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EC number: 202-088-8 | CAS number: 91-66-7
- 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
Ames assay:
The test chemical was studied for its ability to induce mutations in strains of Salmonella typhimurium. The test compound was dissolved in DMSO and was tested at concentration of 0, 1, 3, 10, 33, 100 or 333 µg/plate in lab using Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of 10 % and 30 % rat and hamster liver S9 metabolic activation system. Preincubation assay was performed with a preicubation for 20 mins. The plates were observed for histidine independence after 2 days incubation period. Concurrent solvent and positive controls were included in the study. The test chemical is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
In vitro mammalian chromosome aberration study:
In vitro mammalian cell gene mutation assay:
In a gene toxicity test, Chinese Hamster Ovary (CHO) cells were exposed to the test chemical in the concentration of 0, 1, 2.5, 5 or 10 mM and with and without S9-induced metabolic activation for 3 hours. The results showed that there was evidence of cytotoxicity after treatment with 5 mM or above. Independently of tested concentration with S9 metabolic activation system, the results showed no evidence of gene toxicity. However, treatment with 5 mM of test chemical showed evidence of potential gene toxicity. Therefore, it is considered that the test chemical in the concentration of 0, 1, 2.5, 5 or 10 mM does not cause genetic mutation(s) when CHO cells are exposed to the test chemical in the presence of metabolic activation. The test chemical however in the concentrations of 2.5 mM or below caused no genetic mutation(s), while concentrations at 5mM or above may, when CHO cells are exposed to the test chemical in the absence of metabolic activation.
Link to relevant study records
- 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:
- 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 journal
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- Preincubation method was performed to determine the mutagenic nature of the test chemical
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine
- Species / strain / cell type:
- S. typhimurium, other: TA100, TA1535, TA97 and TA98
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Cytokinesis block (if used):
- No data
- Metabolic activation:
- with and without
- Metabolic activation system:
- 10% and 30% HLI and RLI S-9 (9,000 g supernatant) fractions were prepared from Aroclor 1254-induced, male Sprague- Dawley rat and male Syrian hamster livers
- Test concentrations with justification for top dose:
- 0, 1, 3, 10, 33, 100, 333 µg/plate
- Vehicle / solvent:
- Dimethyl Sulfoxide- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical was dissolved in DMSO - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Dimethyl Sulfoxide
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- in the absence of S9 activation
- Positive control substance:
- 9-aminoacridine
- sodium azide
- other: 4-nitro-o-phenylenediamine (TA98, with S9) ; The positive control for metabolic activation with all strains was 2-aminoanthracene.
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 mins
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data available
- 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: Triplicate
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: No data available - Evaluation criteria:
- Evaluations were made at both the individual trial and overall chemical levels.
Individual trials were judged mutagenic (+), weakly mutagenic (+ W), questionable
(?), or nonmutagenic (-), depending on the magnitude of the increase of his+ revertants, and the shape of the dose-response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of “ +W,” if only a single dose was elevated over the control, or if the increase seen was not dose related. The distinctions between a questionable mutagenic response and a nonmutagenic or weak mutagenic response, and between a weak mutagenic response and mutagenic response are highly subjective. It was not necessary for a response to reach two fold over background for a chemical to be judged mutagenic.
A chemical was judged mutagenic (+) or weakly mutagenic (+ W) if it produced a reproducible dose-related reponse over the solvent control in replicate trials. A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a “+W” response, or if only single doses produced increases in his+ revertants in repeat trials.
Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response. The chemicals were decoded by the chemical repository only after a determination had been made regarding their mutagenicity or nonmutagenicity. - Statistics:
- Mean ± SD
- Species / strain:
- S. typhimurium, other: TA100, TA1535, TA97 and TA98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- 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: All chemicals were tested initially in a toxicity assay to determine the appropriate dose range for the mutagenicity assay. The toxicity assay was performed using TA100. Toxic concentrations were those that produced a decrease in the number of his+ colonies, or a clearing in the density of the background lawn, or both.
