Toxicology and Applied Pharmacology 198 (2004) 209– 230

Mercury exposure in children: a review

S. Allen Counter, and Leo H. Buchanan

Abstract

Exposure to toxic mercury (Hg) is a growing health hazard throughout the world today. Recent studies show that mercury exposure may occur in the environment, and increasingly in occupational and domestic settings. Children are particularly vulnerable to Hg intoxication, which may lead to impairment of the developing central nervous system, as well as pulmonary and nephrotic damage.

Several sources of toxic Hg exposure in children have been reported in biomedical literature: (1) methylmercury, the most widespread source of Hg exposure, is most commonly the result of consumption of contaminated foods, primarily fish; (2) ethylmercury, which has been the subject of recent scientific inquiry in relation to the controversial pediatric vaccine preservative thimerosal; (3) elemental Hg vapor exposure through accidents and occupational and ritualistic practices; (4) inorganic Hg through the use of topical Hg-based skin creams and in infant teething powders; (5) metallic Hg in dental amalgams, which release Hg vapors, and Hg2+ in tissues. This review examines recent epidemiological studies of methylmercury exposure in children.

Reports of elemental Hg vapor exposure in children through accidents and occupational practices, and the more recent observations of the increasing use of elemental Hg for magico-religious purposes in urban communities are also discussed. 

Studies of inorganic Hg exposure from the widespread use of topical beauty creams and teething powders, and fetal/neonatal Hg exposure from maternal dental amalgam fillings are reviewed. Considerable attention was given in this review to pediatric methylmercury exposure and neurodevelopment because it is the most thoroughly investigated Hg species. Each source of Hg exposure is reviewed in relation to specific pediatric health effects, particularly subtle neurodevelopmental disorders.

Introduction

Over the past century, there has been an increasing awareness throughout the world of the health and developmental risks associated with environmental exposure to toxic metals, such as, lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (AS). While exposure to toxic levels of any of these environmental contaminants may result in impaired health in adults, the toxicological effects of these metal are often more devastating in the developing central nervous system and general physiological systems of children.

Although Pb is perhaps the most publicized and well known of the pediatric metal intoxicants, Hg is at least equally toxic if less well known. Mercury is ubiquitous in the global environment and derives from both natural sources and human enterprise. The presence of Hg in fish, thermometers, dental amalgams, vaccine preservatives, and in the atmosphere has made this particular toxic metal an increasing focus of health authorities and interest groups. Many industrialized nations have established procedures and policies to assess, minimize, and prevent exposure to Hg. owever, many developing, lowincome countries have only recently begun to identify sources of toxic Hg exposure in the milieu and diet, and to establish ways of protecting children, adults, and nonhuman species.

The recent popular media attention given to pediatric Hg exposure reflects the growing concerns by the general public, health officials, and policymakers about the detrimental effects of Hg on the health and development of  exposed children. In the United States, for example, several federal agencies have examined data on Hg exposure and its consequences, and have attempted to establish standards for health-based biological limits for Hg exposure in children  and pregnant women, and have informed the public of the associated health hazards through advisories (ATSDR, 1999; EPA, 1997). 

The element Hg is classified as a heavy metal (at. wt.: 200.59) and exists in three species: elemental mercury (Hg0) (also known as metallic mercury), inorganic mercury compounds (I-Hg) (primarily mercuric chloride), and organic m ercury [primarily methylmercury (MeHg)]. Exposure to each species results in both specific and general toxicological effects in children and adults. The toxicological features of each species are summarized in Table 1. 

There are several earlier and more contemporary reviews  of the toxicology of Hg available to the reader that cover a spectrum of findings ranging from sources of Hg exposure to the toxicity of different species and biological outcomes (ATSDR, 1992, 1999; Chang, 1977; Clarkson, 2002; Koos and Longo, 1976; NRC, 2000; Satoh, 2000;  Sweet and Zelikoff, 2001). The American Academy of Pediatrics, for example, issued a recent technical report reviewing the  general health effects of Hg exposure (Goldman and Shannon, 2001). One of the more comprehensive, critical reviews of the general effects of Hg exposure was compiled by Ratcliffe et al. (1996).

