produce lasting effects on rodents (Isaacson et al. 2003). The histological effects of transportation and relocation include neuronal losses and substantial instances of shrunken or bloated cells, including some with condensed cytoplasmic inclusions. Other signs of stress and neural insult can be seen, including the presence of reactive microglia throughout the brain. These changes might well interact with later fluoride treatments. In essence, this means comparisons between groups can be legitimately made within the several experiments but not between them. Mullenix et al. (1995) interpreted their behavioral results to imply the interruption of hippocampal dysfunction. Another plausible interpretation is that the behavioral change might have involved alterations in the adrenal-pituitary axis (Gispen and Isaacson 1986).

The results of the Mullenix studies are difficult to compare with studies from other laboratories. The apparatus used has a unique configuration, the chambers were small, and the paired animals were in visual, olfactory, and auditory contact with each other. The data generated are largely derived in idiosyncratic ways by the hardware and software of a relatively complex computer program. From a practical standpoint, it would be extremely difficult for other investigators to replicate the study. The committee is aware there has been debate about the interpretation and significance of the findings of this study. For example, Ross and Daston (1995) note that decreased grooming can be an indication of illness. Because of the high concentrations of fluoride used in the study, it is possible that the animals had gastrointestinal or renal disturbances (Whitford and Taves 1973; Pashley et al. 1984; also see Chapter 9). As discussed above, the committee agrees there are difficulties with interpreting the results of the study, but those difficulties do not warrant dismissal of the results. The study provided some evidence that exposure to fluoride (prenatal, weaning, or in adulthood) might have affected the behavior of rats, albeit almost always in a gender-specific fashion.

In a different type of study, Swiss albino mice were treated with NaF at 30, 60, and 120-mg/L in water for 30 days and behavioral tests were performed daily 1 hour after treatment. The testing included akinesia, catalepsy, swim endurance, and simple maze tests. Animals in the 120 mg/L group scored more poorly in all the tests. Histological changes observed in the brains of these animals are discussed later in this chapter (Bhatnagar et al. 2002).

Paul et al. (1998) investigated the effects of NaF on the motor activity and coordination of female Wistar rats. The rats were treated with NaF at 20 or 40 mg/kg/day by gastric intubation for 2 months and were tested in an activity chamber and on a rota-rod apparatus. Only female rats were used because of the high mortality rates among males in preliminary studies. In both treatment groups, food intake and body weight gain were reduced in



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