COMPARISON WITH HISTORICAL CONTROL DATA: Yes
ADDITIONAL INFORMATION ON CYTOTOXICITY: No data available - Remarks on result:
- other: No mutagenic potential
- Conclusions:
- The test chemical is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
- Executive summary:
The test chemical was studied for its ability to induce mutations in strains of Salmonella typhimurium.
The test compound was dissolved in DMSO and was tested at concentration of 0, 1, 3, 10, 33, 100 or 333 µg/plate in lab using Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of 10 % and 30 % rat and hamster liver S9 metabolic activation system. Preincubation assay was performed with a preicubation for 20 mins. The plates were observed for histidine independence after 2 days incubation period. Concurrent solvent and positive controls were included in the study.
The test chemical is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from study report
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Principles of method if other than guideline:
- The purpose of this study was to assess toxic and genotoxic effects of the test chemical on Chinese Hamster Ovary (CHO) cells by using several different in vitro-based assays, including genotoxicity tests based on the OECD Guideline No. 476 “In Vitro Mammalian Cell Gene Mutation Test”.
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Cells deficient in hypoxanthine-guanine phosphoribosyl transferase (HPRT) due to the mutation HPRT+/- to HPRT-/- are resistant to cytotoxic effects of 6-thioguanine (TG). HPRT proficient cells are sensitive to TG (which causes inhibition of cellular metabolism and halts further cell division since HPRT enzyme activity is important for DNA synthesis), so mutant cells can proliferate in the presence of TG, while normal cells, containing hypoxanthine-guanine phosphoribosyl transferase cannot.
This in vitro test is an assay for the detection of forward gene mutations at the in hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus on the X chromosomes of hypodiploid, modal No. 20, CHO cells. Gene and chromosome mutations are considered as an initial step in the carcinogenic process.
The hypodiploid CHO cells are exposed to the test item with and without exogenous metabolic activation. Following an expression time the descendants of the treated cell population are monitored for the loss of functional HPRT enzyme.
HPRT catalyses the transformation of the purine analogues 6-thioguanine (TG) rendering them cytotoxic to normal cells. Hence, cells with mutations in the HPRT gene cannot phosphoribosylate the analogue and survive treatment with TG.
Therefore, mutated cells are able to proliferate in the presence of TG whereas the non-mutated cells die. However, the mutant phenotype requires a certain period of time before it is completely expressed. The phenotypic expression is achieved by allowing exponential growth of the cells for 7 days. - Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- Cell line used: Chinese Hamster Ovary (CHO) cells
- Type and identity of media: Ham's F-12K (Kaighn's) Medium containing 2 mM L-Glutamine supplemented with 10% Fetal Bovine Serum and 1% Penicillin-Streptomycin (10,000 U/mL).
- Properly maintained: Yes
- Periodically checked for Mycoplasma contamination: Not applicable
- Periodically checked for karyotype stability: Not applicable - Additional strain / cell type characteristics:
- other: Hypodiploid, modal No. 20
- Cytokinesis block (if used):
- No data
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 liver microsomal fraction obtained from Arcolor 1254-induced male Sprague-Dawley rats
- Test concentrations with justification for top dose:
- 0.1, 2.5, 5 or 10 mM
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: The test chemical was soluble in ethanol - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Remarks:
- N-ethyl-N-nitrosourea (ENU) was the positive control substance in the tests done without S9
- Details on test system and experimental conditions:
- Pre-incubation
One week involving 3 days of incubation with Hypoxanthine-aminopterin-thymidine (HAT) in medium as a mutant cleansing stage, followed by overnight incubation with hypoxanthine-thymidine (HT) in medium prior to a 3-4 days incubation in regular cell medium. After seeding and prior to treatment, the mutant-free cells were incubated for an additional of 24 hours.
Exposure duration
3 hours
Expression time
7 days
Selection time
14 days
Fixation time
7 days (harvest of cells)
SELECTION AGENT (mutation assays): 6-thioguanine (TG)
STAIN (for cytogenetic assays): Crystal violet
NUMBER OF REPLICATIONS: A minimum of 2 replicates per dose concentration including negative and positive control.
