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Toxicological information

Neurotoxicity

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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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
TS-Freetext:
no data

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals 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]