In this review, we cite and report the findings of a wide spectrum of studies on Hg exposure in children. Additionally, this review examines some of the studies of Hg exposure in adults and in experimental animals that may have implications for the effects of Hg exposure on children. Specifically, this review examines studies of Hg exposure in children, including fetal exposure (as a result of maternal consumption of fish, inhalation of Hg vapors,  nd the use of Hg-containing topical creams), neonatal and infant exposure from the same sources, as well as from breast milk of lactating mothers, fish consumption in young children, and finally dental amalgam in older children.

Studies of the pediatric health effects of different forms of Hg exposure, including MeHg, ethylmercury, Hg0 vapors, and I-Hg are covered. Since the most thoroughly investigated Hg species is, MeHg, particularly in the recent large  cohort studies (Davidson et al., 1998, 2000; Grandjean et al., 1997, 1998; Myers et al., 2003), this review gives substantial attention to pediatric MeHg intoxication and neurodevelopment. Secondly, this review examines exposure  to ethylmercury from pediatric vaccines that contain the controversial preservative thimerosal.

The increasing number of clinical reports of Hg0 vapor exposure in children through accidents and occupational and ritualistic practices is reviewed. Recent observations of the widespread use of Hg0 in modern, urban communities for magico-religious purposes, and its impact on children are covered. The significance of maternal dental amalgam fillings on fetal Hg levels and the Hg exposure levels of children with dental amalgams are also discussed.

Finally, we review the use of I-Hg in infant teething powders and in popular Hg-based beauty creams, which may be used by mothers, an in some cases applied by parents to children to lighten their skins, or may affect the fetus through placental transfer. Reports of Hg intoxication among some indigenous peoples who are frequently exposed  to Hg0 vapors in occupations, such as gold mining, and MeHg through dietary exposure from industrial discharge into traditional fishing waterways, are covered in a subsection. 

Biological effects of mercury exposure: an overview Elemental mercury Numerous experimental animal studies have been conducted  to elucidate the effects of Hg0 exposure, and the cellular and physiological mechanisms involved with Hg0 toxicity. For example, heavy Hg deposits were found in thealveolar macrophages of the lungs of Hg0-vapor-exposed rats by Moller-Madsen (1992). Further, animals exposed to Hg0 vapor at a level of 500 Ag Hg/m3 in air showed CNS Hg staining in the cerebral cortex, thalamus, corpus striatum, mesencephalic nucleus of the trigeminal nerve, cerebellar nuclei, and motor neurons of the spinal cord (Moller- Madsen, 1992).

Yoshida et al. (1999a) found lung damage in mice that had been exposed to Hg0 vapors. They also reported that the lungs of metallothionein-null mice exposed to Hg0 vapors were significantly more impaired than that of matched wild types, suggesting a protective role for metallothionein against pulmonary toxicity of Hg0 vapor (Yoshida et al., 1999b). Sorensen et al. (2000) reported that Hg0 vapor intoxication induced significant neuronal reduction in  the CNS, particularly in the cerebellum of rats.

They further suggested that Hg0 may have a different toxicological profile from that of MeHg, which may affect both the CNS and the peripheral nervous system. Evidence of Hg0 poisoning of the fetus from inhaled Hg0 vapors has been found in the developing blood vessels, sensory ganglia, and nervous system of mice exposed in the late  prenatal and early neonatal stages to Hg0 vapors at levels of 500 AM3 (Pamphlett and Kum-Jew, 2001).

In an investigation of the long-term effects of prenatal Hg vapor exposure on learning and motor function, Newland et al. (1996) exposed squirrel monkeys to high levels of Hg0 vapors and observed a diminution in performance on leverpress behavioral responses that may reflect Hg-induced neuromotor involvement. Warfvinge (2000) also found that  pregnant squirrel monkeys exposed to Hg0 vapors at levels of 0.5–1.0 mg Hg/m3 in air for scheduled daily periods had extensive accumulations of Hg in cerebellar nuclei, as did their offspring.

