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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 203-569-5 | CAS number: 108-29-2
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Data published in 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Objective of study:
- distribution
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: Comparison of CNS activity of different lactones in mice.
- Short description of test conditions: In a study in mice, the CNS activity of five different lactones was investigated. Groups of six mice, three males and three females weighting 17-27 g, were injected intraperitoneally with an aqueous solution of the test item. Signs of CNS activity or other changes were observed continuously for 2 hours and then at regular intervals for 2 days.
- Parameters analysed / observed: Cage side observations, neurological parameters (righting reflex, paralysis of the hind legs). - GLP compliance:
- no
- Specific details on test material used for the study:
- Not specified
- Radiolabelling:
- no
- Species:
- mouse
- Strain:
- not specified
- Details on species / strain selection:
- Not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 17-27 g - Route of administration:
- intraperitoneal
- Vehicle:
- water
- Details on exposure:
- Not specified
- Duration and frequency of treatment / exposure:
- Single treatment
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose / concentration:
- 3 males and 3 females
- Control animals:
- not specified
- Positive control reference chemical:
- Not specified
- Details on study design:
- Not specified
- Details on dosing and sampling:
- Not specified
- Statistics:
- Not specified
- Type:
- metabolism
- Results:
- The test item in alkaline medium showed no appreciable hydrolysis by liver ersterase preparations that were reactive toward methyl butyrate.
- Type:
- distribution
- Results:
- - decreased CNS depressant activity of lactones when a methyl group is attached to the α or γ position
- no loss of righting reflex at 2000 mg/kg bw after treatment with the test item
- potential local anesthetic activity on the peripheral nervous system - Details on absorption:
- Not specified
- Details on distribution in tissues:
- Partial paralysis of the hind legs was observed at 1000 mg/kg bw, indicating local anesthetic activity on the peripheral nervous system. Mild sedation at 1000 mg/kg bw, indicating a decreased CNS activity compared to γ-butyrolactone, although the lipophilic character is increased.
- Metabolites identified:
- not specified
- Details on metabolites:
- Not specified
- Enzymatic activity measured:
- Not specified
- Bioaccessibility (or Bioavailability) testing results:
- Not specified
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Adequacy of study:
- weight of evidence
- Study period:
- Data published in 1963
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Objective of study:
- metabolism
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: Short summary of results from a data collection. The effect of pH on lactone ring hydrolysis of γ-valerolactone was studied in vitro by incubating the material with simulated intestinal fluid.
- Short description of test conditions: 1 mM of γ-valerolactone (purity 98.7%) was incubated with 50 mL of simulated intestinal fluid for 15, 30, 45, 60, and 240 min; an additional 1mM was incubated with 100 mL of intestinal fluid for 60 and 240 min. All samples were maintained at 37 °C and pH 7.5.
- Parameters analysed / observed: The degrees of opening of the lactone ring at 15, 30, 45, 60, and 240 min following incubation with 50 mL of intestinal fluid and after 60 and 240 min following incubation with 100 mL intestinal fluid
Original data from RIFM, 1962 / NTRL, 1985 - GLP compliance:
- not specified
- Specific details on test material used for the study:
- Purity: 98.7%
- Radiolabelling:
- no
- Type:
- metabolism
- Results:
- 32%, 34%, 31%, 35%, and 32% opening of the lactone ring at 15, 30, 45, 60, and 240 min (50 mL intestinal fluid) and 48% and 50% after 160 and 240 min (100 mL intestinal fluid)
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Data published in 1963
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Objective of study:
- metabolism
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: Short summary of results from a data collection. The metabolism of γ-valerolactone was studied in vitro by incubation with rat liver homogenate and measurement of the degree of lactone ring opening.
- Short description of test conditions: 2 g of rat liver homogenate was incubated for 1 hour with the test item (purity 98.6%) at concentrations of 0, 0.5, 1, and 2 mM in 50 mL of phosphate buffer (pH 7.5) at 37 °C.
- Parameters analysed / observed: The degrees of opening of the lactone ring at 0.50, 1, and 2mM were measured as 93%, 92%, and 93%, respectively.
Original data from RIFM, 1963 / NTRL, 1985 - GLP compliance:
- not specified
- Specific details on test material used for the study:
- Not specified
- Radiolabelling:
- no
- Type:
- metabolism
- Results:
- 93%, 92% and 93% opening of lactone rings at 0.5, 1 and 2 mM of the test item in rat liver homogenate
- Metabolites identified:
- yes
- Details on metabolites:
- Degrees of opened lactone rings
- Enzymatic activity measured:
- Not specified
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: Neurotoxicity study, γ-valerolactone was administered to male rats intraperitoneally at dose levels of 0 (vehicle) and 400 mg/kg/day and metabolites were measured in blood and brain.
