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EC number: 416-730-1 | CAS number: -
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- July 27th 1995
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch number of test material: E0986
- Expiration date of the lot/batch: not specified
- Purity test date: not specified
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in dry room at the temperature < 30°C
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: According to the information from Sponsor the main component of the test substance is insoluble in the used vehicle (water for injection). Mixture of sample and deionised water results in yellow non-transparent suspension but undissolved particles of the test substance were easily visible in the application form and homogeneity could be checked by eye.
Stability of the test substance in the application form cannot be verified analytically. The application form was prepared just before the application and there was no indication that test substance would have been unstable in the suspension in deionised water for that short time period.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: The concentrations of suspensions at all dose levels were adjusted to ensure the administration of 1 mL per 100 g of body weight.
FORM AS APPLIED IN THE TEST (if different from that of starting material) : test substance suspension in water for injection (prepared daily just before administration) - Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- The preferred rodent species according to the guidelines is the rat. The test facility has long experience with this species.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SPF breeding, VELAZ s.r.o., Kolec u Kladna, Czech Republic, RCH CZ 21760152
- Age at study initiation: 10 weeks
- Weight at study initiation: males 307.89 - 309.22g, females: 224.33 - 226.55g
- Housing: 2 rats of the same sex in one cage; during mating period - one male and one female in one cage; pregnant females individually, offspring - with mother
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: from: 19.01.2011 To: 23.02.2011 (males); 07.03. - 14.03.2011 (females) - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw - Details on mating procedure:
- - M/F ratio per cage: 1 to 1
- Length of cohabitation: 7d
- Proof of pregnancy: sperm in vaginal smear, referred to as day 0 of pregnancy
- Further matings after two unsuccessful attempts: not specified
- After successful mating each pregnant female was caged (how): individually - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- According to the information from Sponsor the main component of the test substance is insoluble in the used vehicle (water for injection).
Mixture of sample and deionised water results in yellow non-transparent suspension but undissolved particles of the test substance were easily visible in the application form and homogeneity could be checked by eye. Stability of the test substance in the application form cannot be verified analytically. The application form was prepared just before the application and there was no indication that test substance would have been unstable in the suspension in deionised water for that short time period. - Duration of treatment / exposure:
- males and females - 2 weeks prior to the mating period and during the mating period,
pregnant females - during pregnancy and till the 3rd day of lactation,
males - after mating period - totally for 28 days,
non-pregnant females (mated females without parturition) - for 25 days after the confirmed mating - Frequency of treatment:
- daily, 7d/week
- Details on study schedule:
- - Age at mating of the mated animals in the study: 12 weeks
- Dose / conc.:
- 160 mg/kg bw/day (nominal)
- Dose / conc.:
- 400 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on data of 14d range finder
The dose-range finding experiment with 14-day application period was performed with 4 groups of treated animals. The doses for the dose-range finding experiment were chosen with respect to the literature
data as folIows: 125, 250, 500 and 1000 mg/kg/day.
In the dose-range finding experiment with the test substance changes of body weight increments were not observed in treated males and females. Health condition control and clinical observation did not detect adverse impact of the test substance on the health condition, clinical status and behaviour of animals at all dose levels. Results of haematological examination showed the test substance influence on white blood component in females of the dose levels 500 and 1000 mg/kg/day. Pathological examination revealed only changes related to colour of the test substance at the dose levels 500 and 1000 mg/kg/day. No animal died during the 14-day application period. - Positive control:
- no
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations:
males - weekly
females - weekly in premating and mating period,
during pregnancy: day 0, 7th , 14th, 20th day, during lactation: 0. or 1st and 4th day
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Time schedule for examinations:
males - weekly
females - weekly during premating period and after mating period
during pregnancy and lactation - on the same days as bodyweight
WATER CONSUMPTION: No - Oestrous cyclicity (parental animals):
- - vaginal smears: daily in mating period
- Sperm parameters (parental animals):
- Parameters examined in P male parental generations:
testis weight, epididymis weight, prostate gland weight, pituitary glands weight, sperm motility, sperm morphology - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, physical or behavioural abnormalities
Dead pups were sexed and externally examined; the stomach was examined for the presence of milk. Pups killed on the 4th day of lactation were sexed and subjected to external examination of the cranium, and to macroscopic examination of the thoracic and abdominal tissues and organs.
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: no
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY: no - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals, males were killed at the end of the administration period - after 28 days of administration
- Maternal animals: All surviving animals, parental females were killed on the 4th day of lactation. Mated females without delivery were killed 26th day after confirmed mating.
