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MERCURY BIOMONITORING IN MINNESOTA
A Senior Project submitted to the Faculty of the Biology, Society, and
Environment Program, University of Minnesota, in partial fulfillment of the
requirements for the Bachelor of Arts
Allison E. Fast
10 May, 2013
1
Abstract
There is considerable biomonitoring data nationwide on human exposure to various chemicals.
Despite this, there are often disparities in biomonitoring data that limit the full knowledge of
exposure. In the state of Minnesota, these disparities include a lack of data on mercury exposure
in vulnerable populations and at a baseline level in the general state population. The results of a
pilot Minnesota Department of Health mercury biomonitoring study revealed ten percent of
newborns in a Lake Superior Basin population had blood mercury concentration levels that
exceeded the United States Environmental Protection Agency’s Reference Dose for methyl
mercury of 5.8 µg/l. These results sparked additional interest in mercury biomonitoring on a
statewide level, the characterization of human mercury exposure, as well as the validation of the
novel laboratory procedure used to measure total mercury in the Minnesota Department of
Health pilot mercury study. With goals of exploring the characteristics of mercury exposure in
the state of Minnesota, the Minnesota Department of Health embarked on a series of mercury
biomonitoring studies. These studies, along with increasing the biomonitoring capacity of the
state, have allowed for the continued exploration of statewide mercury exposure, novel ways of
analyzing exposure levels in the laboratory, and intervention efforts to increase public awareness
and education of the dangers of mercury exposure.
2
Acknowledgements
I thank my project adviser, Dr. Ruby Nguyen, for her continued structure, guidance, and support
throughout the entirety of this project. In addition, I thank Patricia McCann and Dr. Jessica
Nelson for their clarification of MN LSB and EHTB, and my Biology, Society, and Environment
adviser, Dr. Jeanette Simmonds, for her advice and aid in the planning of this project.
3
Abstract ………………………………………………..………………………………………… 1
Acknowledgements …………………………………………………..………………………….. 2
Mercury Biomonitoring in Minnesota ……………………………….………………………….. 4
References... ……………………………………………………………………………………. 22
4
Human exposure to mercury is a significant public health issue that affects individuals
nationwide. The public health concern over the sources, distribution, and severity of mercury
exposure in Minnesota is addressed through the efforts of the Minnesota Department of Health
(MDH). Through the biological monitoring, or biomonitoring, of chemicals and their
metabolites in human hair, blood, or urine, the measurement of human exposure to harmful
substances is a useful tool in determining characteristics of human exposure to chemicals (Minn.
Stat. §144.995 2008). Initiated in 2007 along with the Environmental Health Tracking Program,
the Biomonitoring Program at MDH is instrumental in developing a baseline of mercury
exposure, as well as exploring the characteristics of exposure in vulnerable populations in
Minnesota. In addition to its work in characterizing the determinants and distribution of mercury
exposure in the state, the MDH Environmental Health Tracking and Biomonitoring Program
(EHTB) pioneered a novel laboratory method for the measurement of total mercury
concentration in dried blood spots (DBS). Created with the intention of increasing the
biomonitoring capacity of state, EHTB helped increase the knowledge of the distribution and
characteristics of mercury exposure in Minnesota (Environmental Health Tracking and
Biomonitoring 2013). The results of a pilot MDH study, that showed elevated blood mercury
concentrations in a population of Minnesota newborns, initiated a subsequent series of mercury
exposure studies. In addition, the results of the pilot MDH study led to the creation of multiple
long term goals of increasing the understanding of mercury exposure throughout the state to
better educate and protect populations from dangerous exposure. Through the investigation of
the characteristics and measurement of mercury exposure, mercury biomonitoring in Minnesota
was successful in establishing a baseline of exposure, increasing the biomonitoring capacity of
5
MDH, and increasing awareness and education of the dangers of mercury exposure in the state of
Minnesota.
Mercury is a metallic chemical element that is naturally occurring in the environment. In
its metallic state, mercury is a shiny, silver-white, odorless liquid that when heated, becomes a
colorless and odorless gas (ChemicalBook 2008). Mercury exists in three separate oxidation
states including mercuric (𝐻𝑔2+
), mercurous (𝐻𝑔2
2+
), and metallic (𝐻𝑔0
). Forming various
inorganic and organic compounds, mercury undergoes a consistent transformation and speciation
change that influences its environmental effects and toxicity. Mercury undergoes a global cycle
in which it transforms its chemical forms, as well as cycles through the environment, in a process
known as the “ping-pong” effect (World Health Organization 1990, 29-30). Constantly cycling
between water, land, and the atmosphere, mercury undergoes a biological transformation from an
inorganic to an organic state in aquatic systems. Once in water, inorganic mercury may begin the
conversion to an organic mercury compound, such as methyl mercury, through the process of
methylation. The conversion is enabled by the non-enzymatic methylation of inorganic mercury
by the compound methyl cobalamine. Once converted to methyl mercury, or another organic
compound, mercury enters the food chain by rapidly diffusing throughout the aquatic system and
tightly binding to proteins in wildlife. Unlike other forms of mercury, organic mercury is able to
accumulate in humans and animals. Because of this, methyl mercury is rapidly accumulated by
most aquatic organisms and is able to attain high concentrations in fish at the top of the food
chain through the process of biomagnification (World Health Organization 1990, 29-31). The
mercury that has accumulated in fish and other aquatic species enters the human body when the
fish are consumed. Upon being absorbed by the gastrointestinal tract, mercury from the tissue of
the fish is transferred to the blood and tissue of the human, where it accumulates and is
6
eventually excreted. The methylation of inorganic mercury and its subsequent accumulation in
the aquatic food chain through biomagnification assures ingestion as the most common form of
methyl mercury exposure (Eccles and Annau 1987).
The bioaccumulation of methyl mercury in many aquatic species, such as fish, is enabled
through the emission of mercury into the surrounding environment through a variety of natural
and manmade sources. Emissions from volcanoes, bodies of water, and the degassing of the
earth’s crust, all release metallic mercury into the atmosphere where it is then washed down to
land and bodies of water through precipitation or dry atmospheric deposition (World Health
Organization 1990, 24-31). Various anthropogenic activities, such as mining, have increased the
release of metallic mercury from the earth into the atmosphere, as well as emitting additional
mercury into the atmosphere through the process of smelting. In addition to the leaching of
mercury into the environment from mining and natural degassing, a variety of industrial
processes utilize various forms of mercury or mercury-containing compounds in products and
manufacturing. Pollution and runoff from mining and industrial processes contribute to the
burden of mercury in bodies of water and the atmosphere through the direct discharge of waste
(U.S. Geological Survey 2010). The presence and accumulation of mercury in the environment
is a cumulative effect of natural and anthropogenic sources, each of which contributes to the
global burden of mercury and its related concerns to the health of both the environment and
humans.
The toxicity of mercury and mercury containing compounds has been well documented in
the United States and around the world for decades (World Health Organization 1990, 69). With
the ability to cause damage when ingested, absorbed through the skin or mucous membranes, or
inhaled as a vapor, mercury is a potent toxin that is dangerous to humans and other life forms.
7
As a result of this, the United States Environmental Protection Agency (EPA) has set a blood
methyl mercury Reference Dose (RfD) of 5.8 µg/l and a Benchmark Dose Limit (BMDL) of 58
µg/l. The BMDL is the lowest dose or concentration that produces a predetermined change in
incidence of an adverse effect (United States Environmental Protection Agency 2012d).
Determined based on the BMDL, the RfD is an estimate that states a blood concentration
equivalent of the maximum daily oral exposure that is likely to be without a significant risk of
deleterious effects during a lifetime (United States Environmental Protection Agency 2012c).
Where inorganic mercury compounds are not usually toxic to humans, organic compounds, such
as methyl mercury, can cause mild to severe neuromuscular disorders with moderate to severe
exposure (Eccles and Annau 1987, 17-18). Unlike many inorganic compounds, whose
insolubility prevents their absorption through the gastrointestinal tract, methyl mercury is readily
absorbed by the human body when consumed in the diet. In addition, the relatively long half life
of methyl mercury impedes the excretion of the compound, allowing for accumulation within the
human body. To add to the dangers of exposure, methyl mercury is especially toxic because of
its hydrophobic nature, allowing the compound easy transport across various membrane barriers,
such as the blood brain barrier and the placental barrier. In humans and other mammals, every
form of mercury is converted to its mercuric form during the process of excretion. Depending on
the original state of the mercury, this process may happen at different rates. For the compound
methyl mercury, the decomposition of the organic compound is a slow process. As a result of
this, methyl mercury is allowed time to accumulate and circulate throughout the body and
through protective barriers (Eccles and Annau 1987, 17-24).
