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Diss Factsheets
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EC number: 202-777-3 | CAS number: 99-66-1
- 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
Carcinogenicity
Administrative data
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1976-1978
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Only short information available
Data source
Reference
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- yes
- GLP compliance:
- no
- Remarks:
- stated in the report
Test material
- Reference substance name:
- Valproic acid
- IUPAC Name:
- Valproic acid
- Details on test material:
- - Name of test material (as cited in study report): Valproic acid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 5 weeks
- Weight at study initiation: 80 to 150 g
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- corn oil
- Details on exposure:
- Treatment of controls: 2% v/w corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 107 weeks
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
90 and 180 mg/kg/day
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
81 and 161 mg/kg/day
Basis:
actual ingested
males
- Remarks:
- Doses / Concentrations:
85 and 172 mg/kg/day
Basis:
actual ingested
females
- No. of animals per sex per dose:
- 50 animals per sex per group for treatment
100 animals per sex for control - Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: not indicated
BODY WEIGHT: Yes
- Time schedule for examinations: not indicated
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- 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
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Clinical signs: foot pad ulceration, ocular discharges and corneal opacity
Mortality: no significant mortality between the different groups
Survival in the various groups was comparable and ranged from 54-78% at the end of the treatment period.
BODY WEIGHT AND WEIGHT GAIN
Mean body weight: decrease of 7.8% and 10.9% in the high-dose male and female groups respectively
Mean body weight gain: decrease in the high-dose male and female groups of 9.4% and 14.9% respectively
HISTOPATHOLOGY: NON-NEOPLASTIC
A wide variety of incidental and spontaneous non-tumor lesions were observed and not considered to be drug-related
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Both benign and malignant spontaneous and incidental neoplasms (liver cell neoplasms, subcutaneous fibrosarcomas and fibromas, malignant mammary lesions, adrenal cortical adenomas, pheochromocytomas, thyroid C cell adenomas) were observed. None of the neoplasms were considered to be drug-related. - Relevance of carcinogenic effects / potential:
- None of the neoplasms and non-tumor lesions were considered to be drug-related.
Effect levels
open allclose all
- Dose descriptor:
- dose level:
- Effect level:
- 161 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: body weight gain: decrease of 9.4 % and 14.9 % in male and female groups respectively in comparison with controls during the last 6-12 months of treatment
- Remarks on result:
- other: Effect type: toxicity (migrated information)
- Dose descriptor:
- dose level:
- Effect level:
- 172 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: body weight gain: decrease of 9.4 % and 14.9 % in male and female groups respectively in comparison with controls during the last 6-12 months of treatment
- Remarks on result:
- other: Effect type: toxicity (migrated information)
Applicant's summary and conclusion
- Conclusions:
- Valproic acid was not considered to be carcinogenic to male rats up to 161 mg/kg/day or to female rats up to 172 mg/kg/day when administered for 2 years.
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