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EC number: 210-112-3 | CAS number: 606-28-0
- 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 vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Methyl 2-benzoylbenzoate
- EC Number:
- 210-112-3
- EC Name:
- Methyl 2-benzoylbenzoate
- Cas Number:
- 606-28-0
- Molecular formula:
- C15H12O3
- IUPAC Name:
- methyl 2-benzoylbenzoate
- Reference substance name:
- GENOCURE* MBB
- IUPAC Name:
- GENOCURE* MBB
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- Identity: GENOCURE* MBB
Chemical Name: Methyl 2-benzoylbenzoate
CAS No.: 606-28-0
Batch No.: G07001
Aggregate state at
room temperature: Solid
Colour: Off white, light yellow
Molecular weight: 240.26 g/mol
Purity: > 99 %
Solubility: Soluble in water <1 g/L
Stability in solvent: Stable for at least 30 days at THF and acetone
Storage: At room temperature
Expiration Date: June 30, 2008
On the day of the experiment, the test item was formulated in 30% DMSO / 70% PEG 400. The vehicle was chosen to its relative non-toxicity for the animals. All animals received a single standard volume of 10 mL/kg body weight orally.
Constituent 1
Constituent 2
- Specific details on test material used for the study:
- Identity: GENOCURE* MBB
Chemical Name: Methyl 2-benzoylbenzoate
Batch No.: G07001
CAS No.: 606-28-0
Batch No.: G07001
Aggregate state: Solid
Colour: off-white, light yellow
Molecular weight: 240.26 g/mol
Purity: > 99 %
Solubility: soluble in water <1 g/L
Stability in solvent: stable for at least 30 days at THF and acetone
Storage: at room temperature
Expiration Date: June 30, 2008
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Strain: NMRI
Source Harlan Winkelmann GmbH
33178 Borchen,Germany
Number of Animals: 81 (45 males/36 females)
Initial Age at Start of
Acclimatisation: 8 - 10 weeks
Acclimatisation: minimum 5 days
Initial Body Weight
at Start of Treatment:
Mutagenicity experiment:
males mean value 37.5 g (SD +/- 1.6 g)
females mean value 31.2 g (SD +/- 2.1 g)
Bioanalysis:
males mean value 36.7 g (SD +/- 2.2 g)
ENVIRONMENTAL CONDITIONS
Housing: single
Cage Type: Makrolon Type I, with wire mesh top
(EHRET GmbH, D-79302 Emmendingen)
Bedding: granulated soft wood bedding
(Harlan Winkelmann GmbH, D-33178 Borchen)
Feed: pelleted standard diet, ad libitum
(Harlan Winkelmann GmbH, D-33178 Borchen)
Water: tap water, ad libitum, (Gemeindewerke, D-64380 Roßdorf)
Environment: temperature 22 3 °C
relative humidity 30 - 70 %
artificial light 6.00 a.m. - 6.00 p.m.
IN-LIFE DATES: From: April 21, 2008 To: May 07, 2008
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Name: 30% DMSO / 70% PEG 400
DMSO Supplier: VWR International (64293 Darmstadt)
Catalogue no.: 1.02931.1000
PEG 400 Supplier: VWR International (64293 Darmstadt)
Catalogue no.: 1.09726.0100
Route and Frequency
of Administration: orally, once
Volume Administered: 10 mL/kg b.w. - Details on exposure:
- orally
- Frequency of treatment:
- once
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500, 1000, 2000
Basis:
- No. of animals per sex per dose:
- 2 males and 2 females used in the pre-experiment
81 (45 males/36 females) used in the main experiment - Control animals:
- yes
- Positive control(s):
- Name: CPA; Cyclophosphamide
Supplier: Sigma-Aldrich Vertriebs GmbH
82041 Deisenhofen
Catalogue no.: C 0768 (purity: > 98 %)
Dissolved in: deionised water
Dosing: 40 mg/kg b.w.
Route and frequency
of administration: orally, once
Volume administered: 10 mL/kg b.w.
Examinations
- Tissues and cell types examined:
- bone marrow
- Details of tissue and slide preparation:
- The animals were sacrificed using CO2 followed by bleeding. The femora were removed, the epiphyses were cut off and the marrow was flushed out with foetal calf serum using a syringe. The cell suspension was centrifuged at 1500 rpm (390 x g) for 10 minutes and the supernatant was discarded. A small drop of the re-suspended cell pellet was spread on a slide. The smear was air-dried and then stained with May-Grünwald (Merck, D-64293 Darmstadt)/Giemsa (Merck, D-64293 Darmstadt). Cover slips were mount¬ed with EUKITT (Kindler, D-79110 Freiburg). At least one slide was made from each bone marrow sample.
- Evaluation criteria:
- Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion objectives. At least 2000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei. To describe a cytotoxic effect the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and expressed in polychromatic erythrocytes per 2000 erythrocytes. The analysis was performed with coded slides.
Ten animals (5 males, 5 females) per test group were evaluated as described. The remaining 6th animal of each sex in the respective test group is usually evaluated in case an animal dies in its test group spontaneously.
The study was considered valid as the following criteria are met:
- the negative controls are in the range of our historical control data.
- the positive controls are in the range of our historical control data.