Although toxic to all humans, methylated mercury is especially dangerous to the fetus
and children, whose developing tissues and nervous systems are particularly vulnerable to the
8
effects of the organic compound (World Health Organization 1990, 69). If present in levels
above the RfD, methyl mercury may have disastrous effects on the fetus, due to the ability of the
compound to cross through the placental barrier of the mother and into the womb (Grandjean et
al. 2005, 905-908). In addition, the increased sensitivity of the fetus to methyl mercury may
result in damage to the fetus while the mother remains asymptomatic and unaffected. Once
across the placental barrier, methyl mercury may cause severe damage to the developing nervous
system and brain of the fetus, putting the developing fetus at greater risk for deficits in memory,
learning, sight, hearing, or motor skills. Along with the devastating effects of methyl mercury on
the developing tissue of the fetus, impaired development and maturation of the brain as a result
of fetal exposure may result in the delay of achieving developmental milestones later in life
(Eccles and Annau 1987, 46-47).
Although the negative effects of mercury on humans and the environment had been
established years before, large-scale interest in mercury exposure in the state of Minnesota did
not take shape until 2007 (Patricia McCann, interview by Allison Fast, St. Paul, MN, February
21, 2013). The Environmental Health Division of MDH became interested in mercury exposure
in vulnerable populations, such as pregnant women and children. Seeing health care providers as
an effective way to communicate with women of childbearing age the dangers of mercury
exposure, the Environmental Health Division became interested in collecting concrete data on
mercury exposure levels in the state so health care providers would be more inclined to share this
data with women (McCann, interview). In addition to providing information to women and
families on mercury, there was a statewide and national interest in characterizing the distribution
of mercury exposure. Along with the interest of the Environmental Health Division, the Fish
Consumption Advisory Program of MDH, the EPA, and various Lake Superior regional
9
organizations expressed interest in developing a study in which the determinants and distribution
of mercury exposure were investigated. The lack of data on mercury exposure in the state, as
well as the desire to engage the health community in educating the public on mercury exposure,
led to the creation of a regional study in the Lake Superior Basin. The combined interest of
MDH, the EPA, and numerous Lake Superior regional organizations, shaped the initial interest in
mercury exposure to a more regional interest in mercury exposure in women and children. The
various interests of numerous statewide organizations, along with the allocation of funding for a
study in the Lake Superior region on mercury exposure from the EPA, led to the creation of the
Mercury Levels in Blood from Newborns in the Lake Superior Basin study (MN LSB) (McCann,
interview).
Mercury exposure in the state further attracted the attention of the MDH later in 2007
when state legislation mandated a study on mercury exposure be conducted in Minnesota
(Environmental Health Tracking and Biomonitoring 2013). The legislation passed in 2007 was
responsible for the creation of the Environmental Health Tracking Program, along with the
creation of the Biomonitoring Program at MDH. The two programs were then linked to form
EHTB. To provide guidance and recommendations for projects within EHTB, an external
Advisory Panel of experts in public health and environmental science was established (Minn.
Stat. §144.998 2008). Although the Environmental Health Tracking Program and the
Biomonitoring Program were linked, the two programs were established with separate goals.
The ultimate goal of the Environmental Health Tracking Program was to collect and share public
health data in order to identify health priorities that can provide the basis for actions to improve
public health. In contrast, the Biomonitoring program had multiple goals. The first was to
answer questions about the magnitude and range of exposure to specific chemicals in certain
10
communities in Minnesota. Other goals were centered on building an infrastructure at MDH for
implementing an ongoing biomonitoring program and building biomonitoring capacity in the
state (Environmental Health Tracking and Biomonitoring 2011). Advancing the capacity of the
Public Health Laboratory to measure chemicals and toxic metals in human hair, blood, and urine,
as well as the development of a baseline for exposures in the state, would allow the
Biomonitoring Program to track progress over time in reducing exposure (Environmental Health
Tracking and Biomonitoring 2013).
In addition to the establishment of EHTB, the 2007 state legislation mandated that four
separate pilot studies be conducted in Minnesota. Each pilot study was to investigate exposure to
various chemicals including arsenic, perfluorinated chemicals, and mercury, in voluntary
populations in the state. Due to funding concerns, EHTB, as well as the Advisory Panel,
explored the possibility of joining a preexisting mercury exposure study (Environmental Health
Tracking and Biomonitoring 2013). At that time, MN LSB was still in its planning stages with
the Fish Consumption Advisory Program of the Environmental Health Division of MDH. In lieu
of conducting a separate mercury biomonitoring study, and out of interest in MN LSB, EHTB
offered their support and some funding to the Environmental Health Division (Minnesota
Department of Health 2008). By the end of the planning stage of MN LSB, EHTB was working
in accordance with the Environmental Health Division to track mercury exposure in newborns in
the Lake Superior Basin.
With funding from the EPA Great Lakes National Program, as well as support and
funding from EHTB, MN LSB began recruiting participants in the fall of 2008. During the
planning phase, various goals were established for the study that reflected the contributions of
both the Environmental Health Division as well as EHTB. Two main goals of the study were to
11
measure mercury exposure in a population of newborns in the United States portion of the Lake
Superior Basin, as well as determine characteristics of the exposure in this population
(Environmental Health Tracking and Biomonitoring 2011). Another important goal of MN LSB
was to utilize and evaluate a novel laboratory method for biomonitoring with the use of DBS.
The collection of DBS is a routine newborn screening procedure in hospitals throughout the
country. Requiring only five drops of blood from a newborn’s heel, twenty four to forty eight
hours after birth, the blood is spotted on a filter paper card to be analyzed. Once the sample has
dried, the blood is analyzed in a laboratory to identify newborns at risk for various health
conditions. After analysis, a small amount of blood remains on the filter paper card, so the card
is stored as a residual sample for the future use of the family, the laboratory, and public health
and biomedical research (Genetic Alliance). In MN LSB, this dried blood sample was analyzed
to determine the mercury concentration in Lake Superior Basin newborns. Though not a
common or well-refined method for the measurement of mercury in a newborn blood specimen,
there are various advantages to utilizing DBS over more traditional methods. In addition, the
novel use of DBS in analyzing mercury exposure was an effective way to increase the
biomonitoring capacity of EHTB and the Public Health Laboratory (McCann, interview).
Although a novel and relatively unrefined procedure with no available data for
comparison of results or technique, there are various advantages to the use of DBS. One of the
most common and effective measures of mercury exposure in a newborn is through the analysis
of umbilical cord blood collected after birth (Grandjean et al. 2005, 905-908). Umbilical cord
blood analysis allows for the speciation of the mercury and also has large amounts of published
literature available for comparison of results and technique (Minnesota Department of Health
2013). Although an effective exposure biomarker of mercury, especially methyl mercury for
12
which the placenta does not constitute a barrier, the collection of umbilical cord blood requires
trained hospital personnel (Grandjean et al. 2005, 905-908). In addition, the collection of
umbilical cord blood it is not a routine procedure, is costly, and must be done immediately
following birth (Minnesota Department of Health 2013). In comparison, DBS are routinely
collected within forty eight hours after birth, and residual DBS are stored for multitudes of
newborns nationwide after their analysis in newborn screening programs (Genetic Alliance).
Unlike umbilical cord blood, DBS collection is not costly and does not require specially trained
personnel to obtain. Despite this, the use of DBS in biomonitoring is a novel procedure whose
results, technique, and efficacy have not been validated. Additionally, the small quantity of
blood in the sample makes the speciation of mercury impossible (Minnesota Department of
Health 2013). Due to the advantages of DBS to umbilical cord blood and the potential of the
novel procedure to increase the biomonitoring capacity of MDH and the nation, the use of DBS
was an attractive and groundbreaking option for biomonitoring in Minnesota.
The recruitment of Lake Superior Basin newborns for MN LSB began November 2008
and was a collaboration between MDH and state newborn screening programs in Minnesota,
Wisconsin, and Michigan. The geographic boundary of the United States portion of the Lake
Superior Basin was defined by watershed boundary data. Participants were determined based on
this geographic boundary and the zip code of the mother’s residence. Newborns of eligible
participants were identified from the Newborn Screening Database at MDH. Newborns were
excluded from participation if there were complications in the pregnancy, the infant had died or
was born with certain health problems, or the quality of the DBS was insufficient for analysis
(Environmental Health Tracking and Biomonitoring 2011). Local and state public health
departments mailed written communication to mothers of eligible newborns, explaining the
13
project and inviting their participation. The written communication consisted of a consent form
and a letter that informed mothers that the specimens would be anonymized, that their individual
babies’ results would not be available, and that MDH would not inform them of the aggregate
findings (McCann 2011). Mothers of eligible newborns were contacted three weeks after giving
birth and invited to participate in the study. If no response was received within three weeks of
the initial communication, a second letter was sent (Environmental Health Tracking and
Biomonitoring 2011). A total of 2,566 parents of eligible newborns were contacted in
Minnesota, inviting their participation in MN LSB and requesting informed consent of the use of
their newborns’ blood. Of these Minnesota parents that were contacted, 1,130 gave their consent
(McCann 2011). Similar methods were utilized in Wisconsin and Michigan to invite mothers of
newborns to participate in the study and acquire informed consent. Of the Wisconsin and
Michigan mothers that were contacted, consent from 140 mothers in Wisconsin and 810 mothers
from Michigan was received. Due to funding concerns and issues with the storage and custody
of DBS in Michigan specimens, the number of specimens from Michigan was reduced from 810
to 200 (McCann 2011). The recruitment of participants continued until November 2010, when
the beginning stages of data collection and specimen analysis began.
