The LD50 was obtained as the geometric mean of the determined experimental data on mice lethality. The value for sodium fluoride was 32 mg/kg and for sodium perborate the result was 775 mg/kg. The results concerning the SCE rate induced by sodium fluoride are shown in Table 1. Although no significant increase was observed with the two low doses tested (from 2 to 4 mg/kg), a significant SCE increase was found with the three highest doses. The cumulative frequency of these data reveals about 70% of cells with four SCE in the group treated with the high dose, a value which is twice the level of the negative control (Figure 1).
Also, a tendency for an SCE increase relative to the used doses is observed in the figure. The cellular proliferation kinetics and the MI are indicated in Table 1. With respect to the first parameter, the distribution of the evaluated cell divisions in the experimental groups gave rise to no significant variations of the AGT; in regard to the MI, the variability among the studied groups made it difficult to reach a conclusion. The results obtained in the animals treated with sodium perborate are presented in Table 2. In this case, a statistical difference of the tested compound in comparison with the control level was observed in all four tested doses, although no dose response was detected. The SCE cumulative curve shows a homogeneous distribution of the groups administered with the chemical, inducing about 50% of cells with two SCE, while control treated mice have only one SCE (Figure 2). With respect to the AGT, we found no alterations induced by the treatments, and no tendency for a significant Ml decrease.
The determination of the genotoxic potential of compounds that are present in the environment is necessary before taking the appropriate and timely preventive measures. The present report includes two examples of chemicals involved in various human activities, which have not clearly shown their mutagenic potential.
In the case of sodium fluoride numerous in vitro studies have produced contradictory information. The mammalian in vivo approach is usually considered the final step for determining genotoxicity and defining risk assessment, before regulatory measures may be taken. About fifteen in vivo studies using different research models were made between 1970 and 1998 (Kram et al. 1978; Mohamed and Chandler 1982; Li et al. 1987; van Asten et al. 1998). Most of these reports reveal negative results; in fact, only one of them is clearly positive showing increases of chromosomal aberrations in somatic and germ cells of mice that had drunk fluoridated water. The concern regarding the sodium fluoride hazard is understandable because of the direct exposure of humans to the chemical for more than 50 years; however, most in vivo reports, suggest that only high doses of the chemical may pose a danger for the genetic material and that the usual low amounts to which humans are exposed in the environment are harmless. Our data agree with this assumption, moreover, if we consider that the highest daily intake of the chemical in fluoridated water is about 6 mg/kg (Zeiger et al. 1993). In our case, we determined a genotoxic effect starting with 8 mg/kg, and only 24 mg/kg (75% of the LD50) induced a duplication of the basal level.