- Email: [email protected]
Mercury in Fish: Human Health Risks
Mercury in Fish: Human Health Risks HM Chan, University of Northern British Columbia, Prince George, BC, Canada & 2011 Elsevier B.V. All rights reserved.
Abbreviations AA BMDL DGAC DHA JECFA NRC PBPK PUFA SCAN
arachidonic acid benchmark dose level US Dietary Guidelines Advisory Committee docosahexanoic acid Joint Expert Committee on Food Additives and Contaminants US National Research Council physiologically based pharmacokinetic polyunsaturated fatty acid Scientific Advisory Committee on Nutrition
Introduction Owing to its high toxicity to both humans and animals, Mercury (Hg) is one of the most commonly studied trace elements in the environment. It is released into the environment through both natural and anthropogenic sources and can exist in three forms: elemental, inorganic, and organic. In both freshwater and saltwater ecosystems, the organic form (methylmercury, MeHg) is predominant and has a high propensity to accumulate in fish tissue through ingestion and absorption. Therefore, dietary consumption of fish and other seafood including shellfish and molluscs is a major route of mercury exposure among human populations. The commercial production of organic mercury, including MeHg, began in the 1930s; however, its use in chemical research and records as a potential toxicant dates as far back as the 1860s. Since then, MeHg has come to be known as one of the most hazardous environmental pollutants. Many endemic disasters are attributed to MeHg, such as the Minamata disease in Japan and poisoning from the distribution of wheat seeds dressed with MeHg in Iraq. The amount of mercury being released into the atmosphere has increased due to human activities such as burning of fossil fuels and municipal waste incineration. Metal mining and smelting, the use of Hg in gold mining, chloralkali production, and biomedical waste are also anthropogenic sources contributing to increased Hg in the environment. Some human activities can alter the biogeochemical character of aquatic systems without actually increasing the environmental deposition of Hg; for instance, the flooding of soils to create reservoirs
increases the decomposition of vegetation, the dissolution of organic carbon, and the release of Hg bound to organic material in the water. This causes increase in net Hg methylation rates, resulting in increased Hg bioavailability and, in turn, MeHg exposure in humans. Higher-than-normal levels of Hg in the environment can be attributed to industrial activities such as mining, the pulp and paper industry, and the production of chlorine from the chloralkali industry. Further, appreciable quantities of Hg can also enter the environment from weathering of mineral deposits and the ongoing geochemical recycling of Hg and volcanic disruption. Recent studies have found that burning of fossil fuel for power generation plants is becoming a major source of Hg pollution globally. As emission in the form of metallic Hg, whose atmospheric residence time is long enough to cause nearly uniform mixing in the hemisphere, much of the impact is global. In 2008, Sunderland and colleagues used sophisticated atmospheric models and estimated that anthropogenic emissions in the United States and Canada account for 28–33% of contemporary atmospheric deposition in this region, with the rest from natural (14–32%) and global sources (41–53%). They also suggested that at present atmospheric Hg deposition rates by 2050 Hg concentrations in the North Pacific Ocean would double relative to c.1995. Many populations around the world depend on fish as their major source of food and nutrients. The presence of Hg in fish poses a potential threat to their health. This article discusses the risk of Hg exposure in the context of the nutritional benefits associated with fish consumption.
Factors for Increased Mercury Levels in Environment and Fish Mercury is different from most environmental contaminants in that it is naturally occurring and can be detected almost anywhere in the environment, although at low quantities. Normal background levels of mercury in sediments are usually below 0.1 mg g1 (ranges between 0.01 and 0.2 mg g1). When not affected by anthropogenic activities, Hg makes its way into aquatic ecosystems mainly by deposition from the atmosphere and runoff from soils. It is well known that Hg is a toxic element and that its toxicity is very much dependent on its chemical form. The common Hg species found in the environment are elemental Hg (HgO), mercurial ion (Hg2þ), and
697
698
Mercury in Fish: Human Health Risks
methylmercury ion (MeHg or CH3Hgþ) complexing with various inorganic and organic ligands, and various solid forms of Hg such as mercury sulfide and oxide. The most toxic Hg species is MeHg due to its lipophilic nature and effectiveness in penetrating into cell membrane and sensitive organs such as placenta and brain, where it can cause severe damages. Although the concentration of Hg in the earth’s crust is very low at approximately 0.05 mg g1, its potential environmental risk is high because Hg can transform from one chemical form to another and can be transported through air by particles and as HgO. Hg is the only metal that is volatile at room temperature. It can also be volatilized from Hg2þ in aquatic systems through the effects of solar irradiation. The movement of Hg within the environment, and in particular within the hydrosphere, is influenced by a number of factors. Inorganic forms of Hg are easily bound to other molecules; therefore, anything affecting the characteristics of sediment or the water column will often determine the Hg mobility. Studies have shown that sediment-binding capacity increases with increased organic content and decreases with relative oxidation; thus, sediment grain size, organic content, oxidation conditions, redox potentials, and the density of aquatic organisms will all affect Hg uptake. It is well documented that over 90% of Hg in lake systems is found in the bottom sediment and that these sediments will retain Hg for a long period of time. The main mobilization mechanism for Hg in the environment is through the formation of organic forms. Alkylation is a process that combines inorganic Hg with one or two methyl groups forming monomethylmercury or dimethylmercury. Methylation of Hg is a detoxification process that is performed by microorganisms such as bacterium, fungi, and mold; hence the rate of methylation is dependent on the abundance of these organisms. Further, factors such as oxidative state and pH levels affect the numbers of microorganisms in sediments or in the water column, which in turn affects the production of mono- and dimethylmercury. Bioaccumulation of Hg is dependent on the type of ecosystem an organism occupies. Characteristics such as water chemistry and food abundance determine the amount of Hg available to fish and, therefore, the amount that can possibly be concentrated in fish tissue. It is well known that Hg concentrations in fish can be elevated in newly flooded areas. The flooding of vegetation and terrestrial soils through natural and anthropogenic sources contributes to elevated Hg concentrations in the food web of flooded environment. It has been proven that reservoir formation often leads to elevated Hg levels in fish relative to preimpoundment concentrations, even in cases where no point source discharges of Hg are evident. This has been reported in Canada, the United States, Finland, and India. In many
cases, it seems that the source of Hg is a redistribution of the metal from materials already in the lake or river before flooding. Reservoirs can cause severe environmental impacts, generally due to the very rapid and drastic changes in the flooding conditions of upstream and downstream areas. Evaporative loss of water can occur due to the presence of large areas of artificial reservoirs, which would otherwise be available for downstream human and ecological uses. Further, seepage may also occur from the porous foundations underlying hydroelectric reservoirs. The magnitude of increases in Hg concentration depends on many factors, including the area of land and vegetation inundated, water temperature, pH, age and retention time of the reservoir, and trophic status and species of fish. The relationship between the rising concentration of Hg in fish tissue and the size and age of the fish is also well known. The levels of increase depend on trophic status and diet; the lowest levels are in aquatic plants, intermediate in invertebrates, and highest in fish and piscivorous mammals and birds. Almost all Hg found in biological systems has been absorbed in the form of MeHg, which can bioaccumulate and biomagnify within aquatic food webs and is highly absorbable (95–100%) from the diet compared to inorganic Hg (5–10%). As a result of bioaccumulation of MeHg through multiple levels of the aquatic food web, higher trophic level pelagic fish can be contaminated with MeHg at concentrations in excess of 1 mg g1. The mean concentrations of total Hg vary widely across fish and shellfish species, with the mean values differing by as much as 100-fold. MeHg is bound to proteins as well as free amino acids that are components of muscle tissues and are not removed by any cooking or cleaning processes that do not destroy muscle tissues. Because MeHg is the main form of Hg found in fish (490%), the following sections will focus on the toxic effects of MeHg.