The results of MN LSB revealed a wide range of total mercury concentrations, with the
majority of specimens exhibiting low mercury levels. Of the 1,470 parents that had given
informed consent, the total number of specimens analyzed was 1,465, with 1,126 specimens
from Minnesota, 139 from Wisconsin, and 200 from Michigan (McCann 2011). After the
recruitment of participants concluded in 2010, data collection and analysis began and continued
until its conclusion in the fall of 2011. The analysis of the total mercury concentration in the
1,465 specimens showed forty three percent of the specimens to be below the method detection
14
limit (MDL) of 0.7 µg/l, indicating a low or nonexistent mercury concentration in nearly half the
specimens (McCann 2011). About one percent of the specimens were found to be above the
BMDL of 58 µg/l, with eight percent of specimens above the RfD of 5.8 µg/l. Of the blood
mercury concentrations that exceeded the RfD, Minnesota had the highest rate at ten percent of
the 1,126 specimens exceeding a blood mercury concentration of 5.8 µg/l. In comparison to the
Wisconsin and Michigan specimens, three percent of the 139 Wisconsin specimens, and none of
the 200 Michigan specimens, exceeded the RfD (Myers 2012). The maximum exposure
measured was 211 µg/l (McCann 2011). The results depicted a trend of higher mercury exposure
in Minnesota specimens as well as an exposure pattern with highest mercury concentrations in
the summer births. The seasonal exposure pattern with highest mercury concentrations in
summer births supports a local fish consumption exposure pathway. Despite this clear pattern, it
is impossible to validate a fish consumption exposure pathway without the ability to speciate
mercury in DBS analysis. In addition, the analysis of DBS only enabled the detection of
mercury when it exceeded the MDL, limiting the characterization of low exposure levels
(McCann 2011). As a result of this and other challenges, the findings of MN LSB raised
questions from researchers and MDH about the exposure pathway, as well as the distribution and
characteristics of mercury exposure in the Lake Superior Basin and throughout the state of
Minnesota. In addition, the uncertainty surrounding the use of DBS raised questions about the
validity of the laboratory method and the efficacy of DBS as an indicator of mercury exposure in
newborns (Environmental Health Tracking and Biomonitoring 2013).
The multiple challenges of MN LSB and recommendations from MDH Advisory Panel
led to various goals and plans to conduct further research on mercury exposure in Minnesota.
The results of MN LSB that showed ten percent of Minnesota specimens had a mercury
15
concentration in their blood that exceeded the EPA RfD of 5.8 µg/l sparked interest in additional
biomonitoring and raised questions on the limitations of the study. The results of MN LSB were
limited to babies born to mothers who gave their consent and were living in the Lake Superior
Basin area of Minnesota, Wisconsin, and Michigan. Because of this, the sample was biased and
therefore was not necessarily representative of a statewide distribution of mercury. In addition,
the MN LSB sample did not take into account that some Minnesota communities may be more
exposed than others due to geographic, cultural, or ethnic differences. The MN LSB sample
lacked the ability to characterize mercury exposure on a statewide level and shed light on any
potential disparities in vulnerability or exposure to mercury in various populations in Minnesota.
Another challenge of MN LSB was the lack of MDH data on vulnerable groups, as well as any
statewide or national data available for comparison of mercury exposure in newborns
(Environmental Health Tracking and Biomonitoring 2013). The DBS analysis data lacked
published literature or data for comparison of methods and results of mercury levels in newborn
blood. In addition, the laboratory method used for analysis was a novel method that had not
been validated or peer reviewed (McCann 2011). The uncertainty of laboratory results and
methods, along with the absence of data or published literature for comparison, led to questions
on the accuracy of the use of DBS as an indicator of newborn mercury exposure.
The analysis of newborn blood in MN LSB effectively identified a public health issue
that required more action and investigation in Minnesota. In addition, the use of DBS as a
potential biomonitoring method generated interest in MDH, and specifically the Public Health
Laboratory, in further statewide biomonitoring of mercury. Because of the questions that were
raised on the characteristics of mercury exposure on a wider scale, the MDH Advisory Panel
made various recommendations for additional biomonitoring. First, the Advisory Panel
16
recommended additional biomonitoring in newborns be done at a statewide level in order to
identify disparities in exposure and to provide a baseline for tracking progress in vulnerable
populations. In addition, the Advisory Panel recommended subsequent biomonitoring be done to
validate the fish consumption exposure pathway, identify additional sources of mercury
exposure, and refine methods for mercury biomonitoring in Minnesota. To confirm DBS as an
accurate indicator of mercury exposure in newborns, the Advisory Panel recommended further
research be conducted in which the results of DBS analysis be compared to a traditional measure
of mercury concentration in newborns (Environmental Health Tracking and Biomonitoring
2013).
With MDH Advisory Panel recommendations in mind, additional mercury biomonitoring
began in Minnesota in 2012 with three separate initiatives. The first was a collaboration of the
MDH Biomonitoring Program and the University of Minnesota in the Pregnancy and Newborns
Exposure Study (Minnesota Department of Health 2012b). The second is a planned
collaboration of EHTB with the former National Children’s Study (NCS) South Dakota State
University Vanguard pilot study in the Minnesota National Children’s Study (NCS) Newborn
Mercury Project (Minnesota Department of Health 2013d). The third study was the Fond du Lac
(FDL) Community Biomonitoring Study, which is part of the Great Lakes Restoration Initiative
(GLRI). This study was a collaboration of MDH with the FDL Band of Lake Superior Chippewa
(Minnesota Department of Health 2013a). Although different in various respects, each study
was designed to further statewide mercury biomonitoring, identify disparities in mercury
exposure in vulnerable populations, and refine and validate the use of DBS analysis as an
indicator of newborn mercury exposure (Environmental Health Tracking and Biomonitoring
2013).
17
The Pregnancy and Newborns Exposure Study compared mercury levels in paired
newborn umbilical cord blood and DBS specimens. The study recruited participants already
enrolled in a larger study being conducted in part at the University of Minnesota, called The
Infant Development and Environmental Study (TIDES) (Minnesota Department of Health
2012b). A four year, National Institutes of Health-funded project, TIDES focused on exploring
the effects of various exposures on infants during gestation at research sites in Minnesota, New
York State, Washington, and California (Minnesota Department of Health 2012b). The
Pregnancy and Newborns Exposure Study began recruiting University of Minnesota TIDES
participants in June 2012 with the goal of addressing various questions raised by MN LSB
results (Minnesota Department of Health 2012a). In response to MN LSB results, and
recommendations made by MDH Advisory Panel, the Pregnancy and Newborns Exposure Study
progressed with three main goals. The first goal was to compare total mercury content in paired
umbilical cord blood and DBS in order to obtain a measure of the ratio of mercury concentration
between the whole blood and DBS paired samples. Due to the inability of DBS analysis to
speciate mercury as either organic or inorganic, the second goal of the study was to speciate
mercury in the umbilical cord blood specimens. The final goal of the Pregnancy and Newborns
Exposure Study was to further refine laboratory methods for measuring mercury exposure in
newborns (Minnesota Department of Health 2012b).
Beginning in June 2012 and lasting until January 2013, informed consent was obtained
from forty nine women currently enrolled in University of Minnesota TIDES (Minnesota
Department of Health 2013d). After recruitment had concluded, data collection began with the
obtainment of forty nine matched pairs of infant umbilical cord blood and DBS specimens,
collected after birth by hospital staff. After collection, specimens were sent to the Public Health
18
Laboratory to begin data analysis. Analysis of umbilical cord blood specimens for total mercury,
lead, and cadmium concentration in each of the forty nine samples was concluded in March
2013. Analysis revealed one specimen with a mercury concentration greater than the RfD, and
no specimens that exceeded the RfD for lead (Minnesota Department of Health 2013d).
Currently, results letters are being prepared and mailed to the participants, dictating
individualized results. With the analysis of total mercury concentration in umbilical cord blood
specimens complete, the next steps of the Pregnancy and Newborns Exposure Study are to
analyze the DBS for total mercury content and to speciate the mercury in the umbilical cord
blood (Minnesota Department of Health 2013d). After the completion of data analysis, the next
steps for the Pregnancy and Newborns Exposure Study are to formulate long term goals of
pursuing additional mercury research on the extent of exposure in various populations in
Minnesota. Additional long term goals include investigation of additional sources of mercury
exposure statewide and the refinement of laboratory methods involving DBS (Minnesota
Department of Health 2012a).
