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EC number: 446-620-9 | CAS number: 120983-72-4
- 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
Bacterial reverse mutation assays (Ames test):
Evidence of mutagenic activity of JAU 6476 Chloromethylketone was seen. On Salmonella typhimurium TA 1535, TA 100, TA 98 and TA 102, a biologically relevant increase was found in the mutant count compared to the corresponding negative control. Both with and without S9 mix, there was a positive response and the effect was comparable.
Chromosomal abberation test mammalian cells:
In the absence and in the presence of S9 mix cultures treated with JAU 6476- Chloromethylketone showed biologically relevant and statistically significant increased numbers of aberrant metaphases.
In silico Ames Test:
Strong alert on mutagenicty when using state-of the-art prediction models (DEREK, Leadscope, VITIC) [Analysis April 07, 2021]
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
- Study period:
- Sept 2002 - Jan 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 473
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- purity 93.2%, Identity and stability tested analytically
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- The karyotype of the V79 cells (modal number of chromosomes: 22) was confirmed on August 9, 2002.
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9 mix
- Test concentrations with justification for top dose:
- Concentration range in the main test (with metabolic activation): 1 - 8 µg/ml
Concentration range in the main test (without metabolic activation): 0.5 - 4 µg/ml - Details on test system and experimental conditions:
- Exposure period (with metabolic activation): 4 hours
Exposure period (without metabolic activation): 4 hours
Expression time:
4 h
Selection time:
Experiment 1: 18 h (with and without metabolic activation)
Experiment 2: 30 h (with and without metabolic activation)
Fixation time:
2 h - Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (>2 µg/ml)
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 7 µg/ml)
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Observations:
The substance showed clear cytotoxic effects. An indirect
cyctoxicity based mutagenic effect may be possible. - Conclusions:
- Based on the results of this test, JAU 64 76-Chloromethylketone is considered to be clastogenic for mammalian cells in vitro. Since nucleus disintegration was observed at 2 μg/ml (without S9 mix) and at 8 μg/ml (with S9 mix), an indirect cytotoxicity based effect may be possible.
- Executive summary:
The clastogenic potential of JAU 64 76-Chloromethylketone was evaluated in a chromosome aberration test in vitro. lnitially Chinese hamster V79 cells were exposed in the absence of S9 mix for 4 hours to concentrations of 0.5, 1, 2, 3 and 4 μg/ml of JAU 6476-Chloromethylketone. Cultures of all concentrations were harvested 18 hours after the beginning of the treatment. In addition, cells treated with 2, 3 and 4 μg/ml were harvested 30 hours after the beginning of the treatment. In the presence of S9 mix cells were exposed for to concentrations of 1, 3, 6, 7 and 8 μg/ml of JAU 6476 Chloromethylketone. Cultures of all concentrations were harvested 18 hours after the beginning of the treatment. In addition, cells treated with 6, 7 and 8 μg/ml were harvested 30 hours after the beginning of the treatment. Based on their cytotoxicity concentrations were selected for reading of metaphases. Without S9 mix cytotoxic effects were observed at 2 μg/ml and above. With S9 mix cytotoxic effects were observed at 7 μg/ml and above. Precipitation of JAU 6476 -Chloromethylketone in the medium was not observed. Therefore, concentrations of 0.5, 1 and 2 μg/ml JAU 6476-Chloromethylketone were chosen for reading in the absence of S9 mix. In the presence of S9 mix 1, 6 and 8 μg/ml of JAU 6476-Chloromethylketone were employed. All of these cultures harvested 18 hours after the beginning of the treatment were included. In addition, cultures treated in the absence of S9 mix with 2 μg/ml and harvested 30 hours after the beginning of the treatment were used. The same was true for cultures treated in the presence of S9 mix with 8 μg/ml. In the absence and in the presence of S9 mix cultures treated with JAU 6476- Chloromethylketone showed biologically relevant and statistically significant increased numbers of aberrant metaphases. The positive controls mitomycin C and cyclophosphamide induced clastogenic effects and demonstrated the sensitivity of the test system and the activity of the used S9 mix. Based on this test, JAU 64 76-Chloromethylketone is considered to be clastogenic for mammalian cells in vitro. Since nucleus disintegration was observed at 2 μg/ml (without S9 mix) and at 8 μg/ml (with S9 mix), an indirect cytotoxicity based effect may be possible.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Oct - Dec 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- July 1997
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- 92.1 % (analytical result dated August 30, 2000); stability in vehicle (DMSO) tested and confirmed
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9 mix
- Test concentrations with justification for top dose:
- Concentration range (pre-test): 50-5000 µg/plate
Concentration range (main test): 0.75 - 96 µg/plate (due to the substance’s toxicity) - Vehicle / solvent:
- Solvent: DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- no
- Remarks:
- Sufficient evidence available in the literature (e.g. Maron and Ames, 1983) and from own experience, indicating that this solvent had no influence on the spontaneous mutant counts of the used strains.