GROSS NECROPSY
- macroscopically examined for any pathological changes with special attention to the organs of the reproductive systems
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated below were prepared for microscopic examination and weighed, respectively:
relevant gross lesions, pituitary gland, coagulation gland, prostate gland, seminal vesicles, epididymis and testes (fixed in Davidson's suspension), cervix of uterus, ovaries, uterus and vagina - Postmortem examinations (offspring):
- SACRIFICE
- sacrificed on day 4 of lactation
GROSS NECROPSY
- examination of thoracic and abdominal tissues and organs - Statistics:
- The ANOVA test - Analysis of Variance (QC.Expert 2.5) at significance level 0.05 was used for the statistical analysis. This statistical analysis was used for the results of body weight, biometry of organs and number of pups. Control group with vehicle was compared with three treated groups.
- Reproductive indices:
- Post-implantation loss, Pre-implantation loss, Post-natal loss, Male mating index, Female mating index, Male fertility index, Female fertility index
- Offspring viability indices:
- Gestation index, Survival index
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- yellow stained feces at mid and high dose groups (both sexes)
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- The mean food consumption of males at the dose level 1000 mg/kg bw/day was slightly decreased against control males for the whole time of application period.
The mean food consumption of mothers at all dose levels was slightly decreased against control mothers far the whole time of pregnancy (without dependence on the dose level).
Mean food consumption of treated females was slightly lower than in control females (without dependence on the dose level). - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- atrophic changes in prostate gland of high dose males
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOEL
- Effect level:
- 400 mg/kg bw/day
- Sex:
- male
- Basis for effect level:
- other: the value is based on the incidence of atrophic changes in prostate gland
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: No effects observed up to and including the highest tested dose.
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed up to and including the highest tested dose.
- Critical effects observed:
- no
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- One still born pup (female) was detected at the dose level 1000 mg/kg bw/day - unaerial lungs, other organs were without pathological changes.
One pup (male) at the dose level 400 mg/kg bw/day died during lactation period - autolysis of GIT organs, other organs were without pathological changes.
No differences in development of pups were observed at the control and treated groups. - Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The mean weights of the litters and pups were relatively balanced in the control and treated groups except for the mean weight of litter at the lowest dose level on the 4th day of lactation period.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- no effects observed
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed up to and including the highest tested dose.
- Critical effects observed:
- no
- Reproductive effects observed:
- no
- Conclusions:
- The NOEL (No Observed Effect Level) for the toxic effect on reproduction organs of males was established as 400 mg/kg body weight/day (the value is based on the incidence of atrophic changes in prostate gland).
The NOEL (No Observed Effect Level) for the toxic effect on reproduction organs of females was established as 1000 mg/kg body weight/day.
The NOAEL (No Observed Adverse Effect Level) for reproduction was established as 1000 mg/kg body weight/day. - Executive summary:
The influence of the test substance treatment expressed mainly at the highest dose level (limit dose) - decrease of absolute and relative weight of prostate gland and occurrence of atrophic changes in prostate gland of parental males. The changes relating to prostate gland at the dose level 1000 mg/kg bw/d were considered of effect related to the test substance (without negative influence on fertility of parental males). Reproductive performance - ability of male and female animals to successfully mate and produce viable offspring was unaffected by the test substance treatment. Also development of pups was not changed in treatment groups.
- females: Dose dependent decreased relative weight of uterus was recorded in females at the dose level 1000 mg/kg/day (connection with oestrous cycle)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- July 27th 1995
- GLP compliance:
- yes
- Limit test:
- no
Test material
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch number of test material: E0986
- Expiration date of the lot/batch: not specified
- Purity test date: not specified
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in dry room at the temperature < 30°C
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: According to the information from Sponsor the main component of the test substance is insoluble in the used vehicle (water for injection). Mixture of sample and deionised water results in yellow non-transparent suspension but undissolved particles of the test substance were easily visible in the application form and homogeneity could be checked by eye. Stability of the test substance in the application form cannot be verified analytically. The application form was prepared just before the application and there was no indication that test substance would have been unstable in the suspension in deionised water for that short time period.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: The concentrations of suspensions at all dose levels were adjusted to ensure the administration of 1 mL per 100 g of body weight.
FORM AS APPLIED IN THE TEST (if different from that of starting material) : test substance suspension in water for injection (prepared daily just before administration)
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SPF breeding, VELAZ s.r.o., Kolec u Kladna, Czech Republic, RCH CZ 21760152
- Age at study initiation: 10 weeks
- Weight at study initiation: males 307.89 - 309.22g, females: 224.33 - 226.55g
- Housing: 2 rats of the same sex in one cage; during mating period - one male and one female in one cage; pregnant females individually, offspring - with mother
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: from: 19.01.2011 To: 23.02.2011 (males); 07.03. - 14.03.2011 (females)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- suspension
- Details on exposure:
- VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- According to the information from Sponsor the main component of the test substance is insoluble in the used vehicle (water for injection).