- at least 5 animals per group and sex can be evaluated
- PCE to erythrocyte ratio should not be less than 20 % of the negative control. - Statistics:
- (nonparametric Mann-Whitney test)
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- other: see vehicle control
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
In a pre-experiment 4 animals (2 males, 2 females) received orally a single dose of 2000 mg/kg b.w. GENOCURE*MBB formulated in 30% DMSO / 70% PEG 400. The volume administered was 10 mL/kg b.w..
The animals treated with 2000 mg/kg b.w. expressed toxic reactions as shown in the table:
toxic hours post-treatment
reactions male / female
1 h 2-4 h 6 h 24 h 30 h 48 h
ruffled fur 2/2 2/0 0/0 0/0 0/0 0/0
On the basis of these data 2000 mg/kg b.w. were estimated to be suitable.
RESULTS OF DEFINITIVE STUDY
In the main experiment for the highest dose group 24 animals (12 males, 12 females) received orally a single dose of 2000 mg/kg b.w. GENOCURE*MBB formulated in 30% DMSO / 70% PEG 400. The volume administered was 10 mL/kg b.w..
The animals treated with 2000 mg/kg b.w. expressed toxic reactions as shown in the table:
Toxic hours post-treatment
hours post-treatment
Reactions male / female
1 h 2-4 h 6 h 24 h 48 h*
ruffled fur 12/12 12/12 12/12 3/1 1/0
*: data only from 6 animals per sex.
For the mid dose group 12 animals (6 males, 6 females) received orally a single dose of 1000 mg/kg b.w. GENOCURE*MBB formulated in 30% DMSO / 70% PEG 400. The volume administered was 10 mL/kg b.w..
The animals treated with 1000 mg/kg b.w. expressed toxic reactions as shown in the table:
toxic hours post-treatment
reactions male / female
1 h 2-4 h 6 h 24 h
ruffled fur 3/4 4/4 4/4 2/1
For the low dose group 12 animals (6 males, 6 females) received orally a single dose of 500 mg/kg b.w. GENOCURE*MBB formulated in 30% DMSO / 70% PEG 400. The volume administered was 10 mL/kg b.w..
The animals treated with 500 mg/kg b.w. expressed toxic reactions as shown in the table:
toxic hours post-treatment
reactions male / female
1 h 2-4 h 6 h 24 h
ruffled fur 0/0 4/3 4/3 2/1
The animals treated with the vehicle control (30% DMSO / 70% PEG 400) did not express any toxic reactions.
Any other information on results incl. tables
Summary of Micronucleus Test Results
test group |
dose mg/kg b.w. |
sampling time (h) |
PCEs with micronuclei (%) |
range |
PCE per 2000 erythocytes |
||||||
vehicle |
0 |
24 |
0.060 |
0 -4 |
1091 |
||||||
test item |
500 |
24 |
0.075 |
0 -6 |
1025 |
||||||
test item |
1000 |
24 |
0.110 |
0 -5 |
1160 |
||||||
test item |
2000 |
24 |
0.085 |
0 -3 |
1176 |
||||||
positive control |
40 |
24 |
3.205 |
41 -93 |
1166 |
||||||
test item |
2000 |
48 |
0.065 |
0 -4 |
1120 |
1.2 Biometry
Statistical significance at the five per cent level (p < 0.05) was evaluated by means of the non-parametric Mann-Whitney test.
Vehicle control |
Significance |
p |
500 mg GENOCURE*MBB/kg b.w.; 24 h |
- |
0.4170 |
1000 mg GENOCURE*MBB/kg b.w.; 24 h |
- |
0.0769 |
2000 mg GENOCURE*MBB/kg b.w.; 24 h |
- |
0.2041 |
40 mg CPA/kg b.w.; 24 h |
+ |
< 0.0001 |
2000 mg GENOCURE*MBB/kg b.w.; 48 h |
- |
0.5000 |
- = not
significant
+ = significant
Applicant's summary and conclusion
- Conclusions:
- In conclusion, it can be stated that during the study described and under the experimental conditions reported, the test item did not induce micronuclei as determined by the micronucleus test in the bone marrow cells of the mouse.
- Executive summary:
The test item GENOCURE*MBB was assessed in the micronucleus assay for its potential to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse. The test item was formulated in 30% DMSO / 70% PEG 400, which was also used as vehicle control. The volume administered orally was 10 mL/kg b.w.. 24 h and 48 h after a single administration of the test item the bone marrow cells were collected for micronuclei analysis. Ten animals (5 males, 5 females) per test group were evaluated for the occurrence of micronuclei. At least 2000 polychromatic erythrocytes (PCEs) per animal were scored for micronuclei. To describe a cytotoxic effect due to the treatment with the test item the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and reported as the number of PCEs per 2000 erythrocytes.
The following dose levels of the test item were investigated:
- 24 h preparation interval: 500, 1000, and 2000 mg/kg b.w..
- 48 h preparation interval: 2000 mg/kg b.w..
As estimated by a pre-experiment 2000 mg GENOCURE*MBB per kg b.w. (the maximum guideline-recommended dose) was suitable. The mean number of polychromatic erythrocytes was not decreased after treatment with the test item as compared to the mean value of PCEs of the vehicle control indicating that GENOCURE*MBB did not have any cytotoxic properties in the bone marrow. In comparison to the corresponding vehicle controls there was no statistically significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test item. The mean values of micronuclei observed after treatment with GENOCURE*MBB were near to the value of the vehicle control group. 40 mg/kg b.w. Cyclophosphamide administered orally was used as positive control which showed a statistically significant increase of induced micronucleus frequency.
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