MeHg Intake from Fish Consumption Fish is an important source of food in many countries and communities. The average apparent per capita consumption increased from approximately 9 kg per year in the early 1960s to 16 kg per year in 1997. The proteins derived from fish, crustaceans, and molluscs account for between 13.8% and 16.5% of the animal protein intake of the human population. Currently, two-thirds of the total food fish supply is obtained from capture fisheries in marine and inland waters, whereas the remaining onethird is derived from aquaculture. The contribution of inland and marine capture fisheries to per capita food supply has stabilized to approximately 10 kg per capita in the period 1984–98. Fish contributes up to 180 kcal per
Mercury in Fish: Human Health Risks
capita per day or 9% of energy intake, assuming average daily intake at 2000 kcal, but reaches such high levels only in a few countries where there is a lack of alternative protein foods grown locally or where there is a strong preference for fish (e.g., Iceland, Japan, and some small island states). More typically, fish provides approximately 20–30 kcal per capita per day or 1–2% daily energy intake. Worldwide, approximately a billion people rely on fish as their main source of animal proteins. Dependence on fish is usually higher in coastal areas than in inland areas. Approximately 20% of the world’s population derives at least one-fifth of its animal protein intake from fish, and some small island states depend almost exclusively on fish. High levels of MeHg exposure have been identified in numerous fish-eating populations throughout the world. Many of these live near oceans, major lakes, and rivers or hydroelectric dams and are often dependent on local catch, with fish as an integral part of their cultural traditions. For many Northern communities, the problem is often compounded by the consumption of fish-eating marine mammals. Despite the importance of local catch, fish is also a global commodity. In the United States, individuals with elevated blood Hg concentrations have been reported among affluent urbanites, who consume large quantities of marine fish, high in the food web. Thus, elevated MeHg exposure, around the globe, has no geographic, social, economic, or cultural boundaries. Although most reports on MeHg exposure have focused on specific populations, generally assumed to have high levels of fish consumption and correspondingly elevated levels of MeHg intake, estimates of general population exposure exist for the United States, the EU, and Japan. Most studies have identified a clear association between the frequency of fish consumption and Hg exposure. However, several factors can modulate this relationship. For the most part, those who eat mainly carnivorous fish or fish-eating birds or mammals have higher levels of Hg compared to those who eat mainly noncarnivorous fish. Thus, the rate of fish consumption by itself is not necessarily a reliable predictor of MeHg exposure. The species of fish consumed, the presence of pollution source, and the geochemical characteristics of the water bodies are also important factors in this variability. Consumption of farmed fish can also lead to MeHg exposures, due in part to the presence of MeHg in feed. Some studies have shown no significant difference in MeHg levels in farmed versus wild salmon, although with relatively low values in both cases. A relatively small number of studies have reported MeHg levels in farmed freshwater fish, with concentrations both slightly higher and lower than wild-caught fish from nearby waters.
699
Kinetics of MeHg Methylmercury is easily and efficiently absorbed through the gastrointestinal tract into the bloodstream, where it is rapidly transported to other parts of the body. Approximately 95% of the MeHg ingested through fish consumption is absorbed in the gastrointestinal tract. In the bloodstream, more than 90% of the MeHg accumulates in red blood cells and plasma, where it is bound mainly to the plasma proteins. Approximately 5% of the body burden is found in the blood compartment and approximately 10% settles in the brain. In animal studies, variation in absorption kinetics has been related to factors such as sex and age, as well as dietary elements, including macronutrients, lipid and fatty acid content, fiber, and protein and amino acid supplements. In humans, there is evidence of ethnic differences in Hg accumulation, suggesting that diet and metabolic differences may be influencing mercury uptake and excretion. Dietary elements can modulate Hg uptake in humans. Several studies suggest that selenium may play a role in MeHg absorption or excretion; for example, fruit consumption was associated with lower hair Hg concentrations in the Brazilian Amazon. MeHg can be metabolized to inorganic mercury, which accumulates primarily in the kidneys. Kidney levels of inorganic mercury tend to build up after longterm exposure to MeHg. MeHg is also converted to inorganic mercury in the brain. Elevated concentrations of inorganic Hg have been found in autopsy brain samples from people who died many years after an acute exposure to MeHg. The inorganic mercury is believed to be in an inert, insoluble form that can remain in brain tissues for many years, perhaps for the lifetime of the individual. The toxicological role of the inert, insoluble form remains a matter of some debate as new evidence has shown that inorganic Hg is more impotent in inhibition of neurotransmitter receptors in neurons. MeHg is excreted slowly over a period of several months, mostly as inorganic Hg in the feces. It may take 45–70 days for the MeHg concentrations to fall by half in a person’s blood, and 70–80 days in the entire body, but substantial variations in time scale can occur. The kidneys retain the highest tissue concentrations of Hg, though the total amount deposited in muscles can be higher. The mean total Hg level in blood in the general population is approximately 1–8 mg l1. The International Commission on Occupational Health and the Commission on Toxicology of the International Union of Pure and Applied Chemistry determined, using a metaanalysis of published studies, that the background blood level (mean value) in persons who do not eat fish was 2 mg l1. This background value represents the average level in blood in the general population. However, in populations without dental amalgam and who do not
700
Mercury in Fish: Human Health Risks
consume fish, the blood mercury levels are even lower. Nevertheless, in communities with high fish consumption, individuals have been estimated to have blood levels of 200 mg l1 associated with daily Hg intake of 200 mg per day. MeHg is actively transferred to the fetus across the placenta via neutral amino acid carriers during gestation. Maternal and cord blood Hg concentration is highly correlated, but cord blood Hg is consistently higher than the corresponding maternal concentration, with an average ratio of approximately 1.7. The maternal body burden of MeHg tends to decrease during gestation, consistent with the transfer of a portion of the maternal body burden to the fetus. Neonatal and infant exposure to MeHg occurs through intake of mother’s milk, which is derived from maternal plasma, enriched in inorganic Hg relative to the whole blood. Thus, lactational exposure to MeHg is reduced compared to what would be expected on the basis of maternal blood Hg. Following birth, fetal MeHg levels decline to approximately 40–50% at 2–3 months of age. During this period, infants’ body weight increases approximately 1.5–2 times. Consequently, the rapid increase in body weight and the limited MeHg transfer appear to explain the dilution of MeHg in infants during breast-feeding. Toxicokinetic (pharmacokinetic) models and physiologically based pharmacokinetic (PBPK) models have been developed to predict changes in MeHg concentration in various tissues in response to changes in MeHg intake, and in response to physiological changes (e.g., pregnancy and growth).
Hair as Biomarker for MeHg Exposure MeHg accumulates in hair. The brain–blood concentration ratio ranges from 3:1 to 6:1, and the hair–blood concentration ratio is between 250:1 and 300:1 in humans at the time of incorporation of Hg into the hair. Hair is often used as a biomarker for chronic MeHg exposure. As hair grows on an average of 1 cm per month, measuring hair in 1 cm segments can document the exposure in previous months and can account for seasonal variations in intake. Hair Hg is predominantly MeHg, which constitutes from 80% to 90–98% of total hair Hg. Once Hg is incorporated into the hair, it remains unchanged. The hair Hg level is dependent on the amount of fish consumed. The background level of hair Hg associated with little or no fish consumption or with the consumption of fish with low MeHg concentrations is usually between 0.2 and 1.0 mg g1. Much higher hair Hg levels can result from the consumption of large amounts of fish or sea mammals. In the Faeroe Islands population, the mean hair Hg level ranges from 1.6 to 5.2 mg g1. In Indigenous
populations from northern Canada, levels higher than 40 mg g1 were reported. Biomarkers like hair Hg concentrations reflect the cumulated dose of Hg exposure over time. Under some circumstances, episodic exposures can result in large bolus doses of MeHg, which arise, for example, from the infrequent consumption of fish or fish-eating mammals with high concentrations of MeHg. Bolus doses, particularly during putative discrete windows of sensitivity in brain development, may not be fully revealed by biomarkers, but may have an effect that cannot be clearly predicted from longer-term average estimates of exposure. Recent advances in a single hair strand analysis including measurement of Hg at micron resolution using laser ablation will yield more information on the relationship between Hg uptake and deposition in hair. It is common practice to compare studies of Hg exposure in different populations using different biomarkers assuming that there is a constant ratio between blood and hair Hg mercury concentrations. However, there is considerable inter- and intraindividual variability. To some extent, this may result from the temporal differences in Hg accumulation by each biomarker, particularly with infrequent or intermittent fish consumption.