The Minnesota NCS Newborn Mercury Project will compare matched specimens of
umbilical cord blood spot, DBS, whole umbilical cord blood, and maternal blood (Minnesota
Department of Health 2013d). In addition, the project will provide added data to the Pregnancy
and Newborns Exposure Study, in order to increase the sample size for analysis of the
comparison of matched blood specimens. Utilizing previously collected specimens of umbilical
cord blood, DBS, and maternal blood from the former NCS South Dakota State University
Vanguard pilot study, EHTB will obtain and analyze the matched specimens in order to
accomplish three main biomonitoring goals. The first goal of the Minnesota NCS Newborn
Mercury Project is to assess the comparability of different measures of prenatal exposure to
19
mercury. Based on the desire to validate the use of DBS as an effective biomonitoring tool for
mercury, the second goal is to compare paired whole umbilical cord blood and umbilical cord
blood spot mercury levels to determine how accurately mercury levels in blood spots reflect
levels in the original, whole blood sample. The final goal of the Minnesota NCS Newborn
Mercury Project is to explore the extent of newborn mercury exposure on a statewide level in
order to determine if the elevated mercury levels found in MN LSB were applicable to other
parts of Minnesota. Upon completion of data collection and analysis, results of the Minnesota
NCS Newborn Mercury Project will be compared to the results of other mercury biomonitoring
research. Due to the very limited availability of published literature and data on newborn
mercury exposure, comparison of newborn mercury levels and blood analysis methods will
likely be restricted to the MN LSB and the Pregnancy and Newborns Exposure Study data for
comparison (Minnesota Department of Health 2013d).
The FDL Community Biomonitoring Study is a part of the GLRI that was enabled in
2010 by a grant from the EPA (United States Environmental Protection Agency 2012b). The
study was a collaboration of MDH with the FDL Band of Lake Superior Chippewa (Minnesota
Department of Health 2013a). The Fond du Lac Community Biomonitoring Study was enabled
by an additional EPA grant that was awarded to MDH in 2012 to reduce mercury exposure risk
for women and children who live along Lake Superior’s north shore (United States
Environmental Protection Agency 2012a). The study is conducting biomonitoring in non-
pregnant, adult Native Americans that have been residents of northeast Minnesota for at least the
past twelve months. The purpose of the FDL Community Biomonitoring Study is to explore the
characteristics of mercury exposure in a vulnerable population and to compare these results to
the general population (Minnesota Department of Health 2013a). In collaboration with GLRI,
20
the FDL Community Biomonitoring Study developed goals for improving health screening in the
community and forming more effective fish consumption advisories (United States
Environmental Protection Agency 2012a). Beginning in December 2012, letters and consent
form were mailed to potential participants, describing the study and inviting their participation.
Due to increased community interest in the study, outreach and recruitment campaigns have been
largely successful. As of February 2013, fifty five participants had enrolled in the study. With
the increased levels of community interest, participation recruitment is expected to enroll many
more participants by the end of recruitment in the fall of 2013. In addition to the biomonitoring
of other vulnerable populations, such as pregnant women and babies, the FDL Community
Biomonitoring Study is another piece to the puzzle in identifying vulnerable groups in Minnesota
who may have a higher risk of mercury exposure (Minnesota Department of Health 2013a).
Beginning in 2007 with the creation of EHTB and its related Advisory Panel, the
exploration of mercury exposure in Minnesota has experienced a statewide increase in attention
and interest. The results of MN LSB that showed elevated mercury concentrations in ten percent
of Minnesota Lake Superior Basin newborn specimens captured the attention of local and
national government organizations, health care providers, and the public. Along with increasing
the visibility and recognition of mercury exposure as an important issue in Minnesota health, the
results of MN LSB kindled interest in the further characterization and exploration of mercury
exposure in other vulnerable populations, as well as the general population statewide. Through
its innovative use of DBS, the novel laboratory method used in MN LSB increased the visibility
of mercury exposure in the state, as well as the biomonitoring capacity of the Public Health
Laboratory and MDH. The cultivation of further exploration into the distribution, exposure
pathways, and methods of measuring and analyzing mercury exposure in Minnesota allowed for
21
additional mercury biomonitoring studies and intervention projects to be undertaken. The
continued interest in mercury exposure that has been demonstrated by the Pregnancy and
Newborns Exposure Study, the Minnesota NCS Newborn Mercury Project, and the FDL
Community Biomonitoring Study, illustrates a biomonitoring program that is continually
interested in the health and wellbeing of both the population and environment of the state.
Through continued health exposure education and intervention efforts, the efforts of MDH have
increased community and health care provider awareness to the dangers of mercury exposure.
Although further research, intervention efforts, and increased concern for environmental mercury
contamination are necessary, MDH and EHTB are effectively diminishing levels of human
mercury exposure throughout the state of Minnesota. The further characterization of mercury
exposure and understanding of exposure pathways will increase the efficacy of community
education and intervention projects, decreasing the harmful exposure of individuals to mercury
and fostering the health of communities in Minnesota.
22
References
Agency for Toxic Substances and Disease Registry. Toxic substances portal- mercury. 2011
[cited March 2013]. Available from
http://www.atsdr.cdc.gov/toxfaqs/tf.asp?id=113&tid=24.
Bienkowski, Brian. 2012. Mercury in newborns likely from mothers eating contaminated fish.
Great Lakes Echo (February 21, 2012), http://greatlakesecho.org/2012/02/21/mercury-in-
newborns-likely-from-mothers-eating-contaminated-fish/.
Chaudhuri, S. N., S. J. Butala, R. W. Ball, C. T. Braniff, and Rocky Mountain Biomonitoring
Consortium. 2009. Pilot study for utilization of dried blood spots for screening of lead,
mercury and cadmium in newborns. Journal of Exposure Science & Environmental
Epidemiology 19 (3) (Mar): 298-316.
ChemicalBook. Mercury. 2008 [cited April 2013]. Available from
http://www.chemicalbook.com/ProductChemicalPropertiesCB7355066_EN.htm.
Eccles, Christine U. and Zoltan Annau, eds. The toxicity of methyl mercury. The Johns Hopkins
series in environmental toxicology. Baltimore: The Johns Hopkins University Press, 11-105.
Environmental Health Tracking and Biomonitoring. 2013. Minnesota Department of Health
report to the Legislature 2013.
Environmental Health Tracking and Biomonitoring. 2011. Report to the Minnesota
Legislature April 2011. Available from
http://www.health.state.mn.us/divs/hpcd/tracking/pubs/ehtblegreport2011.pdf.
Environmental Health Tracking and Biomonitoring. 2008. Report to the Minnesota
Legislature on the pilot program for biomonitoring January 15, 2008. Available from
http://www.health.state.mn.us/divs/hpcd/tracking/pubs/ehtblegreport2008.pdf.
Genetic Alliance. Residual dried blood spots. [cited April 2013]. Available from
http://www.geneticalliance.org/nbs.bloodspots.
Grandjean, P., E. Budtz-Jorgensen, P. J. Jorgensen, and P. Weihe. 2005. Umbilical cord mercury
concentration as biomarker of prenatal exposure to methylmercury. Environmental Health
Perspectives 113 (7) (Jul): 905-8.
Karagas, M. R., A. L. Choi, E. Oken, M. Horvat, R. Schoeny, E. Kamai, W. Cowell, P.
Grandjean, and S. Korrick. 2012. Evidence on the human health effects of low-level
methylmercury exposure. Environmental Health Perspectives 120 (6) (Jun): 799-806.
23
Mahaffey, K. R., R. P. Clickner, and R. A. Jeffries. 2009. Adult women's blood mercury
concentrations vary regionally in the united states: Association with patterns of fish
consumption (NHANES 1999-2004). Environmental Health Perspectives 117 (1) (Jan): 47-
53.
McCann, Patricia. 2011. Mercury levels in blood from newborns in the Lake Superior basin. A
final report submitted to the US Environmental Protection Agency. St Paul. GLNPO ID
2007-942.
Meador, Ron. 2012. After decades of warnings and pollution controls, newborns arrive with a
burden of mercury. Minnpost (February 6, 2012), http://www.minnpost.com/earth-
journal/2012/02/after-decades-warnings-and-pollution-controls-newborns-arrive-burden-
mercury.
MINN. STAT. §144.998 (2008).
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MINN. STAT. §144.996 (2008).
MINN. STAT. §144.995 (2008).
Minnesota Department of Health. Biomonitoring study of a tribal community living in the lake
superior basin. 2013 [cited March 2013]. Available from
http://www.health.state.mn.us/divs/eh/risk/studies/tribalstudy.html.