In a related study, fetuses of squirrel monkeys exposed to Hg0 vapors at levels of 0.5–1.0 mg Hg/m3 in air daily for two-thirds of the pregnancy showed a distribution of Hg in the optic nerve, ganglion cells, and retinal pigment epithelium (Warfvinge and Bruun, 2000). A more recent study by Yoshida et al. (2002) reported that Hg0 vapors at suprathreshold levels penetrated the placental barrier of experimental animals to intoxicate the fetal liver, kidneys, and brain, with placenta metallothionein playing a critical defensive role in the maternal to fetus transfer.

Elemental Hg vapors undergo a biotransformation in neuronal tissue the mercuric cation Hg2+, which is neurotoxic. At the cellular level, Hg0 may induce an alteration in structural proteins, enzymes, and synaptic transmitter substances. The neurotransmitter glutamate, for example, has been implicated in the neurotoxicity of I-Hg (Albrecht and Matyja, 1996; Brookes, 1992). It has been reported that Hg2+ selectively inhibits the uptake of synaptic  lutamate in neurons of the brain, resulting in an excitotoxic elevation of glutamate in the extracellular space and associated neuronal damage (Albrecht and Matyja, 1996). 

The effects of I-Hg on transduction at cellular membrane channels have been investigated through studies of Hg2+. In a study on the effects of inorganic Hg on cell membranes, Liang et al. (2003) found that Hg2+ induced channelopathies in guinea pig sensory cells by impairing K+ channels and changing the permeability of the cell membrane. Leong et al. (2001), for example, found that Hg2+ ions suppressed neuronal somata sprouting, thus inhibiting neurite growth in snails. It has been reported that inorganic and organic mercury block voltage-activated Ca2+ channels in nerve terminals and disrupt ligand-gated ion channels (Denny and Atchison, 1996; Sirois and Atchison, 1996).

These  and other experimental animal studies demonstrate a wide range of biological effects from exposure to different species of Hg (Castoldi et al., 2001; Gopal, 2003; Shafer et al., 2002; Yoshida et al., 2002). Sources of mercury exposure in humans

Elemental mercury

Elemental mercury (Hg0) is a naturally occurring metal (commonly called quicksilver) that exists uniquely in liquid form at room temperature and quickly turns to vapor when heated. It has a vapor pressure of 0.0007775 mm at 10 jC, which increases exponentially as the temperature is doubled.  The natural sources of Hg0 in the environment include the release of Hg gases from volcanic eruptions and the erosion of ores that contain Hg. Sources of Hg0 exposure from human enterprise include industrial fossil fuel emissions, topical medicines, cathartics, dental amalgam, thermometers, sphygmomanometer, barometers, incandescent lights, batteries, medical waste incineration, and Hg-based substances used in ritualistic practices (American Family Physician, 1992; Cranmer et al., 1996; Goldman and Shannon, 2001; Hudson et al., 1987; Isselbacher et al., 1994; Vroom  and Greer, 1972; WHO, 1991).

The toxicological effects of Hg0 are summarized in Table 1. Elemental Hg is more hazardous to humans in the vaporized state. The toxic effects of Hg0 vapors in humans have been known for centuries, especially in association with occupational endeavors. Reports of Hg0 intoxication have been traced back to the writings of Hippocrates and Galen, and in western clinical literature to Ulrich Ellenbog in 1524 (Goldwater, 1957). The occupational use of Hg0 in Japan was reported as early as the eighth century (Satoh, 2000).

Because children were often a source of labor in early large and small cottage industries in both Eastern and Western societies of past centuries, it is likely that Hg0 exposure was equally common among children and adults f earlier periods. In the early 20th century, systematic andi well-documented clinical and scientific reports of the effects of exposure to Hg0 vapors appeared in the literature. However, most early clinical reports of Hg0 intoxication ypically involved adults with occupational exposure to Hg vapors or dust (Malm, 1998; Ratcliffe et al., 1996; Sweet and Zelikoff, 2001; Vroom and Greer, 1972; WHO, 1991; Williams and Schram, 1937).

