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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 204-398-9 | CAS number: 120-46-7
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- genetic toxicity in vivo, other
- Remarks:
- In vivo mammalian Alkaline Comet Assay
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian comet assay
Test material
- Reference substance name:
- 1,3-diphenylpropane-1,3-dione
- EC Number:
- 204-398-9
- EC Name:
- 1,3-diphenylpropane-1,3-dione
- Cas Number:
- 120-46-7
- Molecular formula:
- C15H12O2
- IUPAC Name:
- 1,3-diphenylpropane-1,3-dione
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- WI(Han)/ young healthy adult
- Details on species / strain selection:
- iat. Rattus norvegicus
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Body weight: males 239 – 282 g. The weight variation at the commencement of treatment did not exceed ± 20% of the mean weight.
The animals were derived from a controlled full barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare [9] the animals were bred for experimental purposes and underwent an adequate acclimatisation period after arrival (at least five days). The animals were distributed into test groups at random.
Environment: Temperature 19-25°C
Relative humidity 55 10%
Artificial light 6:00 - 18:00
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- PEG400 as vehicle of the test item was used as negative control. All control animals were handled in an identical manner to the test group subjects. The sampling time for the solvent control was 4 h after the second treatment.
Name: PEG400
Supplier: Sigma
Batch No.: MKBZ9899V
Route and frequency of
Administration: oral, twice within 24 h
Volume administered: 10 mL/kg bw
Sampling time: 28 h
Expiry date: 05/2017
Negative and solvent control groups were included to verify the test results as the assay was newly established at the testing facility with few historic control data - Details on exposure:
- The maximum dose applied in the pre-experiment was 2000 mg/kg bw/d according to OECD 489 [5]. The maximum volume administered was 10 mL/kg bw. The animals received the test item twice at 0 h and 24 h after the first application.
- Frequency of treatment:
- oral, twice within 24 h
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw/day
- Dose / conc.:
- 1 000 mg/kg bw/day
- Dose / conc.:
- 2 000 mg/kg bw/day
- No. of animals per sex per dose:
- 5 males and/or females per dose group
- Control animals:
- yes
- Positive control(s):
- Name: EMS; ethyl methanesulfonate
CAS No.: 62-50-0
Supplier: Sigma
Batch No. BCBS6100V
Dissolved in: NaCl (0.9 %)
Dosing: 200 mg/kg bw
Route and frequency of administration: oral, single dose
Volume administered: 10 mL/kg bw
Sampling time: 4 h
Expiry date: 11/2017
Examinations
- Tissues and cell types examined:
- liver, duodenum and stomach
- Details of tissue and slide preparation:
- Cells from liver, duodenum and stomach were isolated, embedded in agarose, lysed and DNA allowed to migrate under electrophoresis conditions. 150 cells per animal tissue were evaluated if possible. DNA migration during electrophoresis was determined and expressed as tail intensity.
- Evaluation criteria:
- Liver, stomach and duodenum were evaluated because the former is the primary organ for the metabolism of absorbed chemicals, and the two latter are a site of first contact of chemicals after oral administration.
According to literature reference data, the acceptance criteria of the negative control group should be between 1-8% tail intensity in the liver and between 1-30% (preferably 1-20%) tail intensity in the stomach. No data are yet available from the JaCVAM trial for duodenum cells. However, the control range of stomach cells will be taken as a basis for duodenum cells as both organs consist of epithelial cells. All tail intensities of the negative and solvent control of this study were within the reference data of the JaCVAM trial. Therefore, the concurrent data were accepted for addition to the laboratory historical control data
The historical data of the negative control group showed the following values:
The evaluation of different rat cells of the negative control group revealed a tail intensity of 0.78 – 5.03% (LCL and UCL of liver cells), 4.25 – 7.00% (LCL and UCL of stomach cells) and 4.66 – 5.87% (LCL and UCL of duodenum cells) The values of the negative control group in the different organs were all within the historic ranges. The tail intensities of each treatment group and organ will be discussed in detail in the following sections.
