Toxicology. 2001 Jun 21;163(2-3):115-26.
Release of mercury from dental amalgam fillings in pregnant rats and distribution of mercury in maternal and fetal tissues.
Takahashi Y, Tsuruta S, Hasegawa J, Kameyama Y, Yoshida M.
Mercury vapor released from a single amalgam restoration in pregnant rats and mercury concentrations in maternal and fetal rat tissues were studied.
Dental treatment was given on day 2 of pregnancy. Mercury concentration in air sample drawn from the metabolism chamber with the rat was measured serially for 24 h on days 2, 8 and 15 of pregnancy. An average mercury concentration in the air samples from the rats given amalgam restorations was 678.6+/-167.5 ng/day on day 2.
The average mercury concentration in the air samples tended to decline as time elapsed but a marked amount (423.2+/-121.5 ng/day) was observed even on day 15.
The amount of mercury in the air samples increased 7--20-fold after chewing. The placement of the single amalgam restoration (3.8--5.5 mg in weight) increased the levels of mercury approximately three to 6 times in the maternal brain, liver, lung, placenta and 20 times in the kidneys. The highest mercury concentration among fetal organs was found in the liver, followed by the kidneys and brain.
Mercury concentrations in maternal organs and fetal liver were significantly higher than those of the controls, and concentrations in maternal whole blood, erythrocytes and plasma, and in fetal whole blood were also significantly higher. Mercury concentrations in the fetal brain, liver, kidneys and whole blood were lower than those of the maternal tissues.
Dental amalgams have been used in the treatment of decayed teeth because of the ease of manipulation and their adequate mechanical properties. However, dental fillings contain approximately 0.2—0.6 g in weight of elemental mercury mixed with amalgam alloy and this may have an adverse impact on human health. In recent years, the mercury controversy centering on dental amalgams appears to have gained more attention around the world and inorganic mercury and mercury vapor released from amalgam fillings are problems. In fact, mercury vapor released in the mouth leads to an increased uptake of mercury in the body tissues. In human studies; mercury vapor was detected in the oral cavity from amalgam placement in teeth, and the release rate of mercury increased dramatically when the amalgam was stimulated by continuous chewing (Vimy and Lorscheider, 198521; Aronsson et al., 1989). Further, Nylander et al. (1987), and Friberg and Nylander (1987) found that the mercury levels in tissues of subjects with amalgam filling were higher than those of amalgam-free subjects.
The investigators also demonstrated using various animals that when amalgam was placed in teeth, mercury levels rose in various organs and tissues (Fredin, 1987; Hahn et al., 1989, 1990; Danscher et al., 1990; Hultman et 211., 1998; Galic et a1., 1999). Vimy et al. (1990) found increased mercury in the placenta and fetal organ of pregnant ewes having occlusal amalgam filling and inferred that continued employment of dental amalgam as a tooth restorative material in pregnant women should be reconsidered. However, the relationship between the amount of mercury vapor released from amalgam placement in the mother and the mercury transfer to the fetus needs further clarification.
Studies in humans on mercury concentration in different tissues of fetuses and infants are scarce, but there was a study in 1994 (Drasch et a1., 1994) which found a correlation between the number of maternal amalgam restorations and the concentration of mercury in fetal liver and kidneys. A similar correlation was not observed in newborns or younger children. It is known that dental amalgam releases mercury as ions, as vapor, and as particulate matter. Among the various forms in which mercury can exist, elemental mercury vapor is the form of major concern within dentistry, since about 80% of inhaled mercury vapor is
absorbed across the pulmonary epithelium into the blood stream (WHO, 1991). In our preliminary animal experiment, we found a mercury uptake in maternal and fetal tissues from the maternal amalgam fillings. However, we could not elucidate whether mercury levels in maternal and fetal tissues were influenced by the mercury vapor or not.
It is common to use animals instead of humans for these studies because some confounding factors can be eliminated and, more importantly, more precise data can be obtained.
The purpose of this study was to examine the mercury vapor released from a single amalgam restoration and to determine whether the placement of a single amalgam restoration would produce statistically significant differences in level of mercury measured in maternal and fetal rat tissues when compared to controls.
It is clear that mercury concentration in 24-h air samples from the pregnant rats given a single amalgam restoration increased significantly compared with amalgam-free pregnant rats. In an in vitro study the amalgam made from Dispersalloy that was used in the present study emitted significantly more mercury for the first 24-h period but the mercury vapor emission rate from this amalgam alloy decreased with the second and third 24-h periods, and mercury vapor was not detected for more than 5 days (Chan and Svare, 1972). Dispersalloy is an admixed high-copper amalgam alloy and is Gamma-2 free. Its consistent mix of lathe-cut particles an"d silver—copper eutectic spheres virtually eliminates the Gamma-2 phase, yielding exceptional corrosion resistance and reduced ditching. During the first 24-h period, a significant amount of the liquid mercury probably had reacted with the alloy to become chemically more firmly bound in the gamma-1 and iota
phases that form during the setting of the amalgam. Therefore, large amounts of mercury on day 2 of pregnancy were mainly influenced by the mercury vapor emission from the liquid mercury because the amalgamation with the alloy may progress gradually. On the other hand, fair amounts of mercury were still observed on days 8 and 15 of pregnancy (i.e. 7 days and 14 days after the amalgam filling). The 24-h monitoring revealed that the amount of mercury in 10-min air samples increased when the rats took food, and the amounts showed a value from 7 to 20 times as much after eating. Therefore, the amount of mercury in 24-h air samples at the 8th and 15th days of the gestation period were mainly affected by chewing. This finding is consistent with the human studies which have shown a significant increase in mercury vapor levels after intakes of hot drinks, when chewing or brushing teeth (Gay et a1., 1979; Svare et al., 1981; Patterson et a1., 1985; Vimy and Lorscheider, 1985b; Berglund, 1990; Fredin, 1994).
