γ-valerolactone

Neurotoxicity

Description of key information

In a study in mice, the CNS activity of γ-valerolactone was studied after a single intraperitoneal injection of 1000 and 2000 mg/kg bw γ-valerolactone. Mild sedation and partial paralysis of the hind legs were already observed at 1000 mg/kg bw.

 

In a study in rats, γ-valerolactone was administered intraperitoneally at dose levels of 0, 200, 400, 800 and 1600 mg/kg once a week for 5 weeks in total. γ-valerolactone showed an dose-dependent decrease in both the Noise Alone acoustic startle reflex (ASR) and for the Startle-Anticipated Potentiated Startle (SAPS).

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Neurotoxicity i.p., mouse, RL2

The CNS activity of different lactones was studied in mice. 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. 4/6 mice were found with both hind legs streched out at 1000 mg/kg bw, 6/6 mice showed mild sedation at 1000 mg/kg bw and a partial paralysis of the hind legs was observed at 1000 mg/kg bw in 4/6 mice. 6/6 mice showed mild sedation at 1000 mg/kg bw (Lien, 1973).

 

Neurotoxicity i.p., rat, RL2

γ-valerolactone (GVL) and γ-butyrolactone (GBL) were administered to male rats intraperitoneally at dose levels of 18.75, 37.5, 75, 150 mg/kg (GBL) and 0, 200, 400, 800 and 1600 mg/kg (GVL) once a week. In experiment I, all subjects were tested Noise Alone acoustic startle reflex (ASR) and for the Startle-Anticipated Potentiated Startle (SAPS) effect on 14 occasions over the course of 7 weeks. In experiment II, rats were pre-tested for their Noise Alone ASR (average over 20 Noise Alone trials); they were then treated with vehicle or a mid-range dose of GBL (75 mg/kg) or GVL (400 mg/kg), and 10 min later Noise Alone ASR was re-assessed for 20 trials. Immediately after testing, the subjects were sacrificed and blood and brain tissue were collected for analysis of the metabolites gamma hydroxybutyrate (GHB), 4-methyl-GHB, GBL and GVL concentrations. GBL treatment resulted in a reduction in Noise Alone ASR startle amplitude and also resulted in measurable levels of GHB in blood and brain, but no formation of 4-methyl-GHB in either tissue. Similarly, GVL treatment resulted in a reduction in Noise Alone ASR startle amplitude and an increase in 4-methyl-GHB in both blood and brain, but no formation of GHB in either tissue (Marinetti, 2012).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable but not sufficient for classification purposes under Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/217.