Tetrahydrofuran

Neurotoxicity

Description of key information

Single, 6-hour exposures in rats to THF at concentrations as high as 5000 ppm resulted in transient sedation.  Similarly, after 90-day exposures to THF (6 hours/day, 5 days/week) at concentrations as high as 3000 ppm there were no biologically relevant changes in behavioral parameters, in any clinical measurements of neurotoxicity, or in any morphological endpoints observed following neuropathology.  Compound-related and transient sedation was noted in the 90-day exposures.   

Key value for chemical safety assessment

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

NOAEC

1 457 mg/m³

Additional information

Tetrahydrofuran (THF) has been tested for neurotoxicity in rats following single 6 -hour inhalation exposures to concentrations of 0, 500, 2500 or 5000 ppm. Exposure at the highest two concentrations produced sedative effects which occured immediately following exposures and that resolved within a few hours at 2500 ppm and within 19 hours at 5000 ppm. Neurobehavior, as measured by motor activity (MA) tests and a functional observational battery (FOB) assessment, indicated minor decreases in the number and duration of movements in female rats at the 5000 ppm concentration. The FOB assessment showed a lack of effects. The NOAEC was reported as 500 ppm and was based on the transient sedation.

THF has also been tested in rats for neurotoxicity following inhalation exposures for approximately 90 days at concentrations of 0, 500, 1500 or 3000 ppm (6 hours/day, 5 days/week). In this study there were no biologically relevant compound-related clinical observations, changes in body weights, mortality, changes in food consumption, behavioral endpoints or changes in morphology observed in neuropathological evaluations. A NOEL of 500 ppm was determined in this study based on clinical signs of transient sedation. There was no evidence of progressive or permanent damage to the nervous system. A NOEL of 3000 ppm was assigned based on a lack of neurological or neuropathological findings.

Justification for classification or non-classification

Based on a NOAEC of 500 ppm (1.5 mg/L) for sedative effects determined in both single and repeated inhalation exposure studies in rats, THF would receive an R67 rating (Vapors may cause drowsiness and dizziness) based on the EU DSD classification criteria (EU Directive 67/548/EEC). THF is rated for Specific Target Organ Systemic Toxicity (Single Exposure) as a Categroy 3 due to the sedative (narcotic) effects under the EU CLP (GHS) criteria (EU Regulation 1272/2008).