Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 208-577-2 | CAS number: 533-75-5
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 3 Sep - 9 Oct 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM, UK
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 2-hydroxycyclohepta-2,4,6-trienone
- EC Number:
- 208-577-2
- EC Name:
- 2-hydroxycyclohepta-2,4,6-trienone
- Cas Number:
- 533-75-5
- Molecular formula:
- C7H6O2
- IUPAC Name:
- 2-hydroxycyclohepta-2,4,6-trien-1-one
Constituent 1
Method
- Target gene:
- his operon
Species / strain
- 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:
- cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital/β-naphthoflavone (80/100 mg/kg bw/day for 3 consecutive days)
- Test concentrations with justification for top dose:
- Pre-experiment:
0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate with and without metabolic activation
First and second experiment: 1.5, 5, 15, 50, 150, 500 and 1500 µg/plate with and without metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test substance was fully soluble at 50 mg/mL in DMSO.
Controls
- Untreated negative controls:
- yes
- Remarks:
- untreated controls
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 1,8-dihydroxyanthraquinone (DAN), 2-aminoanthracene (2-AA), N-ethyl-N-nitro-N-nitrosoguanidine (ENNG), 9-aminoacridine (9-AA), mitomycin C (MMC), 4-nitroquinoline-N-oxide (4-NQO), benzo(a)pyrene (BaP)
- Remarks:
- +S9: 2-AA (1 µg/plate, TA100; 2 µg/plate, TA1535, TA1537); BaP (5 µg/plate, TA98); DAN (10 µg/plate, TA102) -S9: ENNG (3 µg/plate, TA100; 5 µg/plate, TA1535); 9-AA (80 µg/plate, TA1537); MMC (0.5 µg/plate, TA102); 4-NQO (0.2 µg/plate, TA98)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: 3 replications each in 2 independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: reduction in revertant colony frequency or reduction of the bacterial background lawn - Evaluation criteria:
- Several criteria for determining a positive result, such as a dose-related increase in revertant frequency over the dose range tested and/or a reproducible increase at one or more concentrations in at least one bacterial strain with or without metabolic activation, were considered. However, biological relevance of the results was considered first. Additionally, statistical methods were used as an aid to evaluate a positive response.
Results and discussion
Test results
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (exp. 1: -S9: at 150 µg/plate in TA1535 and TA102; at 500 µg/plate in remaining strains; +S9: at 150 µg/plate in TA102; at 500 µg/plate in rem. strains; exp. 2: -S9: at 150 µg/plate; +S9: at 500 µg/plate in TA1537; at 150 µg/plate in rem. strains)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation was observed on the plates at any of the doses tested in either the presence or absence of metabolic activation.
RANGE-FINDING/SCREENING STUDIES: In order to select appropriate dose levels for the main study, a preliminary experiment was carried out to determine the toxicity of the test material. The test substance was toxic at and above 1500 µg/plate in TA100.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
The test substance caused a visible reduction in the growth of the bacterial background lawn of all tester strains in both the presence and absence of metabolic activation, initially from 150 µg/plate for TA100 and 500 µg/plate for the remaining tester strains. Several of the bacterial strains also exhibited substantial decreases in revertant colony frequency at 150 µg/plate in both the presence and absence of metabolic activation. The toxicity of the test substance to the tester strains varied slightly between experiment number and strain type and was of sufficient severity to prevent the test substance from being tested up to the maximum recommended dose level of 5000 µg/plate.
Any other information on results incl. tables
Table 2. Test results of Experiment 1 (plate incorporation).