Toxicity of MeHg Long-term exposure to either inorganic or organic Hg can permanently damage the brain, kidneys, and developing fetus. Organic Hg ingested in contaminated fish may cause greater harm to the brain and developing fetus because MeHg readily crosses the placenta and the blood–brain barrier and is neurotoxic. The developing fetal nervous system is especially sensitive to Hg effects. Prenatal poisoning with high-dose MeHg causes mental retardation and cerebral palsy. The scientific evidence indicates that exposure to MeHg is more dangerous for young children than for adults. This is because of the lower thresholds for neurological effects from MeHg and the higher levels of distribution of MeHg to the developing brains of young children, which can result in interference with the development of motor and cognitive skills. MeHg was the main pollutant that caused the severe neurological impairment of individuals in the vicinity of Minamata Bay, Japan, during the 1950s to the 1970s. The action of MeHg on adults is characterized by a latency period between exposure and the onset of symptoms. The latency period can vary from several weeks to months depending on the dose and exposure period. In adults, the earliest effects are nonspecific symptoms such as paresthesia, malaise, and blurred vision; with increasing exposure, there are signs such as constriction of the visual field, deafness, dysarthria, and ataxia, ultimately
Mercury in Fish: Human Health Risks
leading to coma and death. The symptoms of Minamata disease include the following: sensory disorders in the extremities (loss of sensation in the hands and feet), ataxia (difficulty in coordinating the movements of hands and feet), narrowing of the field of vision, hearing impairment, difficulty in maintaining balance, and speech impediments. In very severe cases, victims fall into a state of disorientation and confusion, lose consciousness, and may die. In relatively mild cases, symptoms include headaches, chronic fatigue, and a generalized inability to distinguish tastes and smells. In infants exposed to high levels of MeHg during pregnancy, it is difficult to distinguish the cerebral palsy caused by other factors. The main symptoms include microcephaly, hyperreflexia, gross motor and mental impairment, and, in rare cases, blindness or deafness. In milder cases, the effects may become apparent only at a later stage, taking the form of psychomotor and mental impairment and persistent pathological reflexes.
Fish Consumption and Child Development Because there are many populations around the world that consume large amounts of fish, epidemiological studies were undertaken in the past two decades to determine whether populations frequently consuming fish were indeed at risk. The focus of these studies was on prenatal exposure and its association with child development because the developing brain appears to be most sensitive to the effects of MeHg. Investigations into the risks from prenatal exposure have been carried out in Canada, Peru, New Zealand, the Faeroe Islands, the Seychelles, the United States, and Japan. Their results show that MeHg exposure from the consumption of fish by pregnant women, even at low mercury concentrations (i.e., approximately one-tenth to one-fifth of the observed effect levels in adults), may have subtle, persistent effects on the children’s mental development. However, conclusions from these studies have not been consistent. Some reported an association between prenatal MeHg exposure at levels achieved by fish consumption and the child’s scores on developmental tests, whereas others found no association using similar or identical tests. These studies are complex to execute and thus difficult to compare because of differences in study populations, end points measured, covariates assessed, statistical methods utilized, and other factors. The most comprehensive investigations performed so far are the studies that were conducted in New Zealand, the Seychelles, and the Faeroe Islands. Using multiple regression analyses, the results of clinical examinations and neuropsychological testing were compared with MeHg exposure in the mothers. No clear-cut Hg-related clinical abnormalities were found in all these studies.
701
A maternal hair Hg level above 6 mg g1 was associated with lower intelligence quotients (IQs) (from 93 to 90) in children in the New Zealand study. In the Seychelles prospective study, the study population was a cohort of 779 children born to mothers exposed to MeHg from a diet high in fish (typically 10–15 meals per week). The neurological and developmental effects in the children were evaluated at 6.5, 19, 29, 66, and 107 months and 10.7 years of age. No definite adverse neurodevelopmental effects were observed in infants up to 29 months of age at maternal hair levels of up to 12 mg g1. At hair levels greater than 12 mg g1, the percentage of infants with normal Revised Denver 25 Developmental Screening Test scores decreased from 93% to 87%, but there was no effect on the developmental milestones of walking and talking. In this study, no consistent adverse association between prenatal MeHg exposure at maternal hair levels of up to 12 mg g1 (from fish consumption) and child development was identified in 643 children aged up to 9 years. Twenty-one neurodevelopmental end points were assessed. In the Faeroe Islands prospective study, the population was exposed to MeHg primarily from pilot whale meat with MeHg concentrations ranging from o1 mg kg1 to more than 3 mg kg1. The original birth cohort of 1022 started between 1986 and 1987. In 900 children from the Faeroe Islands, prenatal exposure to MeHg was associated with a neurological deficit at 7 years of age. Neurological deficits were found in the areas of language, attention, and memory, and were found to be related to increasing Hg exposure. Developmental delays were significantly associated with MeHg exposures, even when children whose mothers had hair Hg levels above 10 mg g1 were excluded. Within the lowexposure range, each doubling of the prenatal exposure concentration was associated with a developmental delay of 1–2 months. There is some suggestion that the neurological deficit may be due to an interaction between MeHg and polychlorinated biphenyl present in the diet (in whale blubber) of these mothers. However, the results were approximately the same when polychlorinated biphenyl levels were taken into account, and increased prenatal exposure to MeHg appeared to enhance the toxicity of these hydrocarbons. Researchers of the Seychelles study repeated their study on children aged 10.7 years using the same assessment method used by the researchers of the Faeroe study and still found no significant association between prenatal exposure and adverse developmental effects. A recent study has used dose–response information collected from all these studies conducted in the Faeroe Islands, New Zealand, and the Seychelles islands to estimate the relationship between maternal mercury body burden and subsequent childhood decrements in IQ , using a Bayesian hierarchical model to integrate data from three epidemiological studies. They found a central
702
Mercury in Fish: Human Health Risks
estimate of 0.18 IQ points (95% confidence interval: 0.378 to 0.009) for each parts per million increase in maternal hair Hg, similar to the estimates for both the Faeroe Islands and the Seychelles study, and lower in magnitude than the estimate for the New Zealand study. IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study. In a recent cohort study conducted in the United States, an inverse relation was observed between Hg concentration in maternal hair and infants’ performance on a visual recognition memory task at levels of Hg exposure consistent with background exposure in the US population (maternal hair levels varied between 0.02 and 2.38 mg g1). Interestingly, in this study, fish consumption per se was associated with better performance. This suggests that some positive aspects of fish consumption are reduced, or antagonized by the MeHg contained in the same fish. This risk benefit of fish consumption will be discussed in the section ‘Balancing Benefits and Risks’. It is important to note that even though the effects at these dose levels may not seem severe on an individual basis, they may have serious implications for populations. In 2008, Sparado and Rabl estimated that the average global lifetime impact and cost per person at current emission levels are 0.02 IQ points lost and $78.
Health Agency Efforts to Establish Safe Levels of MeHg Exposure Various public health agencies have tried to determine the risk of MeHg ingestion to the general population. In 1972, the World Health Organization (WHO) established a tolerable weekly intake of 3.3 mg kg1 (0.47 mg kg1 per day) MeHg in the diet, based on data from Japan. Based on the information generated from the recent epidemiological data, the US National Research Council (NRC), the Joint Expert Committee on Food Additives and Contaminants (JECFA) under the Food and Agriculture Organization (FAO), and the WHO have developed lower tolerable levels for women of child-bearing age. To put the methylmercury exposure levels in perspective, for the neurodevelopmental effects, the benchmark dose level (BMDL) for a 5% effect (BMDL 05) from the Faeroe Islands study was approximately 58 ppb (mg l1) for mercury in cord blood. This was based on the neurobehavioral end points in infants. On the basis of a BMDL 05 of 58 ppb (58 mg l1) for cord blood mercury and with the application of a conversion (cord blood to
maternal hair) factor of 200, this BMDL 05 would be equivalent to a 12 ppm (12 mg g1) maternal hair Hg level, or 48 mg l1 in terms of the maternal blood mercury level. Using this BMDL, the NRC recommended intake level at 0.1 mg kg1 per day. These varying limits of the amount of MeHg that can be safely consumed appear to result from the different studies on which they are based, the uncertainty or safety factor that each agency felt was most appropriate, and differences in definitions (i.e., RfD, MRL, and tolerable weekly intake). Because fish is the primary source of Hg exposure among the general population, many governments provide dietary advice to limit fish consumption where there are elevated Hg levels. The WHO and the FAO of the United Nations recommend a maximum of 0.5 ppm of Hg in nonpredatory fish and 1 ppm in predatory fish. The US Food and Drug Administration has set a maximum level of 1 ppm in fish, shellfish, and aquatic animals. Canada and the European Community allow 0.5 ppm in fishery products, and Japan allows up to 0.3 ppm.