Minnesota Department of Health. Biomonitoring: Chemicals in people. 2013 [cited March 2013].
Available from http://www.health.state.mn.us/divs/hpcd/tracking/biomonitoring/.
Minnesota Department of Health. Newborn screening program: Past studies using specimens and
test results after newborn screening. 2013 [cited March 2013]. Available from
http://www.health.state.mn.us/newbornscreening/research.html.
Minnesota Department of Health Environmental Health Tracking and Biomonitoring Advisory
Panel. 2013. Environmental Health Tracking and Biomonitoring Program Advisory Panel
Meeting Agenda, March 12, 2013. St. Paul. Available from
http://www.health.state.mn.us/divs/hpcd/tracking/panel/2013marmaterials.pdf.
Minnesota Department of Health Environmental Health Tracking and Biomonitoring Advisory
Panel. 2012. Summary: June 12, 2012 Meeting of the EHTB Advisory Panel. St. Paul.
Available from
http://www.health.state.mn.us/divs/hpcd/tracking/panel/2012junsummary.pdf.
24
Minnesota Department of Health Environmental Health Tracking and Biomonitoring Advisory
Panel. 2012. Summary: March 13, 2012 Meeting of the EHTB Advisory Panel. St. Paul.
Available from
http://www.health.state.mn.us/divs/hpcd/tracking/panel/2012marsummary.pdf.
Minnesota Department of Health Environmental Health Tracking and Biomonitoring Advisory
Panel. 2011. Advisory Panel Meeting March 8, 2011. St. Paul. Available from
http://www.health.state.mn.us/divs/hpcd/tracking/panel/2011marmaterials.pdf.
Minnesota Department of Health Environmental Health Tracking and Biomonitoring Advisory
Panel. 2008. Minnesota Department of Health Environmental Health Tracking and
Biomonitoring Advisory Panel Meeting June 3, 2008. St. Paul: Snelling Office Park.
Available from
http://www.health.state.mn.us/divs/hpcd/tracking/panel/2008junmaterials.pdf.
Minnesota Department of Health Environmental Health Tracking and Biomonitoring Advisory
Panel. 2007. Minnesota Department of Health Environmental Health Tracking and
Biomonitoring Advisory Panel Meeting December 17, 2007. St. Paul: Snelling Office Park.
Available from
http://www.health.state.mn.us/divs/hpcd/tracking/panel/2007decmaterials.pdf.
Minnesota Department of Health. Fish consumption advice. [cited March 2013]. Available from
http://www.health.state.mn.us/fish#sthash.baYyJ8aH.dpuf.
Minnesota Department of Health. Mercury in newborns in the lake superior basin. [cited
February 2013]. Available from
http://www.health.state.mn.us/divs/eh/hazardous/topics/studies/newbornhglsp.html.
Minnesota Pollution Control Agency. Reducing mercury emissions from power plants in
minnesota. 2006 [cited March 2013]. Available from
http://www.pca.state.mn.us/index.php/view-document.html?gid=11651.
Morita, Masatoshi, Jun Yoshinaga, and John S. Edmonds. 1998. The determination of mercury
species in environmental and biological samples. Pure & Appl. Chem. 70 (8): 1585-1615.
Myers, John. 2012. Effort targets mercury levels in newborns. Duluth News Tribune, October 5,
2012, 2012.
Stern, A. H. 2005. A revised probabilistic estimate of the maternal methyl mercury intake dose
corresponding to a measured cord blood mercury concentration. Environmental Health
Perspectives 113 (2) (Feb): 155-63.
Trevors, J. T. 1986. Mercury methylation by bacteria. Journal of Basic Microbiology 26 (8):
499-504.
25
U.S. Geological Survey. Mercury in aquatic ecosystems. 2010 [cited March 2013]. Available
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United States Environmental Protection Agency. 2012. EPA awards grant to protect women and
children from mercury in lake superior fish. (October 4 2012),
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80046785257a8d0072d8cf!OpenDocument#areahttp://yosemite.epa.gov/opa/admpress.nsf/d
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#area.
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[cited April 2013]. Available from http://www.epa.gov/glnpo/glri/.
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2013]. Available from http://www.epa.gov/risk_assessment/glossary.htm#r.
World Health Organization. 1990. Methylmercury. Environmental health criteria. Vol. 101.
Geneva, 13-126.

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Mercury Biomonitoring in Minnesota

  • 1. MERCURY BIOMONITORING IN MINNESOTA A Senior Project submitted to the Faculty of the Biology, Society, and Environment Program, University of Minnesota, in partial fulfillment of the requirements for the Bachelor of Arts Allison E. Fast 10 May, 2013
  • 2. 1 Abstract There is considerable biomonitoring data nationwide on human exposure to various chemicals. Despite this, there are often disparities in biomonitoring data that limit the full knowledge of exposure. In the state of Minnesota, these disparities include a lack of data on mercury exposure in vulnerable populations and at a baseline level in the general state population. The results of a pilot Minnesota Department of Health mercury biomonitoring study revealed ten percent of newborns in a Lake Superior Basin population had blood mercury concentration levels that exceeded the United States Environmental Protection Agency’s Reference Dose for methyl mercury of 5.8 µg/l. These results sparked additional interest in mercury biomonitoring on a statewide level, the characterization of human mercury exposure, as well as the validation of the novel laboratory procedure used to measure total mercury in the Minnesota Department of Health pilot mercury study. With goals of exploring the characteristics of mercury exposure in the state of Minnesota, the Minnesota Department of Health embarked on a series of mercury biomonitoring studies. These studies, along with increasing the biomonitoring capacity of the state, have allowed for the continued exploration of statewide mercury exposure, novel ways of analyzing exposure levels in the laboratory, and intervention efforts to increase public awareness and education of the dangers of mercury exposure.
  • 3. 2 Acknowledgements I thank my project adviser, Dr. Ruby Nguyen, for her continued structure, guidance, and support throughout the entirety of this project. In addition, I thank Patricia McCann and Dr. Jessica Nelson for their clarification of MN LSB and EHTB, and my Biology, Society, and Environment adviser, Dr. Jeanette Simmonds, for her advice and aid in the planning of this project.
  • 4. 3 Abstract ………………………………………………..………………………………………… 1 Acknowledgements …………………………………………………..………………………….. 2 Mercury Biomonitoring in Minnesota ……………………………….………………………….. 4 References... ……………………………………………………………………………………. 22
  • 5. 4 Human exposure to mercury is a significant public health issue that affects individuals nationwide. The public health concern over the sources, distribution, and severity of mercury exposure in Minnesota is addressed through the efforts of the Minnesota Department of Health (MDH). Through the biological monitoring, or biomonitoring, of chemicals and their metabolites in human hair, blood, or urine, the measurement of human exposure to harmful substances is a useful tool in determining characteristics of human exposure to chemicals (Minn. Stat. §144.995 2008). Initiated in 2007 along with the Environmental Health Tracking Program, the Biomonitoring Program at MDH is instrumental in developing a baseline of mercury exposure, as well as exploring the characteristics of exposure in vulnerable populations in Minnesota. In addition to its work in characterizing the determinants and distribution of mercury exposure in the state, the MDH Environmental Health Tracking and Biomonitoring Program (EHTB) pioneered a novel laboratory method for the measurement of total mercury concentration in dried blood spots (DBS). Created with the intention of increasing the biomonitoring capacity of state, EHTB helped increase the knowledge of the distribution and characteristics of mercury exposure in Minnesota (Environmental Health Tracking and Biomonitoring 2013). The results of a pilot MDH study, that showed elevated blood mercury concentrations in a population of Minnesota newborns, initiated a subsequent series of mercury exposure studies. In addition, the results of the pilot MDH study led to the creation of multiple long term goals of increasing the understanding of mercury exposure throughout the state to better educate and protect populations from dangerous exposure. Through the investigation of the characteristics and measurement of mercury exposure, mercury biomonitoring in Minnesota was successful in establishing a baseline of exposure, increasing the biomonitoring capacity of
  • 6. 5 MDH, and increasing awareness and education of the dangers of mercury exposure in the state of Minnesota. Mercury is a metallic chemical element that is naturally occurring in the environment. In its metallic state, mercury is a shiny, silver-white, odorless liquid that when heated, becomes a colorless and odorless gas (ChemicalBook 2008). Mercury exists in three separate oxidation states including mercuric (𝐻𝑔2+ ), mercurous (𝐻𝑔2 2+ ), and metallic (𝐻𝑔0 ). Forming various inorganic and organic compounds, mercury undergoes a consistent transformation and speciation change that influences its environmental effects and toxicity. Mercury undergoes a global cycle in which it transforms its chemical forms, as well as cycles through the environment, in a process known as the “ping-pong” effect (World Health Organization 1990, 29-30). Constantly cycling between water, land, and the atmosphere, mercury undergoes a biological transformation from an inorganic to an organic state in aquatic systems. Once in water, inorganic mercury may begin the conversion to an organic mercury compound, such as methyl mercury, through the process of methylation. The conversion is enabled by the non-enzymatic methylation of inorganic mercury by the compound methyl cobalamine. Once converted to methyl mercury, or another organic compound, mercury enters the food chain by rapidly diffusing throughout the aquatic system and tightly binding to proteins in wildlife. Unlike other forms of mercury, organic mercury is able to accumulate in humans and animals. Because of this, methyl mercury is rapidly accumulated by most aquatic organisms and is able to attain high concentrations in fish at the top of the food chain through the process of biomagnification (World Health Organization 1990, 29-31). The mercury that has accumulated in fish and other aquatic species enters the human body when the fish are consumed. Upon being absorbed by the gastrointestinal tract, mercury from the tissue of the fish is transferred to the blood and tissue of the human, where it accumulates and is
  • 7. 6 eventually excreted. The methylation of inorganic mercury and its subsequent accumulation in the aquatic food chain through biomagnification assures ingestion as the most common form of methyl mercury exposure (Eccles and Annau 1987). The bioaccumulation of methyl mercury in many aquatic species, such as fish, is enabled through the emission of mercury into the surrounding environment through a variety of natural and manmade sources. Emissions from volcanoes, bodies of water, and the degassing of the earth’s crust, all release metallic mercury into the atmosphere where it is then washed down to land and bodies of water through precipitation or dry atmospheric deposition (World Health Organization 1990, 24-31). Various anthropogenic activities, such as mining, have increased the release of metallic mercury from the earth into the atmosphere, as well as emitting additional mercury into the atmosphere through the process of smelting. In addition to the leaching of mercury into the environment from mining and natural degassing, a variety of industrial processes utilize various forms of mercury or mercury-containing compounds in products and manufacturing. Pollution and runoff from mining and industrial processes contribute to the burden of mercury in bodies of water and the atmosphere through the direct discharge of waste (U.S. Geological Survey 2010). The presence and accumulation of mercury in the environment is a cumulative effect of natural and anthropogenic sources, each of which contributes to the global burden of mercury and its related concerns to the health of both the environment and humans. The toxicity of mercury and mercury containing compounds has been well documented in the United States and around the world for decades (World Health Organization 1990, 69). With the ability to cause damage when ingested, absorbed through the skin or mucous membranes, or inhaled as a vapor, mercury is a potent toxin that is dangerous to humans and other life forms.