NUMBER OF CELLS EVALUATED: 0.5 x 10 E5 cells - Rationale for test conditions:
- No data
- Evaluation criteria:
- The cell line were observed for gene mutation at the HGPRT locus
- Statistics:
- No data
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- genotoxicity was ambiguous without S9 metabolic activation
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not valid
- Positive controls validity:
- valid
- Additional information on results:
- No data
- Remarks on result:
- other: No mutagenic potential
- Conclusions:
- Interpretation of results (migrated information):
negative with metabolic activation
N,N-diethylaniline in the concentration of 0.1, 2.5, 5 or 10 mM did not show any evidence of gene toxicity when CHO cells were exposed to the test chemical.
Without S9 metabolic activation the interpretation of results = Ambiguous without metabolic activation
Cells treated with N,N-diethylaniline in the concentration of 0, 1, 2.5, 5 or 10 mM showed evidence of potential gene toxicity in CHO cells when exposed to the test chemical at 5 mM. - Executive summary:
In a gene toxicity test, Chinese Hamster Ovary (CHO) cells were exposed to the test chemical in the concentration of 0, 1, 2.5, 5 or 10 mM and with and without S9-induced metabolic activation for 3 hours. The results showed that there was evidence of cytotoxicity after treatment with 5 mM or above. Independently of tested concentration with S9 metabolic activation system, the results showed no evidence of gene toxicity. However, treatment with 5 mM of test chemical showed evidence of potential gene toxicity. Therefore, it is considered that the test chemical in the concentration of 0, 1, 2.5, 5 or 10 mM does not cause genetic mutation(s) when CHO cells are exposed to the test chemical in the presence of metabolic activation. The test chemical however in the concentrations of 2.5 mM or below caused no genetic mutation(s), while concentrations at 5mM or above may, when CHO cells are exposed to the test chemical in the absence of metabolic activation.
Referenceopen allclose all
Table: Mutagenicity of the test chemical
Dose (µg/plate) |
TA100 |
|||||||||
-S9 |
10% HLI |
30% HLI |
10% RLI |
30% RLI |
||||||
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
|
0 |
127 |
7.0 |
98 |
3.3 |
129 |
3.6 |
93 |
1.2 |
147 |
6.2 |
1 |
119 |
6.6 |
||||||||
3 |
116 |
11.7 |
96 |
2.6 |
134 |
7.9 |
103 |
6.7 |
119 |
8.3 |
10 |
96 |
7.9 |
96 |
10.2 |
124 |
4.3 |
103 |
6.1 |
132 |
10.5 |
33 |
123 |
10.0 |
97 |
6.5 |
143 |
4.4 |
104 |
5.0 |
123 |
7.1 |
100 |
127 |
14.3 |
97 |
5.0 |
131 |
8.5 |
97 |
7.0 |
123 |
8.1 |
333 |
|
|
52 |
226.2 |
136 |
10.6 |
80 |
4.5 |
112 |
6.4 |
Positive control |
375 |
12.3 |
1828 |
130.2 |
873 |
46.0 |
725 |
24.1 |
449 |
7.0 |
Dose (µg/plate) |
TA1535 |
|||||||||
-S9 |
10% HLI |
30% HLI |
10% RLI |
30% RLI |
||||||
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
|
0 |
24 |
3.4 |
11 |
3.3 |
12 |
2.4 |
10 |
4.0 |
12 |
6.0 |
1 |
23 |
4.4 |
||||||||
3 |
26 |
3.8 |
14 |
5.0 |
10 |
2.9 |
10 |
1.5 |
12 |
3.5 |
10 |
18 |
1.2 |
9 |
1.8 |
9 |
3.2 |
7 |
1.7 |
22 |
1.5 |
33 |
22 |
4.3 |
10 |
2.2 |
13 |
0.6 |
11 |
2.7 |
14 |
2.0 |
100 |
12 |
0.7 |
7 |
1.9 |
7 |
1.5 |
10 |
1.5 |
12 |
1.5 |
333 |
|
|
4 |
0.3 |
15 |
1.9 |
7 |
2.7 |
15 |
2.8 |
Positive control |
418 |
23.1 |
557 |
10.3 |
616 |
69.9 |
205 |
12.4 |
162 |
27.5 |
Dose (µg/plate) |
TA97 |
|||||||||
-S9 |
10% HLI |
30% HLI |
10% RLI |
30% RLI |
||||||
