Draft Report of Quantitative Risk and Benefit Assessment of Consumption of Commercial Fish, Focusing on Fetal Neurodevelopmental Effects (Measured by Verbal Development in Children) and on Coronary Heart Disease and Stroke in the General Population: Section II, Exposure to Methylmercury in the United States
January 15, 2009
This section discusses methylmercury and reviews sources of data on exposure within the U.S. population, primarily as a result of eating commercial fish, and compares U.S. exposures against exposures elsewhere.
(a) What Are Mercury and Methylmercury?
Mercury occurs in three basic forms: metallic, or elemental mercury, inorganic mercury, and organic mercury. Each form can be toxic to humans when exposure is high enough, although they behave differently in terms of absorption into the body and the degree to which they migrate to body organs. Although it has been postulated that these different forms may interact at a cellular level, there is no scientific evidence to support this hypothesis and the available evidence (e.g., toxicokinetic differences and dissimilar clinical presentation) argues against such an interaction taking place at the relevant target organs (e.g., central nervous system) and levels of exposure. Because our focus is on estimating the impact to certain health endpoints of the consumption of commercial fish, the risk and benefit analysis focuses only on methylmercury.
Elemental mercury occurs naturally, mostly in the form of ores. It enters the environment as a result of volcanic activity and erosion from wind and water. As a consequence, everyone is exposed to very low levels. Mercury is also emitted into the environment through human activity, mostly from the burning of fossil fuels, mining, smelting, and solid waste incineration.
Metallic, or elemental mercury, is also the form that is found in mercury thermometers and formerly in dental amalgams. Inorganic mercury compounds are used in small amounts in some antibacterial products.
Methylmercury is the most common organic form of mercury. It is converted in the environment from inorganic mercury through natural, biological processes, e.g., the activity of bacteria, phytoplankton and fungi. Methylmercury can enter the food chain by accumulating in fish and marine mammals. (2) Longer-lived predator fish tend to have more mercury in them than other fish because they spend their lives eating fish that also contain methylmercury and it is stored in tissue.
Methylmercury is easily absorbed from the gastrointestinal tract and readily enters the brain, including the brain of the developing fetus. It is excreted from the human body. The average half life has been measured at about 50 days with a range of 42-70 days (Sherlock et al., 1984).
(b) Exposure to Methylmercury
The connection between fish consumption and exposure to methylmercury in the United States is well established(3) (CDC 2004; Hightower, et al., 2003). Levels in the body can be inferred from how much fish people eat and how much methylmercury is typically in these fish, but they also can be measured more directly from the amount of mercury in hair or blood.
The data on exposure presented in this section derive from a national survey of hair and blood levels in the U.S. conducted by the Centers for Disease Control and Prevention (CDC) and from FDA's surveillance database on concentrations of mercury in commercial fish in the United States. We also conducted exposure modeling for purposes of risk and benefit assessment, as described in Section IV and in Appendix A. Among other things, exposure modeling enables us to estimate what exposures would be in various hypothetical scenarios. It enables us to predict, for example, how exposures to methylmercury could change as a result of changes in fish consumption.
(c) Methylmercury Exposure as Revealed by the National Health and Nutrition Examination Survey of Blood and Hair Levels
In 1999 , CDC expanded its National Health and Nutrition Examination Survey (NHANES) to measure exposure to methylmercury in U.S. women of childbearing age and children aged one through five. NHANES is a continuous survey of the health and nutritional status of the U.S. population that collects data from individual participants through interviews and physical examinations and publishes collective results every two years.
Studies that have looked for an association between prenatal exposure to methylmercury and the results of neurodevelopmental tests in children have used mercury levels in pregnant women (e.g., concentrations of mercury in hair and blood) as a surrogate for fetal exposure. Consequently, data on mercury levels in women of childbearing age are relevant to an understanding of risk to the fetus. To date, CDC has released six years worth of data, from 1999 through 2004(4) (CDC 2003; CDC 2004; CDC 2005). Women of childbearing age and children through five years of age are included in all six years. The 2003-2004 data also include males ages 16 and above, and older women (CDC 2005).
