Annals of Clinical & Laboratory Science, vol. 34, no.

3, 2004 235

Review:
Interpreting Mercury in Blood and Urine of Individual Patients

Kern L. Nuttall
Consultant in Laboratory Medicine, Bellingham, Washington
.
Abstract. The effects of mercury exposure are determined by: (a) chemical form, (b) route of exposure, (c)
dose, and (d) patient factors. Patient factors include age, genetics, environmental aspects, and nutritional
status, and are responsible for different individual responses to similar doses. When blood and urine are
collected to evaluate exposure, the results are influenced by (a) specimen collection, (b) analysis, and (c) the
time elapsed from exposure. Interpretation is influenced by the patient’s symptoms and is facilitated by
comparison to published reports. The ranges reported in the literature are broad, with elevations as high as
16,000 µg/L in blood and 11,000 µg/L in urine. Interpretation is relatively straightforward when the results
are massively elevated, but becomes increasingly difficult as concentrations approach the population norms
(blood and urine mercury < 10-20 µg/L). Interpretation can be aided by biological markers (eg, urine
porphyrins, β2-microglobulin, and N-acetyl-β-D-glucosaminidase). (received 8 March 2004; accepted 19 May 2004)

Keywords: Heavy metals, mercury poisoning, mercury metabolism, porphyrins, biological markers

Introduction improvement in the patient and not in the laboratory

Mercury is a problem because it has the potential to
be toxic in different forms, because it is blamed for
things it does not do [1], and because the toxic
responses are often markedly different among
individuals [2]. Conflicting information about
mercury toxicity is also common. The goals of this
paper are to describe the main factors that influence
mercury toxicity, review a portion of the literature,
and provide a framework for interpretation of
mercury levels in blood and urine of individuals.
Mercury levels in other body fluids, feces, tissues,
hair, and nails are not addressed. This discussion is
intended primarily for pathologists and clinical
chemists who are asked to interpret mercury values
generated in the clinical laboratory.
Although the treatment of mercury poisoning
is not reviewed here, several points are worth
summarizing: (a) the most important aspects of
treatment are supportive care and the prevention of
further exposure, (b) the object of treatment is
Address correspondence to Kern Nuttall, M.D., Ph.D., 2112
Birch Circle, Bellingham, WA 98229, USA; tel 360 647-5212;
e-mail: kern_nuttall@yahoo.com.
values, and (c) chelation treatment is most
appropriate for patients who show significant signs
and symptoms of toxicity. While chelation increases
mercury excretion, the benefits of doing so have not
been established in asymptomatic individuals.
Common adverse effects of chelating agents include
abdominal cramps, drowsiness, dizziness, rash,
pruritus, and flu-like symptoms [3].
Nomenclature and Basic Biochemistry
Mercury [4] exists in 1 of 3 oxidation states: 0, +1,
or +2, which can be labeled as mercury(0),
mercury(I) and mercury(II), respectively
(pronounced ‘mercury zero’, ‘mercury one’, and
‘mercury two’). While the historic terms ‘mercurous’
for mercury(I) and ‘mercuric’ for mercury(II) are in
common use, they are avoided here to simplify
nomenclature and reduce ambiguity.
Mercury(0) is also known as elemental or
metallic mercury, and is a dense, silver-grey liquid
at room temperature. When mercury(0) is oxidized
to mercury(I) and (II), it forms compounds with
various electron donors. Mercury bound to a carbon

0091-7370/04/0300-0235 $4.00. © 2004 by the Association of Clinical Scientists, Inc.

