 0.4ml/20g bw. 20h after the 2nd
gavage, mice were executed by cervical dislocation.
Femur marrow was fetched out and mixed with bovine serum.
Slides were smeared, fixed and stained by Giemsa's solution. Observed under the
microscope, 2000 polychromatic erythrocytes (PCE) of each mouse were counted and the number of
PCE containing micronucleus was recorded, and then rate of cell containing micronucleus was
calculated as per mil. As 200 polychromatic erythrocytes (PCE) were counted, normal chromatic
erythrocytes (NCE) were also counted to obtain the value of PCE/RBC. Compared with the negative
group, rate of cell containing micronucleus of the dosage groups was analyzed by U test of Poisson
distribution.
Result and conclusion:
Mammalian Erythrocyte Micronucleus Test of 2,2'-iminobis[4,6-diamino-1,3,5-triazine] (CAS No.: 3576-88-3) is negative.
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