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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
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
Study report: ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993; conducted with male and female Wistar rats; result: NOAEL = 2 mg/kg bw based on postimplantation losses and general toxicity in males.
Study report: ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993; conducted with inseminated female Wistar rats; result: NOAEL = 10 mg/kg bw based on postimplantation losses.
Study report: ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993; conducted with female Himalayan rabbits; result: NOAEL = 20 mg/kg bw based on absence of effects up to the highest dose.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993
- Version / remarks:
- 1993
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- (Hsd Cpb:WU)
- Route of administration:
- oral: gavage
- Vehicle:
- other: ethanol/Solutol ® HS 15/demineralized water (1:4:5 v/v/v)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was administered by gavage in ethanol/Solutol® HS 15/demineralized water (1:4:5 v/v/v). The purity was taken into account. The administration volume was 10 mL/kg body weight. The formulations were prepared as needed taking into account the analytically determined stability. The test substance was administered as a suspension in the vehicle. The formulation was stored at room temperature. It was stirred with a magnetic stirrer for several minutes (until an obviously homogenous distribution occurred) before administration. It was also stirred during administration. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Before start of treatment, the suitability of the formulation was confirmed by the analysis of concentration, homogeneity, and stability of dosage forms prepared in the same way as it was done in the study (0.5 and 5 mg/mL, covering the concentration range used). Analyses were carried out before the start of the study. Homogeneity tests and content checks of the active ingredient in samples with concentrations of 0.3, 1 (content checks, only), and 3 mg/mL were carried out twice during the study.
- Details on mating procedure:
- The animals were mated by placing one or two females overnight into a Type IIIh cage together with one male rat. If sperm was detected in the vaginal smear taken on the morning following mating, this day was regarded as day 0 of gestation.
- Duration of treatment / exposure:
- The females were treated daily from days 6 to 17 of gestation.
- Frequency of treatment:
- daily
- Dose / conc.:
- 30 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 3 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 22 females in the main groups and 4 females in the satellite groups
- Control animals:
- yes, concurrent vehicle
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- pre and post implantation loss
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- placenta
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- fetal/pup body weight changes
- external malformations
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- external: eye
- Developmental effects observed:
- not specified
- Executive summary:
In the present study 22 inseminated female Wistar rats were exposed to 0, 3, 10, and 30 mg/kg bw of the test item in ethanol/Solutol ® HS 15/demineralized water (1:4:5 v/v/v) as vehicle daily from day 6 to day 17 p.c. The fetuses were delivered by cesarean section on day 21 of gestation. Investigation was performed on general tolerance of the test substance by the females as well as on its effect on intrauterine development. Four additional females per group were treated with the doses of 0, 3, 10, and 30 mg/kg from days 6 to 17 p.c. for determination of test substance in the plasma of the females. Appearance, behavior, and mortality were unaffected at dose levels up to 30 mg/kg bw/day. Mean body weight development was decreased at dose level of 30 mg/kg bw/day. Food intake was transiently decreased at the dose levels of 30 mg/kg bw/day. No treatment related gross pathological findings occurred at dose levels up to 30 mg/kg bw/day.
The gestation rate was unaffected by treatment at dose levels up to 30 mg/kg bw/day. Morphological appearance and weight of placentas were only affected by treatment at dose level 30 mg/kg bw/day. Postimplantation loss was increased in dose level 30 mg/kg. Fetal sex distribution was unaffected by treatment at dose levels up to 30 mg/kg bw/day. Weights of fetuses were statistically significantly decreased at dose levels of 30 mg/kg bw/day. Dosing with Molidustat at 30 mg/kg revealed an increased incidence of ocular malformations. A treatment related effect on skeletal deviations was not seen up to a dose level of 30 mg/kg bw/day.
In summary, treatment-related maternal toxicity and developmental toxicity characterized mainly by ocular malformations, reduced fetal weight and increased postimplantation loss were seen at a daily dose of 30 mg/kg of the test item. Consequently, the following no-observed-adverse-effect levels (NOAELs) were determined:
Maternal toxicity: 10 mg/kg bw/day
Developmental toxicity: 10 mg/kg bw/day
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993
- Version / remarks:
- 1993
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Route of administration:
- oral: gavage
- Vehicle:
- other: ethanol/Solutol® HS 15/tap water (1:4:5 v/v/v)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was administered by gavage in ethanol/Solutol ® HS 15/tap water (1:4:5 v/v/v).