236 Annals of Clinical & Laboratory Science
atom is ‘organic mercury,’ examples of which include
methylmercury and ethylmercury. Organic mercury
is always mercury(II) [4]. When not bound to
carbon, mercury is ‘inorganic.’
Although other reactions occur, the principal
reaction of mercury in biological systems is with
sulfhydryl (-SH) groups [5]. The predominant
biological sulfhydryl compound is the amino acid
cysteine. Toxicity is caused primarily by mercury
binding and inactivation of cysteine residues in
enzymes and structural proteins. Metallothioneins,
a family of cysteine-rich proteins, and glutathione
play protective roles. Chelation treatment to increase
mercury excretion employs sulfhydryl compounds
such as 2,3-dimercaptosuccinic acid (DMSA) and
sodium 2,3-dimercapto-1-propane sulfonate
(DMPS) [3].
Methylmercury nomenclature. Some terms in the
mercury literature are used loosely and it is helpful
to define the context carefully. The label ‘methyl-
mercury’ on a reagent bottle refers to dimethyl-
mercury (H3C-Hg-CH3) [6], a dense, concentrated
liquid that is insoluble in water and highly dangerous
to handle [7]. In contrast, methylmercury in fish
and other foodstuffs refers to the methylmercury
ion (H3C-Hg+) and to the adducts it forms with
sulfhydryl ligands (H3C-Hg-S-R) [8]. The adduct
methylmercury cysteine is water soluble and
considerably less toxic than the closely related
compound, methylmercury chloride [9]. Since the
mercury-chloride bond (H3C-Hg-Cl) is largely
covalent and remains intact even in dilute aqueous
solution, methylmercury chloride is not equivalent
to methylmercury ion.
Routes of Exposure
The physical properties of mercury(0) and mercury
compounds determine the dose transmitted by a
particular route of exposure. Significant exposure
through oral ingestion requires a compound that
has a degree of solubility in both aqueous and lipid
environments. Exposure through inhalation requires
volatility; exposure through skin requires lipid
solubility. Liquid mercury(0), for example, is
extremely insoluble in water (6 x 10-6 g/100 g water)
and organic solvents (3 x 10-7 g/100 g n-hexane)
[4], and therefore is not readily absorbed through
oral or cutaneous routes. However, mercury(0) is
volatile, exists as a monoatomic gas in the vapor
phase, and is sparingly soluble in water when air is
also present. Thus mercury vapor is easily inhaled
and dissolves readily in the bloodstream. As a
dissolved gas, mercury(0) reacts readily due in part
to the large surface area of its finely divided state. In
contrast, liquid mercury(0) in the bloodstream is
markedly less active because it exists as insoluble
droplets with limited surface area.
Inhalation. Due to its volatility, mercury(0) is
responsible for most cases of inhalation exposure.
Heating increases its volatility and the intensity of
exposure. Heating cinnabar, the mineral form of
mercury(II) sulfide, can release mercury(0) and has
been associated with fatal inhalation [10]. Many
organic compounds such as dimethylmercury are
also volatile [4].
Ingestion. Mercury(II) chloride (HgCl2) is soluble
in water and organic solvents, and is markedly toxic
when ingested in sufficiently high dose [11]. In
contrast, mercury(0) and mercury(I) chloride
(Hg2Cl2) are insoluble in both water and lipid
environments [4], and therefore show low toxicity
by oral ingestion. Mercury(I) chloride is an
historically important laxative and vermifuge
commonly known as ‘calomel’ and ‘mild mercury
chloride’ [6]. It is not dependable as a non-toxic
laxative, however, because it easily degrades to give
mercury(II) chloride and mercury(0).
Cutaneous. Cutaneous absorption is probable for
mercury compounds that are lipid soluble,
particularly with prolonged contact and high
concentrations. Mercury(II) chloride is soluble in
organic solvents (1 g in 200 ml benzene [6]), whereas
mercury(0) and mercury(I) chloride are much less
soluble. A limited amount of mercury(0) can be
absorbed directly through the intact skin, but its
release into the circulation is slow and of little
practical significance [12].
Reagent dimethylmercury is rapidly absorbed
through the skin, even when latex gloves are worn