With or without S9-Mix |
Test substance concentration [μg/plate] |
Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation) |
||||
Base-pair substitution type |
Frameshift type |
|||||
TA100 |
TA1535 |
TA102 |
TA98 |
TA1537 |
||
– |
0 |
135 |
25 |
316 |
14 |
9 |
– |
0 (DMSO) |
138 ± 21.7 |
28 ± 2.3 |
350 ± 4.9 |
14 ± 0.6 |
10 ± 0.6 |
– |
1.5 |
145 ± 19.7 |
30 ± 5.0 |
329 ± 19.1 |
16 ± 5.7 |
9 ± 2.0 |
– |
5 |
149 ± 8.7 |
31 ± 6.7 |
349 ± 50.1 |
18 ± 6.8 |
9 ± 0.6 |
– |
15 |
134 ± 20.5 |
25 ± 4.6 |
360 ± 10.8 |
12 ± 3.8 |
10 ± 2.5 |
– |
50 |
124 ± 8.5 |
27 ± 5.5 |
278 ± 34.9 |
17 ± 4.4 |
9 ± 1.2 |
– |
150 |
151 ± 3.2 |
11 ± 1.0 |
91 ± 14.2 |
14 ± 0 |
6 ± 1.2 |
– |
500 |
0T |
0T |
0T |
0T |
0T |
– |
1500 |
0T |
0T |
0T |
0T |
0T |
Positive controls, –S9 |
Name |
ENNG |
ENNG |
MMC |
4-NQO |
9-AA |
Concentrations [μg/plate] |
3 |
5 |
0.5 |
0.2 |
80 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
495 ± 25.2 |
319 ± 19.1 |
2525 ± 5.5 |
455 ± 22.7 |
626 ± 48.2 |
|
+ |
0 (DMSO) |
146 ± 25.1 |
17 ± 7.0 |
369 ± 16.2 |
24 ± 5.2 |
11 ± 3.6 |
+ |
1.5 |
143 ± 14.2 |
14 ± 8.4 |
385 ± 12.5 |
26 ± 1.5 |
12 ± 1.0 |
+ |
5 |
140 ± 20.0 |
11 ± 2.1 |
364 ± 28.9 |
25 ± 2.0 |
12 ± 2.1 |
+ |
15 |
129 ± 7.9 |
14 ± 7.0 |
311 ± 11.0 |
21 ± 1.2 |
13 ± 4.4 |
+ |
50 |
116 ± 13.4 |
14 ± 1.2 |
320 ± 12.1 |
19 ± 1.2 |
12 ± 6.2 |
+ |
150 |
96 ± 11.5 |
11 ± 2.3 |
188 ± 14.0 |
15 ± 5.2 |
7 ± 2.1 |
+ |
500 |
0T |
0V |
0T |
0T |
0T |
+ |
1500 |
0T |
0T |
0T |
0T |
0T |
Positive controls, +S9 |
Name |
2-AA |
2-AA |
DAN |
BaP |
2-AA |
Concentrations [μg/plate] |
1 |
2 |
10 |
5 |
2 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
660 ± 49.0 |
498 ± 53.6 |
1080 ± 95.2 |
435 ± 80.0 |
397 ± 33.3 |
DMSO: dimethylsulphoxide
BaP: benzo(a)pyrene
DAN: 1,8-dihydroxyanthraquinone
ENNG: N-ethyl-N-nitro-N-nitrosoguanidine
4-NQO: 4-nitroquinoline-N-oxide
2-AA: 2-aminoanthracene
9-AA: 9-aminoacridine
MMC: mytomycin C
T: toxic, no bacterial background lawn
V: very weak bacterial background lawn
Table 3. Test results of Experiment 2 (plate incorporation).
