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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 614-598-1 | CAS number: 68553-12-8
- 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
Effects on fertility
Description of key information
In a reliable reproduction and developmental screening study conducted in male and female Wistar rats the animals were dosed with a structurally similar substance at 0, 100, 300 or 1000 mg/kg bw/day via oral gavage for 2 weeks before mating, during the 2 -week mating period and 1 -week remating period, during gestation, lactation and up to the day of necropsy (day 40 for males and days 4 -7 post partum for females). Increased salivation was observed at the 1000 mg/kg bw/day dose group in both males and females, and possibly transiently in the 300 mg/kg bw/day dose group for females. The mild bodyweight loss observed with females at the highest dose group (1000 mg/kg bw/day) was considered to be non adverse treatment related effect as it follows a statistically significant increased body weight gain, as compared to control, in the premating phase.
The following NOEL/NOAELs were determined from this study:
General toxicity in males (NOAEL): 1000 mg/kg bw/day
General toxicity in females (NOAEL): 300 mg/kg bw/day (based on loss of body weight during lactation)
Reproduction/Developmental NOAEL: 1000 mg/kg bw/day
Male NOEL: 300 mg/kg bw/day (based on salivation)
Female NOEL: 100 mg/kg bw/day (based on salivation)
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- Read-across to K1 study therefore K2 is the maximum Klimisch value.
- Justification for type of information:
- Read-across approach - see read-across justification in section 13.
- Reason / purpose for cross-reference:
- read-across source
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: Hsd Cpb:WU
- Source: Harlan-Winkelmann GmbH, Borchen Germany
- Age at start of treatment: males: 11-12 weeks, females: 12-13 weeks
- Weight at study initiation: males: 321-348g; females: 181-206g
- Housing: individual
- Diet (e.g. ad libitum): ad libitum(Provimi Kliba maintenance Diet)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 50
- Air changes (per hr): ≥ 10 passages/hour
- Photoperiod (hrs dark / hrs light): 12 hours rhythm
IN-LIFE DATES: From: January 31st to May 10, 2005 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Amount of vehicle (if gavage): 10 ml/kg bw
- Details on mating procedure:
- MATING PROCEDURES: Pairing was performed overnight by placing one F0 female animal together with one F0 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. Animals were paired daily during the 2-week mating and one week remating period. Females in which insemination had not been detected by the end of the 2-week mating period, were mated for another week with another male of the respective dose group which had successfully inseminated a female paired with it. F0 females found sperm-positive after the first matings but where body weight gain did not indicate pregnancy by the end of the 2-week mating period were paired again for 7 days during the remating period.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Liquid chromatography.
- Frequency of treatment:
- Daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Doses were selected according to a preceding subacute rat study were the same doses were applied over 4 weeks by gavage.
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: The experimental animals were inspected twice a day for morbidity and mortality (once on weekends and public holidays). General clinical examinations (in the home cage) were made daily (especially findings occurring during littering e.g. prolonged parturition) some time (about 30 to 60 minutes) after the administration and recorded, if any.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: F0-Males: Prior to the treatment and then weekly up to necropsy.
F0-Females: Prior to the treatment and then weekly during premating and mating
period. Additionally, during pregnancy and lactation period daily.
BODY WEIGHT: Yes
- Time schedule for examinations: The individual body weights of all parental animals were determined just prior before the first treatment of animals and then daily thereafter.
FOOD CONSUMPTION: Yes
- Time schedule for examinations: The food intake of F0 males was measured weekly during the premating period on a seven day basis.
In F0 females food intake was measured in the same way during the premating period. During gestation period determination of food intake was done on post-coital days 0-7, 7-14 and 14-20. During lactation period determination of food intake was done on day 0-4 p.p.
WATER CONSUMPTION : No - Litter observations:
- -The numbers of live and dead pups as well as the sex of the pups (including those of dead pups, if possible) were determined shortly after birth (on postpartum day 0) and on day 4 p.p. At these time points individual body weights and clinical signs were recorded as well. Note was taken of any apparent malformations.