Benefits of Fish Consumption The importance of fish consumption for health and nutritional status is immense, and it has provided humanity with an essential food source for thousands of years. Fish is a protein source superior to beef, pork, chicken, and even milk proteins due to its amino acid profile and ability to support growth. Further, the fatty acid profile of fish differs significantly from these alternative sources of protein: approximately 50% of the fatty acids in lean fish and 25% in fatty fish are polyunsaturated fatty acids (PUFAs). In comparison, only 4–10% of fatty acids are polyunsaturated in beef, whereas 40–45% are saturated. Fish are also a source of many vitamins, including niacin and vitamins B12, D, and A. Also, fish provide a dietary source of micronutrients including selenium, iodine, taurine, fluoride, calcium, copper, and zinc. Maternal intake of fish has also been observed to be valuable to fulfill fetal requirements. Docosahexanoic acid (DHA) is a long-chain polyunsaturated omega-3 fatty acid, which is found in lipids from fish and other seafood. This, and other omega-3 fatty acids, may protect against several adverse health effects, and contribute to enhanced cardiovascular health. Further, DHA and arachidonic acid (AA), an omega-6 PUFA, are essential for the development of the central nervous system in mammal. Therefore, during the last trimester of pregnancy, fetal requirements for DHA and AA are very high due to the rapid synthesis of brain tissue. The main source of the DHA and AA that accumulate in the brain is drawn from maternal circulation during pregnancy and through breast milk for newborns. In preterm and lowbirth-weight babies, DHA deficiency has been related to
Mercury in Fish: Human Health Risks
visual impairment and delayed cognitive development. Also, there is some evidence that increased maternal intake of fish or fish oil supplements may prolong gestation in populations where shorter gestation periods are observed. A number of studies have shown strong evidence that fish or fish oil consumption reduces all-cause mortality and various cardiovascular disease outcomes. Further, a report released by the Scientific Advisory Committee on Nutrition (SACN) of the United Kingdom and the US Dietary Guidelines Advisory Committee (DGAC) states that all adults, including pregnant women, should consume at least two portions of fish per week, of which one should be fatty. This recommendation for consumption of at least two servings of fish per week correlates with improved cardiovascular health.
Balancing Benefits and Risks Results from the major surveys show that only a small portion of the US or Canadian population is heeding the recommendation of including fish at least twice a week in their diet. However, the consumption of Hg from fish in adults who consume the recommended two servings per week of fish may be approaching the threshold levels set by FAO/WHO. Currently, various organizations provide advice or recommendations concerning fish consumption. Some health agencies issue advice about maximum acceptable consumption with the objective of protecting the population from the risks associated with contaminants exposure, whereas others present their recommendations in terms of minimal recommended consumption to decrease the cardiovascular disease risks and of nonoptimal development of the nervous system of the child, the two identified beneficial effects associated with n 3 fatty acids. These two seemingly contradictory messages are thus transmitted to the public, which can cause confusion. The Institute of Medicine convened an expert committee to review the benefits and risks of seafood consumption and published their results in a report titled ‘Seafood Choices: Balancing Benefits and Risks’ in 2006. From its review of consumption, benefits, and risks, the committee made the following recommendations: 1. Dietary advice to the general population from federal agencies should emphasize that seafood is a component of a healthy diet, particularly as it can displace other protein sources higher in saturated fat. 2. Although advice from federal agencies should also support inclusion of seafood in the diets of pregnant females or those who may become pregnant, any consumption advice should stay within
3.
4.
5.
6.
7. 8.
9.
10.
11.
12.
703
federal advisories for specific seafood types and state advisories for locally caught fish. Appropriate federal agencies should increase monitoring of MeHg and persistent organic pollutants in seafood and make the resulting information readily available to the general public. Changes in the seafood supply (source and type of seafood) must be accounted for – there is inconsistency in sampling and analysis methodology used for nutrients and contaminant data that are published by state and federal agencies. Appropriate federal agencies should develop tools for consumers, such as computer-based interactive decision support and visual representations of benefits and risks that are easy to use and interpret. New tools apart from traditional safety assessments should be developed, such as consumer-based benefit–risk analyses. A consumer-directed decision path needs to be properly designed, tested, and evaluated. Consolidated advice is needed that brings together different benefit and risk considerations, and is tailored to individual circumstances, to better inform consumer choices. Consumer messages should be tested to determine if there are spillover effects for segments of the population not targeted by the message. The decision pathway the committee recommends, which illustrates its analysis of the current balance between benefits and risks associated with seafood consumption, should be used as a basis for developing consumer guidance tools for selecting seafood to obtain nutritional benefits balanced against exposure risks. The sponsor should work together with appropriate federal and state agencies concerned with public health to develop an interagency task force to coordinate data and communications on seafood consumption benefits, risks, and related issues such as fish stocks and seafood sources, and begin development of a communication program to help consumers make informed seafood consumption decisions. Partnerships should be formed between federal agencies and community organizations.
Even though the recommendations were targeted to the US agencies, many of them apply to other countries worldwide. Implementation of some or all of these recommendations will improve the confidence of consumers on public health messages. However, more research is needed to achieve some of the recommended change in assessment paradigm. For example, the comparison of risks and benefits in a quantitative manner remains to be a challenge as they are not usually on a linear scale. Furthermore, specific populations such as Indigenous
704
Mercury in Fish: Human Health Risks
Peoples in Canada, who depend on fishing for subsistence living, have to deal with other health issues such as diabetes, obesity, and hypertension when fish consumption decreases in their diet. The benefit of fish consumption also goes beyond simply biophysical benefits. Subsistence fishing is associated with their traditions and the indigenous culture.
Conclusions Hg is a global pollutant. Fish can accumulate high level of Hg emitted from industrial sources that are thousands of kilometers away. Environmental changes such as global warming, soil erosion due to deforestation, and building of hydrodams can increase the methylation or bioavailability of Hg. Many of the fish species found in ‘unpolluted’ water bodies far from point source industrial emissions have Hg levels that are not safe for sustained human consumption. This can have major health impacts on local human populations as fish often comprises an important part of their diets. Public health interventions need to balance the risk against the benefits of fish consumption including cultural values. See also: Mercury Toxicity.
Further Reading Axelrad DA, Bellinger DC, Ryan LM, and Woodruff TJ (2007) Dose– response relationship of prenatal mercury exposure and IQ: An integrative analysis of epidemiologic data. Environmental Health Perspectives 115: 609--615. Chan HM and Receveur O (2000) Mercury in the traditional diet of indigenous peoples in Canada. Environmental Pollution 110: 1--2. Chan HM, Scheuhammer AM, Ferran A, Loupelle C, Holloway J, and Weech S (2003) Impacts of mercury on freshwater fish-eating wildlife and humans. Human and Ecological Risk Assessment 9: 867--883. Clarkson TW and Magos L (2006) The toxicology of mercury and its chemical compounds. Critical Reviews in Toxicology 36: 609--662.
Committee on the Toxicological Effects of Methylmercury (2000) Toxicological Effects of Methylmercury. Washington, D.C: National Academy Press. DGAC (2005) Dietary Guidelines Advisory Commitee Report. http:// www.health.gov/dietaryguidelines/dga2005/report/default.htm (accessed November 2009). Health Canada (2007) Human Health Risk Assessment in Mercury in Fish and Health Benefits of Fish Consumption. http://hc-sc.gc.ca/ fn-an/pubs/mercur/merc_fish_poisson_e.html (accessed November 2009). Mergler D, Anderson HA, Chan HM, et al. (2007) Methylmercury exposure and health effects in humans: A worldwide concern. Ambio 36: 3--11. Myers GJ and Davidson PW (2000) Does methylmercury have a role in causing developmental disabilities in children? Environmental Health Perspectives 108: 413--420. Nesheim MC and Yaktine AL (eds.) (2006) Seafood Choices: Balancing Benefits and Risks. Washington, D.C: National Academy Press. Oken E, Radesky JS, Wright RO, et al. (2008) Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort. American Journal of Epidemiology 167: 1171--1181. Spadaro JV and Rabl A (2008) Global health impacts and costs due to mercury emissions. Risk Analysis 28: 603--613. Smith KM and Sahyoun NR (2005) Fish consumption: Recommendations versus advisories, can they be reconciled? Nutrition Reviews 63: 39--46. Sunderland EM, Cohen MD, Selin NE, and Chmura GL (2008) Reconciling models and measurements to assess trends in atmospheric mercury deposition. Environmental Pollution 156: 526--535. Sunderland EM, Krabbenhoft DP, Moreau JW, Strode SA, and Landing WM (2009) Mercury sources, distribution, and bioavailability in the North Pacific Ocean: Insights from data and models. Global Biogeochemical Cycles 23: GB2010. SACN (2004) Advice on Fish Consumption: Benefits and Risks. www.tso.co.uk/bookshop (accessed November 2009). World Health Organization (2008) Global and Regional Food Consumption Patterns and Trends. http://www.who.int/nutrition/ topics/3_foodconsumption/en/index5.html (accessed November 2009). World Health Organization (2008) Guidance for identifying populations at risk from mercury exposure. Issued by UNEP DTIE Chemicals Branch and WHO Department of Food Safety, Zoonoses and Foodborne Diseases, Geneva, Switzerland. World Health Organization (2008) Health risks of heavy metals from long-range transboundary air pollution. Issued by the Joint WHO/ Convention Task Force on the Health Aspects of Air Pollution, Copenhagen, Denmark.