For statistical analysis One-way ANOVA with Dunnett’s test was performed to verify the results. To test for normality, Kolmogorov-Smirnov-test was done. Statistically significant differences in DNA damage (p < 0.05) were marked with an (related to the solvent control) or Δ (related to the negative control) in the following figures. A linear trend test to determine statistical significances at the 5% level (p < 0.05) was performed to test whether there is a concentration-related increase in DNA damage. - Statistics:
- All slides, including those of positive, negative and solvent controls were independently coded before microscopic analysis. The median %tail DNA for each slide was determined and the mean of the median values was calculated for each animal [18]. The mean of the individual animal means was then determined to give a group mean. Statistical analysis was done using a variety of approaches
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- not valid
- Negative controls validity:
- not valid
- Positive controls validity:
- valid
Any other information on results incl. tables
negative control | solvant control | 500 mg/kg bw | 1000 mg/kg bw | 2000 mg/kg bw | |||
liver cells | 1.88% | tail intensity of 5.65% | male: 5.68% | male: 6.36% | male: 2.17% | ||
Stomach Cells | 6.38% | 9.15% | male: 7.46% | male: 10.23% | male: 8.16% | ||
Duodenum Cells: | 5.05% | 10.48% | male: 7.24% | male: 4.68% | male: 4.06% |
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 1,3-diphenylpropane-1,3-dione did not induce biologically relevant DNA-strand breaks in rodent liver, duodenum and stomach cells after oral administration of rats.
Therefore, 1,3-diphenylpropane-1,3-dione is considered to be non-DNA damaging under these experimental conditions in the in vivo mammalian Alkaline Comet Assay. - Executive summary:
This study was performed to assess the genotoxic potential of 1,3-diphenylpropane-1,3-dione by measuring the ability to induce DNA-strand breaks in different organs of rats (liver, duodenum and stomach). The organs were selected to cover two first-contact organs (stomach and duodenum) upon peroral exposure and liver as theprimary organ for the metabolism of absorbed chemicals.
The test item was suspended in PEG400and applied to 5 male rats by daily gavage at10 mL/kg bw (body weight) for two days. The organs were collected 4 h after the second application of the test item.
Basedon the outcome of a dose range finding study, a dose of 2000 mg/kg bw was selected as maximum tolerated dose (MTD).
In the main experiment three dose levels (500, 1000 and 2000 mg/kg bw/d) were used covering a range from the maximum tolerated dose to little or no toxicity.
The animals treated with a dose of 1 MTD showed slight signs of systemic toxicity (reduction of spontaneous activity). Slight diarrhea was observed in the solvent and test item dose groups in the main experiment after the second application. As the test item was resuspended in the solvent PEG400 and the symptom was also present in the solvent control group, the diarrhea was induced by the solvent and not related to the test item.
Cells from liver, duodenum and stomach were isolated, embedded in agarose, lysed and DNA allowed to migrate under electrophoresis conditions.150 cells per animal tissue were evaluated if possible.DNA migration during electrophoresis was determined and expressed as tail intensity. The tail intensities of each concentration and tissue per sex are summarised inTable 1.
The validity criteria were met:
Negative controls fell into the historic control range of the test facility and were within the literature reference data[18]for theacceptance criteria of the negative control group.
The tail intensities of the concurrent solvent controls were within the ranges of the reference data set[18]. Therefore, the data were accepted for addition to the laboratory solvent control data set.
Ethyl methansulfonate (200 mg/kg bw) administered orally was used as positive control, which induced a statistically significant increase in DNA damage for all evaluated organs compared to the solvent control group or negative control group.
In liver and stomach cells, the test item values were in the same range as the corresponding solvent control group. In duodenum cells, the solvent control was increased, however the tail intensities of the middle and high test item dose group were lower than the negative control. As the tail intensities induced by the test item were all within the literature reference data[18]and no biologically relevant increase of tail intensity were found after treatment with the test item in any of the dose groups evaluated as well asin absence of a dose-response,the test item did not induce DNA damage under the conditions tested.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)