Tin, dioctylbis(2,4-pentanedionato-.kappa.O2,.kappa.O4)-

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: sub-chronic inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no guideline, well ducumented study

Data waiving:

other justification

Justification for data waiving:

other:

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1995

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

subchronic neurotoxicity:
6h / day, 5 days / week, 14 weeks

- Animals were observed daily for sinces of toxic and/or pharmacologial effects
- Monthly Irin screeb test an before first exposure
- Necropsy of brain, lumbar spinal cord, tibal and sciatic nerves
- additional histologials examination: (1. celebral cortex and main body candate nucleus putamen, 2. celebral cortex with thalamus and hyphothalamus, 3. celebral cortex with nidbrain, 4. cerebellum and pons, 5. meilla obongata)

GLP compliance:

not specified

Limit test:

no

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

IUPAC Name:

pentane-2,4-dione

Constituent 2

Reference substance name:

2,4-pentadione

IUPAC Name:

2,4-pentadione

Details on test material:

2,4-Pentadione, Purity 99%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

air

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

acute study: 1250, 1850 ppm for 4 h
subchronic sturdy: 100, 300, 650 ppm for 6h

Frequency of treatment:

acute study: 1 time, 4 hours
subchronic sturdy: 6h, 5 days per wk, 14 wk

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
acute: 1250 ppm
Basis:
other: concentration in air

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1acute: 1850 ppm
Basis:
other: concentration in air

Doses / concentrations 3

Remarks:

Doses / Concentrations:
subchronic: 100 ppm
Basis:
other: concentration in air

Doses / concentrations 4

Remarks:

Doses / Concentrations:
subchronic: 300 ppm
Basis:
other: concentration in air

Doses / concentrations 5

Remarks:

Doses / Concentrations:
subchronic: 650 ppm
Basis:
other: concentration in air

No. of animals per sex per dose:

acute study: 10 male and female per concentration
subchronic sturdy: 100, 200 ppm: 20 male and female, 650 ppm: 30 male, 20 female

Control animals:

other: only exposured to air

Results and discussion

Any other information on results incl. tables

not relevant, in due no developmental study

Applicant's summary and conclusion

Conclusions:

In due in absence of adverse effects in the groups exposed to concentrations of 101 and 307 ppm the NOEC (subchronic) is ste to 307 ppm.

Executive summary:

1. Male and female Fischer 344 rats were exposed to 2,4-pentanedione (2,4-PD) vapour acutely (4 h) at 1265 or 1811 ppm, or for 6 h day-1, 5 days a week for 14 weeks to 0, 101, 307 or 650 ppm. 2. Mortality occurred during or within a few hours of the acute exposures (10% at 1265 ppm; 70% at 1811 ppm). No animal had gross or microscopic brain lesions. 3. All female rats (20) and 10 of 30 male rats exposed to 650 ppm 2,4-PD vapour died by the 38th study day (29 exposures); there were no subsequent male deaths. Twenty-five of the 30 animals that died, and seven of the 15 males that survived, had light microscopical evidence of degenerative lesions, principally within the caudate/putamen nuclei, nuclei of the cerebellar medulla, and vestibular nuclei. Less frequently involved, in animals that died, were various regions of the cerebral cortex. The early histopathological lesions, seen from the 16th study day (12 exposures) to the 38th study day (28 exposures) were characterised by malacia. When present, lesions in male rats surviving the 14-weeks of 650 ppm 2, 4-PD exposure were characterised by malacia and gliosis. No peripheral nerve lesions were seen by light or transmission electron microscopy. 4. Neither mortality nor neuropathology were seen in rats subchronically exposed to 101 or 307 ppm, 2,4-PD vapour.