Abbreviations AA BMDL DGAC DHA JECFA NRC PBPK PUFA SCAN
arachidonic acid benchmark dose level US Dietary Guidelines Advisory Committee docosahexanoic acid Joint Expert Committee on Food Additives and Contaminants US National Research Council physiologically based pharmacokinetic polyunsaturated fatty acid Scientific Advisory Committee on Nutrition
Introduction Owing to its high toxicity to both humans and animals, Mercury (Hg) is one of the most commonly studied trace elements in the environment. It is released into the environment through both natural and anthropogenic sources and can exist in three forms: elemental, inorganic, and organic. In both freshwater and saltwater ecosystems, the organic form (methylmercury, MeHg) is predominant and has a high propensity to accumulate in fish tissue through ingestion and absorption. Therefore, dietary consumption of fish and other seafood including shellfish and molluscs is a major route of mercury exposure among human populations. The commercial production of organic mercury, including MeHg, began in the 1930s; however, its use in chemical research and records as a potential toxicant dates as far back as the 1860s. Since then, MeHg has come to be known as one of the most hazardous environmental pollutants. Many endemic disasters are attributed to MeHg, such as the Minamata disease in Japan and poisoning from the distribution of wheat seeds dressed with MeHg in Iraq. The amount of mercury being released into the atmosphere has increased due to human activities such as burning of fossil fuels and municipal waste incineration. Metal mining and smelting, the use of Hg in gold mining, chloralkali production, and biomedical waste are also anthropogenic sources contributing to increased Hg in the environment. Some human activities can alter the biogeochemical character of aquatic systems without actually increasing the environmental deposition of Hg; for instance, the flooding of soils to create reservoirs
increases the decomposition of vegetation, the dissolution of organic carbon, and the release of Hg bound to organic material in the water. This causes increase in net Hg methylation rates, resulting in increased Hg bioavailability and, in turn, MeHg exposure in humans. Higher-than-normal levels of Hg in the environment can be attributed to industrial activities such as mining, the pulp and paper industry, and the production of chlorine from the chloralkali industry. Further, appreciable quantities of Hg can also enter the environment from weathering of mineral deposits and the ongoing geochemical recycling of Hg and volcanic disruption. Recent studies have found that burning of fossil fuel for power generation plants is becoming a major source of Hg pollution globally. As emission in the form of metallic Hg, whose atmospheric residence time is long enough to cause nearly uniform mixing in the hemisphere, much of the impact is global. In 2008, Sunderland and colleagues used sophisticated atmospheric models and estimated that anthropogenic emissions in the United States and Canada account for 28–33% of contemporary atmospheric deposition in this region, with the rest from natural (14–32%) and global sources (41–53%). They also suggested that at present atmospheric Hg deposition rates by 2050 Hg concentrations in the North Pacific Ocean would double relative to c.1995. Many populations around the world depend on fish as their major source of food and nutrients. The presence of Hg in fish poses a potential threat to their health. This article discusses the risk of Hg exposure in the context of the nutritional benefits associated with fish consumption.
Factors for Increased Mercury Levels in Environment and Fish Mercury is different from most environmental contaminants in that it is naturally occurring and can be detected almost anywhere in the environment, although at low quantities. Normal background levels of mercury in sediments are usually below 0.1 mg g1 (ranges between 0.01 and 0.2 mg g1). When not affected by anthropogenic activities, Hg makes its way into aquatic ecosystems mainly by deposition from the atmosphere and runoff from soils. It is well known that Hg is a toxic element and that its toxicity is very much dependent on its chemical form. The common Hg species found in the environment are elemental Hg (HgO), mercurial ion (Hg2þ), and
697
698
Mercury in Fish: Human Health Risks
methylmercury ion (MeHg or CH3Hgþ) complexing with various inorganic and organic ligands, and various solid forms of Hg such as mercury sulfide and oxide. The most toxic Hg species is MeHg due to its lipophilic nature and effectiveness in penetrating into cell membrane and sensitive organs such as placenta and brain, where it can cause severe damages. Although the concentration of Hg in the earth’s crust is very low at approximately 0.05 mg g1, its potential environmental risk is high because Hg can transform from one chemical form to another and can be transported through air by particles and as HgO. Hg is the only metal that is volatile at room temperature. It can also be volatilized from Hg2þ in aquatic systems through the effects of solar irradiation. The movement of Hg within the environment, and in particular within the hydrosphere, is influenced by a number of factors. Inorganic forms of Hg are easily bound to other molecules; therefore, anything affecting the characteristics of sediment or the water column will often determine the Hg mobility. Studies have shown that sediment-binding capacity increases with increased organic content and decreases with relative oxidation; thus, sediment grain size, organic content, oxidation conditions, redox potentials, and the density of aquatic organisms will all affect Hg uptake. It is well documented that over 90% of Hg in lake systems is found in the bottom sediment and that these sediments will retain Hg for a long period of time. The main mobilization mechanism for Hg in the environment is through the formation of organic forms. Alkylation is a process that combines inorganic Hg with one or two methyl groups forming monomethylmercury or dimethylmercury. Methylation of Hg is a detoxification process that is performed by microorganisms such as bacterium, fungi, and mold; hence the rate of methylation is dependent on the abundance of these organisms. Further, factors such as oxidative state and pH levels affect the numbers of microorganisms in sediments or in the water column, which in turn affects the production of mono- and dimethylmercury. Bioaccumulation of Hg is dependent on the type of ecosystem an organism occupies. Characteristics such as water chemistry and food abundance determine the amount of Hg available to fish and, therefore, the amount that can possibly be concentrated in fish tissue. It is well known that Hg concentrations in fish can be elevated in newly flooded areas. The flooding of vegetation and terrestrial soils through natural and anthropogenic sources contributes to elevated Hg concentrations in the food web of flooded environment. It has been proven that reservoir formation often leads to elevated Hg levels in fish relative to preimpoundment concentrations, even in cases where no point source discharges of Hg are evident. This has been reported in Canada, the United States, Finland, and India. In many
cases, it seems that the source of Hg is a redistribution of the metal from materials already in the lake or river before flooding. Reservoirs can cause severe environmental impacts, generally due to the very rapid and drastic changes in the flooding conditions of upstream and downstream areas. Evaporative loss of water can occur due to the presence of large areas of artificial reservoirs, which would otherwise be available for downstream human and ecological uses. Further, seepage may also occur from the porous foundations underlying hydroelectric reservoirs. The magnitude of increases in Hg concentration depends on many factors, including the area of land and vegetation inundated, water temperature, pH, age and retention time of the reservoir, and trophic status and species of fish. The relationship between the rising concentration of Hg in fish tissue and the size and age of the fish is also well known. The levels of increase depend on trophic status and diet; the lowest levels are in aquatic plants, intermediate in invertebrates, and highest in fish and piscivorous mammals and birds. Almost all Hg found in biological systems has been absorbed in the form of MeHg, which can bioaccumulate and biomagnify within aquatic food webs and is highly absorbable (95–100%) from the diet compared to inorganic Hg (5–10%). As a result of bioaccumulation of MeHg through multiple levels of the aquatic food web, higher trophic level pelagic fish can be contaminated with MeHg at concentrations in excess of 1 mg g1. The mean concentrations of total Hg vary widely across fish and shellfish species, with the mean values differing by as much as 100-fold. MeHg is bound to proteins as well as free amino acids that are components of muscle tissues and are not removed by any cooking or cleaning processes that do not destroy muscle tissues. Because MeHg is the main form of Hg found in fish (490%), the following sections will focus on the toxic effects of MeHg.
