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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 616-392-7 | CAS number: 76820-34-3
- 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:
- 19.8 .- 7.10.2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- N,N'-bis(2,3-dihydroxypropyl)-5-nitrobenzene-1,3 dicarboxamide
- EC Number:
- 616-392-7
- Cas Number:
- 76820-34-3
- Molecular formula:
- C14H19N3O8
- IUPAC Name:
- N,N'-bis(2,3-dihydroxypropyl)-5-nitrobenzene-1,3 dicarboxamide
- Reference substance name:
- Unknown impurities
- Molecular formula:
- Not available
- IUPAC Name:
- Unknown impurities
- Test material form:
- solid
Constituent 1
impurity 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00601016
- Expiration date of the lot/batch: 03/2022
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
- Stability under test conditions: Stable
Method
- Target gene:
- gene for histidine or tryptophan synthesis
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- supernatant of rat liver and a mixture of cofactors
- Test concentrations with justification for top dose:
- 50, 150, 500, 1500, 5000 μg
The maximum test item concentration used has been determined with respect to results of previous cytotoxicity test. - Vehicle / solvent:
- Water for injection, water for injection, Ardeapharma lots 1706090515 and 1706090516, exp. 12/2019
- Justification for choice of solvent/vehicle: solubility of the substance
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- N-ethyl-N-nitro-N-nitrosoguanidine
- other: 4-nitro-o-phenylenediamine, 2-aminofluorene, 2-aminoanthracene
- Details on test system and experimental conditions:
- Salmonella typhimurium come from Czech Collection of Microorganisms (CCM), Brno (CZ). Lots of strains used for this study are: TA 1535 CCM Cat. No. 3814, lot. No. 2101200916917, TA 98, Cat. No. CCM 3811, lot No. 0102201220053, TA 100 Cat. No.CCM 3812, lot No. 0102201220054 and TA 1537 Cat. No. CCM 3815, lot No. 2101200916918.
Escherichia coli WP2 uvrA was obtained from Xenometrix (lot No. U20).
NUMBER OF REPLICATIONS: two series
DETERMINATION OF CYTOTOXICITY: The cytotoxicity experiment was performed in Salmonella typhimurium TA 100 as plate incorporation test without metabolic activation and at concentrations 10, 100, 500, 1000, 2500 and 5000 μg per plate, which were applied to plates in volume of 0.1 mL. - Evaluation criteria:
- The main criterion used for the evaluation of reversion results was a modified two-fold increase rule, which is compatible with the application of statistical methods. Per this rule, the result is positive if a reproducible dose-response effect occurs and/or a doubling of the ratio Rt/Rc is reached (Rt – number of revertants at tested dose, Rc – number of revertants of the solvent control).
An increase is considered as ”biologically relevant“:
- if the number of reversions is at least twice as high as that in the solvent control for the strains having spontaneous reversion >10;
- if the number of reversions is at least three times as high as that in the solvent control for the strains having spontaneous reversion ≤10;
A test item producing neither a dose-related increase in the number of revertants nor a reproducible biologically relevant positive response at any of the dose groups is considered to be non-mutagenic in this system. - Statistics:
- According to OECD TG 471, the biological relevance is the criterion for the interpretation of results, and a statistical evaluation of the results is not necessary.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- HISTORICAL CONTROL DATA: Spontaneous reversions, solvent controls and positive controls were compared with historical controls in the laboratory (see table below).
ADDITIONAL INFORMATION ON CYTOTOXICITY:
The test item was dissolved in water for injection up to the highest concentration recommended in the OECD TG 471 – 5 mg per 0.1 millilitre (plate). For cytotoxicity experiment the highest concentration was diluted to the other 5 concentrations within the range of 3 orders of magnitude. The concentration series was tested for toxicity in strain TA 100 without metabolic activation. Neither cytotoxicity nor precipitation was observed in any concentration.
Any other information on results incl. tables
TableA:Current historical ranges ofrevertant numbers in bacterial strains used in the studyand live bacteria count used in experiments
Control
Strain |
Spont.rev. |
water |
PC - S9 |
PC + S9 |
Number of CFU/mL |
S.t. TA 100 |
69-177 (859) |
74-169 (357) |
341-597 (44) |
875-3015 (40) |
2.03*109 1.46.109 |
S.t. TA 1535 |
9-29 (669) |
8-29 (312) |
434-730 (40) |
64-420 (38) |
1.82*109 |
S.t. TA 98 |
13-49 (915) |
13-49 (356) |
1310-3346 (42) |
1904-5024 (42) |
1.76*109 |
S.t. TA 1537 |
5-21 (710) |
6-20 (279) |
1419-4139 (38) |
5-405 (31) |
1.37*108 4.00*109 |
E.c. WP2 uvrA |
11-51 (691) |
12-51 (281) |
479-1919 (39) |
216-1056 (12) |
7.25*109 5.50.109 |
Applicant's summary and conclusion
- Conclusions:
- Under the above-described experimental design, the test item, NBA-A, was non mutagenic for all the used indicator strains in experiments with and without metabolic activation. Change of experimental conditions performed in the second experiments had no influence on effect detected.
- Executive summary:
The test item, NBA-A, was assayed for the mutagenicity by the Bacterial Reverse Mutation Test. The test was performed according to EU method B.13/14 Mutagenicity – Reverse mutation test using bacteria, which is analogous to the OECD Test Guideline No. 471.
Four indicator Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and one indicator Escherichia coli WP2 uvrA strain were used. The test item was diluted in water for injection and assayed in concentrations 50, 150, 500, 1500 and 5000 μg per plate. The maximum test item concentration used has been determined with respect to results of previous cytotoxicity test.
The first mutagenicity experiments were performed as plate incorporation test without and with the metabolic activation using a supernatant of rat liver (volume of S9 was 30 μL per plate) and a mixture of cofactors by the plate incorporation test with a dose range of 50-5000 μg per plate, which were applied to plates in volume of 0.1 mL.
In the of first series of mutagenicity experiments no cytotoxicity, precipitation or signs of mutagenicity were observed.
In the second experiments the same concentrations were used but experiments were performed with 30 minutes of pre-incubation at 37±1°C and the metabolic activation was slightly modified (volume of S9 increased to 50 μL per plate). Experimental conditions were changed due to improve the contact of bacteria with the test item and metabolic activation, according to OECD requirements.
The concurrent positive controls verified the sensitivity of the assay and the metabolising activity of the liver preparations. Average revertant colony counts for the vehicle controls were within the current historical control range for the laboratory.
In the arrangement given above, the test item, NBA-A, was non-mutagenic for all the used indicator strains in experiments with and without metabolic activation.
Change of experimental conditions performed in the second experiments had no influence on effect detected.
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.