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EC number: 875-892-5 | CAS number: 1375799-59-9
- 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
Phototoxicity in vitro
Administrative data
- Endpoint:
- phototoxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Study period:
- 12-01-2012 to 24-07-2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
- Type of study:
- in vitro 3T3 NRU phototoxicity test
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD TG 432 (In Vitro 3T3 NRU Phototoxicity Test)
- Version / remarks:
- 13 April 2004
- GLP compliance:
- yes
Test material
- Reference substance name:
- Sodium 1-[6-(morpholin-4-yl)pyrimidin-4-yl]-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-5-olate
- EC Number:
- 875-892-5
- Cas Number:
- 1375799-59-9
- Molecular formula:
- C13 H14 N8 O2 . Na
- IUPAC Name:
- Sodium 1-[6-(morpholin-4-yl)pyrimidin-4-yl]-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-5-olate
Constituent 1
Test system
Species / strain
- Species / strain / cell type:
- BALB/c 3T3
Controls
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- chloropromazine HCL
- Details on test system and experimental conditions:
- IN VITRO 3T3 NRU PHOTOTOXICITY TEST
INCUBATION BEFORE AND AFTER TREATMENT
- type and composition of culture medium: DMEM (Dulbecco's Modified Eagle's Medium): No. 21885-025, Gibco (Eggenstein, Germany); FBS (Fetal Bovine Serum): No. S 1800, Biowest (Nuaille, France); NCS (Newborn Calf Serum): No. N-4637, Sigma (Deisenhofen); Penicillin/streptomycin solution: No. P-4333, 10000 U/mL Penicillin, 10 mg/mL
Streptomycin, Sigma (Deisenhofen)
- incubation conditions (CO2 concentration, temperature, humidity): The cells were cultivated in a humidified incubator at 37°C and 5% C02.
- duration of incubation (pre- and post-treatment): preincubation time 24h and postincubation time 24h
TREATMENT WITH THE CHEMICAL
- rationale for selection of concentrations of the test chemical used in the presence and in the absence of irradiation: according to OECD test guideline
- in case of limited solubility of the test chemical and absence of cytotoxicity: rationale for the highest concentration tested: The highest dose used for the test item corresponds to the solubility limit in PBS.
- type and composition of treatment medium (buffered salt solution): PBS
- duration of the chemical treatment: 1 h plus 50 min irradiation
IRRADIATION
- rationale for selection of the light source used: UV -lamp equipped with a H1 filter (SoB, Dr. Hönle GmbH, Gräfelfing) with an intensity of 1.7 mW/cm² (5 J/cm²) for 50 min
NEUTRAL RED VIABILITY TEST
- composition of Neutral Red treatment medium: 50 µL per well of a Neutral red stock solution (3.3 g/L) were added to the cell cultures for ca 2h at 37°C.
- incubation conditions (CO2 concentration; temperature; humidity): 37°C, 5%CO2
- Neutral Red extraction conditions (extractant, duration): 50% ethanol, 1% glacial acetic acid
- wavelength used for spectrophotometric reading of Neutral Red optical density: 540 nm, reference 630 nm - Vehicle:
- yes
- Vehicle / solvent:
- DMSO
- Evaluation criteria:
- Phototoxicity determination
With the software "Phototox Version 2.0" (Federal Institute of Risk Assessment, Berlin), a Photo-Irritation-factor (PIF) was calculated directly from the raw data per single assay. PIF is defined as the ratio of the half effective concentration for cytotoxicity (EC50) without (-UV) and with UV-irradiation (+UV). In an iterative process, whereby datapoints were randomly excluded in each round, many - and +UV concentration response curves models were approximated, yielding mathematically determined EC50 values. Pairing each curve of the -UV experiment with each curve of the +UV experiment resulted in a set of PIFs. These were averaged and given as PIF Mean per assay, which is the output of the software. An overall average PIF was then be calculated from the 3 replicate assays. Based on the validation study (Spielmann et al. 1998), a test substance with a PIF ≤ 2 predicts "no phototoxicity", a PIF > 2 and< 5 predicts "probable phototoxicity", and a PIF ≥ 5 predicts "phototoxicity".
Results and discussion
- Key result
- Results:
- IN VITRO 3T3 NRU PHOTOTOXICITY TEST
- cell viability obtained at each concentration of the test chemical, expressed in percent viability of mean, concurrent solvent controls:
- concentration response curves (test chemical concentration vs. relative cell viability) obtained in concurrent +Irr and –Irr experiments:
- analysis of the concentration-response curves:
- computation/calculation of IC50 (+Irr) and IC50 (-Irr):
- comparison of the two concentration response curves obtained in the presence and in the absence of irradiation, either by calculation of the Photo-Inhibition-Factor (PIF), and/or by calculation of the Mean-Photo-Effect (MPE) depending on the dose-response curve:
In the present study the phototoxic potential of the test substance was investigated at the concentrations 0.1 µg/mL, 1 µg/mL, 3 µg/mL, 10 µg/mL, 30 µg/mL, 100 µg/mL 300 µg/mL, 500 µg/mL. Chlorpromazine hydrochloride (from 0.01- 100 µg/mL) was used as a positive control. The three independent assays with the test item yielded an average PIF = 1. Molidustat was thus identified as a non-phototoxic compound.
After treatment of the cells with chlorpromazine hydrochloride the average PIF was 27. Thus, as expected, chlorpromazine hydrochloride was identified as a phototoxic compound
For more detailed results please refer to 'Any other information on results incl. tables'
Any other information on results incl. tables
| PIF Mean per assay |
|
| ||
Compound | Assay 1 | Assay 2 | Assay 3 | Average PIF | Evaluation |
Test item | 1.119 | 0.923 | 1.055 | 1.032 | non-phototoxic |
Chlorpromazine-HCl | 29.999 | 25.476 | 26.752 | 27.409 | phototoxic |
Applicant's summary and conclusion
- Validity criteria fulfilled:
- not applicable
- Conclusions:
- The three independent assays with Molidustat yielded an average PIF = 1, thus, it was identified as a non-phototoxic compound.
- Executive summary:
In the present test conducted according to OECD test guideline 432, mouse fibroblasts were exposed to the test item in DMSO and to Chlorpromazine hydrochloride as positive control at concentrations of 0.1 µg/mL, 1 µg/mL, 3 µg/mL, 10 µg/mL, 30 µg/mL, 100 µg/mL 300 µg/mL, 500 µg/mL and Chlorpromazine hydrochloride (from 0.01- 100 µg/mL)), for 1h before radiation with a UV-lamp for 50 min. After a post-incubation period of 24h the viability was determined using neutral red. Each assay was performed in triplicate. Based on the validation study (Spielmann et al. 1998), a test substance with a PIF ≤ 2 predicts "no phototoxicity", a PIF > 2 and< 5 predicts "probable phototoxicity", and a PIF ≥ 5 predicts "phototoxicity", Molidustat was non-phototoxic under the conditions of the test.
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