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
|
0 |
121 |
8.1 |
117 |
5.5 |
234 |
15.2 |
193 |
8.2 |
236 |
9.4 |
1 |
134 |
0.3 |
||||||||
3 |
108 |
7.8 |
133 |
4.4 |
204 |
12.1 |
169 |
10.3 |
207 |
21.5 |
10 |
129 |
637 |
143 |
5.8 |
206 |
15.2 |
156 |
10.5 |
211 |
4.6 |
33 |
132 |
11.2 |
138 |
6.4 |
207 |
10.7 |
139 |
7.1 |
223 |
13.0 |
100 |
108 |
2.0 |
144 |
6.1 |
197 |
10.2 |
123 |
9.0 |
186 |
23.8 |
333 |
|
|
113 |
6.0 |
186 |
9.2 |
129 |
18.0 |
222 |
14.5 |
Positive control |
1156 |
22.0 |
1885 |
76.9 |
61.9 |
1452 |
80.7 |
480 |
60.6 |
7.0 |
Dose (µg/plate) |
TA1535 |
|||||||||
-S9 |
10% HLI |
30% HLI |
10% RLI |
30% RLI |
||||||
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
Mean |
SEM |
|
0 |
20 |
2.6 |
26 |
4.7 |
28 |
2.5 |
28 |
2.9 |
33 |
2.8 |
1 |
16 |
5.0 |
||||||||
3 |
16 |
2.6 |
26 |
3.2 |
27 |
1.7 |
24 |
3.6 |
25 |
3.5 |
10 |
17 |
2.9 |
31 |
4.5 |
31 |
3.8 |
26 |
1.9 |
23 |
3.8 |
33 |
22 |
3.6 |
35 |
3.2 |
27 |
1.9 |
30 |
0.3 |
25 |
2.6 |
100 |
12 |
1.7 |
31 |
9.0 |
27 |
3.3 |
32 |
2.5 |
26 |
2.4 |
333 |
|
|
30 |
0.9 |
29 |
1.5 |
23 |
3.5 |
28 |
3.9 |
Positive control |
845 |
69.2 |
1187 |
29.6 |
576 |
116.6 |
408 |
20.3 |
246 |
18.1 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Bone Marrow Chromosomal Aberration was performed to determine the mutagenic nature of the test chemical in vivo. The study was performed using male and female Bor: NMRI (SPF Han). The test chemical was tested at dose concerntration of 0 or 600 mg/Kg/day. The animals were given a single repeated administration of the test chemical. There was an altered ratio between polychromatic and normochromatic erythrocytes. However the test chemical did not induce clastogenic effects on the cells. Based on the observations made, thetest chemical did not induce chromosome aberrations in the bone marrow cells in vivo isolated from the test chemical treated male and female NMRI mice and hence it is not likely to classify as a gene mutant in vitro.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- data is from secondary literature
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Principles of method if other than guideline:
- Bone Marrow Chromosomal Aberration was performed to determine the mutagenic nature of the test chemical in vivo.
- GLP compliance:
- not specified
- Type of assay:
- other: Bone Marrow Chromosomal Aberration
- Species:
- mouse
- Strain:
- NMRI
- Remarks:
- Bor: NMRI (SPF Han)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data
- Route of administration:
- intraperitoneal
- Vehicle:
- No data
- Details on exposure:
- No data
- Duration of treatment / exposure:
- No data
- Frequency of treatment:
- Single administration
- Post exposure period:
- No data
- Remarks:
- 0 or 600 mg/Kg/day
- No. of animals per sex per dose:
- No data
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- No data
- Tissues and cell types examined:
- Bone marrow polychromatic and normochromatic erythrocytes
- Details of tissue and slide preparation:
- No data
- Evaluation criteria:
- The cells were observed for chromosome aberrations
- Statistics:
- No data
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: No mutagenic potential
- Additional information on results:
- No data
- Conclusions:
- The test chemical did not induce chromosome aberrations in the bone marrow cells in vivo isolated from the test chemical treated male and female NMRI mice and hence it is not likely to classify as a gene mutant in vitro.