Exposure to toxic  g0 vapors may be acute or chronic, cupational or residential. Inhalation of Hg0 vapors in concentrations greater than 0.05 mg/m3 for significant periods is considered unsafe by the ATSDR (1992). The minimum risk level from chronic Hg0 inhalation is 0.3 Ag/ m3. Both acute and chronic Hg0 exposure may induce a broad sequelae of reactions or symptoms, including cough, dyspnea, fever, tremors, malaise, axonal sensorimotor polyneuropathy, gingivitis, delusions, hallucinations, and mercurial erethism, a syndrome that includes excitability,  loss of memory, insomnia, extreme shyness, and neurocognitive disorders. Children exposed to Hg0 vapors may exhibit many of the above symptoms, as well as breathing difficulty, swelling and erythema of the hands and feet, and pealing pink skin at the tips of the fingers and toes, symptomscollectively called acrodynia (Albers et al., 1982; ATSDR, 1992, 1999; CDC, 1991; Clarkson, 2002; Isselbacher et al., 1994; Satoh, 2000).

More than 80% of inhaled Hg0 vapor is absorbed by the lungs. Elemental Hg diffuses across the membranes of the alveolar sacs and enters the blood to bind with red blood cells in body tissues where it oxidizes to form mercuric ions (Hg0! Hg2 2+!Hg2+) and binds with the sulfhydryl groups. Oxidized Hg0 is accumulated in the brain, liver, and    ortex of the kidneys. The biotransformation of highly lipid soluble Hg vapor to mercuric Hg in the brain may lead to an accumulation of Hg2+ in the cortex and cerebellum, producing impairment of the CNS. Measures of the half-life of mercury involve a two-compartment system, consisting of a short half-life and a longer half-life component.

The half-life of inhaled Hg0 is 60 days (range 31–100 days), with most being eliminated through urine and fecal excretion. A small amount of absorbed Hg0 is eliminated through exhalation, sweat, and saliva (ATSDR, 1992; Goldman and Shannon, 2001; Halbach and Clarkson, 1978; Houeto et al., 1994). Elemental Hg intoxication in children may result from: 

(1) inhalation of Hg vapors

(2) exposure to Hg dust and powders

(3) exposure to latex paint containing a Hg-based fungicide

(4) accidental ingestion of Hg from instruments, such as thermometers

(5) dental amalgams

(Samuels et al., 1982; ATSDR, 1999; Evens et al., 2001; Pesch et al., 2002; Bjo¨rnberg et al., 2003). Children are believed to be at higher risk for Hg0 vapor inhalation in residential settings because the Hg vapor settles on the floor, which is in closer proximity to the crawling infant or walking toddler's respiratory system. In addition, children may handle, play with, or ingest the curiously shiny liquid Hg0 (although only about 0.01% of Hg0 is absorbed from the gastrointestinal tract) or Hg powders.

Pediatric Hg0 exposure is uncommon in most developed countries today and typically occurs only by accident. The medical literature on the toxicological effects of Hg0 exposure in children contains several references to single, isolated accidental Hg0 exposure cases, but large cohort studies are rare. However, some recent studies have reported an increase in Hg0 exposure among urban children who are exposed to vaporized Hg-based powders and metallic Hg used within their homes for ritualistic-spiritual purposes (Forman et al., 2000; Riley et al., 2001). In many gold mining operations of the Amazon Basin, the burning of gold amalgams in the outdoors by gold miners or indoors by miners' families and gold jewelry makers has been found to be a source of toxic Hg0 exposure (Malm, 1998).

