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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 203-744-6 | CAS number: 110-18-9
- 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
- Study period:
- 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- July 1997
- Deviations:
- no
- GLP compliance:
- no
- Remarks:
- published summary of a GLP study
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Purity: 99.86%
CAS number: 110-18-9
Supplied by MACH 1 Inc., King of Prussia, PA - Target gene:
- Reversion to histidine / tryptophan independence
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254 induced rat liver S9
- Test concentrations with justification for top dose:
- 5000 ug/mL, the maximum concentration as cited in the guideline.
- Vehicle / solvent:
- Water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- methylmethanesulfonate
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- Bacterial salmonella strains were received from Dr. Ames (University of California) and Escherichia coli strain was obtained from Pharmacia and Upjohn Co., Kalamazoo, Michigan.
S-9 mix or water was added to tubes containing 2.0 mL of top agar supplemented with histidine-biotin or tryptophan. An aliquot of the bacteria was added (0.1 mL) followed by the test article or vehicle control. The tube was mixed for 2-3 seconds and the contents were evenly distributed over a Vogel-Bonner bottom agar plate. The plates were allowed to set and the plates were inverted and incubated at 37 degrees C for 72 hours. The revertant colonies were counted using automated scoring. - Evaluation criteria:
- Positive response was considered to be an increase in revertant number of 2-fold (strains TA98 and TA100) or 3-fold (strains TA1535, TA1537 and WP2 uvrA) the concurrent control.
- Statistics:
- None.
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- 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:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- TMEDA did not induce increases in the number of revertants for any tester strains in the presence or in the absence of metabolic activation when tested in strains TA98, TA100, TA1535, TA1537 and WP2 uvrA.
- Executive summary:
An Ames test was conducted with TMEDA in accordance with OECD test guideline 471. Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli strain WP2 uvrA were tested in the absence and in the presence of aroclor 1254 induced rat liver S9 fraction. Plate incorporation methodology was employed. TMEDA showed no increases in revertant number which were 2 -fold the concurrent control (strains TA98 and TA100) of 3 -fold the concurrent control (strains TA1535, TA1537 and WP2 uvrA) when tested in two independent assays. TMEDA has shown no evidence of mutagenicity when tested up to 5000 ug/plate, the maximum concentration specified in the guideline.
Results in the absence of S-9 mix
Treatment (mcg/plate) |
Mean revertants per plate |
||||
TA98 |
TA100 |
TA1535 |
TA1537 |
WP2 uvrA |
|
0 (vehicle) |
23 |
111 |
20 |
9 |
16 |
500 |
19 |
102 |
10 |
7 |
16 |
750 |
23 |
90 |
14 |
6 |
16 |
1000 |
22 |
101 |
17 |
5 |
18 |
3000 |
18 |
103 |
10 |
5 |
18 |
5000 |
20 |
117 |
10 |
8 |
22 |
Positive control |
765 |
525 |
759 |
608 |
520 |
Results in the presence of S-9 mix
Treatment (mcg/plate) |
Mean revertants per plate |
||||
TA98 |
TA100 |
TA1535 |
TA1537 |
WP2 uvrA |
|
0 (vehicle) |
37 |
65 |
20 |
11 |
23 |
500 |
29 |
69 |
20 |
6 |
21 |
750 |
3 |
83 |
22 |
11 |
18 |
1000 |
40 |
84 |
23 |
19 |
26 |
3000 |
34 |
69 |
22 |
13 |
22 |
5000 |
37 |
106 |
18 |
8 |
18 |
Positive control |
1019 |
583 |
334 |
354 |
229 |
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2010
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- no
- Remarks:
- published summary of a GLP study
- Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- Purity: 99.86%
CAS number: 110-18-9
Supplied by MACH 1 Inc., King of Prussia, PA - Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Remarks:
- Clone CHO-W-B1
- Cytokinesis block (if used):
- Colcemid (0.1 ug/mL) was present during the final two hours of incubation.