  • 8. 7 As a result of this, the United States Environmental Protection Agency (EPA) has set a blood methyl mercury Reference Dose (RfD) of 5.8 µg/l and a Benchmark Dose Limit (BMDL) of 58 µg/l. The BMDL is the lowest dose or concentration that produces a predetermined change in incidence of an adverse effect (United States Environmental Protection Agency 2012d). Determined based on the BMDL, the RfD is an estimate that states a blood concentration equivalent of the maximum daily oral exposure that is likely to be without a significant risk of deleterious effects during a lifetime (United States Environmental Protection Agency 2012c). Where inorganic mercury compounds are not usually toxic to humans, organic compounds, such as methyl mercury, can cause mild to severe neuromuscular disorders with moderate to severe exposure (Eccles and Annau 1987, 17-18). Unlike many inorganic compounds, whose insolubility prevents their absorption through the gastrointestinal tract, methyl mercury is readily absorbed by the human body when consumed in the diet. In addition, the relatively long half life of methyl mercury impedes the excretion of the compound, allowing for accumulation within the human body. To add to the dangers of exposure, methyl mercury is especially toxic because of its hydrophobic nature, allowing the compound easy transport across various membrane barriers, such as the blood brain barrier and the placental barrier. In humans and other mammals, every form of mercury is converted to its mercuric form during the process of excretion. Depending on the original state of the mercury, this process may happen at different rates. For the compound methyl mercury, the decomposition of the organic compound is a slow process. As a result of this, methyl mercury is allowed time to accumulate and circulate throughout the body and through protective barriers (Eccles and Annau 1987, 17-24). Although toxic to all humans, methylated mercury is especially dangerous to the fetus and children, whose developing tissues and nervous systems are particularly vulnerable to the
  • 9. 8 effects of the organic compound (World Health Organization 1990, 69). If present in levels above the RfD, methyl mercury may have disastrous effects on the fetus, due to the ability of the compound to cross through the placental barrier of the mother and into the womb (Grandjean et al. 2005, 905-908). In addition, the increased sensitivity of the fetus to methyl mercury may result in damage to the fetus while the mother remains asymptomatic and unaffected. Once across the placental barrier, methyl mercury may cause severe damage to the developing nervous system and brain of the fetus, putting the developing fetus at greater risk for deficits in memory, learning, sight, hearing, or motor skills. Along with the devastating effects of methyl mercury on the developing tissue of the fetus, impaired development and maturation of the brain as a result of fetal exposure may result in the delay of achieving developmental milestones later in life (Eccles and Annau 1987, 46-47). Although the negative effects of mercury on humans and the environment had been established years before, large-scale interest in mercury exposure in the state of Minnesota did not take shape until 2007 (Patricia McCann, interview by Allison Fast, St. Paul, MN, February 21, 2013). The Environmental Health Division of MDH became interested in mercury exposure in vulnerable populations, such as pregnant women and children. Seeing health care providers as an effective way to communicate with women of childbearing age the dangers of mercury exposure, the Environmental Health Division became interested in collecting concrete data on mercury exposure levels in the state so health care providers would be more inclined to share this data with women (McCann, interview). In addition to providing information to women and families on mercury, there was a statewide and national interest in characterizing the distribution of mercury exposure. Along with the interest of the Environmental Health Division, the Fish Consumption Advisory Program of MDH, the EPA, and various Lake Superior regional
  • 10. 9 organizations expressed interest in developing a study in which the determinants and distribution of mercury exposure were investigated. The lack of data on mercury exposure in the state, as well as the desire to engage the health community in educating the public on mercury exposure, led to the creation of a regional study in the Lake Superior Basin. The combined interest of MDH, the EPA, and numerous Lake Superior regional organizations, shaped the initial interest in mercury exposure to a more regional interest in mercury exposure in women and children. The various interests of numerous statewide organizations, along with the allocation of funding for a study in the Lake Superior region on mercury exposure from the EPA, led to the creation of the Mercury Levels in Blood from Newborns in the Lake Superior Basin study (MN LSB) (McCann, interview). Mercury exposure in the state further attracted the attention of the MDH later in 2007 when state legislation mandated a study on mercury exposure be conducted in Minnesota (Environmental Health Tracking and Biomonitoring 2013). The legislation passed in 2007 was responsible for the creation of the Environmental Health Tracking Program, along with the creation of the Biomonitoring Program at MDH. The two programs were then linked to form EHTB. To provide guidance and recommendations for projects within EHTB, an external Advisory Panel of experts in public health and environmental science was established (Minn. Stat. §144.998 2008). Although the Environmental Health Tracking Program and the Biomonitoring Program were linked, the two programs were established with separate goals. The ultimate goal of the Environmental Health Tracking Program was to collect and share public health data in order to identify health priorities that can provide the basis for actions to improve public health. In contrast, the Biomonitoring program had multiple goals. The first was to answer questions about the magnitude and range of exposure to specific chemicals in certain
  • 11. 10 communities in Minnesota. Other goals were centered on building an infrastructure at MDH for implementing an ongoing biomonitoring program and building biomonitoring capacity in the state (Environmental Health Tracking and Biomonitoring 2011). Advancing the capacity of the Public Health Laboratory to measure chemicals and toxic metals in human hair, blood, and urine, as well as the development of a baseline for exposures in the state, would allow the Biomonitoring Program to track progress over time in reducing exposure (Environmental Health Tracking and Biomonitoring 2013). In addition to the establishment of EHTB, the 2007 state legislation mandated that four separate pilot studies be conducted in Minnesota. Each pilot study was to investigate exposure to various chemicals including arsenic, perfluorinated chemicals, and mercury, in voluntary populations in the state. Due to funding concerns, EHTB, as well as the Advisory Panel, explored the possibility of joining a preexisting mercury exposure study (Environmental Health Tracking and Biomonitoring 2013). At that time, MN LSB was still in its planning stages with the Fish Consumption Advisory Program of the Environmental Health Division of MDH. In lieu of conducting a separate mercury biomonitoring study, and out of interest in MN LSB, EHTB offered their support and some funding to the Environmental Health Division (Minnesota Department of Health 2008). By the end of the planning stage of MN LSB, EHTB was working in accordance with the Environmental Health Division to track mercury exposure in newborns in the Lake Superior Basin. With funding from the EPA Great Lakes National Program, as well as support and funding from EHTB, MN LSB began recruiting participants in the fall of 2008. During the planning phase, various goals were established for the study that reflected the contributions of both the Environmental Health Division as well as EHTB. Two main goals of the study were to
  • 12. 11 measure mercury exposure in a population of newborns in the United States portion of the Lake Superior Basin, as well as determine characteristics of the exposure in this population (Environmental Health Tracking and Biomonitoring 2011). Another important goal of MN LSB was to utilize and evaluate a novel laboratory method for biomonitoring with the use of DBS. The collection of DBS is a routine newborn screening procedure in hospitals throughout the country. Requiring only five drops of blood from a newborn’s heel, twenty four to forty eight hours after birth, the blood is spotted on a filter paper card to be analyzed. Once the sample has dried, the blood is analyzed in a laboratory to identify newborns at risk for various health conditions. After analysis, a small amount of blood remains on the filter paper card, so the card is stored as a residual sample for the future use of the family, the laboratory, and public health and biomedical research (Genetic Alliance). In MN LSB, this dried blood sample was analyzed to determine the mercury concentration in Lake Superior Basin newborns. Though not a common or well-refined method for the measurement of mercury in a newborn blood specimen, there are various advantages to utilizing DBS over more traditional methods. In addition, the novel use of DBS in analyzing mercury exposure was an effective way to increase the biomonitoring capacity of EHTB and the Public Health Laboratory (McCann, interview). Although a novel and relatively unrefined procedure with no available data for comparison of results or technique, there are various advantages to the use of DBS. One of the most common and effective measures of mercury exposure in a newborn is through the analysis of umbilical cord blood collected after birth (Grandjean et al. 2005, 905-908). Umbilical cord blood analysis allows for the speciation of the mercury and also has large amounts of published literature available for comparison of results and technique (Minnesota Department of Health 2013). Although an effective exposure biomarker of mercury, especially methyl mercury for