The administration volume was 10 mL/kg body weight. The formulations were prepared as needed taking into account the analytically determined stability.
The test substance was administered as a suspension in the vehicle. The formulation was stored at room temperature. It was stirred with a magnetic stirrer for several minutes (until an obviously homogenous distribution occurred) before administration. It was also stirred during administration. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Before the start of treatment, the suitability of the formulation was confirmed by the analysis of concentration, homogeneity, and stability of dosage forms prepared in the same way as it were done in the study (0.15, 0.5, and 5 mg/mL, covering the concentration range used).
Analyses were carried out before the start of the study - Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused: Pairing was performed overnight (from approximately 15.30 to 08.00 CET; on weekends from approximately 12.00 to 08.00 CET), by placing one female rat together with one male rat into a type IIIh Makrolon ® cage. Allocation of the female animals to the relevant male animals was based on the current animal numbers, details of allocation could be found in the raw data. During the two-week mating period each female animal was paired daily. Females with positive sperm detection were not mated again. If sperm was detected in the vaginal smear taken on the morning following mating, this day was regarded as day 0 of gestation.
- M/F ratio per cage: 1/1
- Length of cohabitation: 2 weeks
- Proof of pregnancy: vaginal plug/sprem in vaginal smear referred to as day 0 of pregnancy
- Any other deviations from standard protocol: - Duration of treatment / exposure:
- The male rats were treated daily for 4 weeks prior to mating, during the following mating
period, and up to the day before necropsy. The female rats were treated daily for 2 weeks
prior to mating and during the subsequent mating period. After insemination had been verified (day 0 of gestation), treatment of the females was continued up to and including day 7 p.c. The animals were treated daily between 06.00 and 12.00 CET and received the administration formulations orally by gavage. - Frequency of treatment:
- daily
- Duration of test:
- 4 weeks prior mating until 16th day of gestation
- Dose / conc.:
- 20 mg/kg bw/day (nominal)
- Dose / conc.:
- 6 mg/kg bw/day (nominal)
- Dose / conc.:
- 2 mg/kg bw/day (nominal)
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 24
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The doses were selected on the basis of the results of the 4-week repeat-dose study in rats with doses up to and including 50 mg/kg. The 50 mg/kg dose exceeded the MTD and was associated with mortality and degenerative organ changes due to the strong increase in red blood cell parameters and the impaired hemodynamics.
Thus, 20 mg/kg was chosen as high dose and should result in margins of exposure of about
30-fold of the expected human therapeutic exposure. The low dose of 2 mg/kg should correspond to MoEs of about 3-fold. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other:
- Abnormalities:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Executive summary:
In the present study 24 male and female Wistar rats were exposed to 0, 2, 6, and 20 mg/kg bw of the test item. Males were exposed 4 weeks prior to mating, during mating and up to the days before necropsy. Female rats were treated 2 weeks prior to mating, during mating and after insemination up to and including days 7 p.c. Cesarean sections were performed on days 14 to 16 p.c.
Salivation after administration occurred in males and females of all dose levels, which is most likely caused by the vehicle, since males and females of the current control groups also showed this finding. Four males, 3 of the 20 mg/kg bw group and 1 in the 6 mg/kg bw group were found dead.
Mean food intake and body weight gain was decreased in animals of the 20 mg/kg bw level in males and during the first week of treatment in males and females at 6 mg/kg bw. Generalized enlarged blood vessels occurred in males and females at dose levels of 6 mg/kg and 20 mg/kg. Testes weights and ovary weights were unaffected by treatment. Insemination, fertility, and gestation indices were not affected by treatment with the test item at dose levels up to 20 mg/kg bw/day. The mean number of corpora lutea and thus the mean number of implantation sites were unaffected by treatment with Molidustat at dose levels up to 20 mg/kg.