- Short description of test conditions: Male rats were administered 400 mg/kg/day of γ-valerolactone
- Parameters analysed / observed: Detection of the metabolites in the blood and brain - GLP compliance:
- not specified
- Specific details on test material used for the study:
- No details given
- Radiolabelling:
- not specified
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Not specified
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Not specified
- Route of administration:
- intraperitoneal
- Vehicle:
- not specified
- Details on exposure:
- Not specified
- Duration and frequency of treatment / exposure:
- Not specified
- Dose / conc.:
- 400 mg/kg bw/day
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- vehicle
- No. of animals per sex per dose / concentration:
- Not specified
- Control animals:
- not specified
- Positive control reference chemical:
- Not specified
- Details on study design:
- Not specified
- Details on dosing and sampling:
- Not specified
- Statistics:
- Not specified
- Type:
- metabolism
- Results:
- Metabolism to 4-methyl hydroxybutyrate, both 4-methyl hydroxybutyrate and γ-valerolactone were detected in the blood and brain.
- Type:
- distribution
- Results:
- 4-methyl hydroxybutyrate (metabolite) and γ-valerolactone were detected in the blood and brain
Referenceopen allclose all
The degrees of opening of the lactone ring at 15, 30, 45, 60, and 240 min following incubation with 50 mL of intestinal fluid resulted in 32%, 34%, 31%, 35%, and 32%, respectively; whereas incubation with 100 mL for 60 and 240 min resulted in 48% and 50%, respectively. The results indicated that there was only a partial breakdown of the lactone ring at intestinal pH levels.
The degrees of opening of the lactone ring at 0.50, 1, and 2mM were reported as 93%, 92%, and 93%, respectively.
Description of key information
The metabolism of γ-valerolactone was studied in two in vitro studies, revealing that the γ-valerolactone is metabolised up to 50% in intestinal fluid and up to 93% in rat liver homogenate. In an in vivo study, γ-valerolactone as well as a metabolite, 4-methyl-γ-hydroxybutyrate, was detected in blood and brain of male rats after intraperitoneal administration. In an in vivo study in mice, γ-valerolactone induced mild CNS depressant activity and local anesthetic activity on the peripheral nervous system at 1000 mg/kg bw, indicating that γ-valerolactone partially crosses the blood-brain-barrier and is distributed to the peripheral nervous system.
Conclusion: After oral uptake, γ-valerolactone may be partially broke down by intestinal fluid, absorbed and partially metabolised to its metabolite 4-methyl γ-hydroxybutyrate. It is presumably distributed to different organs, including the brain and the peripheral nervous system via the blood.
Key value for chemical safety assessment
Additional information
Metabolism in vitro, RL2
The metabolism of γ-valerolactone was studied in vitro. 2 g of rat liver homogenate was incubated for 1 hour with the test item (purity 98.6%) at concentrations of 0, 0.5, 1, and 2 mM in 50 mL of phosphate buffer (pH 7.5) at 37 °C. The degrees of opening of the lactone ring at 0.50, 1, and 2 mM were measured as 93%, 92%, and 93%, respectively (Api et al., 2019 a, based on RIFM, 1963; NTRL, 1985).
Metabolism in vitro, RL2
The effect of pH on lactone ring hydrolysis of γ-valerolactone was studied in vitro by incubating the material with simulated intestinal fluid. 1 mM of γ-valerolactone (purity 98.7%) was incubated with 50 mL of simulated intestinal fluid for 15, 30, 45, 60, and 240 min; an additional 1 mM was incubated with 100 mL of intestinal fluid for 60 and 240 min. All samples were maintained at 37 °C and pH 7.5. The degrees of opening of the lactone ring at 15, 30, 45, 60, and 240 min following incubation with 50 mL of intestinal fluid resulted in 32%, 34%, 31%, 35%, and 32%, respectively; whereas incubation with 100 mL for 60 and 240 min resulted in 48% and 50%, respectively. The results indicated that there was only a partial breakdown of the lactone ring at intestinal pH levels (Api et. al 2019b, based on RIFM, 1962; NTRL, 1985).
Metabolism and distribution in vivo, RL2
In a neurotoxicity study (no details on GLP or guidelines used) conducted on male rats, γ-valerolactone was administered intraperitoneally at dose levels of 0 (vehicle) and 400 mg/kg/day. At the end of the study, 4-methyl hydroxybutyrate and γ-valerolactone were detected in the blood and brain. 4-Methyl γ-hydroxy butyrate was found in the blood and brains of all rats examined, which indicated that γ-valerolactone is metabolized to 4-methyl-γ-hydroxy butyrate and that it can cross the blood-brain barrier with a potential to cause locomotor dysfunction (Marinetti et al., 2012).
Distribution in vivo, RL2
In a study in mice, the CNS activity of five different lactones was investigated. Groups of six mice, three males and three females weighting 17-27 g, were injected intraperitoneally with an aqueous solution of the test item. Signs of CNS activity or other changes were observed continuously for 2 hours and then at regular intervals for 2 days. Mild sedation, but no loss of the righting reflex was observed at 1000 mg/kg bw of γ-valerolactone. At the same dose level, paralysis of the hind legs was observed, indicating local anesthetic acticity on the peripheral nervous system. The five investigated lactones decreased in CNS activity with additional alkyl groups and increasing lipophily (Lien et al., 1973).
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.