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EC number: 202-936-7 | CAS number: 101-37-1
- 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
Triallylcyanurate does not cause genotoxic effects in in vitro studies.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-report according to guideline.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- not applicable
- Species / strain / cell type:
- lymphocytes: human, healthy donors without medication
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9-mix of Aroclor 1254 induced rats
- Test concentrations with justification for top dose:
- 0, 31.25, 62.5, 125, 250, 500 µg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solvent was chosen according to its solubility properties and its non-toxicity for the cells. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO 1% (v/v)
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without metabolic activation
Migrated to IUCLID6: 0.1 or 0.2 µg/mL - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO 1% (v/v)
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
Migrated to IUCLID6: 10 or 20 µg/ mL - Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: 48 h
- Exposure duration: 4 h or 24 h without metabolic activation, 4 h with metabolic activation
- Fixation time (start of exposure up to fixation or harvest of cells): 22 h
SPINDLE INHIBITOR (cytogenetic assays): colcemid 0.9 µg/mL
STAIN (for cytogenetic assays): Giemsa stain
NUMBER OF REPLICATIONS: two cultures each two slide preparations
NUMBER OF CELLS EVALUATED: 100 metaphase per slide were evaluated
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
OTHER EXAMINATIONS:
- Determination of polyploidy: yes - Evaluation criteria:
- Comparison of the number of chromosome aberrations of the samples with those of the solvent control. Total number of cells with aberrations exclusive of gap damage are analysed.
evaluation criteria:
The test is regarded to have a positive result, if the number of chromosomal aberrations is significantly increased (p<=0.05) compared with the solvent control, this increase is dose-dependent and both duplicate cultures lead to the same results. The increase should not occur in the severly cytotoxic range (mitotic index < 0.25). - Statistics:
- Fisher-test (p<= 0.05)
- Species / strain:
- lymphocytes: human, healthy donors without medication
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 125 µg/ mL 24 h exposure, 250 µg/ mL 4 h exposure
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: other: human peripheral lymphocytes
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- ; 1983
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- ; 1983
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His C3076, His D3052 or His G46
- Species / strain / cell type:
- S. typhimurium, other: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9-mix of Aroclor 1254 induced male Wistar rats
- Test concentrations with justification for top dose:
- up to 2.5 mg/plate
remark:
In a preliminary cytotoxicity test where 0, 0.0005, 0.005, 0.05, 0.5, 5 or 50 mg/plate were applied, slight cytotoxicity was observed using 0.5 mg plate in strains TA 1537 and TA 100. Precipitation and evident cytotoxicity were observed in all test strains at 5 mg/plate. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- test solution
- first assay: 0, 0.123, 0.37, 1.11, 3.33 and 10 mg/mL DMSO
- second assay: 0, 0.31, 0.93, 2.78, 8.33 and 25 mg/mL DMSO - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- without S9-mix
Migrated to IUCLID6: 1 µg per plate TA 1535 and TA 100 - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- without S9-mix
Migrated to IUCLID6: 2 µg per plate TA1538, TA 98 - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- without S9-mix
Migrated to IUCLID6: 80 µg per plate TA 1537 - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- 2 µg per plate TA 1535, TA 1538, TA 98, TA 100; 5 µg per plate TA 1537
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- with S9-mix
- Details on test system and experimental conditions:
- IUCLID4 Type: Ames test
METHOD OF APPLICATION: in agar (plate incorporation);
DURATION
- Exposure duration: 3 d
- Selection time (if incubation with a selection agent): 3 d
SELECTION AGENT (mutation assays): histidine deficient agar
NUMBER OF REPLICATIONS: triplicates; two assays
DETERMINATION OF CYTOTOXICITY
- Method:relative total growth prior to mutagenicity experiment with up to 50 mg/ plate - Evaluation criteria:
- a positive response in the assay system is taken to be a two-fold or greater increase in the mean number of revertant colonies appearing in the test plates over and above the background spontaneous reversion rate observed with the vehicle, together with evidence of a dose-response
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 2.5 mg/plate with and without S9
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 0.833 mg/plate without S9-mix and 2.5 mg/plate with S9
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 0.833 mg/plate without S9-mix and 2.5 mg/plate with S9
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 2.5 mg/plate with and without S9
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- precipitation occured at concentrations of 1 mg/ plate and more.