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/B-naphthoflavone-induced rat hepatic S9 fraction
- Test concentrations with justification for top dose:
- Seven concentrations ranging from 10 to 5000 mcg/mL in the Range-Finder Experiment
Concentrations of 50, 100, 500, 1000, 2500 and 5000 mcg/mL in the Main Experiment - Vehicle / solvent:
- Water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- The cells were suspended in cell culture medium (McCoy's 5A). A 5 mL sample was seeded into a T-25 tissue culture flask. The flasks were incubated at 37°C for 20-24 hours prior to treatment. The cells were exposed to the test article for 3 hours. The medium was removed and the cells were rinsed with phosphate buffer solution, replenished with 5 mL of fresh medium and incubated for an additional 15 hours. Colcemid (0.1 mcg/mL) was present during the final two hours. The monolayer of cells was dissociated with 0.05% trypsin and resuspended in medium. An aliquot of cell suspension was counted using an electronic cell counter. The number of cells per flask was calculated for each concentration and the relative cell growth (RCG) was calculated as a percentage of the number of cells in the test flask divided by the number of cells in the solvent flask. The remaining cell suspension was collected by centrifugation (800 rpm), ruptured in 0.075M KCl and fixed with methanol:glacial acetic acid (3:1) and dropped onto microscope slides. The slides were air-dried, stained with 5% Giemsa and mounted in Cytoseal using cover glasses. The slides were scored for Mitotix Index (MI). For each concentration, 1000 cells were scored and the numbers of dividing cells were recorded. The MI and Relative Mitotic Index (RMI) for each concentration was calculated as follows:
MI=number of dividing cells from 1000 cells divided by 10.
RMI=test concentration MI divided by solvent control MI expressed as a percentage.
Cytotoxicity was evaluated on the basis of the reduction in RCG and/or RMI. Chromosome aberrations were scored from 3 concentrations of test material, the vehicle and positive control. Two hundred 200 metaphases were scored from each concentrations and the controls. - Evaluation criteria:
- The test material was considered to have caused a positive response in this assay if the test article showed a positive concentration response trend and a statistically significant increase over the solvent controls in the percentage of cells with chromosome aberrations, at one or more concentrations.
- Statistics:
- Chi-squared test was used for statistical analysis
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- A positive response was seen only at the highest concentration tested, which exceeds the highest recommended concentration in the current guideline of 10mM, equivalent to 1140 mcg/mL.
- Remarks on result:
- other:
- Remarks:
- Clastogenic
- Conclusions:
- TMEDA was negative in this assay when tested up to 2500 mcg/mL, a concentration which exceeds the highest concentration of 10mM based on the OECD test guideline 473. TMEDA was positive only at 5000 mcg/mL, a concentration which far exceeded the 10mM concentration in the OECD TG.
- Executive summary:
TMEDA was assessed for clastogenicity in an in vitro chromosomal aberration study in CHO cells based on OECD test guideline 473. Concentrations of 1000, 2500 and 5000 ug/mL were examined for chromosome aberrations in the absence and in the presence of S-9 following a 3 hour treatment and 15 hour recovery. The increases in the number of aberrations at 5000 ug/mL in the absence and presence of S-9 were statistically significant compared to the concurrent vehicle controls when data were analysed at the 5% level using the Chi-squared test. However, test concentrations of 1000 and 2500 ug/mL showed no statistically significant increases in the number of aberrations. The highest concentration recommended by the OECD guideline 5000 ug/mL, 5 mcL/mL or 10mM, whichever is the lowest. A concentration of 10 mM is equivalent to 1140 ug/mL. TMEDA is considered to be not clastogenic when tested up to 2500 ug/mL, a concentration which exceeds the maximum concentration recommended for this assay.
