Graduation date: 1994

Two factorial experiments were conducted to determine if high dietary fluoride would inhibit selenite toxicity in rats. In each study, two levels of selenite (0.05 and 5 mg/kg diet) were matched against two levels of fluoride (1 and 150 mg/kg diet) for either 6 or 8 weeks. Fluoride failed to prevent the depressive effect of selenite on food intake and body weight gain in either study. Although liver selenium concentration was slightly (15%) but significantly (P < 0.005) reduced when the highest fluoride and selenium level were combined in the first study, this effect could not be repeated. These three measures therefore failed to provide evidence for a fluoride and selenium interaction. Fluoride, however, prevented hepatic necrosis seen in most of the selenite-toxic rats. Hepatic lesions seen histologically in selenite-toxic rats were not observed for either kidney or heart. With regard to a possible mechanism for the fluoride effect upon selenite liver pathology, fluoride partially (26%) but significantly (P < 0.025) reduced thiobarbituricreactive substances (an indicator of peroxidative cell membrane damage) in selenite-toxic rats, but there was no fluoride effect on an enzyme system (liver xanthine oxidase) that potentially could generate an initiator of lipid peroxidation. In agreement with results of others, fluoride deposition into bone was inconsistently affected by selenite, Overall, the protective effect of fluoride on selenite toxicity appears to be confined to liver pathology. The exact mechanism for this effect, however, remains unclear. / Graduation date: 1992

Brain stem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SEP), recorded from subcutaneously placed electrodes in anesthetized rats, were used to detect the neurotoxic effects of acrylamide and 2,5-hexanedione. Sixty adult male rats were equally divided into four groups: acrylamide (20 mg/kg/day), 2,5-hexanedione (350 mg/kg/day), food restricted and control. Brain stem auditory evoked potentials and somatosensory evoked potentials were recorded on weeks 0,1,2 and 3 of treatment. SEP waveforms were considerably more variable than BAEP results. Mean latencies in the control, food restricted and acrylamide groups were similar for the entire three weeks. A nonsignificant increase was seen in the mean latencies in the 2,5-hexanedione group. Brain stem auditory evoked potential latencies recorded on the pretreatment week were compared to each successive week within a treatment group. The control group had small but statistically significant prolongations in the latencies of wave II on weeks 2 and 3, and latencies III and IV on week 3. Results from the food restricted group were not statistically different at any time. The acrylamide group had prolongations in latency II and IV by week 3 of treatment. Latencies of all waveforms from the 2,5-hexanedione group were significantly longer than pretreatment values on weeks 2 and 3. Mean latencies of the two consistently identified somatosensory evoked potential waves (Pl, Nl) recorded from the contralateral cortex on the pretreatment week were comparable to values reported in the literature. Brain stem auditory evoked potentials recorded from subcutaneously placed electrodes in anesthetized rats can detect the neurotoxic effects of acrylamide and 2,5-hexanedione. Lack of significant differences in the food restricted group indicates the observed effects in the groups receiving neurotoxicant were not related to weight loss. Differences in the control group were of small magnitude and variance and therefore may be statistically but not biologically significant. / Master of Science