- Remarks on result:
- other: strain/cell type: S. typhimurium TA 1535
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative - Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP-Guideline study with acceptable restrictions: since the test was performed according to a previous guideline, only 1000 cells (instead of 2000 as required for the recent version of the guideline) were assessed.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- Cited as Directive 87/302/EEC, part B, p. 61
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hessisches Ministerium für Umwelt, Energie, Jugend, Familie und Gesundheit
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- hypoxanthine-guanine phosphoribosyl transferase
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: minimal essential medium (SEROMED, Berlin, Germany) with 10% FCS
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9-mix of Aroclor 1254 induced male Wistar rats
- Test concentrations with justification for top dose:
- experiment I : 1, 3, 10, 20, 50, 80, 100, 200 or 300 µg/mL
experiment II : 5, 50, 100, 150, 180, 200, 220 or 250 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solvent was chosen according to its solubility properties and its non-toxicity for the cells. Final DMSO-concentration in the culture medium did not exceed 1 %. - Untreated negative controls:
- yes
- Remarks:
- untreated cells
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- 0.6 mg/ mL
Migrated to IUCLID6: without metabolic activation - Untreated negative controls:
- yes
- Remarks:
- untreated cells
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Remarks:
- 3.85 µg/mL
Migrated to IUCLID6: with metabolic activation - Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: 1 d
- Exposure duration: 4 h
- Expression time (cells in growth medium): 7 d
- Selection time (if incubation with a selection agent): 9 d
- Fixation time (start of exposure up to fixation or harvest of cells): 17 d
SELECTION AGENT (mutation assays): 11µg/ mL thioguanine
STAIN (for cytogenetic assays): methylene blue (10%) in 0.01% KOH solution
NUMBER OF REPLICATIONS: five replications, two independent experiments
NUMBER OF CELLS EVALUATED: about 3-5 x 10^5 cells/flask, stained colonies with more than 50 cells were counted
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency, duplicates, two independent experiments - Evaluation criteria:
- the gene mutation assay is considered acceptable if it meets the following criteria:
1. the number of mutant colonies per 10^6 cells found in the negative and/or solvent controls fall within the laboratory historical control data range: 0-45 mutants/ 10^6 cells
2. the positive control substance must produce a significant increase in mutant colony frequencies
3. The cloning efficiency (absolute value) of the negative and/or solvent controls must exceed 50%
A test substance is classified as mutagenic if it induces a reproducible mutation frequency that is at least three times higher than the spontaneous mutation frequency in the experiment at one or more of the concentrations. The test substance is classified as mutagenic if there is a reproducible concentration-related increase of the mutation frequency. Such evaluation may be considered also in the case that a threefold increase of the mutant frequency is not observed. However, in a case by case evaluation this decision depends on the level of the corresponding and historical negative control data. - Statistics:
- since the distribution of mutant cells does not follow known statistical models, an adequate statistical method is not available
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 100 µg/mL without S9-mix, 200 µg/mL with S9-mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
RANGE-FINDING/SCREENING STUDIES: yes, XTT-Assay determining cytotoxicity up to 2.5 mg/mL tested. Here cytotoxicity was evident at concentrations higher than 100 µg/mL without S9-mix and 300 µg/mL with S9-mix.