  • 13. 12 which the placenta does not constitute a barrier, the collection of umbilical cord blood requires trained hospital personnel (Grandjean et al. 2005, 905-908). In addition, the collection of umbilical cord blood it is not a routine procedure, is costly, and must be done immediately following birth (Minnesota Department of Health 2013). In comparison, DBS are routinely collected within forty eight hours after birth, and residual DBS are stored for multitudes of newborns nationwide after their analysis in newborn screening programs (Genetic Alliance). Unlike umbilical cord blood, DBS collection is not costly and does not require specially trained personnel to obtain. Despite this, the use of DBS in biomonitoring is a novel procedure whose results, technique, and efficacy have not been validated. Additionally, the small quantity of blood in the sample makes the speciation of mercury impossible (Minnesota Department of Health 2013). Due to the advantages of DBS to umbilical cord blood and the potential of the novel procedure to increase the biomonitoring capacity of MDH and the nation, the use of DBS was an attractive and groundbreaking option for biomonitoring in Minnesota. The recruitment of Lake Superior Basin newborns for MN LSB began November 2008 and was a collaboration between MDH and state newborn screening programs in Minnesota, Wisconsin, and Michigan. The geographic boundary of the United States portion of the Lake Superior Basin was defined by watershed boundary data. Participants were determined based on this geographic boundary and the zip code of the mother’s residence. Newborns of eligible participants were identified from the Newborn Screening Database at MDH. Newborns were excluded from participation if there were complications in the pregnancy, the infant had died or was born with certain health problems, or the quality of the DBS was insufficient for analysis (Environmental Health Tracking and Biomonitoring 2011). Local and state public health departments mailed written communication to mothers of eligible newborns, explaining the
  • 14. 13 project and inviting their participation. The written communication consisted of a consent form and a letter that informed mothers that the specimens would be anonymized, that their individual babies’ results would not be available, and that MDH would not inform them of the aggregate findings (McCann 2011). Mothers of eligible newborns were contacted three weeks after giving birth and invited to participate in the study. If no response was received within three weeks of the initial communication, a second letter was sent (Environmental Health Tracking and Biomonitoring 2011). A total of 2,566 parents of eligible newborns were contacted in Minnesota, inviting their participation in MN LSB and requesting informed consent of the use of their newborns’ blood. Of these Minnesota parents that were contacted, 1,130 gave their consent (McCann 2011). Similar methods were utilized in Wisconsin and Michigan to invite mothers of newborns to participate in the study and acquire informed consent. Of the Wisconsin and Michigan mothers that were contacted, consent from 140 mothers in Wisconsin and 810 mothers from Michigan was received. Due to funding concerns and issues with the storage and custody of DBS in Michigan specimens, the number of specimens from Michigan was reduced from 810 to 200 (McCann 2011). The recruitment of participants continued until November 2010, when the beginning stages of data collection and specimen analysis began. The results of MN LSB revealed a wide range of total mercury concentrations, with the majority of specimens exhibiting low mercury levels. Of the 1,470 parents that had given informed consent, the total number of specimens analyzed was 1,465, with 1,126 specimens from Minnesota, 139 from Wisconsin, and 200 from Michigan (McCann 2011). After the recruitment of participants concluded in 2010, data collection and analysis began and continued until its conclusion in the fall of 2011. The analysis of the total mercury concentration in the 1,465 specimens showed forty three percent of the specimens to be below the method detection
  • 15. 14 limit (MDL) of 0.7 µg/l, indicating a low or nonexistent mercury concentration in nearly half the specimens (McCann 2011). About one percent of the specimens were found to be above the BMDL of 58 µg/l, with eight percent of specimens above the RfD of 5.8 µg/l. Of the blood mercury concentrations that exceeded the RfD, Minnesota had the highest rate at ten percent of the 1,126 specimens exceeding a blood mercury concentration of 5.8 µg/l. In comparison to the Wisconsin and Michigan specimens, three percent of the 139 Wisconsin specimens, and none of the 200 Michigan specimens, exceeded the RfD (Myers 2012). The maximum exposure measured was 211 µg/l (McCann 2011). The results depicted a trend of higher mercury exposure in Minnesota specimens as well as an exposure pattern with highest mercury concentrations in the summer births. The seasonal exposure pattern with highest mercury concentrations in summer births supports a local fish consumption exposure pathway. Despite this clear pattern, it is impossible to validate a fish consumption exposure pathway without the ability to speciate mercury in DBS analysis. In addition, the analysis of DBS only enabled the detection of mercury when it exceeded the MDL, limiting the characterization of low exposure levels (McCann 2011). As a result of this and other challenges, the findings of MN LSB raised questions from researchers and MDH about the exposure pathway, as well as the distribution and characteristics of mercury exposure in the Lake Superior Basin and throughout the state of Minnesota. In addition, the uncertainty surrounding the use of DBS raised questions about the validity of the laboratory method and the efficacy of DBS as an indicator of mercury exposure in newborns (Environmental Health Tracking and Biomonitoring 2013). The multiple challenges of MN LSB and recommendations from MDH Advisory Panel led to various goals and plans to conduct further research on mercury exposure in Minnesota. The results of MN LSB that showed ten percent of Minnesota specimens had a mercury
  • 16. 15 concentration in their blood that exceeded the EPA RfD of 5.8 µg/l sparked interest in additional biomonitoring and raised questions on the limitations of the study. The results of MN LSB were limited to babies born to mothers who gave their consent and were living in the Lake Superior Basin area of Minnesota, Wisconsin, and Michigan. Because of this, the sample was biased and therefore was not necessarily representative of a statewide distribution of mercury. In addition, the MN LSB sample did not take into account that some Minnesota communities may be more exposed than others due to geographic, cultural, or ethnic differences. The MN LSB sample lacked the ability to characterize mercury exposure on a statewide level and shed light on any potential disparities in vulnerability or exposure to mercury in various populations in Minnesota. Another challenge of MN LSB was the lack of MDH data on vulnerable groups, as well as any statewide or national data available for comparison of mercury exposure in newborns (Environmental Health Tracking and Biomonitoring 2013). The DBS analysis data lacked published literature or data for comparison of methods and results of mercury levels in newborn blood. In addition, the laboratory method used for analysis was a novel method that had not been validated or peer reviewed (McCann 2011). The uncertainty of laboratory results and methods, along with the absence of data or published literature for comparison, led to questions on the accuracy of the use of DBS as an indicator of newborn mercury exposure. The analysis of newborn blood in MN LSB effectively identified a public health issue that required more action and investigation in Minnesota. In addition, the use of DBS as a potential biomonitoring method generated interest in MDH, and specifically the Public Health Laboratory, in further statewide biomonitoring of mercury. Because of the questions that were raised on the characteristics of mercury exposure on a wider scale, the MDH Advisory Panel made various recommendations for additional biomonitoring. First, the Advisory Panel
  • 17. 16 recommended additional biomonitoring in newborns be done at a statewide level in order to identify disparities in exposure and to provide a baseline for tracking progress in vulnerable populations. In addition, the Advisory Panel recommended subsequent biomonitoring be done to validate the fish consumption exposure pathway, identify additional sources of mercury exposure, and refine methods for mercury biomonitoring in Minnesota. To confirm DBS as an accurate indicator of mercury exposure in newborns, the Advisory Panel recommended further research be conducted in which the results of DBS analysis be compared to a traditional measure of mercury concentration in newborns (Environmental Health Tracking and Biomonitoring 2013). With MDH Advisory Panel recommendations in mind, additional mercury biomonitoring began in Minnesota in 2012 with three separate initiatives. The first was a collaboration of the MDH Biomonitoring Program and the University of Minnesota in the Pregnancy and Newborns Exposure Study (Minnesota Department of Health 2012b). The second is a planned collaboration of EHTB with the former National Children’s Study (NCS) South Dakota State University Vanguard pilot study in the Minnesota National Children’s Study (NCS) Newborn Mercury Project (Minnesota Department of Health 2013d). The third study was the Fond du Lac (FDL) Community Biomonitoring Study, which is part of the Great Lakes Restoration Initiative (GLRI). This study was a collaboration of MDH with the FDL Band of Lake Superior Chippewa (Minnesota Department of Health 2013a). Although different in various respects, each study was designed to further statewide mercury biomonitoring, identify disparities in mercury exposure in vulnerable populations, and refine and validate the use of DBS analysis as an indicator of newborn mercury exposure (Environmental Health Tracking and Biomonitoring 2013).