NHANES takes advantage of the fact that it is possible to calculate the concentration of methylmercury in a person's body from the concentration of total mercury in blood and/or scalp hair so long as the individual has not been significantly exposed to forms of mercury other than methylmercury, i.e., inorganic and elemental. Variations in concentration along a hair strand can reveal differences in the person's exposure over weeks and possibly months, depending on the length of the hair. Hair cannot provide information, however, about exposure at the moment the sample was taken because of the time it takes for methylmercury to concentrate in hair. Conversely, concentrations in blood cannot reveal variations over time, but can provide information about recent exposure (McDowell, et al., 2004). Both blood and hair levels were measured during the first two years of mercury testing under NHANES; only blood levels have been measured thereafter.(5)
NHANES blood levels for all population groups surveyed are provided in Table II-1.
|Percentile||Children 2-5||Men 16-45||Men 46+||Women 16-45||Women 46+|
|All values are in blood (ppb or µg/L). The values have been corrected for inorganic mercury content, meaning that inorganic mercury has been subtracted from total blood mercury in order to show the level of organic mercury in the blood.|
Presumably, exposure data from NHANES mostly reflects long term, or "steady state" exposure from fish consumption over time. NHANES is not designed to obtain information on relatively short term peaks in blood levels although it could sometimes include the results from such exposures.
Because NHANES is designed to provide a nationally representative picture of exposure in the United States (CDC 2004a), it does not lend itself to regional analysis, i.e., it does not reveal whether there are regional exposures to methylmercury that are notably different from the national picture (McDowell, et al., 2004, see p. 1,170; Schober, 2006). As a consequence, NHANES is likely to miss subgroups of high fish consumers such as sport and subsistence fishers (IOM 2006, page 124).
NHANES' national focus would appear to reduce its utility in any assessment of risk for localized situations, or for exposures that largely involve recreational or subsistence consumption. However, the limitations do not significantly affect the utility of NHANES in a nationally representative assessment of risk relating primarily to commercial species. Modeling that FDA has performed to estimate methylmercury levels in U.S. consumers (Carrington and Bolger, 2002) closely track body levels as reported by NHANES. The exposure assessment described in this report builds on these models.
The NHANES data show that U.S. exposures to methylmercury tend to be low when compared against populations that eat a lot of fish. For example:
- On average, U.S. women of childbearing age are exposed to methylmercury at levels about 1/15th those of the women in the Seychelles Islands study and about 1/10th those of the women in the Faroe Islands study.
- women of childbearing age are also exposed to methylmercury at levels that are: (a) about 1/8th of those in Japanese women on average, based on a survey of five districts in Japan (Yasutake et al., 2003); (b) at least 1/3rd of those in a study population of slightly more than 1,000 women of childbearing age in Hong Kong (Fok et al., 2006); and (c) about 1/9th those in 65 pregnant women in Taiwan who were participating in a study of the relationship between fish consumption and mercury levels (Hsu et al., 2007).
- children ages 1-5 are exposed to methylmercury at levels that are about 1/25th of those experienced by the children in the Faroe Islands study population (McDowell et al., 2004, page 1,169).
(d) Methylmercury Concentrations in Fish Sold Commercially
FDA and others have been analyzing commercial fish species in the United States for years for concentrations of methylmercury (measured as total mercury) in their tissues. The results can be found on the FDA web site. The findings are generally consistent with databases maintained in other countries for the same species (CCFAC 2006; Health Canada 2007; Montwill 2007).
For each listed species and product type (e.g., canned light tuna), the database includes the average mercury concentration in that species or product type, the median concentration, the minimum and maximum concentrations that have been found in individual samples, and the number of samples upon which the above values are based. The primary utility of the database is that it can be used to estimate how much fish of various species a person would have to eat on a regular basis in order to reach a certain concentration of methylmercury in his or her body. In the risk and benefit assessment described in this report we used the concentrations in the database to estimate how exposures to methylmercury would change if people ate more or less fish or if they changed the types of fish they ate. Previously, data on the concentrations of methylmercury in commercial species were used to estimate what methylmercury exposures would be if the FDA/EPA consumption advisory for methylmercury were followed by consumers.