The cloning efficiency of the cells was reduced to approx. 35 % without and approx. 26 % with metabolic activation at the highest evaluated concentration.- Remarks on result:
- other: strain/cell type: Chinese hamster lung fibroblasts (V79)
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
Referenceopen allclose all
Treatment |
µg/mL |
S9-mix |
4 h exposure |
24 h exposure |
||||
Mitotic index# |
number of metaphases scored |
% of cells with aberrations excluding gaps |
Mitotic index# |
number of metaphases scored |
% of cells with aberrations excluding gaps |
|||
DMSO |
- |
- |
1.00 |
200 |
1.5 |
1.00 |
200 |
2.0 |
test substance |
31.25 |
- |
- |
- |
- |
0.86 |
200 |
2.5 |
62.5 |
- |
0.92 |
200 |
1.5 |
0.55 |
200 |
3.5 |
|
125 |
- |
1.27 |
200 |
1.5 |
0.47 |
164# |
3.7 |
|
250 |
- |
0.58 |
183# |
4.5 |
0.28 |
35# |
3.2 |
|
500 |
- |
0.43 |
101# |
5.2 |
- |
- |
- |
|
Mitomycin C |
0.2 |
- |
0.62 |
200 |
12.0* |
0.55 |
200 |
13.0* |
the following concentrations were not evaluated:
31.25 µg/ mL (4 h exposure), 500 µg/ mL ( 24 h exposure) 0.1 µg mitomycin C (4 and 24 h exposure)
Treatment |
µg/mL |
S9-mix |
4 h exposure |
||
Mitotic index# |
number of metaphases scored |
% of cells with aberrations excluding gaps |
|||
DMSO |
- |
+ |
1.00 |
200 |
1.0 |
test substance |
31.25 |
+ |
- |
- |
- |
62.5 |
+ |
0.77 |
200 |
2.0 |
|
125 |
+ |
1.62 |
200 |
1.0 |
|
250 |
+ |
0.40 |
183# |
4.5 |
|
500 |
+ |
0.13 |
11# |
0.0 |
|
Cyclophosphamide |
10 |
+ |
0.63 |
200 |
10.5* |
the following concentrations were not evaluated:
31.25 µg/ mL, 20 µg/ mL cyclophosphamide
# mitotic
index: number of metaphases/ 1000 cells: negative control = 1.00
## no more metaphase
of sufficient quality for evaluation due to cytotoxicity of
Triallylcyanurate
* significantly
different from negative control (p=0.05)
Experiment I |
c/ mL |
S9-Mix |
numbers of mutant colonies/ flask* found after plating in TG medium |
mean (A,B,C,D,E) |
S.D. |
cell survival after plating in TG medium |
mutant colonies /10^6 cells** |
||||
A |
B |
C |
D |
E |
|||||||
negative control |
0 |
- |
3 |
4 |
3 |
3 |
5 |
3.6 |
0.9 |
335272 |
10.7 |
solvent control DMSO |
0 |
- |
6 |
0 |
4 |
1 |
3 |
2.8 |
2.4 |
371280 |
7.5 |
positive control EMS |
0.6 |
- |
129 |
123 |
97 |
100 |
120 |
113.8 |
14.4 |
365366 |
311.5 |
test substance |
1 |
- |
culture was not continued |
||||||||
test substance |
3 |
- |
0 |
0 |
1 |
0 |
0 |
0.2 |
0.4 |
351879 |
0.6 |
test substance |
10 |
- |
culture was not continued |
||||||||
test substance |
20 |
- |
0 |
1 |
1 |
0 |
1 |
0.6 |
0.5 |
347809 |
1.7 |
test substance |
50 |
- |
2 |
2 |
0 |
5 |
1 |
2.0 |
1.9 |
350195 |
5.7 |
test substance |
80 |
- |
3 |
1 |
1 |
3 |
2 |
2.0 |
1.0 |
360000 |
5.6 |
negative control |
0 |
+ |
1 |
3 |
3 |
1 |
0 |
1.6 |
1.3 |
323112 |
5.0 |
solvent control DMSO |
0 |
+ |
2 |
0 |
3 |
0 |
2 |
1.4 |
1.3 |
349956 |
4.0 |
positive control DMBA |
3.85 |
+ |
128 |
126 |