MeHg Intake from Fish Consumption Fish is an important source of food in many countries and communities. The average apparent per capita consumption increased from approximately 9 kg per year in the early 1960s to 16 kg per year in 1997. The proteins derived from fish, crustaceans, and molluscs account for between 13.8% and 16.5% of the animal protein intake of the human population. Currently, two-thirds of the total food fish supply is obtained from capture fisheries in marine and inland waters, whereas the remaining onethird is derived from aquaculture. The contribution of inland and marine capture fisheries to per capita food supply has stabilized to approximately 10 kg per capita in the period 1984–98. Fish contributes up to 180 kcal per
Mercury in Fish: Human Health Risks
capita per day or 9% of energy intake, assuming average daily intake at 2000 kcal, but reaches such high levels only in a few countries where there is a lack of alternative protein foods grown locally or where there is a strong preference for fish (e.g., Iceland, Japan, and some small island states). More typically, fish provides approximately 20–30 kcal per capita per day or 1–2% daily energy intake. Worldwide, approximately a billion people rely on fish as their main source of animal proteins. Dependence on fish is usually higher in coastal areas than in inland areas. Approximately 20% of the world’s population derives at least one-fifth of its animal protein intake from fish, and some small island states depend almost exclusively on fish. High levels of MeHg exposure have been identified in numerous fish-eating populations throughout the world. Many of these live near oceans, major lakes, and rivers or hydroelectric dams and are often dependent on local catch, with fish as an integral part of their cultural traditions. For many Northern communities, the problem is often compounded by the consumption of fish-eating marine mammals. Despite the importance of local catch, fish is also a global commodity. In the United States, individuals with elevated blood Hg concentrations have been reported among affluent urbanites, who consume large quantities of marine fish, high in the food web. Thus, elevated MeHg exposure, around the globe, has no geographic, social, economic, or cultural boundaries. Although most reports on MeHg exposure have focused on specific populations, generally assumed to have high levels of fish consumption and correspondingly elevated levels of MeHg intake, estimates of general population exposure exist for the United States, the EU, and Japan. Most studies have identified a clear association between the frequency of fish consumption and Hg exposure. However, several factors can modulate this relationship. For the most part, those who eat mainly carnivorous fish or fish-eating birds or mammals have higher levels of Hg compared to those who eat mainly noncarnivorous fish. Thus, the rate of fish consumption by itself is not necessarily a reliable predictor of MeHg exposure. The species of fish consumed, the presence of pollution source, and the geochemical characteristics of the water bodies are also important factors in this variability. Consumption of farmed fish can also lead to MeHg exposures, due in part to the presence of MeHg in feed. Some studies have shown no significant difference in MeHg levels in farmed versus wild salmon, although with relatively low values in both cases. A relatively small number of studies have reported MeHg levels in farmed freshwater fish, with concentrations both slightly higher and lower than wild-caught fish from nearby waters.
699
Kinetics of MeHg Methylmercury is easily and efficiently absorbed through the gastrointestinal tract into the bloodstream, where it is rapidly transported to other parts of the body. Approximately 95% of the MeHg ingested through fish consumption is absorbed in the gastrointestinal tract. In the bloodstream, more than 90% of the MeHg accumulates in red blood cells and plasma, where it is bound mainly to the plasma proteins. Approximately 5% of the body burden is found in the blood compartment and approximately 10% settles in the brain. In animal studies, variation in absorption kinetics has been related to factors such as sex and age, as well as dietary elements, including macronutrients, lipid and fatty acid content, fiber, and protein and amino acid supplements. In humans, there is evidence of ethnic differences in Hg accumulation, suggesting that diet and metabolic differences may be influencing mercury uptake and excretion. Dietary elements can modulate Hg uptake in humans. Several studies suggest that selenium may play a role in MeHg absorption or excretion; for example, fruit consumption was associated with lower hair Hg concentrations in the Brazilian Amazon. MeHg can be metabolized to inorganic mercury, which accumulates primarily in the kidneys. Kidney levels of inorganic mercury tend to build up after longterm exposure to MeHg. MeHg is also converted to inorganic mercury in the brain. Elevated concentrations of inorganic Hg have been found in autopsy brain samples from people who died many years after an acute exposure to MeHg. The inorganic mercury is believed to be in an inert, insoluble form that can remain in brain tissues for many years, perhaps for the lifetime of the individual. The toxicological role of the inert, insoluble form remains a matter of some debate as new evidence has shown that inorganic Hg is more impotent in inhibition of neurotransmitter receptors in neurons. MeHg is excreted slowly over a period of several months, mostly as inorganic Hg in the feces. It may take 45–70 days for the MeHg concentrations to fall by half in a person’s blood, and 70–80 days in the entire body, but substantial variations in time scale can occur. The kidneys retain the highest tissue concentrations of Hg, though the total amount deposited in muscles can be higher. The mean total Hg level in blood in the general population is approximately 1–8 mg l1. The International Commission on Occupational Health and the Commission on Toxicology of the International Union of Pure and Applied Chemistry determined, using a metaanalysis of published studies, that the background blood level (mean value) in persons who do not eat fish was 2 mg l1. This background value represents the average level in blood in the general population. However, in populations without dental amalgam and who do not
700
Mercury in Fish: Human Health Risks
consume fish, the blood mercury levels are even lower. Nevertheless, in communities with high fish consumption, individuals have been estimated to have blood levels of 200 mg l1 associated with daily Hg intake of 200 mg per day. MeHg is actively transferred to the fetus across the placenta via neutral amino acid carriers during gestation. Maternal and cord blood Hg concentration is highly correlated, but cord blood Hg is consistently higher than the corresponding maternal concentration, with an average ratio of approximately 1.7. The maternal body burden of MeHg tends to decrease during gestation, consistent with the transfer of a portion of the maternal body burden to the fetus. Neonatal and infant exposure to MeHg occurs through intake of mother’s milk, which is derived from maternal plasma, enriched in inorganic Hg relative to the whole blood. Thus, lactational exposure to MeHg is reduced compared to what would be expected on the basis of maternal blood Hg. Following birth, fetal MeHg levels decline to approximately 40–50% at 2–3 months of age. During this period, infants’ body weight increases approximately 1.5–2 times. Consequently, the rapid increase in body weight and the limited MeHg transfer appear to explain the dilution of MeHg in infants during breast-feeding. Toxicokinetic (pharmacokinetic) models and physiologically based pharmacokinetic (PBPK) models have been developed to predict changes in MeHg concentration in various tissues in response to changes in MeHg intake, and in response to physiological changes (e.g., pregnancy and growth).
Hair as Biomarker for MeHg Exposure MeHg accumulates in hair. The brain–blood concentration ratio ranges from 3:1 to 6:1, and the hair–blood concentration ratio is between 250:1 and 300:1 in humans at the time of incorporation of Hg into the hair. Hair is often used as a biomarker for chronic MeHg exposure. As hair grows on an average of 1 cm per month, measuring hair in 1 cm segments can document the exposure in previous months and can account for seasonal variations in intake. Hair Hg is predominantly MeHg, which constitutes from 80% to 90–98% of total hair Hg. Once Hg is incorporated into the hair, it remains unchanged. The hair Hg level is dependent on the amount of fish consumed. The background level of hair Hg associated with little or no fish consumption or with the consumption of fish with low MeHg concentrations is usually between 0.2 and 1.0 mg g1. Much higher hair Hg levels can result from the consumption of large amounts of fish or sea mammals. In the Faeroe Islands population, the mean hair Hg level ranges from 1.6 to 5.2 mg g1. In Indigenous
populations from northern Canada, levels higher than 40 mg g1 were reported. Biomarkers like hair Hg concentrations reflect the cumulated dose of Hg exposure over time. Under some circumstances, episodic exposures can result in large bolus doses of MeHg, which arise, for example, from the infrequent consumption of fish or fish-eating mammals with high concentrations of MeHg. Bolus doses, particularly during putative discrete windows of sensitivity in brain development, may not be fully revealed by biomarkers, but may have an effect that cannot be clearly predicted from longer-term average estimates of exposure. Recent advances in a single hair strand analysis including measurement of Hg at micron resolution using laser ablation will yield more information on the relationship between Hg uptake and deposition in hair. It is common practice to compare studies of Hg exposure in different populations using different biomarkers assuming that there is a constant ratio between blood and hair Hg mercury concentrations. However, there is considerable inter- and intraindividual variability. To some extent, this may result from the temporal differences in Hg accumulation by each biomarker, particularly with infrequent or intermittent fish consumption.
Toxicity of MeHg Long-term exposure to either inorganic or organic Hg can permanently damage the brain, kidneys, and developing fetus. Organic Hg ingested in contaminated fish may cause greater harm to the brain and developing fetus because MeHg readily crosses the placenta and the blood–brain barrier and is neurotoxic. The developing fetal nervous system is especially sensitive to Hg effects. Prenatal poisoning with high-dose MeHg causes mental retardation and cerebral palsy. The scientific evidence indicates that exposure to MeHg is more dangerous for young children than for adults. This is because of the lower thresholds for neurological effects from MeHg and the higher levels of distribution of MeHg to the developing brains of young children, which can result in interference with the development of motor and cognitive skills. MeHg was the main pollutant that caused the severe neurological impairment of individuals in the vicinity of Minamata Bay, Japan, during the 1950s to the 1970s. The action of MeHg on adults is characterized by a latency period between exposure and the onset of symptoms. The latency period can vary from several weeks to months depending on the dose and exposure period. In adults, the earliest effects are nonspecific symptoms such as paresthesia, malaise, and blurred vision; with increasing exposure, there are signs such as constriction of the visual field, deafness, dysarthria, and ataxia, ultimately
Mercury in Fish: Human Health Risks
leading to coma and death. The symptoms of Minamata disease include the following: sensory disorders in the extremities (loss of sensation in the hands and feet), ataxia (difficulty in coordinating the movements of hands and feet), narrowing of the field of vision, hearing impairment, difficulty in maintaining balance, and speech impediments. In very severe cases, victims fall into a state of disorientation and confusion, lose consciousness, and may die. In relatively mild cases, symptoms include headaches, chronic fatigue, and a generalized inability to distinguish tastes and smells. In infants exposed to high levels of MeHg during pregnancy, it is difficult to distinguish the cerebral palsy caused by other factors. The main symptoms include microcephaly, hyperreflexia, gross motor and mental impairment, and, in rare cases, blindness or deafness. In milder cases, the effects may become apparent only at a later stage, taking the form of psychomotor and mental impairment and persistent pathological reflexes.
