Studies on the method of measuring nerve conduction velocity in rat's tail and on the comparative toxicity of n-hexane, methyl n-butyl ketone and 5,5-hexanedione (author's transl)

Abstract

n-Hexane is widely used in industry as a solvent and is one of the main ingredients of many petroleum solvents. It is well known as a neurotoxic agent causing polyneuropathy. Methyl n-butyl ketone (MBK) is one of the new so vents but is not widely used in industry today, because it was found to be severely neurotoxic in the U.S.A. 2, 5-Hexanedione is not used as an organic solvent but is known to be neurotoxic. Their neurotoxicity and metabolism have been studied by some reseachers, because they may have similar metabolites. However, comparative toxicity of these three chemicals had not yet been studied enough. Comparative toxicity of them to the peripheral nerve was electrophysiologically studied in the present experiment. Conduction velocity and residual latency were measured in the rat's tail without anesthesia and operation in order to observe the changes of peripheral nerve function for a long time (Fig. 1). n-Hexane, MBK and 2, 5-hexanedione were orally administered to Wistar strain male rats everyday for 4 weeks (Table 1). Motor conduction velocity (MCV), mixed nerve conduction velocity (MNCV) and residual latency (RL) were repeatedly measured for 8 weeks. Nerve conduction velocity increased lineally in the rate of about 1 m/sec/°C within the temperature range from 21 to 38°C in the liquid paraffin bath (Fig. 3), and increased lineally with age from 42 to 110 days after rat's birth (Fig. 4). In n-hexane 0.1 ml/day group, MNCV (CA, i.e. for the span of tail between the points as indicated in Fig. 1) was significantly slower than the control on and after 4 weeks, and MCV and MNCV (CB, Fig. 1) were significantly slower than the control after 8 weeks, and the residual latency was significantly longer than the control after 8 weeks. In n-hexane 0.2 ml/day group, MCV and MNCV (CA, CB) were significantly slower than the control on and after 4 weeks. In MBK 0.1 ml/day group and MBK 0.2 ml/day group, MCV and MNCV (CA, CB) were significantly slower than the control on and after 4 weeks, and the residual latency in MBK 0.2 ml/day group was significantly longer than the control after 8 weeks. In 2, 5-hexanedione 0.05 ml/day group, MCV and MNCV (CA, CB) were significantly slower than the control on and after 2 weeks. In 2, 5-hexanedione 0.1 ml/day group, MCV was significantly slower than the control on and after 1 week, and MNCV (CB) on and after 2 weeks and MNCV (CA) on and after 4 weeks. And the residual latency was significantly longer than the control on and after 4 weeks (Figs. 5-9). Changes of nerve conduction velocities were correlative to body weights in the control and body weights of all groups administered with chemicals were significantly smaller than the control. Therefore, the increase ratio of conduction velocity per body weight gain (ΔCV/ΔBW) of rats was calcurated and compared with the control (Fig. 10). The calcurated values (ΔCV/ΔBW) in MBK and 2, 5-hexanedione groups were significantly smaller than the control. ΔCV/ΔBW in n-hexane group also tended to be smaller than the control, but the differences were statistically not significant. The experiment demonstrated that these chemicals could cause neuropathy in rats by oral administration as well as by inhalation and injection, and they were toxic to the peripheral nerve in the order of 2, 5-hexanedione>MBK>n-hexane. It also showed that the present method was relatively simple and useful to detect the early impairment of the peripheral nerve.