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EC number: 806-795-8 | CAS number: 909419-73-4
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- reproductive toxicity, other
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
Data source
Reference
- Reference Type:
- secondary source
- Title:
- APPROVAL PACKAGE FOR: APPLICATION NUMBER 20-825. Pharmacology Review(s).
- Bibliographic source:
- Food and Drug Administration - Center for Drug Evaluation and research.
- Report date:
- 2000
Materials and methods
Test material
- Reference substance name:
- 5-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]-6-chloro-1,3-dihydroindol-2-one;hydrate;hydrochloride
- Cas Number:
- 138982-67-9
- Molecular formula:
- C21H24Cl2N4O2S
- IUPAC Name:
- 5-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]-6-chloro-1,3-dihydroindol-2-one;hydrate;hydrochloride
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- Dose / conc.:
- 40 mg/kg bw/day (nominal)
- Dose / conc.:
- 160 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 20/grp
Results and discussion
Any other information on results incl. tables
There were no unscheduled deaths during the study. Clinical signs, consisting of ptosis, prostration, piloerection, and dyspnea were observed in all MD and HD animals. Body weight was reduced throughout the dosing period at all doses (3, 7, and 10% in LDF, MDF, and HDF, compared to CF).
There were no apparent gross pathology findings in the dams. In terms of litter parameters, there were no drug-related effects on no. of corpora lutea, implantation sites, viable fetuses, dead implants, or male/female ratio. Fetal body wt was lower in all dosed grps (male and female); however, the effect was statistically significant at the MD and HD in males, and at the HD in females.
There were no clear drug-related extemal fmdings; flexed paws were detected in 1 LD fetus and 4 HD fetuses (1 litter). Hematomas were observed in 2-4 fetuses in each grps, including controls. There were also no drug-related visceral findings. The sponsor provided summaries only of selected skeletal findings, i. e., variations in ribs and degree of ossification of selected bones.
PK data were collected in satellite animals (5/grp) on Day 17 (the last day of dosing). The concentration of ziprasidone in maternal plasma, amniotic fluid, and fetal homogenates were quantitated. Mean levels (± SD) were 3.66 ± 1.31 (1-hr value), 0.41 ± 0.15, and 1.31 ± 0.08 microg/mL or g wet wt, respectively.
Applicant's summary and conclusion
- Conclusions:
- There were no unscheduled deaths. Clinical signs (prostration, piloerection, dyspnea) were observed in all MD and HD animals. Body weight was reduced throughout the dosing period in MDF and HDF (7 and 10% compared to CF). There were no drug-related effects on the number of viable fetuses, dead implants, or the male/female ratio. Fetal body weight was reduced (compared to CF) at all doses, although differences were statistically significant only at the MD and HD. There were no external or visceral findings in fetuses, however, delays in ossification of certain skeletal components were noted at all doses.
In the separate maternal toxicity drug-related clinical signs (prostration, piloerection) were evident at all doses, with hunched posture and lacrimation observed in all MD and HD animals. Body weight loss was observed in MD and HDF and body weight gain was reduced in LDF during the first few days of dosing (i.e., Days 6-9 of gestation). Body weight gain was reduced in MDF and HDF during the rest of the dosing period, whereas in LDF, body wt gain tended to normalize. Catch-up growth occurred after the end of dosing in HDF. Even though clinical signs and body weight effects were consistent with maternal toxicity, none of the reproductive parameters measured (including viable litters, no. of fetuses, embryomortality rate, fetal body wt) was affected. - Executive summary:
In the Segment II study in rats, ziprasidone was administered at doses of 0, 10, 40, and 160 mg/kg from Day 6 through Day 17 of gestation. There were no unscheduled deaths. Clinical signs (prostration, piloerection, dyspnea) were observed in all MD and HD animals. Body weight was reduced throughout the dosing period in MDF and HDF (7 and 10% compared to CF). There were no drug-related effects on the number of viable fetuses, dead implants, or the male/female ratio. Fetal body weight was reduced (compared to CF) at all doses, although differences were statistically significant only at the MD and HD. There were no external or visceral findings in fetuses, however, delays in ossification of certain skeletal components were noted at all doses. In a separate maternal toxicity, ziprasidone was administered to Sprague-Dawley rats at doses of 0, 10, 40, and 160 mg/kg from Day 6 to Day 15 of gestation.
Drug-related clinical signs (prostration, piloerection) were evident at all doses, with hunched posture and lacrimation observed in all MD and HD animals. Body weight loss was observed in MD and HDF and body weight gain was reduced in LDF during the first few days of dosing (i.e., Days 6-9 of gestation). Body weight gain was reduced in MDF and HDF during the rest of the dosing period, whereas in LDF, body wt gain tended to normalize. Catch-up growth occurred after the end of dosing in HDF. Even though clinical signs and body weight effects were consistent with maternal toxicity, none of the reproductive parameters measured (including viable litters, no. of fetuses, embryomortality rate, fetal body wt) was affected.
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