Highlights from the Database:
- The range: The methylmercury concentrations in the FDA database include some fish for which the value has been nondetectable based on current methods of analysis. For the fish for which methylmercury has been detectable (most of them), the lowest average methylmercury concentrations are between 0.01 and 0.02 ppm. Those with the highest average concentrations have averages that are just under 1.0 ppm, although the highest average concentration is 1.4 ppm for tilefish from the Gulf of Mexico.
- The average concentration for all commercial fish: An "average" commercial fish in the U.S. marketplace, weighted for consumption, contains 0.086 ppm methylmercury. "Weighted for consumption" means that the more popular a species is, the more "weight" it is given when calculating the average methylmercury concentration for all commercial fish. Most commercial fish are at the low end of the range, as described above.
- Methylmercury in the "top 10" fish: On a per-species basis, the average amount of methylmercury in the top 10 most consumed commercial species in the United States ranges from nondetectable to 0.2 ppm, with the exception of albacore canned tuna, which averages 0.35 ppm. The top 10 species comprise approximately 73 percent of commercial fish consumed in the United States (Montwill 2008).
- Canned tuna: One of the most highly consumed commercial fish products, canned tuna in the aggregate contains on average 0.17 ppm. As stated above, the average for canned albacore "white" or "solid" tuna is 0.35 ppm. Albacore accounts for about one-third of canned tuna (Montwill 2008).
- NOTE: fresh or frozen tuna fillets/steaks average about 0.35 ppm, but are below the top 20 commercial species in terms of consumption. The top 20 represent about 90 percent of all commercial fish consumed in the United States (Montwill 2008; see also Table AA-3 in Appendix A).
- Mid-range species: There are not many species that can be considered "mid-range," i.e., with averages above 0.2 ppm. With the exception of albacore canned tuna, all of them are outside the top 10 consumed commercial species. In addition to fresh or frozen tuna steaks/fillets (average of 0.35 ppm) and albacore as a subset of canned tuna, those commercial species occupying the mid-range between the lowest and highest average between 0.4 – 0.6 ppm (i.e., grouper, red snapper, moonfish, orange roughy, saltwater bass, freshwater trout) and each of them ranks below the top 20 in terms of U.S. consumption.
- High-end species: Long-lived predatory fish tend to accumulate the most methylmercury. Shark and swordfish, which average around 1.0 ppm, are outside the top 20 in terms of U.S. consumption. King mackerel (average of 0.73 ppm) and tilefish from the Gulf of Mexico (average of 1.45 ppm),(6) are also outside of the top 20 in terms of consumption. Collectively, these four species account for six-tenths of one percent of U.S. consumption (Montwill 2008).
- Variability of concentrations within species and product types: As a result of normal variation there is considerable overlap in mercury concentrations among species and product types. For example, canned light tuna has an average concentration that is one-third the average concentration for canned albacore tuna, but the low-to-high range in our database for canned light tuna is nearly identical to that for canned albacore tuna (nondetectable to 0.852 ppm for light; nondetectable to 0.853 ppm for albacore). Consequently, some cans of albacore contain less mercury than some cans of light and some cans of light contain more mercury than some cans of albacore.
(e) Are Concentrations of Methylmercury Increasing in Commercial Fish?
Most commercial fish species sold in the United States are harvested from the open ocean or from aquaculture sites. Aquacultured fish tend to be raised and harvested quickly without much opportunity to accumulate methylmercury. Moreover, aquacultured fish are not usually the large predatory types of fish that accumulate methylmercury over time by eating other fish containing methylmercury.
It has been estimated that human activity contributes over half of the total amount of mercury that is entering the atmosphere annually (EPA 1997). Increases in concentrations of methylmercury are more likely to occur in the vicinity of population sources, e.g., in bodies of water such as rivers downstream from certain types of mining operations, and in relatively small, enclosed bodies of water such as lakes (EPA 1997). Limited data suggest that methylmercury concentrations in commercial fish have not increased or decreased over time.
