Benzylmagnesium chloride

Neurotoxicity

Key value for chemical safety assessment

Effect on neurotoxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

neurotoxicity: acute inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

other: Reliability score is not applicable because available data are on stabilizer agent (as described in sect. 1.2) and not on the benzylmagnesium chloride as such.

Qualifier:

equivalent or similar to guideline

Guideline:

other: U. S. EPA, Toxic substances Control Act Health Effects Testing guideline, 40 CFR Part 798 Subpart G, Neurotoxicity (1985) and USEPA/FIFRA Neurotoxicity Pesticide Assessment Guidelines F, PB 91-154617 (1991)

GLP compliance:

not specified

Species:

rat

Strain:

other: Crl:CD BR

Sex:

male/female

Route of administration:

inhalation: vapour

Vehicle:

other: air distribution line

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

6h

Frequency of treatment:

single exposure

Remarks:

Doses / Concentrations:
0, 500 ppm, 2500 ppm, 5000 ppm
Basis:

No. of animals per sex per dose:

12

Control animals:

yes

Dose descriptor:

NOAEC

Effect level:

500 ppm

Sex:

male/female

Basis for effect level:

other: The most relevant effect of acute inhalation exposure of THF is a transient sedation with exposure concentrations of 2500 ppm and 5000 ppm

Remarks on result:

other:

Conclusions:

Groups of male and female rats received tetrahydrofuran inhalation exposure at concentrations of 0, 500, 2500 and 5000 ppm. The principal neurobehavioral effects of exposure to 1500 ppm or greater is acute behavioral sedation which dissipates rapidly after termination of exposure. Clinical observations, motor activity tests, and functional observational battery assessments conducted on the day following acute exposure did not reveal indications of continuing sedation. Two effects of acute THF exposure that were evident one day after exposure involved slightly increased motor activity and altered body weight change for 5000 ppm males. Acute exposure of rats to 500 ppm had no identifiable effects during or after exposure.

Executive summary:

In this study, four groups of 12 male and 12 female Crl:CD BR rats received tetrahydrofuran acute (6 hours) exposure through inhalation at concentrations 0, 500, 2500 and 5000 ppm. Evaluations conducted immediately after exposure included clinical observations, motor activity assessments (MA), and a battery of functional tests (FOB) designed to reveal nervous system dysfunction. During exposure to 2500 and 5000 ppm, rats had a diminished or absent startle response to a punctate auditory alerting stimulus.

Following exposure to 5000 ppm, male and female rats were lethargic, exhibited abnormal gait or mobility, and splayed rear feet. Lethargy and splayed rear feet were also observed in females esposed to 2500 ppm. During the subsequent FOB, males exposed to 5000 ppm had a lower incidence of palpebral closure, higher incidences of slow or absent righting reflex, and a biphasic pattern of reduced motor activity followed by increased motor activity. Females exposed to 5000 ppm had increased incidences of palpebral closure in the open field, increased incidences of slow or absent righting reflex, and decreased motor activity.

Post-exposure clinical observations and neurobehavioral assessments indicated that THF’s sedative properties waned rapidly after termination of exposure. Acute exposure of rats to 500 ppm had no identifiable effects during or after exposure. The demonstrated no-observed-effect level of tetrahydrofuran exposure is 500 ppm.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

1 500 mg/m³

Species:

rat

Justification for classification or non-classification

Acute inhalation toxicity

On the basis of CNS depression effects on animal studies, tetrahydrofuran has to be classified as R67 under the EU DSD classification criteria. Due to upper respiratory tract irritation in animal studies, tetrahydrofuran has to be classified as Xi;R37 under the EU DSD classification criteria.