Some studies show evidence of increasing pediatric Hg intoxication among certain indigenous Amer-Indians from exposure to Hg0 vapors inhaled during the burning of mercury–gold amalgam by their parents in the gold mining activities (Counter, 2003; Counter et al., 1998, 2002). In fact, the widespread use of Hg in amalgam by families to extract gold from ore may have increased pediatric Hg vapor exposure worldwide (Snodgrass et al., 1981; Solis et al., 2000; Soni et al., 1992).

Pulmonary dysfunction is the primary cause of mortality in children who inhale high levels of toxic Hg0 vapors. For example, Campbell (1948) reported a detailed case of acute pediatric Hg intoxication and death in a 4-month-old following exposure to evaporated metallic Hg vapors from a hot stove in an unventilated apartment. An autopsy revealed pulmonary edema, general edema, nephrotic degeneration, ventricular dilation, and a greyish, necrotic appearance in the mucosa of the stomach and duodenum. Matthes et al. (1958) reported the clinical course andeventual deaths of hree children aged 4, 20, and 30 months from acute Hg0 vapor exposure in the home. The primary pathological findings in the three children were severe interstitial pneumonitis, erosion of the bronchial epithelium, membrane lesions of the alveoli, and alveolar ducts and significantly  elevated Hg in the kidneys and liver. Moutinho et al. (1981) likewise reported a fatal case of accidental Hg0 vapor inhalation in a 7-month-old infant within the home during the melting of metallic Hg by the father in the family kitchen. The infant exhibited dyspnea and eventual apnea over a period of 7 days, rapidly followed by the bilateral collapse of portions of the lungs, severe acidosis, coma, seizures, and death. A postmortem examination revealed severe damage in all five lobes of the lungs, including edema, desquamation of the cells lining the alveoli and alveolar ducts, and degeneration in renal  tubular cells. It is also significant that the family's 6-month-old cat was simultaneously exposed to the Hg0 vapors and died within hours of the initial exposure. A postmortem on the cat revealed diffuse pneumonitis and pleural effusions, suggesting respiratory failure (Moutinho et al., 1981).

During pregnancy, inhaled Hg0 vapors absorbed by the mother's tissues may diffuse across the placenta to accumulate in the fetal brain and induce neurodevelopmental anomalies. For example, Lien et al. (1983) reported elevated blood Hg in three children and a pregnant woman who were accidentally exposed to Hg0 vapors. They found that the blood Hg of the mother and newborn were similar, suggesting direct transfer across the placenta. Impaired gait, numbness in fingers and toes, absence of deep tendon reflexes, elevated blood pressure, and elevated protein in the cerebrospinal fluid were observed in two children exposed to an Hg0 spill of 20 cm3 with indoor air Hg concentrations of 10–40 Ag/m3 in the home (CDC, 1991). Acute cerebellar ataxia, anorexia, fatigue, weakness, and back pain were reported in children (siblings) exposed to vapors from spilled elemental Hg in their residence (Florentine and  Sanfilippo, 1991). Soni et al. (1992) reported acute Hg0 vapor intoxication in a 3-year-old boy and the death of a second child exposed to the heating of Hg by the parents during a Hg amalgamation–gold extraction process. Solis et al. (2000) reported the death of a 13-month-old boy from acute exposure to Hg0 vapors during his parents' use of liquid Hg to extract gold from ore in a poorly ventilated kitchen. The infant had respiratory failure within 24–36 h after admission and died 25 days later showing a cellular filtrate in the alveolar sacs and severe pneumonitis. Other children in the household were similarly intoxicated by the Hg vapors (estimated at a concentration of 0.193 mg/m3 in air) but were treated successfully with chelation therapy (Solis et al., 2000).

Cherry et al. (2002) reported long-term exposure to Hg0 vapors from a Hg spill in a family residence. Over a period of 6 months of exposure to Hg vapor, a 3-year-old child in the household presented with progressive weight loss,  irritability, tremors, abnormal EEG, loss of speech and language, and ataxia. In one study of 23 children of  thermometer plant workers and 39 children in a reference  (control) group, higher urine Hg levels were found in the study group and higher Hg-in-air levels were measured in the homes of the thermometer plant workers than in the homes of the reference group (Hudson et al., 1987). This study demonstrated the risk of Hg intoxication for families  of workers who are exposed to Hg in the workplace and who may inadvertently transport the toxic Hg to their homes via their clothing and shoes. Many states and cities in the United States have banned the manufacture and sale of Hgfilled thermometers.