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- cumene hydroperoxide
- other: Nitrofurantoin (TA100); 4-nitro-1,2-phenylene diamine (4-NPDA) (TA1537, T98); 2-aminoanthracene (2-AA) (w S9 mix)
- Rationale for test conditions:
- The doses for the first trial were routinely determined on the basis of a standard protocol: if not limited by solubility 5000 ug or 5 ul per plate were used as the highest dose. At least four additional doses were routinely used. If less than three doses were used for assessment, at least two repeats were performed. The results of the first experiment were then considered as a pre-test for toxicity. However, in case of a positive response or if at least three doses could be used for assessment, the first trial was included in the assessment. If the second test confirmed the results of the first, no additional repeat was performed. Doses of repeats were chosen on the basis of the results obtained in the first experiment.
In experiments without S9 mix buffer was used as replacement. - Evaluation criteria:
- The toxicity of the substance was assessed in two ways. The first method was a
gross appraisal of background growth on the plates for mutant determination. If a
reduction in background growth was observed, it was indicated in the tables by the
letter “b” after the mutant count. Where only a single “b”, without any other values, is
noted for a concentration, this “b” represents three plates with reduced background
growth. (The same applies to the signs “c”, “v”, “p”, “n” or “%“, which may also be
used in the tables). Secondly, a toxic effect of the substance was assumed when
there was a marked and dose-dependent reduction in the mutant count per plate,
compared to the negative controls. - Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 6 µg/plate)
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 6 µg/plate)
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 6 µg/plate)
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 6 µg/plate)
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 6 µg/plate)
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- positive with metabolic activation and
positive without metabolic activation - Executive summary:
JAU 6476 Chloromethylketone was investigated using the Salmonella/microsome plate incorporation test for point mutagenic effects in doses of up to and including 5000 ug per plate on five Salmonella typhimurium LT2 mutants. These comprised the histidine-auxotrophic strains TA 1535, TA 100, TA 1537, TA 98 and TA 102. Doses up to and including 6 ug per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no inhibition of growth was observed. At higher doses, the substance had a strong, strain-specific bacteriotoxic effect, so that this range could only be used to a limited extent up to and including 96 ug per plate for assessment purposes. Evidence of mutagenic activity of JAU 6476 Chloromethylketone was seen. On Salmonella typhimurium TA 1535, TA 100, TA 98 and TA 102, a biologically relevant increase was found in the mutant count compared to the corresponding negative control. Both with and without S9 mix, there was a positive response and the effect was comparable. The lowest reproducible effective dose was 0.75 ug per plate for Salmonella typhimurium TA 100, 3 ug per plate for TA 1535 and TA 102, and 12 ug per plate for TA 98. The Salmonella/microsome test thus showed JAU 6476 Chloromethylketone to have a mutagenic effect. The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, cumene hydroperoxide and 2-aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls.
Referenceopen allclose all
Mitotic index without S9 mix: In comparison to the solvent control, the mitotic indices in the treated cultures were relevantly reduced at 2 μg/ml and above. The cultures treated with mitomycin C showed no reduction in mitosis rate.
Mitotic index with S9 mix: In comparison to the solvent control, the treated cultures showed no relevant reduction of the mitosis rate. The positive control cyclophosphamide also reduced the mitosis rate.
Survival index without S9 mix: In comparison to the solvent control, the survival indices in the treated cultures were relevantly reduced at 2 μg/ml and above. The cultures treated with mitomycin C showed a reduction in survival rate.
Survival index with S9 mix: In comparison to the solvent control, the treated cultures showed a relevant reduction of the survival rate at 7 μg/ml and above. The positive control cyclophosphamide also reduced the survival rate.
Chromosome Aberrations
JAU 64 76-Chloromethylketone without S9 mix: Biologically relevant and statistically significant increases of numbers of metaphases with aberrations were detected after 18 or 30 hours culture time. The treatment with the positive control mitomycin C resulted in a clear and statistically significant increase of metaphases with aberrations and demonstrated the sensitivity of the test system.