  • 18. 17 The Pregnancy and Newborns Exposure Study compared mercury levels in paired newborn umbilical cord blood and DBS specimens. The study recruited participants already enrolled in a larger study being conducted in part at the University of Minnesota, called The Infant Development and Environmental Study (TIDES) (Minnesota Department of Health 2012b). A four year, National Institutes of Health-funded project, TIDES focused on exploring the effects of various exposures on infants during gestation at research sites in Minnesota, New York State, Washington, and California (Minnesota Department of Health 2012b). The Pregnancy and Newborns Exposure Study began recruiting University of Minnesota TIDES participants in June 2012 with the goal of addressing various questions raised by MN LSB results (Minnesota Department of Health 2012a). In response to MN LSB results, and recommendations made by MDH Advisory Panel, the Pregnancy and Newborns Exposure Study progressed with three main goals. The first goal was to compare total mercury content in paired umbilical cord blood and DBS in order to obtain a measure of the ratio of mercury concentration between the whole blood and DBS paired samples. Due to the inability of DBS analysis to speciate mercury as either organic or inorganic, the second goal of the study was to speciate mercury in the umbilical cord blood specimens. The final goal of the Pregnancy and Newborns Exposure Study was to further refine laboratory methods for measuring mercury exposure in newborns (Minnesota Department of Health 2012b). Beginning in June 2012 and lasting until January 2013, informed consent was obtained from forty nine women currently enrolled in University of Minnesota TIDES (Minnesota Department of Health 2013d). After recruitment had concluded, data collection began with the obtainment of forty nine matched pairs of infant umbilical cord blood and DBS specimens, collected after birth by hospital staff. After collection, specimens were sent to the Public Health
  • 19. 18 Laboratory to begin data analysis. Analysis of umbilical cord blood specimens for total mercury, lead, and cadmium concentration in each of the forty nine samples was concluded in March 2013. Analysis revealed one specimen with a mercury concentration greater than the RfD, and no specimens that exceeded the RfD for lead (Minnesota Department of Health 2013d). Currently, results letters are being prepared and mailed to the participants, dictating individualized results. With the analysis of total mercury concentration in umbilical cord blood specimens complete, the next steps of the Pregnancy and Newborns Exposure Study are to analyze the DBS for total mercury content and to speciate the mercury in the umbilical cord blood (Minnesota Department of Health 2013d). After the completion of data analysis, the next steps for the Pregnancy and Newborns Exposure Study are to formulate long term goals of pursuing additional mercury research on the extent of exposure in various populations in Minnesota. Additional long term goals include investigation of additional sources of mercury exposure statewide and the refinement of laboratory methods involving DBS (Minnesota Department of Health 2012a). The Minnesota NCS Newborn Mercury Project will compare matched specimens of umbilical cord blood spot, DBS, whole umbilical cord blood, and maternal blood (Minnesota Department of Health 2013d). In addition, the project will provide added data to the Pregnancy and Newborns Exposure Study, in order to increase the sample size for analysis of the comparison of matched blood specimens. Utilizing previously collected specimens of umbilical cord blood, DBS, and maternal blood from the former NCS South Dakota State University Vanguard pilot study, EHTB will obtain and analyze the matched specimens in order to accomplish three main biomonitoring goals. The first goal of the Minnesota NCS Newborn Mercury Project is to assess the comparability of different measures of prenatal exposure to
  • 20. 19 mercury. Based on the desire to validate the use of DBS as an effective biomonitoring tool for mercury, the second goal is to compare paired whole umbilical cord blood and umbilical cord blood spot mercury levels to determine how accurately mercury levels in blood spots reflect levels in the original, whole blood sample. The final goal of the Minnesota NCS Newborn Mercury Project is to explore the extent of newborn mercury exposure on a statewide level in order to determine if the elevated mercury levels found in MN LSB were applicable to other parts of Minnesota. Upon completion of data collection and analysis, results of the Minnesota NCS Newborn Mercury Project will be compared to the results of other mercury biomonitoring research. Due to the very limited availability of published literature and data on newborn mercury exposure, comparison of newborn mercury levels and blood analysis methods will likely be restricted to the MN LSB and the Pregnancy and Newborns Exposure Study data for comparison (Minnesota Department of Health 2013d). The FDL Community Biomonitoring Study is a part of the GLRI that was enabled in 2010 by a grant from the EPA (United States Environmental Protection Agency 2012b). The study was a collaboration of MDH with the FDL Band of Lake Superior Chippewa (Minnesota Department of Health 2013a). The Fond du Lac Community Biomonitoring Study was enabled by an additional EPA grant that was awarded to MDH in 2012 to reduce mercury exposure risk for women and children who live along Lake Superior’s north shore (United States Environmental Protection Agency 2012a). The study is conducting biomonitoring in non- pregnant, adult Native Americans that have been residents of northeast Minnesota for at least the past twelve months. The purpose of the FDL Community Biomonitoring Study is to explore the characteristics of mercury exposure in a vulnerable population and to compare these results to the general population (Minnesota Department of Health 2013a). In collaboration with GLRI,
  • 21. 20 the FDL Community Biomonitoring Study developed goals for improving health screening in the community and forming more effective fish consumption advisories (United States Environmental Protection Agency 2012a). Beginning in December 2012, letters and consent form were mailed to potential participants, describing the study and inviting their participation. Due to increased community interest in the study, outreach and recruitment campaigns have been largely successful. As of February 2013, fifty five participants had enrolled in the study. With the increased levels of community interest, participation recruitment is expected to enroll many more participants by the end of recruitment in the fall of 2013. In addition to the biomonitoring of other vulnerable populations, such as pregnant women and babies, the FDL Community Biomonitoring Study is another piece to the puzzle in identifying vulnerable groups in Minnesota who may have a higher risk of mercury exposure (Minnesota Department of Health 2013a). Beginning in 2007 with the creation of EHTB and its related Advisory Panel, the exploration of mercury exposure in Minnesota has experienced a statewide increase in attention and interest. The results of MN LSB that showed elevated mercury concentrations in ten percent of Minnesota Lake Superior Basin newborn specimens captured the attention of local and national government organizations, health care providers, and the public. Along with increasing the visibility and recognition of mercury exposure as an important issue in Minnesota health, the results of MN LSB kindled interest in the further characterization and exploration of mercury exposure in other vulnerable populations, as well as the general population statewide. Through its innovative use of DBS, the novel laboratory method used in MN LSB increased the visibility of mercury exposure in the state, as well as the biomonitoring capacity of the Public Health Laboratory and MDH. The cultivation of further exploration into the distribution, exposure pathways, and methods of measuring and analyzing mercury exposure in Minnesota allowed for
  • 22. 21 additional mercury biomonitoring studies and intervention projects to be undertaken. The continued interest in mercury exposure that has been demonstrated by the Pregnancy and Newborns Exposure Study, the Minnesota NCS Newborn Mercury Project, and the FDL Community Biomonitoring Study, illustrates a biomonitoring program that is continually interested in the health and wellbeing of both the population and environment of the state. Through continued health exposure education and intervention efforts, the efforts of MDH have increased community and health care provider awareness to the dangers of mercury exposure. Although further research, intervention efforts, and increased concern for environmental mercury contamination are necessary, MDH and EHTB are effectively diminishing levels of human mercury exposure throughout the state of Minnesota. The further characterization of mercury exposure and understanding of exposure pathways will increase the efficacy of community education and intervention projects, decreasing the harmful exposure of individuals to mercury and fostering the health of communities in Minnesota.
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