Chromosomal aberration in the absence of S-9 mix
Treatment |
Relative cell growth |
Percentage of aberrations (mean ± standard deviation) |
0 (water) |
100 ± 0 |
0.5 ± 0.7 |
1000 ug/mL |
160 ± 10 |
1.0 ± 0.0 |
2500 ug/mL |
117 ± 8 |
1.5 ± 0.7 |
5000 ug/mL |
90 ± 8 |
13.5 ± 5.0a |
Positive control |
67 ± 10 |
40.5 ± 0.7a |
a Statistically significant (p<0.05)
Chromosomal aberrations in the presence of S-9 mix
Treatment |
Relative cell growth |
Percentage of aberrations (mean ± standard deviation) |
0 (water) |
100 ± 19 |
1.5 ± 0.7 |
1000 ug/mL |
75 ± 0 |
0.5 ± 0.7 |
2500 ug/mL |
88 ± 1 |
2.0 ± 2.8 |
5000 ug/mL |
67 ± 3 |
12.0 ± 0.0a |
Positive control |
63 ± 1 |
35.5 ± 3.5a |
a Statistically significant (p<0.05)
Data source
Reference
- Reference Type:
- publication
- Title:
- Genotoxicity assessment of two hypergolic energetic propellant compounds
- Author:
- Reddy G, Song J, Mecchi MS & Johnson MS
- Year:
- 2 010
- Bibliographic source:
- Mutation Research 700: 26-31
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- not specified
- Remarks:
- published summary of a GLP study
- Type of assay:
- other: In vivo mouse micronucleus assay
Test material
- Reference substance name:
- N,N,N',N'-tetramethylethylenediamine
- EC Number:
- 203-744-6
- EC Name:
- N,N,N',N'-tetramethylethylenediamine
- Cas Number:
- 110-18-9
- Molecular formula:
- C6H16N2
- IUPAC Name:
- [2-(dimethylamino)ethyl]dimethylamine
- Test material form:
- liquid
- Details on test material:
- clear, colourless to pale yellow
Constituent 1
- Specific details on test material used for the study:
- Purity: 99.86%
CAS number: 110-18-9
Supplied by MACH 1 Inc., King of Prussia, PA
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on species / strain selection:
- No further details reported.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Source: Harlan Sprague Dawley, Inc
Diet: Purina Certified Rodent Diet
Water: Tap water; ad libitum
Room temperature: 17 to 23°C
Humidity: 17-54%
Photoperiod: 12 hour light/dark cycle
Acclimatisation period: At least 7 days prior to testing
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Water
- Details on exposure:
- The estimated maximum tolerated dose was 250 mg/kg bw based on an initial dose range-finding test which was conducted with 5, 10, 50, 100, 200 and 300 mg/kg bw with three mice/sex/group. The maximum dose volume was 10 mL/kg bw.
- Duration of treatment / exposure:
- Single dose
- Frequency of treatment:
- Once
- Post exposure period:
- 24 and 48 hours
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Vehicle control
- Dose / conc.:
- 62.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 125 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Five
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide 80 mg/kg bw
Examinations
- Tissues and cell types examined:
- Bone marrow smears prepared and allowed to air dry.
Polychromatic erythrocytes (PCE) and Normochromatic erythrocytes (NCE) examined. - Details of tissue and slide preparation:
- Bone marrow smears allowed to air dry. The slides were fixed in methanol, stained in Wright-Giemsa stain, rinsed in distilled water, allowed to air dry completely and mounted in Cytoseal using cover glasses.
- Evaluation criteria:
- The test material was considered to have caused a positive response in the assay if the material showed a positive dose-response trend and a statistically significant increase in the number of micronucleated polychromatic erythrocytes. at one or more dose levels, relative to that of the concurrent vehicle control. In the event that a statistically significant increases was observed with an unusually low number of micronucleated polychromatic erythrocytes (less than 0.05%) in the concurrent vehicle control, the data from that dose was compared to the historical control data. In the event that there was no positive dose-response trend, at least two consecutive test doses must have produced a statistically significant increase in the number of micronucleated polychromatic erythrocytes to be considered positive. The test article was considered to have caused a negative response if none of the test doses showed a statistically significant increase in the number of micronucleated polychromatic erythrocytes when compared to the vehicle control.
