**3. The toxicology of elemental mercury-Hg**

#### **3.1 Absorption, disposition in the body, and elimination**

Hg is the only metal that takes the form of liquid at room temperature, and releases monoatomic vapours (Hg vapours) that are very stable and may remain in the atmosphere for months or even years on end. Their pressure is in equilibrium with the metal, and their concentrations attain a value of 18.3 mg/m³ at a room temperature of 24C, which is 360 times above the "permissible level" for occupational exposure (0.05 mg Hg/m³) prescribed in the Environmental Health Criteria 1, Mercury (WHO, 1976). We know today that Hg° vapours enter the body mainly through inhalation. As much as 80% of the inhaled amount of Hg° is absorbed in the lungs and then passes across the alveolar membrane very quickly into the plasma and erythrocytes, and through blood circulation into CNS, kidneys and other organs. In the tissue, Hg° oxidizes into the ionic divalent form (Hg++), which takes place by way of the hydrogen peroxide-catalase compound I enzyme system. The oxidation of Hg° in blood, although rapid, is sufficiently prolonged so that the Hg° dissolved in blood can be conveyed to the brain, where it passes the blood-brain barrier and cell membranes. Only a small amount of Hg° is oxidized during the transit time from the lungs to the brain, so that over ninety percent of dissolved Hg° arrives in the brain unoxidized. It is then oxidized in brain cells and complexed to the SH-group of the cell (Hursh et al., 1988; Magos et al., 1978). The divalent ionic Hg++ accumulates primarily in astrocytes, where it mostly binds to reduced glutathione (GSH), cystein, and metallothioneins (MTs) (Aschner, 1997; Tušek-Žnidarič et al., 2007). After Hg° vapour exposure of animals, a marked accumulation of Hg was observed in the cerebellum, nucleus olivarius inferior in the brainstem, and in the nucleus subtalamicus (Berlin et al., 1969). In autopsy samples of retired and ex-miners previously intermittently exposed to Hg°, substantially higher accumulations and retention of Hg were observed in the pituitary gland, pineal gland, hippocampus, nucleus dentatus, and in the cereballar cortex in comparison with the control group (Falnoga et al., 2000; Kosta et al., 1975) (Tab.1). Hg is eliminated in the urine, feces, expired air, sweat, saliva, and milk. In long-term occupational exposure, the kidneys are the major pathway of Hg excretion, and are not only an indicator of kidney burden, but may also be a rough indicator of total body burden. The retention of Hg in the brain observed several years after remote exposure in retired mercury miners suggests that the brain does not follow the some kinetics of elimination as the kidneys (Falnoga et al., 2000; Kosta et al., 1975; WHO, 1991). In the case of intermittent exposure to Hg°, blood Hg was very positively correlated with the spot urine

the median nerve and lower sensory conduction velocities of the ulnar nerve was observed in the subgroup of miners with long-term intermittent exposure and increased Hgº absorption (urine Hg excretion > 100g/L). In contrast to sleep disorder, these subclinical pripheral nerve function changes usually persist many years after the cessation of exposure (Gabrovec-Nahlik et al., 1977; Kobal et al., 2004), which is also in agreement with some other

As already mentioned above, sleep disorders were also mentioned in the monographs on inorganic-elemental mercury published by WHO (1976, 1991) and ATSDR (1999), which place them among the symptoms of erethism. However, no disorders of sleep structure or any possible neurobiological or biochemical mechanisms and EEG changes that could accompany sleep disorders in intoxicated subjects exposed to Hgº are described in these monographs.

Hg is the only metal that takes the form of liquid at room temperature, and releases monoatomic vapours (Hg vapours) that are very stable and may remain in the atmosphere for months or even years on end. Their pressure is in equilibrium with the metal, and their concentrations attain a value of 18.3 mg/m³ at a room temperature of 24C, which is 360 times above the "permissible level" for occupational exposure (0.05 mg Hg/m³) prescribed in the Environmental Health Criteria 1, Mercury (WHO, 1976). We know today that Hg° vapours enter the body mainly through inhalation. As much as 80% of the inhaled amount of Hg° is absorbed in the lungs and then passes across the alveolar membrane very quickly into the plasma and erythrocytes, and through blood circulation into CNS, kidneys and other organs. In the tissue, Hg° oxidizes into the ionic divalent form (Hg++), which takes place by way of the hydrogen peroxide-catalase compound I enzyme system. The oxidation of Hg° in blood, although rapid, is sufficiently prolonged so that the Hg° dissolved in blood can be conveyed to the brain, where it passes the blood-brain barrier and cell membranes. Only a small amount of Hg° is oxidized during the transit time from the lungs to the brain, so that over ninety percent of dissolved Hg° arrives in the brain unoxidized. It is then oxidized in brain cells and complexed to the SH-group of the cell (Hursh et al., 1988; Magos et al., 1978). The divalent ionic Hg++ accumulates primarily in astrocytes, where it mostly binds to reduced glutathione (GSH), cystein, and metallothioneins (MTs) (Aschner, 1997; Tušek-Žnidarič et al., 2007). After Hg° vapour exposure of animals, a marked accumulation of Hg was observed in the cerebellum, nucleus olivarius inferior in the brainstem, and in the nucleus subtalamicus (Berlin et al., 1969). In autopsy samples of retired and ex-miners previously intermittently exposed to Hg°, substantially higher accumulations and retention of Hg were observed in the pituitary gland, pineal gland, hippocampus, nucleus dentatus, and in the cereballar cortex in comparison with the control group (Falnoga et al., 2000; Kosta et al., 1975) (Tab.1). Hg is eliminated in the urine, feces, expired air, sweat, saliva, and milk. In long-term occupational exposure, the kidneys are the major pathway of Hg excretion, and are not only an indicator of kidney burden, but may also be a rough indicator of total body burden. The retention of Hg in the brain observed several years after remote exposure in retired mercury miners suggests that the brain does not follow the some kinetics of elimination as the kidneys (Falnoga et al., 2000; Kosta et al., 1975; WHO, 1991). In the case of intermittent exposure to Hg°, blood Hg was very positively correlated with the spot urine

observations (Albers et al., 1982).

**3. The toxicology of elemental mercury-Hg**

**3.1 Absorption, disposition in the body, and elimination** 


Hg mercury concentration (*r*=0.68, *p* < 0.001), which, in such types of exposure, allows use of urine Hg as a biological indicator of recent exposure (Kobal, 1991).

Table 1. Total Hg concentration in autopsy samples (homogenised tissue) of pituitary gland, pineal gland, hippocampus, nucleus dentatus and cereballar cortex (ng/g fresh weight) in ex-miners of the Idrija Mercury Mine and controls (data adapted by Falnoga et al., 2000).