Fish Consumption and Child Development Because there are many populations around the world that consume large amounts of fish, epidemiological studies were undertaken in the past two decades to determine whether populations frequently consuming fish were indeed at risk. The focus of these studies was on prenatal exposure and its association with child development because the developing brain appears to be most sensitive to the effects of MeHg. Investigations into the risks from prenatal exposure have been carried out in Canada, Peru, New Zealand, the Faeroe Islands, the Seychelles, the United States, and Japan. Their results show that MeHg exposure from the consumption of fish by pregnant women, even at low mercury concentrations (i.e., approximately one-tenth to one-fifth of the observed effect levels in adults), may have subtle, persistent effects on the children’s mental development. However, conclusions from these studies have not been consistent. Some reported an association between prenatal MeHg exposure at levels achieved by fish consumption and the child’s scores on developmental tests, whereas others found no association using similar or identical tests. These studies are complex to execute and thus difficult to compare because of differences in study populations, end points measured, covariates assessed, statistical methods utilized, and other factors. The most comprehensive investigations performed so far are the studies that were conducted in New Zealand, the Seychelles, and the Faeroe Islands. Using multiple regression analyses, the results of clinical examinations and neuropsychological testing were compared with MeHg exposure in the mothers. No clear-cut Hg-related clinical abnormalities were found in all these studies.
701
A maternal hair Hg level above 6 mg g1 was associated with lower intelligence quotients (IQs) (from 93 to 90) in children in the New Zealand study. In the Seychelles prospective study, the study population was a cohort of 779 children born to mothers exposed to MeHg from a diet high in fish (typically 10–15 meals per week). The neurological and developmental effects in the children were evaluated at 6.5, 19, 29, 66, and 107 months and 10.7 years of age. No definite adverse neurodevelopmental effects were observed in infants up to 29 months of age at maternal hair levels of up to 12 mg g1. At hair levels greater than 12 mg g1, the percentage of infants with normal Revised Denver 25 Developmental Screening Test scores decreased from 93% to 87%, but there was no effect on the developmental milestones of walking and talking. In this study, no consistent adverse association between prenatal MeHg exposure at maternal hair levels of up to 12 mg g1 (from fish consumption) and child development was identified in 643 children aged up to 9 years. Twenty-one neurodevelopmental end points were assessed. In the Faeroe Islands prospective study, the population was exposed to MeHg primarily from pilot whale meat with MeHg concentrations ranging from o1 mg kg1 to more than 3 mg kg1. The original birth cohort of 1022 started between 1986 and 1987. In 900 children from the Faeroe Islands, prenatal exposure to MeHg was associated with a neurological deficit at 7 years of age. Neurological deficits were found in the areas of language, attention, and memory, and were found to be related to increasing Hg exposure. Developmental delays were significantly associated with MeHg exposures, even when children whose mothers had hair Hg levels above 10 mg g1 were excluded. Within the lowexposure range, each doubling of the prenatal exposure concentration was associated with a developmental delay of 1–2 months. There is some suggestion that the neurological deficit may be due to an interaction between MeHg and polychlorinated biphenyl present in the diet (in whale blubber) of these mothers. However, the results were approximately the same when polychlorinated biphenyl levels were taken into account, and increased prenatal exposure to MeHg appeared to enhance the toxicity of these hydrocarbons. Researchers of the Seychelles study repeated their study on children aged 10.7 years using the same assessment method used by the researchers of the Faeroe study and still found no significant association between prenatal exposure and adverse developmental effects. A recent study has used dose–response information collected from all these studies conducted in the Faeroe Islands, New Zealand, and the Seychelles islands to estimate the relationship between maternal mercury body burden and subsequent childhood decrements in IQ , using a Bayesian hierarchical model to integrate data from three epidemiological studies. They found a central
702
Mercury in Fish: Human Health Risks
estimate of 0.18 IQ points (95% confidence interval: 0.378 to 0.009) for each parts per million increase in maternal hair Hg, similar to the estimates for both the Faeroe Islands and the Seychelles study, and lower in magnitude than the estimate for the New Zealand study. IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study. In a recent cohort study conducted in the United States, an inverse relation was observed between Hg concentration in maternal hair and infants’ performance on a visual recognition memory task at levels of Hg exposure consistent with background exposure in the US population (maternal hair levels varied between 0.02 and 2.38 mg g1). Interestingly, in this study, fish consumption per se was associated with better performance. This suggests that some positive aspects of fish consumption are reduced, or antagonized by the MeHg contained in the same fish. This risk benefit of fish consumption will be discussed in the section ‘Balancing Benefits and Risks’. It is important to note that even though the effects at these dose levels may not seem severe on an individual basis, they may have serious implications for populations. In 2008, Sparado and Rabl estimated that the average global lifetime impact and cost per person at current emission levels are 0.02 IQ points lost and $78.
Health Agency Efforts to Establish Safe Levels of MeHg Exposure Various public health agencies have tried to determine the risk of MeHg ingestion to the general population. In 1972, the World Health Organization (WHO) established a tolerable weekly intake of 3.3 mg kg1 (0.47 mg kg1 per day) MeHg in the diet, based on data from Japan. Based on the information generated from the recent epidemiological data, the US National Research Council (NRC), the Joint Expert Committee on Food Additives and Contaminants (JECFA) under the Food and Agriculture Organization (FAO), and the WHO have developed lower tolerable levels for women of child-bearing age. To put the methylmercury exposure levels in perspective, for the neurodevelopmental effects, the benchmark dose level (BMDL) for a 5% effect (BMDL 05) from the Faeroe Islands study was approximately 58 ppb (mg l1) for mercury in cord blood. This was based on the neurobehavioral end points in infants. On the basis of a BMDL 05 of 58 ppb (58 mg l1) for cord blood mercury and with the application of a conversion (cord blood to
maternal hair) factor of 200, this BMDL 05 would be equivalent to a 12 ppm (12 mg g1) maternal hair Hg level, or 48 mg l1 in terms of the maternal blood mercury level. Using this BMDL, the NRC recommended intake level at 0.1 mg kg1 per day. These varying limits of the amount of MeHg that can be safely consumed appear to result from the different studies on which they are based, the uncertainty or safety factor that each agency felt was most appropriate, and differences in definitions (i.e., RfD, MRL, and tolerable weekly intake). Because fish is the primary source of Hg exposure among the general population, many governments provide dietary advice to limit fish consumption where there are elevated Hg levels. The WHO and the FAO of the United Nations recommend a maximum of 0.5 ppm of Hg in nonpredatory fish and 1 ppm in predatory fish. The US Food and Drug Administration has set a maximum level of 1 ppm in fish, shellfish, and aquatic animals. Canada and the European Community allow 0.5 ppm in fishery products, and Japan allows up to 0.3 ppm.