The mean postimplantation loss was increased at the 20 mg/kg level and an effect cannot be excluded for 6 mg/kg bw treatment due to slight post-implantation losses. The mean number of viable embryos was statistically significantly decreased at the 20 mg/kg level, corresponding to the increased postimplantation loss at this dose level. Thus, the following no-observed-adverse-effect levels (NOAELs) were determined:
Systemic tolerability: 2 mg/kg bw/day
Fertility and early embryonic development: 2 mg/kg bw/day
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993
- Version / remarks:
- 1993
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rabbit
- Strain:
- Himalayan
- Remarks:
- (CRL:CHBB:HM)
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5 % aqueous Tylose MH 300 P2 (methylhydroxyethylcellulose)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was administered by gavage in 0.5 % aqueous Tylose MH 300 P2 (methylhydroxyethylcellulose). The administration volume was 5 mL/kg body weight. The formulations were prepared as needed taking into account the analytically determined stability. The test substance was administered as a suspension in the vehicle. The formulation was stored at room temperature. It was stirred with a magnetic stirrer for several minutes (until an obviously homogenous distribution occurred) before administration. It was also stirred during administration. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Before the start of treatment, the suitability of the formulation was confirmed by the analysis
of concentration, homogeneity, and stability of dosage forms prepared in the same way as it
were done in the study (0.1, 0.5, and 100 mg/mL, covering the concentration range used).
Analyses were carried out before the start of the study. Homogeneity tests and content checks of the active ingredient in samples with concentrations of 0.4, 1.2 (content checks, only), and 4 mg/mL were carried out twice during the study. - Details on mating procedure:
- The male animals were used for mating only and were not treated. After copulation was ascertained, 80 females were allocated to four experimental groups according to a computer generated randomization plan (random number generator, Dell PC, data are filed by Bayer Pharma AG, 42096 Wuppertal).
The mating was performed between 06.00 and 10.00 CET. One male rabbit was mated with one female rabbit under observation. About one hour after the first mating had occurred, the same animals were mated again. It was recorded which female was mated with which male.
The day on which the copulation was observed was considered as day 0 of gestation. - Duration of treatment / exposure:
- The females were treated daily from days 6 to 20 of gestation.
- Frequency of treatment:
- daily
- Duration of test:
- females were sacrificed 21 or 29 days p.c.
- Dose / conc.:
- 20 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 6 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 2 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 20 in the main groups and 3 in the satellite groups
- Control animals:
- yes, concurrent vehicle
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other:
- Abnormalities:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other:
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Executive summary:
In the present study 20 inseminated female Himalayan rabbits were exposed to 0, 2, 6, and 20 mg/kg bw of the test item in 0.5 % aqueous Tylose MH 300 P2 (methylhydroxyethylcellulose) as vehicle daily from day 6 to day 20 p.c. On day 29 of gestation the fetuses were delivered by cesarean section. Investigation was performed on general tolerance of the test substance by the females as well as on its effect on intrauterine development. Three additional females per group were treated with the doses of 0, 2, 6, and 20 mg/kg from days 6 to 20 p.c. for determination of test substance in the plasma of the females.
All parameter measured, such as
in females:
- body weight development
- corrected body weight gain
- appearance, behavior, mortality and gross morphology
- gross pathological findings
in intrauterine development:
- gestation rate
- weight and appearance of Placentas
- postimplantation loss, number of fetuses
- sex of fetuses
- fetal weight
- fetal malformations
- fetal external and visceral deviations
- fetal skeletal deviations
revealed no influence on general tolerance of the test substance by the females as well as on intrauterine development through dosing with Molidustat up to 20 mg/kg bw/day. Summarizing and evaluating all data investigated the following no-observed-adverse-effect levels (NOAELs) were determined:
Maternal toxicity: 20 mg/kg bw/day
Intrauterine development: 20 mg/kg bw/day
Referenceopen allclose all
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 10 mg/kg bw/day
- Study duration:
- subacute
- Experimental exposure time per week (hours/week):
- 7
- Species:
- rat
- Quality of whole database:
- The studies were conducted accoring to ICH guidelines for testing of medical products, thus, the quality of the database is considered high.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Toxicity to reproduction: other studies
Additional information
- body weight development
- corrected body weight gain
- appearance, behavior, mortality and gross morphology
- gross pathological findings
- gestation rate
- weight and appearance of Placentas
- postimplantation loss, number of fetuses
- sex of fetuses
- fetal weight
- fetal malformations
- fetal external and visceral deviations
- fetal skeletal deviations
In one study according to ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993, 24 male and female Wistar rats were exposed to 0, 2, 6, and 20 mg/kg bw of the test item. Males were exposed 4 weeks prior to mating, during mating and up to the days before necropsy. Female rats were treated 2 weeks prior to mating, during mating and after insemination up to and including days 7 p.c. Cesarean sections were performed on days 14 to 16 p.c.
Salivation after administration occurred in males and females of all dose levels, which is most likely caused by the vehicle, since males and females of the current control groups also showed this finding. Four males, 3 of the 20 mg/kg bw group and 1 in the 6 mg/kg bw group were found dead.
