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EC number: 700-539-8 | CAS number: 175481-26-2
- 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:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2011
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- (R)-2-acetamido-N-benzyl-3-methoxypropionamide
- EC Number:
- 605-756-0
- Cas Number:
- 175481-36-4
- Molecular formula:
- C13H18N2O3
- IUPAC Name:
- (R)-2-acetamido-N-benzyl-3-methoxypropionamide
- Test material form:
- other: Solid, powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Hypromellose
- Duration of treatment / exposure:
- From gestation day 6 through lactation day 20 for a total of 36-38 days of dose administration
- Frequency of treatment:
- Twice daily in equally divided doses (approximately 10 hours apart)
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 50 mg/kg bw/day
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 200 mg/kg bw/day
- No. of animals per sex per dose:
- 25
- Control animals:
- yes
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- no effects observed
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Increased mortality/moribundity at 200 mg/kg/day
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 200 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Based on lower body weights in the 200 mg/kg group F1 males and females, a
dosage level of 100 mg/kg/day was considered to be the NOAEL for F1 male and female
systemic toxicity. - Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Sexual maturation:
- no effects observed
- Anogenital distance (AGD):
- no effects observed
- Nipple retention in male pups:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Other effects:
- no effects observed
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased learning performance was noted only for
females in the 200 mg/kg/day group during PND 22 Biel maze testing and there was no effect
noted for females or for males in this group or in any groups during the PND 62 assessment.
Although based on a transient effect in 1 sex, 100 mg/kg/day was considered to be the
NOAEL for F1 neurobehavioral assessment.
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- no effects observed
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- ca. 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- developmental neurotoxicity
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Due to the absence of effects on reproductive performance at any dosage
level, a dosage of 200 mg/kg/day was considered to be the NOAEL for F1 reproductive
toxicity - Executive summary:
Three groups of bred female Crl:CD(SD) rats were administered the test item, lacosamide
(SPM 927), twice daily (bid) in 2 equally divided doses given approximately 10 hours apart,
by oral gavage.
Based on F0 clinical findings, mean body weight losses and lower mean body weight gains
and food consumption at 100 and 200 mg/kg/day and increased F0 mortality/moribundity at
200 mg/kg/day, the no-observed-adverse-effect level (NOAEL) for F0 maternal systemic
effects was considered to be 50 mg/kg/day of lacosamide (SPM 927). Based on lower F1
postnatal survival (including total litter loss) and lower birth weights for the 200 mg/kg/day
F1 males and females, the dosage level of 100 mg/kg/day was considered to be the NOAEL
for F1 developmental/neonatal toxicity. Decreased learning performance was noted only for
females in the 200 mg/kg/day group during PND 22 Biel maze testing and there was no effect
noted for females or for males in this group or in any groups during the PND 62 assessment.
Although based on a transient effect in 1 sex, 100 mg/kg/day was considered to be the
NOAEL for F1 neurobehavioral assessment. There were no test item-related macroscopic or
microscopic changes in the F1 animals, including no changes assessed in brain structure as
investigated by sensitive techniques (brain weights and macroscopic and microscopic
evaluations). Based on lower body weights in the 200 mg/kg group F1 males and females, a
dosage level of 100 mg/kg/day was considered to be the NOAEL for F1 male and female
systemic toxicity. Due to the absence of effects on reproductive performance at any dosage
level, a dosage of 200 mg/kg/day was considered to be the NOAEL for F1 reproductive
toxicity and F2 development.
The 50, 100, and 200 mg/kg/day dosage levels correspond to lacosamide AUC0-24 values on
lactation day 10 of 151, 277, and 517 μg*h/mL, respectively.
The study was performed in accordance with the GLP principles.
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