Mercury concentrations in major maternal organs in the animals from the experimental group were significantly higher than those of the controls and the highest mercury concentration was observed in the kidneys. In human autopsy studies, the mercury concentrations of subjects with
dental amalgam filling were approximately 2-3fold higher in the brain and l0-fold higher in the kidneys than those of amalgam-free subjects (Nylander et al., 1987). In the present study using rats, the placement of single amalgam restorations increased the level of mercury approximately fold in the maternal brain and 20-fold in the kidneys. An accumulation of the mercury in organs is mainly due to continuous release of the mercury vapor from amalgam fillings since fairly large amounts of mercury vapor were observed during the experiment. Although dental amalgam placed in the oral cavity releases mercury as ions, as vapor, and as a particulate matter, it should be emphasized that mercury release from the dental amalgam fillings is mainly mercury vapor. A blood-brain barrier prevents ionic mercury from entering into brain tissue (Magos, 1968). The placenta and blood-brain barrier are often likened to each other because of their functional similarities (Villee, 1965). These functional similarities were confirmed by Clarkson et al. (1972). They found that fetal uptake of mercury was much greater when pregnant rats were exposed to mercury vapor than when they were exposed to an equivalent dose of ionic mercury. In the present study, the mercury concentrations of the pregnant rats received a single amalgam restoration were Magos et al. (1977) reported that catalase has a great capacity to oxidize mercury vapor into ionic mercury and that this enzyme is found abundantly in the liver. Blood returning from the placenta through the umbilical veins enters the fetal circulation through the ductus venous, mainly by passing through the liver (Guyton, 1976). It is most likely that oxidized mercury accumulated in the placenta and that elemental mercury crossing the placenta was oxidized into ionic mercury in the fetal liver and accumulated in that organ. This oxidation of the mercury vapor may prevent it from affecting the vulnerable fetal brain, because as mentioned above, a blood-brain barrier prevents ionic mercury from entering the brain tissues.
Usually, fetal exposure to elemental mercury is expressed as the ratio of fetal (F) to maternal (M) mercury concentration in the blood or in organs such as the liver and brain. In this study uptake of the mercury in the fetal brain and liver was lower than those of the mothers, the F/M-ratio for brain and liver was 0.3 and 0.4. In a study on ewes (Vimy et al., 1990), 12 amalgam fillings with radioactive mercury were placed in the teeth of five pregnant ewes, and the ratio for the liver was around 0.1 and the uptake of mercury in the fetal brain was almost the same as the maternal cerebrum. In the study of mercury vapor exposure, a pregnant mouse was exposed to mercury vapor (2 mgHg/mm3) on gestation day l7
and killed only 4 h after exposure, and the ratio for brain and liver was 0.1 and 0.3, respectively (Danielsson et al., 1990). A pregnant guinea pig was exposed to mercury vapor (0.2—0.3 mgHg/mm3) in five exposure periods (4-11 days, 2 h/day). The ratio for the brain was 0.2 (Yoshida et al., 1986).
In the case of a pregnant woman, who was accidentally exposed to metallic mercury vapor during pregnancy, the mercury concentration in the infant blood was lower than that in the maternal blood, and the infant to mother ratio was 0.86 (Lien et al., 1983). In the present study using rats, whole blood mercury concentration in fetuses was also lower than that of their mothers, and the ratio was from 0.59 to 0.70.
In other species, such as the monkey (Smith et a1., 1981) and guinea pig (Yoshida et al., 1986), the ratios were found to be less than one after mercury vapor exposure. By contrast, the ratio for blood mercury in late gestation in sheep exceeded one (Vimy et al., 1990), and there is some controversy on this subject between Larsson (Larsson and Sagulin, 1990) and Lorscheider (Lorscheider and Vimy, 1990). The sheep has an epitherochorial placenta, with six layers of tissue, while the rat, guinea pig and monkey have a hemochorial placenta, with three layers separating fetal and maternal blood (Faber and Thronburg, 1983). Thus, it is most likely that the permeability of the placenta of sheep is lower than that of rats and that the passage of the mercury across the placenta of sheep may be lower than that of rats. However, the exact relationship of the number of layers of the placenta to its permeability has not been investigated. Currently it is not considered to be of primary importance in determining the distribution of chemicals to the fetus.
The results of our present research indicate a continuous release of mercury vapor from dental amalgam fillings. Significant uptake and accumulation of mercury from the dental amalgam was observed in maternal major organs and fetal liver, and the highest mercury concentration was observed in the maternal kidneys and in the fetal liver. Accumulation of the mercury in the fetal liver may contribute to the decrease of mercury accumulation in the fetal brain.