125 |
135 |
128 |
128.4 |
3.9 |
264148 |
486.1 |
test substance |
1 |
+ |
5 |
2 |
2 |
4 |
4 |
3.4 |
1.3 |
365147 |
9.3 |
test substance |
10 |
+ |
culture was not continued |
||||||||
test substance |
50 |
+ |
5 |
5 |
3 |
4 |
6 |
4.6 |
1.1 |
300561 |
15.3 |
test substance |
100 |
+ |
6 |
4 |
6 |
6 |
4 |
5.2 |
1.1 |
336894 |
15.4 |
test substance |
200 |
+ |
4 |
1 |
6 |
4 |
2 |
3.4 |
1.9 |
270902 |
12.6 |
test substance |
300 |
+ |
culture was not continued |
Experiment II |
c/ mL |
S9-Mix |
numbers of mutant colonies/ flask* found after plating in TG medium |
mean (A,B,C,D,E) |
S.D. |
cell survival after plating in TG medium |
mutant colonies /10^6 cells** |
||||
A |
B |
C |
D |
E |
|||||||
negative control |
0 |
- |
2 |
4 |
7 |
4 |
4 |
4.2 |
1.6 |
295557 |
14.2 |
solvent control DMSO |
0 |
- |
1 |
4 |
1 |
3 |
3 |
2.4 |
1.3 |
295581 |
8.1 |
positive control EMS |
0.6 |
- |
125 |
114 |
125 |
114 |
113 |
118.2 |
6.2 |
258016 |
458.1 |
test substance |
5 |
- |
5 |
9 |
5 |
6 |
3 |
5.6 |
2.2 |
308325 |
18.2 |
test substance |
50 |
- |
4 |
4 |
6 |
2 |
2 |
3.6 |
1.7 |
289038 |
12.5 |
test substance |
100 |
- |
2 |
3 |
2 |
1 |
3 |
2.2 |
0.8 |
325615 |
6.8 |
test substance |
150 |
- |
1 |
4 |
1 |
2 |
4 |
2.4 |
1.5 |
282530 |
8.5 |
test substance |
180 |
- |
culture was not continued |
||||||||
test substance |
200 |
- |
culture was not continued |
||||||||
negative control |
0 |
+ |
2 |
4 |
2 |
7 |
4 |
3.8 |
2.0 |
238641 |
15.9 |
solvent control DMSO |
0 |
+ |
2 |
1 |
1 |
2 |
2 |
1.6 |
0.5 |
294959 |
5.4 |
positive control DMBA |
3.85 |
+ |
95 |
110 |
93 |
101 |
106 |
101.0 |
7.2 |
186956 |
540.2 |
test substance |
5 |
+ |
2 |
1 |
1 |
0 |
1 |
1.0 |
0.7 |
243616 |
4.1 |
test substance |
50 |
+ |
2 |
5 |
1 |
5 |
5 |
3.6 |
1.9 |
278924 |
12.9 |
test substance |
100 |
+ |
1 |
4 |
0 |
2 |
1 |
1.6 |
1.5 |
323235 |
4.9 |
test substance |
200 |
+ |
2 |
5 |
2 |
4 |
5 |
3.6 |
1.5 |
274105 |
13.1 |
test substance |
220 |
+ |
culture was not continued |
||||||||
test substance |
250 |
+ |
culture was not continued |
* only colonies with more than 50 cells
7 days after seeding were scored
** mean mutant colonies in TG medium* 10^6/
cell survival in TG medium
In the first experiment with metabolic activation, the number of revertants was increased to 15.4 mutant colonies per 10^6 cells at a concentration of 100 µg/mL, compared to 4.0 spontaneaous revertant colonies of the corresponding solvent control. Although a factor of three required to be judged as a relevant increase was exceeded, the absolute value is well within the range of historical controls. Furthermore, there was no indication of a concentration dependent increase of mutant colonies and the effect is considered to be due to the low negative and solvent control levels. In the second experiment there was no relevant increase of mutant colony numbers at any concentration level, neither with or without metabolic activation.
