Neurotoxic effects of 2,5-hexanedione on rapidly growing unmyelinated peripheral nerve axons of a rat fetus: dose-effect relationship.

To investigate the potential neurotoxicity of 2,5-hexanedione (2,5HD) on developing axons we examined peripheral nerves of rat fetuses. Pregnant female Sprague-Dawley rats were injected subcutaneously with 680 mg/kg of 2,5HD once a day from Day 12 of gestation (GD12) to GD16 in one group and with 340 mg/kg of 2,5HD once a day from GD12 to GD20 in the other group. On GD20 live fetuses were removed from the uteri and their sciatic nerves were examined morphologically. By electron microscopical observations, affected nerves revealed axons which were aggregated and fused together, but there were no axons aggregated with neurofilaments. The diameter distributions of axons revealed an increase in the number of small-size axons in the nerves of the 340 mg/kg group and showed an enlargement of part of the axons in the nerves of the 680 mg/kg group, suggested by the appearance of a second peak at a diameter larger than that of the first peak.