In recent years, a novel type of Hg0 poisoning in children has been reported with increased frequency in American medical literature. For example, Forman et al. (2000) investigated nine children in one family that had been  exposed to Hg0 vapors from spilled Hg-filled amulets purportedly used in the Afro-Caribbean religion, Santeria. They found highly elevated pretreatment Hg levels in urine, which they reduced therapeutically with a succimer  (DMSA) treatment regimen (Forman et al., 2000; Miller, 1998). Several earlier studies reported evidence of the use of Hg-filled capsules and beads in magico-religious rituals by urban American minorities (Riley et al., 2001; Wendroff, 1995; Zayas and Ozuah, 1996). As part of the rituals, Hgbased powders are regularly sprinkled about the home  where the Hg0 vaporizes and is inhaled as Hg vapor by the residents, particularly the small children who are more commonly at floor level where the Hg0 vapors settle. Ozuah et al. (2003) conducted a 3-month clinical investigation of the prevalence of Hg exposure in 100 urban, largely Hispanic and African-American children and found that 5% had elevated urinary Hg levels. They suggested that the elevated mercury levels in these children may have resulted from exposure to Hg-filled capsules purchased locally from ''Botanicas,'' mainly by women for magicoreligious purposes. This is a widening health hazard in some urban minority communities and requires increased public health attention. The situation also requires improved education regarding the health risks of Hg for the exposed population, and additional cultural education for the physicians  and other caregivers to increase their sensitivity and awareness of this mode of Hg exposure.

Elemental and inorganic mercury exposure from dental amalgams An elevated level of Hg in the blood and tissue of the fetus and infant from any source is a potential cause of neurodevelopmental disabilities. It has been known for sometime that dental amalgam is a major source of Hg0 exposure in humans because Hg is the principal metal in most dental fillings (approximately 50% Hg by weight) (Nadarajah et al., 1996). The health effects of dental amalgam Hg have been a subject of considerable debate  for years, with no scientific consensus on an association between amalgam Hg exposure and adverse health consequences,  either in adults or children (Clarkson, 2002; Ratcliffe et al., 1996). However, questions have been raised regarding a possible association between maternal Hg dental fillings and the health of the developing fetus, neonate, and infant. Significant levels of Hg have been measured in oral vapor, blood, and in organs of animals and humans with Hgcontaining dental  amalgam restorations (Abraham et al., 1984; Snapp et al., 1989; Vimy et al., 1990, 1997). In the oral cavity, Hg0 vapor is rapidly oxidized to inorganic divalent Hg (Hg2+) in vivo after release from dental amalgam and absorbed through inhalation.

Experimental animal studies have shown that Hg released from amalgam restorations crosses the placenta and induces an increase of Hg  concentration in the blood, liver, and kidney of the fetus (Takahashi et al.,  2001, 2003; Vimy et al., 1997).    Vimy et al. (1990), for example, in a study using sheep with implanted  malgam fillings, reported positive correlations between  increased concentrations of Hg in breast milk, urine, and oral vapor with the number of maternal amalgam fillings. 

In humans, Drasch et al. (1994) found significant positive correlations between I-Hg concentrations in the liver and kidneys of both fetuses and infants and the number of maternal teeth with amalgam fillings. They also reported that maternal fillings may influence the concentration of Hg in the cortex of older children. Oskarsson et al. (1996) reported significant correlations between Hg levels in blood  and the breast milk of lactating women as a  result of   absorption from dental amalgam fillings. Similarly, Vahter  et al. (2000) found that the concentration of I-Hg in the fetus is influenced by the number of maternal dental amalgam  fillings. Ask et al. (2002) reported that the median concentration  of I-Hg in the placenta was four times higher than in maternal and umbilical cord blood, and that the accumulation of placental Hg was influenced by the number of maternal amalgam fillings.