Studies of fish, including tuna and swordfish that were up to 90 years old (Miller et al., 1972; Barber et al., 1972) report levels consistent with today's levels. In both studies the researchers discounted the possibility that these findings could have been affected by the preservatives used to store the fish as well as other conditions of storage, although the researchers in one of the studies admitted that the possibility could not be "rigorously excluded" (Miller et al., 1972). In another study that focused on conditions of preservation, however, the researchers concluded that, depending on circumstances, preservation techniques could substantially alter heavy metal concentrations in museum specimens of fish (Gibbs et al., 1974). For this reason, comparisons of contemporary fish to museum specimens should not be regarded as definitive.
In a more recent timeframe, mercury concentrations in Yellowfin tuna caught off Hawaii in 1998 were found to be essentially identical to those caught in the same area in 1971 – a span of 27 years (Kraepiel et al., 2003). The researchers engaged in "mercury biogeochemistry" modeling for the equatorial and subtropical Pacific in an effort to explain why these fish showed no increase in methylmercury in spite of increases in global mercury emissions over the past century. The most likely explanation, they concluded, is that mercury is converted into methylmercury (the form of mercury in fish) in the deep ocean, with transfer to the upper layer of ocean taking a minimum of 400 years. They noted that Yellowfin tuna and their prey swim in the upper layer. The researchers assumed that the total mercury concentration in the upper ocean layer had doubled between 1860 (the onset of the industrial revolution) and 1990. Nonetheless, that mercury would not convert to methylmercury or be absorbed by fish in the upper layer unless it first sank into the deep ocean and then circulated back over a long period of time.
Mercury concentrations in freshwater commercial species are low. In our database the average mercury concentration for commercial freshwater species is 0.08 ppm on a per species basis, and the highest average for any species is 0.14 ppm (FDA 2006). (Recall that the average for all commercial species, weighted for consumption, is 0.086 ppm.)
FDA's methylmercury database was reviewed for evidence of increases in concentrations over time. The database spans 30 years, starting around 1974. As described previously, for each species it includes the range of concentrations in the samples from highest to lowest and the mean concentration. For some species the database only includes recent sampling because interest in that species has been recent; for others the data span 20-25 years of sampling and for others the data span about 30 years. Overall, the database does not reveal a trend one way or the other, although the size of the database and the time frames of collection are limited.
(5) On the NCTR website, NHANES exposure data are available as both hair levels for 1999-2000 and blood levels for 1999-2004. The blood levels are divided into total mercury, which includes organic mercury (i.e., methylmercury) and inorganic mercury. Methylmercury levels can be calculated by subtracting the inorganic mercury from the total mercury. The remaining organic mercury is overwhelmingly methylmercury. (Another form for organic mercury to which adults can be exposed, ethylmercury from thimerosal preservative in some influenza vaccines, ophthalmic and otic drug products involves exposures that are extremely small, occur once-per-year at most, and are relatively short in duration since ethylmercury leaves the body more quickly than methylmercury.) Consequently, we regard the levels of organic mercury in blood to be the relevant data from NHANES for purposes of this report. We note that CDC's discussion of NHANES data in its Morbidity and Mortality Weekly Report (CDC 2004a) describes the total mercury results but not the organic mercury results.
For the 1999-2000 data, it is also possible to compare the NHANES hair data to the methylmercury blood data since NHANES obtained both types of data from each participant in the survey during those years. In the overwhelming majority of cases, blood levels exceed hair levels by an average of around five to one. At the high end of exposures, however, we see some hair levels that substantially exceed blood levels. The most striking case involves a woman with a mercury hair level of 849 ppm. Such a level would be high relative to the extreme poisoning events that occurred in Japan and Iraq in the last century. By contrast, her methylmercury blood level was relatively normal, although higher than average for the United States. A possible explanation for a hair level this high would be environmental contamination with inorganic mercury.