- Postmortem examinations (parental animals):
- Gross pathological examination:
- Gross pathological examination was performed for all females and males at necrosy. In F0 females the number of implantation sites was counted and the number of corpora lutea was determined.
HISTOPATHOLOGY / ORGAN WEIGHTS
- Organ weights: testes, epididymides,
- Abnormalities and the following organs were preserved: testes, epididymides, prostate, seminal vesicles with coagulating glands, uterus with vagina, ovaries with oviducts.
Histopathological examination of reproductive organs (testes, epididymides, ovaries) from control and 1000 mg/kg (highest dose) group. - Statistics:
- Analysis of Variance (ANOVA) and in case of significant results Dunnett test as post hoc test 2*N CHi2 test; in case of significant differences Fisher's exact test with Bonferroni correction CHi2 test and Fisher’s Exact test.
- Reproductive indices:
- Reproductive indices:
- mating performance
- insemination index
- fertility index
- gestation index - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Transient salivation in in both sexes at 1000 mg/kg. This is due to the administration process of the substance rather than as a result of the substance itself.
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One male of the 100 mg/kg bw dose group was sacrificed in moribund condition displaying a number of adverse clinical sgns. These effects were confirmed to be as a result of missapplication and the oesaphagus was found to be ruptured at necropsy.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Slight body weight loss occurred in females of the 1000 mg/kg dose group during lactation. (Marginal body weight gains during premating period all doses).
- Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-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
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: based on salivation - as concluded in the report.
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: based on salivation - as concluded in the report.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: NOAEL as concluded in the report based on general toxicity (loss of body weight during lactation) as a potential relation to dosing could not be ruled out by the author.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: NOAEL as concluded in the report. No adverse effects observed with males in the Study.
- Key result
- Critical effects observed:
- no
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Four pups with filiformed tip at 1000 mg/kg compared to 3 pups in control. In line with occurrences of filiformed tip in historical control.
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed for any developmental endpoint examined.
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- The following NOEL/NOAELs were determined from this study:
General toxicity in males (NOAEL): 1000 mg/kg bw/day
General toxicity in females (NOAEL): 300 mg/kg bw/day (based on loss of body weight during lactation)
Reproduction/Developmental NOAEL: 1000 mg/kg bw/day
Male NOEL: 300 mg/kg bw/day (based on salivation)
Female NOEL: 100 mg/kg bw/day (based on salivation) - Executive summary:
A reproduction and developmental screening study was conducted in male and female Wistar rats. The animals were dosed with 0, 100, 300 or 1000 mg/kg bw/day via oral gavage for 2 weeks before mating, during the 2 -week mating period and 1 -week remating period, during gestation, lactation and up to the day of necropsy (day 40 for males and days 4 -7 post partum for females). Increased salivation was observed at the 1000 mg/kg bw/day dose group in both males and females, and possibly transiently in the 300 mg/kg bw/day dose group for females. The mild bodyweight loss observed with females at the highest dose group (1000 mg/kg bw/day) was considered to be non adverse treatment related effect as it follows a statistically significant increased body weight gain, as compared to control, in the premating phase.
The following NOEL/NOAELs were determined from this study:
General toxicity in males (NOAEL): 1000 mg/kg bw/day
General toxicity in females (NOAEL): 300 mg/kg bw/day (based on loss of body weight during lactation)
Reproduction/Developmental NOAEL: 1000 mg/kg bw/day
Male NOEL: 300 mg/kg bw/day (based on salivation)
Female NOEL: 100 mg/kg bw/day (based on salivation)
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Sufficient to address requirements.
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
In a reliable reproduction and developmental screening study conducted in male and female Wistar rats the animals were dosed with a structurally similar substance at 0, 100, 300 or 1000 mg/kg bw/day via oral gavage for 2 weeks before mating, during the 2 -week mating period and 1 -week remating period, during gestation, lactation and up to the day of necropsy (day 40 for males and days 4 -7 post partum for females).
The reproduction/developmental NOAEL were determined to be 1000 mg/kg bw/day from this study.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Sufficient to address requirements.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
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.