Genetic toxicity in vivo
Description of key information
Triallylcyanurate does not cause cytogenic effects in the mouse micronucleus test.
Link to relevant study records
- 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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-report according to guideline.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- ; 1983
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Source: Winkelmann, Borchen
Age at study initiation: 6 weeks
Weight at study initiation: males 21-27
females 21-30 - Route of administration:
- oral: gavage
- Vehicle:
- Peanut oil
- Details on exposure:
- Three groups of mice, the negative and positiv control groups (18 animals per sex) and the test material group
(21 animals per sex), each received a single administration by oral gavage (diet withdrawal: 16 h before treatment).
Group 1, the negative control, received peanut oil, group 2, the test material group, received 316 mg/kg body weight of the test material.
Group 3, the positive control, received cyclophosphamide (51.1 mg/kg body weight) dissolved in physiological saline solution (0.9 %). - Duration of treatment / exposure:
- 24, 48 or 72 hours
- Frequency of treatment:
- Single administration
- Post exposure period:
- No
- Remarks:
- Doses / Concentrations:
316 mg/kg
Basis:
nominal conc. - No. of animals per sex per dose:
- control groups: 18
test group: 21 - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide (51.1 mg/kg body weight) dissolved in physiological saline solution (0.9 % (w/w))
- Tissues and cell types examined:
- Bone marrow smears (at least two slides per animal) from the first 5 animals per sex and group were used for evaluation.
One slide per animal was examined. The remaining smears of each sex and group per interval were evaluated if macroscopical examination
of the first smears revealed technical imperfections which precluded aceurate microscopical analysis.
From each animal 1000 polychromatic erythrocytes (PCE) were scored for the incidence of micronuclei.
The ratio of polychromatic to normochromatic erythrocytes (PCE/NCE) was calculated, based on 1000 erythrocytes (PCE + NCE) scored per slide,
as a measure of the toxic efficacy of the test material. - Evaluation criteria:
- If a test material produced no statistically significant and reproducible positive response at any one of the test points compared to the negative
control group, it was considered non-mutagenic. - Statistics:
- Poisson test
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- Triallylcyanurate (TAC) related toxic symptoms were registered in all test material group animals. The symptoms consisted in coordination
disturbances, clonic convulsions, decrease of muscle tone, loss of righting reflexes, loss of pinna reflex, loss of pain reflex, loss of corneal reflex,
ptosis, tear formation, strenuous respiration, and reduced temperature of the body surface. One female animal of the test material group died.
Reduction in the ratio of polychromatic to normochromatic erythrocytes was present in all dose groups of the test material indicating a toxic effect
on the bone marrow. No statistically significant test material-related increase in the number of micronucleated polychromatic erythrocytes was
observed in either male or female animals and also if both sexes were analysed combined at the 48 hr and 72 hr sampling times and in females at the 24 hr sampling time. At the 24 hr sampling time a statistically significant increase in micronuclei was observed only in male animals of the main test.
This increase could not be verified in the repetition test using two additional dose levels and is therefore considered an incidental finding. - Conclusions:
- Triallylcyanurate does not cause cytogenic effects in the mouse micronucleus test.
Reference
Additional information
Outcome of studies with triallyl cyanurate was negative in a bacterial reverse mutation assay (with and without metabolic activation), an in vitrogene mutation test (HPRT test) in Chinese hamster V79 cells (with and without metabolic activation) as well as an in vitro chromosomal aberration assay in human peripheral lymphocytes. The in vivo micronucleus assay in mice was also negative.
Short description of key information:
Not mutagenic in bacteria (Ames Test) with and without metabolic
activation.
Not mutagenic in vitro in Chinese hamster lung fibroblasts (HPRT test).
Not clastogenic in vitro in human peripheral lymphocytes (Chromosome
Aberration Test).
Negative in Mammalian Erythrocyte Micronucleus Test in vivo in mice.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
No genotoxic potential is concluded for triallyl cyanurate and therefore no classification is needed according to DSD (67/548/EEC) and CLP (1272/2008/EC).
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