Mixture of sample and deionised water results in yellow non-transparent suspension but undissolved particles of the test substance were easily visible in the application form and homogeneity could be checked by eye. Stability of the test substance in the application form cannot be verified analytically. The application form was prepared just before the application and there was no indication that test substance would have been unstable in the suspension in deionised water for that short time period. - Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1 to 1
- Length of cohabitation: 7 d
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Further matings after two unsuccessful attempts: not specified
- After successful mating each pregnant female was caged (how): individually - Duration of treatment / exposure:
- males and females - 2 weeks prior to the mating period and during the mating period,
pregnant females - during pregnancy and till the 3rd day of lactation,
males - after mating period - totally for 28 days,
non-pregnant females (mated females without parturition) - for 25 days after the confirmed mating - Frequency of treatment:
- daily, 7d/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 160 mg/kg bw/day (nominal)
- Dose / conc.:
- 400 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on data of 14d range finder
The dose-range finding experiment with 14-day application period was performed with 4 groups of treated animals. The doses for the dose-range finding experiment were chosen with respect to the literature data as folIows: 125, 250, 500 and 1000 mg/kg/day.
In the dose-range finding experiment with the test substance changes of body weight increments were not observed in treated males and females. Health condition control and clinical observation did not detect adverse impact of the test substance on the health condition, clinical status and behaviour of animals at all dose levels. Results of haematological examination showed the test substance influence on white blood component in females of the dose levels 500 and 1000 mg/kg/day.
Pathological examination revealed only changes related to colour of the test substance at the dose levels 500 and 1000 mg/kg/day. No animal died during the 14-day application period.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly in premating and mating period,
during pregnancy: day 0, 7th , 14th, 20th day, during lactation: 0. or 1st and 4th day
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Time schedule for examinations:
females - weekly during premating period and after mating period
during pregnancy and lactation - on the same days as bodyweight
POST-MORTEM EXAMINATIONS: Yes
- Parental females were killed on the 4th day of lactation. Mated females without delivery were killed 26th day after confirmed mating.
- Organs examined: macroscopically examined for any pathological changes with special attention to the organs of the reproductive systems. The tissues indicated below were prepared for microscopic examination and weighed, respectively:
relevant gross lesions, pituitary gland, cervix of uterus, ovaries, uterus and vagina - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: No
- Number of late resorptions: No - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: No
- Head examinations: No data
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, physical or behavioural abnormalities
Dead pups were sexed and externally examined; the stomach was examined for the presence of milk. Pups killed on the 4th day of lactation were sexed and subjected to external examination of the cranium, and to macroscopic examination of the thoracic and abdominal tissues and organs.
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities - Statistics:
- The ANOVA test - Analysis of Variance (QC.Expert 2.5) at significance level 0.05 was used for the statistical analysis. This statistical analysis was used for the results of body weight, biometry of organs and number of pups. Control group with vehicle was compared with three treated groups.
- Indices:
- Male mating index
number of males with confirmed mating x 100 / number of males cohabited
Female mating index
number of sperm-positive females x 100 / number of females cohabited
Male fertility index
number of males impregnating a females x 100 / number of males cohabited
Female fertility index
number of pregnant females x 100 / number of sperm-positive females
Gestation index
number of females with live born pups x 100 / number of pregnant females
Survival index
number of live pups on day 4 post partum* x 100 / number of pups born alive+
Note: * Without still born pups (dead pups with anaerial lungs)
+ with dead pups with aerial lungs
Pre-implantation loss: Number of corpora lutea - number of implantations
Post-implantation loss: Number of implantations - number of live births
Post-natal loss: Number of live births - number of alive at postuatal day 4 - Historical control data:
- yes, 13 control groups from Reproduction / Developmental Toxicity Screening tests
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- yellow stained feces at mid and high dose groups
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- The mean food consumption of mothers at all dose levels was slightly decreased against control mothers far the whole time of pregnancy (without dependence on the dose level).
Mean food consumption of treated females was slightly lower than in control females (without dependence on the dose level). - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In all females of the middle and the highest dose level and one female of the lowest dose level the content of intestine and stomach was test substance-coloured.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Maternal developmental toxicity
- Number of abortions:
- effects observed, treatment-related
- Description (incidence and severity):
- slightly increased number of females with abortion at the dose levels 400 and 1000 mg/kg bw/day
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not examined
- Dead fetuses:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One still born pup (female) was detected at the dose level 1000 mg/kg bw/day.
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Basis for effect level:
- other: No adverse effects observed up to and including the highest tested dose.
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- instead of fetuses pups were examined
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- not examined
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed up to and including the highest tested dose.
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- The NOAEL (No Observed Adverse Effect Level) for development of pups was established as 1000 mg/kg body weight/day.
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.
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