They concluded that the high I-Hg concentration observed in the placenta originated from Hg0 released from Hg amalgam fillings and oxidized to Hg2+ by catalase in the blood. Pesch et al. (2002) examined German children with amalgam fillings and found higher Hg levels in the urine of children with amalgam fillings than in children without amalgam fillings. In addition, Pesch et al. (2002) concluded that more reliable estimates of dental amalgam Hg exposure in children may be derived from the number of fillings rather than the surface of amalgam fillings or salvia.  Recently, Bjo¨rnberg et al. (2003) also reported a significant increase in fetal I-Hg exposure, mainly in cord blood, with increasing maternal dental amalgam fillings. Lindow et al. (2003) investigated hair Hg levels in mother–fetal pairs in relation to maternal dental amalgam restorations.

These investigators found a positive correlation between fetal hair Hg level and the number of maternal amalgam  fillings. By implication, the results of the above-referenced dental amalgam studies suggest that the presence of significant concentrations of Hg in the organs of the fetus, neonate, and infant may be a basis for adverse health effects, including the subtle neurodevelopmental disabilities that are associated with Hg exposure. However, there  still appears to be little definitive scientific evidence of specific adverse health and neurobehavioral effects in children who have been found to have elevated Hg levels from maternal dental amalgam. The neurobiological and neurodevelopmental effects of maternal  dental amalgam Hg exposure in children is an area in need of more extensive scientific investigation.

DISCUSSION:

Elemental Hg exposure through accidents, magico-religious rituals, and vapors from amalgam burning in gold mining operations continues to be a public health concern. The cessation of the manufacture of Hg-containing thermometers, and other such devices will reduce the potential for Hg exposure through accidents and in the workplace.  Further, education of indigenous populations about the hazards of Hg use in gold mining operations, and the introduction of public health information to religious groups that use Hg0 in their ritualistic practices may assist in reduction of pediatric Hg exposure in these groups.

Inorganic Hg remains an important source of Hg intoxication, primarily through the use of skin-lightening creams and teething powders, which may produce neurological, nephrological, and dermatological disorders. Although the manufacturing of some Hg-containing creams is illegal in America and some European nations, the use of Hg-based skin-lightening cosmetics has increased worldwide and has caused widespread Hg-induced health effects in some countries. Because it has been shown that the I-Hg in some cosmetics may cross the placenta to reach the fetus, pregnant women and women of childbearing age should avoid the use of Hg-based cosmetics.

The health effects of Hg amalgam fillings (generally consisting of 50% Hg), which produce a combination of Hg0 vapor in the oral cavity and I-Hg in the blood and body tissues, have been a subject of concern for years. Some scientific studies suggest that Hg from maternal dental amalgam fillings may influence prenatal and postnatal development because of the high concentrations of Hg observed in fetal tissue and neonatal blood.

Numerous studies have shown that as the number of maternal amalgam fillings increase, the amount of Hg in the tissues of the fetus increases. This suggests potentially harmful consequences to the developing nervous system, which is highly vulnerable to neurotoxic metals such as Hg and Pb. However, there appears to be little scientific information on the neurodevelopmental effects in children born to mothers with Hg amalgam fillings. This is an area in which populationbased research is needed. 

In summary, this review presented and overview of the sources and effects of Hg exposure in children. It covered the most recent and ongoing large cohort longitudinal studies of MeHg intoxication in children, as well as contemporary studies of MeHg exposure in pregnant women who consumed varying amounts of fish, the primary source of MeHg intoxication. Accidental, occupational, and ritualistic exposure to Hg0 vapor in both modern and traditional societies was explored. Lastly, the toxic effects of I-Hg from the use of Hg-based topical cosmetics and teething powders, as well as from dental amalgams were examined.