Pentane-2,4-dione

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity

Remarks:

subchronic

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Poor documentation.

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

A series of studies was made to clarify the relationship of 2,4-Pentanedione to neurotoxicity in terms of neuropathy and relative neurotoxic potentials using electrophysiological methods. A 200 mg/kg dose was administered subcutaneously five days a weeks to one group of 8 rats. This program continued for 40 weeks. Electrophysiological studies of the effects of the compounds on the peripheral nerve were performed by measuring of maximum motor conduction velocities (MCV) and sensory conduction velocities (SCV) in the tail nerve of the rats. Residual latencies (RL), motor distal latencies (DL), amplitudes of the muscle action potentials (MAP) and amplitudes of nerve action potentials (NAP) were also estimated.

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentane-2,4-dione

EC Number:

204-634-0

EC Name:

Pentane-2,4-dione

Cas Number:

123-54-6

Molecular formula:

C5H8O2

IUPAC Name:

pentane-2,4-dione

Details on test material:

TS-Freetext:
no data

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

not specified

Details on exposure:

no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

5 days a week, 40 weeks

Frequency of treatment:

consecutive edays

Doses / concentrations

Remarks:

Doses / Concentrations:
200 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

8

Control animals:

not specified

Details on study design:

no data

Examinations

Observations and clinical examinations performed and frequency:

no data

Specific biochemical examinations:

no data

Neurobehavioural examinations performed and frequency:

Neurotoxic evidence was revealed by 2,4-pentanedione. Significant slowing of motor conduction velocities began to be observed in the 2,4-pentanedione group at 10th week. At 8th week, a significant decrease in sensory conduction velocities was also observed. In the 2,4-pentanedione group SCV values were slowed more than the MCV values. In the 2,4-pentanedione group, a significant decrease in nerve action potentials (NAP) amplitudes was observed at 16th week and that in muscle action potentials (MAP) amplitudes at 28th week. Residual latencies (RL) and motor distal latencies (DL) were not affected.

Sacrifice and (histo)pathology:

no data

Other examinations:

none

Positive control:

not applicable

Statistics:

not reported

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Clinical biochemistry findings:

not examined

Behaviour (functional findings):

effects observed, treatment-related

Gross pathological findings:

not examined

Neuropathological findings:

effects observed, treatment-related

Details on results:

Neurotoxic evidence was revealed by 2,4-pentanedione. Significant slowing of motor conduction velocities began to be observed in the 2,4-pentanedione group at 10th week. At 8th week, a significant decrease in sensory conduction velocities was also observed. In the 2,4-pentanedione group SCV values were slowed more than the MCV values. In the 2,4-pentanedione group, a significant decrease in nerve action potentials (NAP) amplitudes was observed at 16th week and that in muscle action potentials (MAP) amplitudes at 28th week. Residual latencies (RL) and motor distal latencies (DL) were not affected.

Effect levels

Dose descriptor:

LOEL

Effect level:

200 mg/kg bw/day

Sex:

not specified

Basis for effect level:

other: electrophysiology

Remarks on result:

other:

Applicant's summary and conclusion

Conclusions:

In this study, neurotoxic evidence was revealed by 2,4-Pentanedione.

Executive summary:

A series of studies was made to clarify the relationship of 2,4-Pentanedione to neurotoxicity in terms of neuropathy and relative neurotoxic potentials using electrophysiological methods. A 200 mg/kg does was administered subcutaneously five days a weeks to one group of 8 rats. This program continued for 40 weeks. Electrophysiological studies of the effects of the compounds on the peripheral nervewere performed by measuring of maximum motor conduction velocities (MCV) and sensory conduction velocities (SCV) in the tail nerve of the rats. Residual latencies (RL), motor distal latencies (DL), amplitudes of the muscle action potentials (MAP) and amplitudes of nerve action potentials (NAP) were also estimated.  Neurotoxic evidence was revealed by 2,4-pentanedione. Significant slowing of motor conduction velocities began to be observed in the 2,4-pentanedione group at 10th week. At 8th week, a significant decrease in sensory conduction velocities was also observed. In the 2,4-pentanedione group SCV values were slowed more than the MCV values. In the 2,4-pentanedione group, a significant decrease in nerve action potentials (NAP) amplitudes was observed at 16th week and that in muscle action potentials (MAP) amplitudes at 28th week. Residual latencies (RL) and motor distal latencies (DL) were not affected [IUCLID 3]