- Statistics:
- The slides were scored blind. The number of polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) among 2000 erythrocytes (PCE+NCE) per animal was determined. The number of micronucleated polychromatic erythrocytes (MPCE) was then determined for 2000 PCE per animal. Data were analysed separately for male and female animals. The frequency of MPCE in each dose group was compared to that in the respective vehicle control group using a one-tailed Student's t-test.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- There were no statistically significant increases in the number of MnPCEs in the treated groups at any dose level for either 24 or 49-hour harvest time as compared to the concurrent vehicle control group or the historical vehicle control group. There was no reduction in the percentage of PCEs at any dose level for either harvest time of more than 20% which would be an indicator of toxicity. The positive controls showed a statistically significant increase at the 5% level in the number of MnPCEs when comapared to the concurrent vehicle controls using the Students t-test.
Any other information on results incl. tables
Micronucleus data for 24-hour harvest
Sex |
Dose (mg/kg bw) |
Number of MN PCEs/2000 PCEs (mean ± standard deviation) |
NCE/PCE per animal (mean ± standard deviation) |
Male |
0 (water) |
0.6 ± 0.5 |
0.6 ± 0.1 |
62.5 |
0.4 ± 0.5 |
0.8 ± 0.3 |
|
125 |
0.8 ± 0.8 |
0.6 ± 0.2 |
|
250 |
0.4 ± 0.5 |
0.9 ± 0.2 |
|
Positive control |
28.8 ± 4.8a |
0.3 ± 0.1 |
|
Female |
0 (water) |
0.0 ± 0.0 |
0.7 ± 0.2 |
62.5 |
0.6 ± 0.5 |
0.9 ± 0.3 |
|
125 |
0.0 ± 0.0 |
0.7 ± 0.2 |
|
250 |
0.6 ± 0.5 |
0.6 ± 0.1 |
|
Positive control |
23.2 ± 6.8a |
0.8 ± 0.1 |
a Statistically significant increases when data were compared to the vehicle control using the Students t-test at the 5% level.
Micronucleus data for 48-hour harvest
Sex |
Dose (mg/kg bw) |
Number of MN PCEs/2000 PCEs (mean ± standard deviation) |
NCE/PCE per animal (mean ± standard deviation) |
Male |
0 (water) |
0.8 ± 0.4 |
1.5 ± 0.4 |
62.5 |
2.2 ± 1.3 |
0.9 ± 0.2 |
|
125 |
0.0 ± 0.0 |
1.4 ± 0.1 |
|
250 |
0.4 ± 0.9 |
1.2± 0.3 |
|
Female |
0 (water) |
0.0 ± 0.0 |
1.3 ± 0.1 |
62.5 |
0.0 ± 0.0 |
1.4 ± 0.2 |
|
125 |
0.2 ± 0.4 |
1.3 ± 0.2 |
|
250 |
0.8 ± 0.4 |
1.3 ± 0.4 |
Applicant's summary and conclusion
- Conclusions:
- The results indicate that TMEDA is negative in this assay.
- Executive summary:
An in vivo micronucleus study was conducted with CD-1 mice using TMEDA dose levels of 0, 62.5, 125 or 250 mg/kg bw. Bone marrow sampling was conducted at 24 and 48 hours post administration. Five mice of each sex were treated for each concentration and sampling time. An additional 5 mice of each sex were treated with the positive control, cyclophosphamide, with a sampling time of 24 hours. There were no statistically significant increases in the number of micronucleated polychromatic erythrocytes for any of the TMEDA treated animals when compared to the concurrent vehicle control treatments or the historical vehicle control ranges. The positive control treated animals showed a statistically significant increase in the number of micronucleated polychromatic erythrocytes. The overall conclusion was that TMEDA had shown no evidence of cytogenicity under the conditions of this study.
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.