γ-valerolactone

Basic toxicokinetics

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

Structural requirements for centrally acting drugs I

Author:

Lien E. J., Tong G.L., Chou J. T., Lien L. L.

Year:

1973

Bibliographic source:

Journal of Pharmaceutical Sciences 62.2 (1973): 246-250.

Materials and methods

Objective of study:

distribution

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

γ-valerolactone

EC Number:

203-569-5

EC Name:

γ-valerolactone

Cas Number:

108-29-2

Molecular formula:

C5H8O2

IUPAC Name:

5-methyloxolan-2-one

Specific details on test material used for the study:

Not specified

Radiolabelling:

no

Test animals

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

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

water

Details on exposure:

Not specified

Duration and frequency of treatment / exposure:

Single treatment

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Doses / concentrations 2

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

Results and discussion

Main ADME results

Main ADME results 1

Type:

metabolism

Results:

The test item in alkaline medium showed no appreciable hydrolysis by liver ersterase preparations that were reactive toward methyl butyrate.

Main ADME results 2

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

Toxicokinetic / pharmacokinetic studies

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.

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

Not specified

Enzymatic activity

Enzymatic activity measured:

Not specified

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

Not specified