With or without S9-Mix |
Test substance concentration [μg/plate] |
Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation) |
||||
Base-pair substitution type |
Frameshift type |
|||||
TA100 |
TA1535 |
TA102 |
TA98 |
TA1537 |
||
– |
0 |
101 |
20 |
318 |
19 |
11 |
– |
0 (DMSO) |
94 ± 9.7 |
30 ± 1.5 |
275 ± 13.3 |
19 ± 3.0 |
14 ± 2.6 |
– |
1.5 |
88 ± 4.6 |
30 ± 2.3 |
256 ± 15.8 |
16 ± 4.4 |
10 ± 1.5 |
– |
5 |
95 ± 11.9 |
31 ± 7.8 |
261 ± 5.7 |
15 ± 6.0 |
11 ± 1.0 |
– |
15 |
87 ± 5.5 |
26 ± 2.9 |
230 ± 20.1 |
16 ± 1.5 |
13 ± 2.1 |
– |
50 |
96 ± 16.1 |
20 ± 2.1 |
229 ± 18.6 |
13 ± 8.5 |
13 ± 3.1 |
– |
150 |
32 ± 3.2S |
8 ± 1.2 |
45 ± 7.6 |
5 ± 1.0 |
4 ± 0.6 |
– |
500 |
0T |
0T |
0T |
0T |
0T |
– |
1500 |
0T |
0T |
0T |
0T |
0T |
Positive controls, –S9 |
Name |
ENNG |
ENNG |
MMC |
4-NQO |
9-AA |
Concentrations [μg/plate] |
3 |
5 |
0.5 |
0.2 |
80 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
505 ± 28.2 |
182 ± 27.2 |
1541 ± 68.8 |
131 ± 2.5 |
884 ± 243.8 |
|
+ |
0 (DMSO) |
86 ± 4.0 |
12 ± 1.7 |
322 ± 9.9 |
21 ± 2.6 |
12 ± 3.8 |
+ |
1.5 |
85 ± 14.0 |
12 ± 4.0 |
290 ± 4.6 |
24 ± 6.0 |
8 ± 5.0 |
+ |
5 |
97 ± 9.2 |
14 ± 2.5 |
251 ± 20.0 |
24 ± 1.2 |
15 ± 3.5 |
+ |
15 |
86 ± 9.9 |
13 ± 4.2 |
247 ± 20.3 |
16 ± 2.6 |
10 ± 4.6 |
+ |
50 |
76 ± 5.3 |
11 ± 0.6 |
216 ± 20.0 |
20 ± 2.3 |
9 ± 3.5 |
+ |
150 |
34 ± 7.2S |
5 ± 1.5 |
111 ± 5.3 |
5 ± 0.6 |
7 ± 3.6 |
+ |
500 |
0T |
0T |
0T |
0T |
0T |
+ |
1500 |
0T |
0T |
0T |
0T |
0T |
Positive controls, +S9 |
Name |
2-AA |
2-AA |
DAN |
BaP |
2-AA |
Concentrations [μg/plate] |
1 |
2 |
10 |
5 |
2 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
596 ± 45.5 |
275 ± 42.0 |
1407 ± 114.5 |
203 ± 16.8 |
183 ± 37.5 |
DMSO: dimethylsulphoxide
BaP: benzo(a)pyrene
DAN: 1,8-dihydroxyanthraquinone
ENNG: N-ethyl-N-nitro-N-nitrosoguanidine
4-NQO: 4-nitroquinoline-N-oxide
2-AA: 2-aminoanthracene
9-AA: 9-aminoacridine
MMC: mytomycin C
S: sparse bacterial background lawn
T: toxic, no bacterial background lawn
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the Ames Assay the substance was not mutagenic in any of the five strains (TA1535, TA1537, TA98, TA100 and TA102) tested with and without metabolic activation.
- Executive summary:
The method was designed to meet the requirements of the OECD Guidelines for Testing of Chemicals No. 471 "Bacterial Reverse Mutation Test", Method B13/14 of Commission Directive 2000/32/EC and the USA, EPA (TSCA) OPPTS harmonised guidelines.
Salmonella typhimurium strains TA1535, TA1537, TA102, TA98 and TA100 were treated with the test material using the Ames plate incorporation method at seven dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolising system (10% liver S9 in standard co-factors). The dose range was determined in a preliminary toxicity assay and was 1.5 to 1500 µg/plate in the first experiment. The experiment was repeated using the same dose range as Experiment 1. Additional dose levels and an expanded dose range were selected to allow for test material induced toxicity, ensuring that at least four non-toxic doses were achieved.
The vehicle (dimethyl sulphoxide) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated. The test material caused a visible reduction in the growth of the bacterial background lawn of all tester strains in both the presence and absence of S9, initially from 150 µg/plate for TA100 and 500 µg/plate for the remaining tester strains. Several of the bacterial strains also exhibited substantial decreases in revertant colony frequency at 150 µg/plate in both the presence and
absence of S9. The toxicity of the test material to the tester strains varied slightly between experiment number and strain type and was of sufficient severity to prevent the test material from being tested up to the maximum recommended dose level of 5000 lag/plate. No test material precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix.
No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation.
In conclusion, the test material was considered to be non-mutagenic under the conditions of this test.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.