JAU 64 76-Chloromethylketone with S9 mix: Biologically relevant and statistically significant increases of metaphases with aberrations were detected after total culture times of 18 or 30 hours. The positive control cyclophosphamide induced statistically significant and biologically relevant increases of metaphases with aberrations and demonstrated the sensitivity of the test system and the activity of the used S9 mix.
Table 2: Results as mean values without S9 mix
Compound | Group | concentration | TA 1535 | TA 100 | TA 1537 | TA 98 | TA102 |
Test substance | 6-10 | 0 | 9 | 93 | 6 | 27 | 170 |
0.75 | 10 | 259 | 4 | 29 | 272 | ||
1.5 | 11 | 388 | 6 | 26 | 268 | ||
3 | 20 | 588 | 5 | 29 | 298 | ||
6 | 25 | 894 | 6 | 39 | 381 | ||
12 | 25 | 1082 | 4 | 45 | 373 | ||
| 24 | 8 | 813 | 1 | 23 | 9 | |
| 48 | 0 | - | 0 | 0 | - | |
Sodium azide |
| 573 | - | - | - | - | |
NF |
| - | 241 | - | - | - | |
4-NPDA |
| - | - | 78 | 146 | - | |
Cumene |
|
| - | - | - | - | 367 |
Test substance | 11-15 | 0 | 16 | 92 | 8 | 34 | 237 |
0.75 | 15 | 236 | 7 | 40 | 345 | ||
1.5 | 18 | 324 | 7 | 36 | 409 | ||
3 | 31 | 576 | 6 | 44 | 455 | ||
6 | 35 | 915 | 6 | 54 | 484 | ||
12 | 39 | 1095 | 4 | 51 | 522 | ||
| 24 | 30 | 406 | 2 | 44 | 253 | |
| 48 | - | 0 | - | - | 0 | |
Sodium azide |
| 793 | - | - | - | - | |
NF |
| - | 248 | - | - | - | |
4-NPDA |
| - | - | 83 | 141 | - | |
Cumene |
|
| - | - | - | - | 417 |
Table 3: Results as mean values with S9 mix
Compound | Group | concentration | TA 1535 | TA 100 | TA 1537 | TA 98 | TA102 |
Test substance | 6-10 | 0 | 9 | 113 | 9 | 37 | 242 |
1.5 | 11 | 231 | 8 | 43 | 316 | ||
3 | 14 | 312 | 8 | 54 | 334 | ||
6 | 16 | 486 | 6 | 47 | 399 | ||
12 | 18 | 875 | 9 | 75 | 516 | ||
24 | 42 | 1323 | 8 | 77 | 597 | ||
| 48 | 23 | 1240 | 5 | 87 | 613 | |
| 96 | - | 344 | - | 17 | 379 | |
2-AA |
| 188 | 1481 | 330 | 1559 | 480 | |
Test substance | 11-15 | 0 | 13 | 118 | 9 | 39 | 298 |
1.5 | 13 | 209 | 9 | 36 | 386 | ||
3 | 16 | 266 | 6 | 44 | 439 | ||
6 | 23 | 488 | 6 | 62 | 473 | ||
12 | 37 | 901 | 12 | 72 | 551 | ||
24 | 53 | 1226 | 12 | 101 | 629 | ||
| 48 | 53 | 944 | 8 | 87 | 592 | |
| 96 | - | - | 2 | 23 | 502 | |
2-AA |
| 239 | 1545 | 396 | 1529 | 602 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In addition to the experimental Ames test an in silico prediction of genotoxicity was performed for assessing the possible DNA reactivity of the substance.
With regard to the results of the prediction models (DEREK, Leadscope, VITIC) the substance raised a concern with respect to possible mutagenicity [April 07, 2021].
Derek Version: Derek Nexus: 6.1.0, Nexus: 2.3.0, Derek KB 2020 1.0 | ||
Leadscope Version: 3.0.0-30, ICH-M7: Bacterial Mutation v2 | ||
VITIC Version: 2.6.1 |
Justification for classification or non-classification
Based on the positive in vitro study results for genetic toxicity (gene mutations in bacteria and chromosomal abberations in mammalian cells) combined with a strong in silico prediction alert allocation to category 2 (H341) according to Regulation (EC) No. 1272/2008 (CLP), ANNEX I, is warranted.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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