Benefits of Fish Consumption The importance of fish consumption for health and nutritional status is immense, and it has provided humanity with an essential food source for thousands of years. Fish is a protein source superior to beef, pork, chicken, and even milk proteins due to its amino acid profile and ability to support growth. Further, the fatty acid profile of fish differs significantly from these alternative sources of protein: approximately 50% of the fatty acids in lean fish and 25% in fatty fish are polyunsaturated fatty acids (PUFAs). In comparison, only 4–10% of fatty acids are polyunsaturated in beef, whereas 40–45% are saturated. Fish are also a source of many vitamins, including niacin and vitamins B12, D, and A. Also, fish provide a dietary source of micronutrients including selenium, iodine, taurine, fluoride, calcium, copper, and zinc. Maternal intake of fish has also been observed to be valuable to fulfill fetal requirements. Docosahexanoic acid (DHA) is a long-chain polyunsaturated omega-3 fatty acid, which is found in lipids from fish and other seafood. This, and other omega-3 fatty acids, may protect against several adverse health effects, and contribute to enhanced cardiovascular health. Further, DHA and arachidonic acid (AA), an omega-6 PUFA, are essential for the development of the central nervous system in mammal. Therefore, during the last trimester of pregnancy, fetal requirements for DHA and AA are very high due to the rapid synthesis of brain tissue. The main source of the DHA and AA that accumulate in the brain is drawn from maternal circulation during pregnancy and through breast milk for newborns. In preterm and lowbirth-weight babies, DHA deficiency has been related to
Mercury in Fish: Human Health Risks
visual impairment and delayed cognitive development. Also, there is some evidence that increased maternal intake of fish or fish oil supplements may prolong gestation in populations where shorter gestation periods are observed. A number of studies have shown strong evidence that fish or fish oil consumption reduces all-cause mortality and various cardiovascular disease outcomes. Further, a report released by the Scientific Advisory Committee on Nutrition (SACN) of the United Kingdom and the US Dietary Guidelines Advisory Committee (DGAC) states that all adults, including pregnant women, should consume at least two portions of fish per week, of which one should be fatty. This recommendation for consumption of at least two servings of fish per week correlates with improved cardiovascular health.
Balancing Benefits and Risks Results from the major surveys show that only a small portion of the US or Canadian population is heeding the recommendation of including fish at least twice a week in their diet. However, the consumption of Hg from fish in adults who consume the recommended two servings per week of fish may be approaching the threshold levels set by FAO/WHO. Currently, various organizations provide advice or recommendations concerning fish consumption. Some health agencies issue advice about maximum acceptable consumption with the objective of protecting the population from the risks associated with contaminants exposure, whereas others present their recommendations in terms of minimal recommended consumption to decrease the cardiovascular disease risks and of nonoptimal development of the nervous system of the child, the two identified beneficial effects associated with n 3 fatty acids. These two seemingly contradictory messages are thus transmitted to the public, which can cause confusion. The Institute of Medicine convened an expert committee to review the benefits and risks of seafood consumption and published their results in a report titled ‘Seafood Choices: Balancing Benefits and Risks’ in 2006. From its review of consumption, benefits, and risks, the committee made the following recommendations: 1. Dietary advice to the general population from federal agencies should emphasize that seafood is a component of a healthy diet, particularly as it can displace other protein sources higher in saturated fat. 2. Although advice from federal agencies should also support inclusion of seafood in the diets of pregnant females or those who may become pregnant, any consumption advice should stay within
3.
4.
5.
6.
7. 8.
9.
10.
11.
12.
703
federal advisories for specific seafood types and state advisories for locally caught fish. Appropriate federal agencies should increase monitoring of MeHg and persistent organic pollutants in seafood and make the resulting information readily available to the general public. Changes in the seafood supply (source and type of seafood) must be accounted for – there is inconsistency in sampling and analysis methodology used for nutrients and contaminant data that are published by state and federal agencies. Appropriate federal agencies should develop tools for consumers, such as computer-based interactive decision support and visual representations of benefits and risks that are easy to use and interpret. New tools apart from traditional safety assessments should be developed, such as consumer-based benefit–risk analyses. A consumer-directed decision path needs to be properly designed, tested, and evaluated. Consolidated advice is needed that brings together different benefit and risk considerations, and is tailored to individual circumstances, to better inform consumer choices. Consumer messages should be tested to determine if there are spillover effects for segments of the population not targeted by the message. The decision pathway the committee recommends, which illustrates its analysis of the current balance between benefits and risks associated with seafood consumption, should be used as a basis for developing consumer guidance tools for selecting seafood to obtain nutritional benefits balanced against exposure risks. The sponsor should work together with appropriate federal and state agencies concerned with public health to develop an interagency task force to coordinate data and communications on seafood consumption benefits, risks, and related issues such as fish stocks and seafood sources, and begin development of a communication program to help consumers make informed seafood consumption decisions. Partnerships should be formed between federal agencies and community organizations.
Even though the recommendations were targeted to the US agencies, many of them apply to other countries worldwide. Implementation of some or all of these recommendations will improve the confidence of consumers on public health messages. However, more research is needed to achieve some of the recommended change in assessment paradigm. For example, the comparison of risks and benefits in a quantitative manner remains to be a challenge as they are not usually on a linear scale. Furthermore, specific populations such as Indigenous
704
Mercury in Fish: Human Health Risks
Peoples in Canada, who depend on fishing for subsistence living, have to deal with other health issues such as diabetes, obesity, and hypertension when fish consumption decreases in their diet. The benefit of fish consumption also goes beyond simply biophysical benefits. Subsistence fishing is associated with their traditions and the indigenous culture.
Conclusions Hg is a global pollutant. Fish can accumulate high level of Hg emitted from industrial sources that are thousands of kilometers away. Environmental changes such as global warming, soil erosion due to deforestation, and building of hydrodams can increase the methylation or bioavailability of Hg. Many of the fish species found in ‘unpolluted’ water bodies far from point source industrial emissions have Hg levels that are not safe for sustained human consumption. This can have major health impacts on local human populations as fish often comprises an important part of their diets. Public health interventions need to balance the risk against the benefits of fish consumption including cultural values. See also: Mercury Toxicity.
Further Reading Axelrad DA, Bellinger DC, Ryan LM, and Woodruff TJ (2007) Dose– response relationship of prenatal mercury exposure and IQ: An integrative analysis of epidemiologic data. Environmental Health Perspectives 115: 609--615. Chan HM and Receveur O (2000) Mercury in the traditional diet of indigenous peoples in Canada. Environmental Pollution 110: 1--2. Chan HM, Scheuhammer AM, Ferran A, Loupelle C, Holloway J, and Weech S (2003) Impacts of mercury on freshwater fish-eating wildlife and humans. Human and Ecological Risk Assessment 9: 867--883. Clarkson TW and Magos L (2006) The toxicology of mercury and its chemical compounds. Critical Reviews in Toxicology 36: 609--662.
Committee on the Toxicological Effects of Methylmercury (2000) Toxicological Effects of Methylmercury. Washington, D.C: National Academy Press. DGAC (2005) Dietary Guidelines Advisory Commitee Report. http:// www.health.gov/dietaryguidelines/dga2005/report/default.htm (accessed November 2009). Health Canada (2007) Human Health Risk Assessment in Mercury in Fish and Health Benefits of Fish Consumption. http://hc-sc.gc.ca/ fn-an/pubs/mercur/merc_fish_poisson_e.html (accessed November 2009). Mergler D, Anderson HA, Chan HM, et al. (2007) Methylmercury exposure and health effects in humans: A worldwide concern. Ambio 36: 3--11. Myers GJ and Davidson PW (2000) Does methylmercury have a role in causing developmental disabilities in children? Environmental Health Perspectives 108: 413--420. Nesheim MC and Yaktine AL (eds.) (2006) Seafood Choices: Balancing Benefits and Risks. Washington, D.C: National Academy Press. Oken E, Radesky JS, Wright RO, et al. (2008) Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort. American Journal of Epidemiology 167: 1171--1181. Spadaro JV and Rabl A (2008) Global health impacts and costs due to mercury emissions. Risk Analysis 28: 603--613. Smith KM and Sahyoun NR (2005) Fish consumption: Recommendations versus advisories, can they be reconciled? Nutrition Reviews 63: 39--46. Sunderland EM, Cohen MD, Selin NE, and Chmura GL (2008) Reconciling models and measurements to assess trends in atmospheric mercury deposition. Environmental Pollution 156: 526--535. Sunderland EM, Krabbenhoft DP, Moreau JW, Strode SA, and Landing WM (2009) Mercury sources, distribution, and bioavailability in the North Pacific Ocean: Insights from data and models. Global Biogeochemical Cycles 23: GB2010. SACN (2004) Advice on Fish Consumption: Benefits and Risks. www.tso.co.uk/bookshop (accessed November 2009). World Health Organization (2008) Global and Regional Food Consumption Patterns and Trends. http://www.who.int/nutrition/ topics/3_foodconsumption/en/index5.html (accessed November 2009). World Health Organization (2008) Guidance for identifying populations at risk from mercury exposure. Issued by UNEP DTIE Chemicals Branch and WHO Department of Food Safety, Zoonoses and Foodborne Diseases, Geneva, Switzerland. World Health Organization (2008) Health risks of heavy metals from long-range transboundary air pollution. Issued by the Joint WHO/ Convention Task Force on the Health Aspects of Air Pollution, Copenhagen, Denmark.