- Executive summary:
Bone Marrow Chromosomal Aberration was performed to determine the mutagenic nature of the test chemical in vivo. The study was performed using male and female Bor: NMRI (SPF Han). The test chemical was tested at dose concerntration of 0 or 600 mg/Kg/day. The animals were given a single repeated administration of the test chemical. There was an altered ratio between polychromatic and normochromatic erythrocytes. However the test chemical did not induce clastogenic effects on the cells. Based on the observations made, thetest chemical did not induce chromosome aberrations in the bone marrow cells in vivo isolated from the test chemical treated male and female NMRI mice and hence it is not likely to classify as a gene mutant in vitro.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Data available for the various test chemicals was reviewed to determine the mutagenic nature of the test chemical. The studies are as mentioned below:
Ames assay:
The test chemical was studied for its ability to induce mutations in strains of Salmonella typhimurium. The test compound was dissolved in DMSO and was tested at concentration of 0, 1, 3, 10, 33, 100 or 333 µg/plate in lab using Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of 10 % and 30 % rat and hamster liver S9 metabolic activation system. Preincubation assay was performed with a preicubation for 20 mins. The plates were observed for histidine independence after 2 days incubation period. Concurrent solvent and positive controls were included in the study. The test chemical is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
In vitro mammalian cell gene mutation assay:
In a gene toxicity test, Chinese Hamster Ovary (CHO) cells were exposed to the test chemical in the concentration of 0, 1, 2.5, 5 or 10 mM and with and without S9-induced metabolic activation for 3 hours. The results showed that there was evidence of cytotoxicity after treatment with 5 mM or above. Independently of tested concentration with S9 metabolic activation system, the results showed no evidence of gene toxicity. However, treatment with 5 mM of test chemical showed evidence of potential gene toxicity. Therefore, it is considered that the test chemical in the concentration of 0, 1, 2.5, 5 or 10 mM does not cause genetic mutation(s) when CHO cells are exposed to the test chemical in the presence of metabolic activation. The test chemical however in the concentrations of 2.5 mM or below caused no genetic mutation(s), while concentrations at 5mM or above may, when CHO cells are exposed to the test chemical in the absence of metabolic activation.
DNA damage/repair assay:
The hepatocyte/DNA repair test which measures unscheduled DNA synthesis (UDS) is known to be sensitive to various classes of DNA-reactive carcinogens and is regarded as a reliable short-term test for the detection of chemical carcinogens. In this study, the genotoxicity of the test chemical was examined by a DNA repair test with rat hepatocytes. The test was performed basically in accordance with the method of Williams et al. The test material was dissolved in DMSO and used at dose level of 10-3, 10-4, 10-5, 10-6M and the positive control used was N-2-fluorenylacetamide. The test chemical did not induce mutation in ACI rat hepatocytes and hence is negative in the rat hepatocyte/ DNA repair test.
Gene mutation in vivo:
Bone Marrow Chromosomal Aberration was performed to determine the mutagenic nature of the test chemical in vivo. The study was performed using male and female Bor: NMRI (SPF Han). The test chemical was tested at dose concerntration of 0 or 600 mg/Kg/day. The animals were given a single repeated administration of the test chemical. There was an altered ratio between polychromatic and normochromatic erythrocytes. However the test chemical did not induce clastogenic effects on the cells. Based on the observations made, thetest chemical did not induce chromosome aberrations in the bone marrow cells in vivo isolated from the test chemical treated male and female NMRI mice and hence it is not likely to classify as a gene mutant in vitro.
Based on the observations made, the test chemical does not exhibit gene mutation in vitro, The negative results are supported by the negative results observed the in vivo study. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
The test chemical does not exhibit gene mutation in vitro, The negative results are supported by the negative results observed the in vivo study. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.
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