American Association for Clinical Chemistry
Better health through laboratory medicine
Mercury and Arsenic

From the humble tuna casserole to artistic displays of sushi, seafood is an integral component of the cuisine of most cultures.  As a rich source of the omega-3 fatty acids thought to aid neurological development and cardiovascular health, seafood consumption is recommended by several health organizations, including the American Heart Association.  However, reports of toxic chemicals and heavy metals in seafood have led many to question what’s really going in their mouths alongside that wasabi.  This article will discuss two well-known toxic metals, mercury (Hg) and arsenic (As), and address common concerns related to their presence in seafood. 

Mercury

Both of these metals are found in multiple forms, with varying degrees of toxicological relevance.  Mercury is released from soil, water, volcanic activity, and industrial sources as unionized vapor (Hg0) into the atmosphere.  There, it can be converted to the water-soluble ion, Hg2+, and fall back to earth with rainwater.  Hg2+, which is also released from industrial sediment, is methylated by aquatic microbes to form methylmercury (MeHg), the primary mercury-containing species in seafood.  MeHg and similar compounds (e.g., ethylmercury, dimethylmercury) are referred to as “organic mercury”, while elemental Hg0 or compounds containing ionized Hg2+ (e.g., HgCl2) are referred to as “inorganic mercury”.

All forms of mercury pose risk of toxicity to humans, but MeHg is by far the most concerning when the route of exposure is ingestion.  Unlike inorganic mercury, MeHg is well-absorbed (~95%) from the gastrointestinal tract; once absorbed, MeHg distributes extensively to tissues such as kidney, liver, and brain, with a systemic half-life of 6-8 weeks.  Inorganic mercury is poorly absorbed and is not methylated by human metabolic enzymes, thus MeHg must be consumed to occur in humans.  MeHg can be measured in blood samples, where it accumulates in erythrocytes to roughly 20 times the plasma concentration.  However, a preferable analytical matrix may be hair, where MeHg accumulates to over 200 times the level in blood.

Although more toxic mercury species (e.g., dimethylmercury) are present in trace levels in seafood, the primary risk of toxicity arises from MeHg.  MeHg is the predominant form of mercury in seafood, is readily absorbed from the digestive tract, and can rapidly cross the blood-brain barrier to exert its neurological effects.  Long-lived and predatory fish (e.g., sharks) absorb MeHg from their diets, leading to higher MeHg levels than those present in species lower on the food chain.  However, the risk of mercury toxicity from seafood consumption is low for most individuals, with the exception of acute poisonings (e.g., Iraq in 1971, Japan in the 1950’s). 

The greatest danger of seafood-derived mercury is posed to the developing fetus:  MeHg readily crosses the placenta and blood-brain barrier, thus it can accumulate in fetal tissues to concentrations significantly higher than maternal blood.  Sufficient MeHg exposure in utero can lead to neurological deficits and developmental delays, even in infants whose mothers exhibit no mercury toxicity or only mild effects.  For this reason, in March 2004, the Food and Drug Administration (FDA) released a safety warning intended to limit mercury exposure in pregnant and nursing mothers, women who may become pregnant, and young children.

The FDA alert recommends those individuals to avoid high-mercury fish (e.g., shark, king mackerel) entirely, and to limit consumption of lower-mercury fish (e.g., shrimp, canned tuna, salmon) to 1-2 meals per week.  Fish consumption is still recommended because of the recognized benefits of specific omega-3 fatty acids for fetal neurodevelopment.  A 2006 review published in JAMA concurred with these guidelines, finding that the benefits of fish consumption outweigh the risks of mercury and other food-borne toxins, and supporting the recommendation for consumption of two seafood meals per week for women of childbearing age.  In January 2009, the FDA released a draft risk-benefit assessment and summary of published research pertaining to fish consumption, both available online.

Arsenic

In contrast to mercury, the arsenic found in seafood presents minimal risk to humans.  Inorganic arsenic (trivalent As[III] or pentavalent As[V]) is ubiquitous in groundwater and seawater; the predominant route of arsenic exposure in humans is through drinking water.  Microbial and marine life transforms inorganic arsenic into a variety of organic species. The best-characterized organic forms include monomethylarsenate (MMA), dimethylarsenate (DMA), and arsenobetaine. Arsenic species are readily absorbed, with rapid elimination typically leading to complete clearance within a few days of a single ingestion.

Inorganic arsenic is highly toxic:  high levels can cause neurological damage, anemia, leucopenia, and vascular disease, while low-level chronic exposure increases an individual’s risk of developing cancer.  MMA and DMA were previously believed to be non-toxic, but have recently been linked to arsenic-induced toxicity.  Humans can metabolize inorganic arsenic to MMA and DMA, and it is believed that these metabolites contribute significantly to carcinogenicity and overall toxicity, particularly in their trivalent (As[III]) forms. 

However, inorganic arsenic, MMA, and DMA comprise only a very small amount (typically <5% combined) of the total arsenic-containing species in seafood, and generally fall well short of the toxic threshold in humans.  The majority of arsenic in marine life takes the form of substituted macromolecules such as sugars.  In fish, most arsenic is found as arsenobetaine (an analog of trimethylglycine), whereas other edible sea life, e.g., seaweed, has substantial quantities of arsenosugars.  Arsenobetaine, arsenosugars, and their metabolites have shown little to no toxic potential in laboratory studies, suggesting that their consumption by humans is of minimal concern. 

Analytical speciation is therefore essential to determine the clinical significance of arsenic levels.  Methods coupling high-performance liquid chromatography to various detectors (e.g., atomic absorption spectroscopy, inductively-coupled plasma mass spectrometry) allow separation of highly-toxic inorganic and organic species from non-toxic arsenicals.  Arsenobetaine is the major arsenic-containing compound found in human urine when the origin is dietary, whereas DMA and other toxic species can be detected after consumption of arsenic-contaminated water.

In conclusion, the major heavy metal risk posed by seafood consumption is exposure of a developing fetus to MeHg, thus women and children should limit intake of certain fish to minimize MeHg toxicity.  Arsenic concentrations in seafood are notable, but the metal is present in the form of non-toxic arsenobetaine and arsenosugars.  Laboratory analysis should include speciation to ascertain the source and clinical importance of urinary arsenic.

References

  • “Toxic Effect of Metals”, in Casarett & Doull’s Toxicology: The Basic Science of Poisons.  7th ed., 2008.  pp 931-980.
  • Mozaffarian, D., and Rimm, E.R. “Fish Intake, Contaminants, and Human Health: Evaluating the Risks and the Benefits”, J Am Med Assoc.  2006. 296: 1885-1899.
  • Borak, J., and Hosgood, H.D.  “Seafood Arsenic: Implications for Human Risk Assessment”, Regul Toxicol Pharmacol.  2007.  47(2): 204-212.