Hexane-2,5-dione

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: sub-chronic oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Axonal Atrophy Is a Specific Component of 2,5-Hexandedione Peripheral Neuropathy

Author:

E.J. Lehning, K.S. Dyer, B.S. Jortner, R.M. LoPachin

Year:

1995

Bibliographic source:

Toxicology and Applied Pharmacology, 135, 1995, 58-66

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexane-2,5-dione

EC Number:

203-738-3

EC Name:

Hexane-2,5-dione

Cas Number:

110-13-4

Molecular formula:

C6H10O2

IUPAC Name:

hexane-2,5-dione

Test material form:

not specified

Details on test material:

Aldrich Chemical Company, 97% purity

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Taconic Farms, GErmantown, NY, 250-275 g bw, Purina Rodent Lab Chow, water ad lib.,

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

0.4 % (w/v), maximum concentration tolerated without severe reduction in daily water consumption

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

77, 86 and 103 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.37 g/kg/d
Basis:
actual ingested

No. of animals per sex per dose:

one dose, male animals only

Control animals:

yes, concurrent vehicle

Details on study design:

Index of hexanedione-induced neurological deficits: hindlimb weakness as indicated by performance on a treadmill.
Rats were sacrificed when developping hindlimb weakness. Sciatic nerve and posterior tibial nerve were analyzed.

Examinations

Observations and clinical examinations performed and frequency:

Index of hexanedione-induced neurological deficits: hindlimb weakness as indicated by performance on a treadmill.

Neurobehavioural examinations performed and frequency:

Sciatic nerve and posterior tibial nerve were analyzed after sacrifice.

Sacrifice and (histo)pathology:

ketamine and xylazine

Positive control:

No

Statistics:

ANOVA

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

reduced body weight gain

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

effects observed, treatment-related

Description (incidence and severity):

approx. 30 % reduction

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

hindlimb weakness

Neuropathological findings:

effects observed, treatment-related

Description (incidence and severity):

Sciatic nerve and posterior tibial nerve

Effect levels

Dose descriptor:

other: axonal atrophy

Effect level:

ca. 370 mg/kg bw/day

Based on:

test mat.

Sex:

male

Remarks on result:

other:

Applicant's summary and conclusion

Conclusions:

Axonal atrophy is a specific, functionally relevant neuropathic component of hexanedione neuropathy.
Male SD rats receiving 370 mg/kg bw day (oral application) developped hindlimb weakness after 77-103 days.
Examination of the sciatic nerve and posterior tibial nerve show axonal swelling and atrophy.