Mean food intake and body weight gain was decreased in animals of the 20 mg/kg bw level in males and during the first week of treatment in males and females at 6 mg/kg bw. Generalized enlarged blood vessels occurred in males and females at dose levels of 6 mg/kg and 20 mg/kg. Testes weights and ovary weights were unaffected by treatment. Insemination, fertility, and gestation indices were not affected by treatment with the test item at dose levels up to 20 mg/kg bw/day. The mean number of corpora lutea and thus the mean number of implantation sites were unaffected by treatment with Molidustat at dose levels up to 20 mg/kg.
The mean postimplantation loss was increased at the 20 mg/kg level and an effect cannot be excluded for 6 mg/kg bw treatment due to slight post-implantation losses. The mean number of viable embryos was statistically significantly decreased at the 20 mg/kg level, corresponding to the increased postimplantation loss at this dose level. Thus, the following no-observed-adverse-effect levels (NOAELs) were determined:
Systemic tolerability: 2 mg/kg bw/day
Fertility and early embryonic development: 2 mg/kg bw/day
In a second study according to ICH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993, 22 inseminated female Wistar rats were exposed to 0, 3, 10, and 30 mg/kg bw of the test item in ethanol/Solutol ® HS 15/demineralized water (1:4:5 v/v/v) as vehicle daily from day 6 to day 17 p.c. The fetuses were delivered by cesarean section on day 21 of gestation. Investigation was performed on general tolerance of the test substance by the females as well as on its effect on intrauterine development. Four additional females per group were treated with the doses of 0, 3, 10, and 30 mg/kg from days 6 to 17 p.c. for determination of test substance in the plasma of the females. Appearance, behavior, and mortality were unaffected at dose levels up to 30 mg/kg bw/day. Mean body weight development was decreased at dose level of 30 mg/kg bw/day. Food intake was transiently decreased at the dose levels of 30 mg/kg bw/day. No treatment related gross pathological findings occurred at dose levels up to 30 mg/kg bw/day.
The gestation rate was unaffected by treatment at dose levels up to 30 mg/kg bw/day. Morphological appearance and weight of placentas were only affected by treatment at dose level 30 mg/kg bw/day. Postimplantation loss was increased in dose level 30 mg/kg. Fetal sex distribution was unaffected by treatment at dose levels up to 30 mg/kg bw/day. Weights of fetuses were statistically significantly decreased at dose levels of 30 mg/kg bw/day. Dosing with Molidustat at 30 mg/kg revealed an increased incidence of ocular malformations. A treatment related effect on skeletal deviations was not seen up to a dose level of 30 mg/kg bw/day.
In summary, treatment-related maternal toxicity and developmental toxicity characterized mainly by ocular malformations, reduced fetal weight and increased postimplantation loss were seen at a daily dose of 30 mg/kg of the test item. Consequently, the following no-observed-adverse-effect levels (NOAELs) were determined:
Maternal toxicity: 10 mg/kg bw/day
Developmental toxicity: 10 mg/kg bw/day
In the last and third study according to CH guideline S5A: Detection of Toxicity to Reproduction for Medicinal Products; EU: CPMP/ICH/386/95, adopted September 1993, 20 inseminated female Himalayan rabbits were exposed to 0, 2, 6, and 20 mg/kg bw of the test item in 0.5 % aqueous Tylose MH 300 P2 (methylhydroxyethylcellulose) as vehicle daily from day 6 to day 20 p.c. On day 29 of gestation the fetuses were delivered by cesarean section. Investigation was performed on general tolerance of the test substance by the females as well as on its effect on intrauterine development. Three additional females per group were treated with the doses of 0, 2, 6, and 20 mg/kg from days 6 to 20 p.c. for determination of test substance in the plasma of the females.
All parameter measured, such as
in females:
in intrauterine development:
revealed no influence on general tolerance of the test substance by the females as well as on intrauterine development through dosing with Molidustat up to 20 mg/kg bw/day. Summarizing and evaluating all data investigated the following no-observed-adverse-effect levels (NOAELs) were determined:
Maternal toxicity: 20 mg/kg bw/day
Intrauterine development: 20 mg/kg bw/day
Justification for classification or non-classification
Based on the presented data, which show effects on development without other toxic effects in rats, Molidustat is classified as reproductive toxicant Category 1B according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
Additional information
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.