[7]. Cutaneous absorption has been claimed for
‘beauty creams’ containing high concentrations of
mercury(I) chloride [13]. While significant exposure
clearly occurs with these products, it is more likely
to proceed through decomposition to mercury(0)
and mercury(II). Cutaneous absorption is more
probable for ‘skin-whitening creams’ containing
‘ammoniated mercury’[14], known as mercury(II)
ammonium chloride (Cl-Hg-NH 2 ) [6]. Some
inadvertent oral ingestion may also be likely.
Injection. Injection of liquid mercury(0) results in
droplets that become trapped in sites such as the
pulmonary capillary bed [15]. Water insolubility and
low surface area render these particles relatively inert
compared to dissolved mercury(0) vapor. Liquid
mercury(0) deposited subcutaneously is stable for
years. In contrast, water soluble mercury compounds
injected subcutaneously can cause local tissue
destruction within days.
Red pigments in tattoos may include the red
isomer of mercury(II) sulfide (vermillion, cinnabar).
This compound is insoluble in water (~1 x 10-6 g/
100 g [4]) and remains largely inert when injected
subcutaneously. A limited number of people with
such tattoos experience inflammation restricted to
the site of pigment deposition, usually within 6
months of tattooing [16]. This is an immune-based
allergic response and mercury(II) sulfide is unlikely
to contribute to blood or urine mercury levels.
Dose
As with toxic agents in general, acute symptoms are
produced by high doses of mercury and chronic
symptoms are produced by lower doses repeated over
time. Chronic exposure can induce a more insidious
form of toxicity dominated by neurologic
abnormalities [5,17]. Effects become increasingly
subtle and difficult to attribute to mercury as the
dose drops into the subclinical range. At some point,
low-dose exposure falls below ‘threshold,’ that is,
below the dose for which there is no response or
observable adverse health effect.
Acute effects. An example of acute mercury toxicity
is seen with the flu-like syndrome that can develop
Interpreting mercury levels in individual patients 237
after high-dose inhalation of mercury(0) vapor. Signs
and symptoms develop within hours and include
weakness, myalgias, chills, fever, nausea, vomiting,
diarrhea, dyspnea, cough, and chest pain [5].
Pulmonary toxicity may lead to interstitial pneumo-
nitis with severe compromise of respiratory function.
Unless fatal, recovery is usually complete, although
it can be complicated by residual interstitial fibrosis.
Chronic effects. Neurologic effects are the most
serious aspect of chronic exposure. With repeated
exposure to mercury(0) vapor, signs and symptoms
include gingivitis, stomatitis, increased salivation,
fatigue, insomnia, anorexia, and renal damage
[5,17]. Neurologic abnormalities can affect three
general areas: (a) the motor system, (b) intellectual
capacity, and (c) emotional state [18]. Motor system
effects are characterized primarily by fine tremor of
the extremities, weakness in the limbs, and impaired
motor speed. Aspects of intellectual capacity most
affected are short-term verbal and spatial memory.
Impairments in emotional state can produce anxiety,
depression, and avoidance. Collectively, these
neurologic symptoms have been termed ‘erethism.’
The single most prominent neurologic abnormality
seen with chronic exposure is tremor. Exposure-
related neurological dysfunction is often reversible,
although some features may be long-lasting.
Methylmercury latency. In contrast to the rapid
response to mercury(0) vapor, high doses of
methylmercury show a latent period of months
between exposure and the onset of clinical symptoms
[7,8]. Symptoms include paresthesia, ataxia,
dysarthria, and hearing loss. There is little ambiguity
in identifying high-dose exposure when blood
specimens are collected, since mercury will be
markedly elevated [7]. This is not the case with lower
doses, however, and low-level chronic exposure can
be associated with latency periods of years. In animal
studies, adverse effects are mild and consist mainly
of impaired dexterity. The developing fetus is
particularly sensitive and intrauterine exposure can
result is permanent disabilities.
Low-dose risks. When considering low-dose mercury
exposure, it is useful to put risks into an appropriate
238 Annals of Clinical & Laboratory Science
context. Consider, for example, a report of increased
risk of myocardial infarction (MI) associated with
chronic, low-dose mercury [19]. Study patients with
MI had significantly higher toenail mercury levels,
but also had higher body-mass index and lower high-
density lipoprotein cholesterol (HDL). And they
were more likely to have hypertension, to be diabetic,
to smoke, and to have a family history of MI. In
other words, low-dose mercury is a risk factor similar
in magnitude to other common risks such as being
overweight. Other studies have not found an
association between mercury and heart disease [20],
emphasizing that the risk of low-dose exposure is
modest. Such modest risk factors are important
public health issues, but the clinical concern should
be kept at an appropriate level.
Dental amalgams. Dental amalgams are a common
source of low-level mercury exposure in patients.
(For dental health care workers, amalgam formul-
ation and manipulation represents a potentially
higher level of exposure. Mercury hygiene guidelines
have been issued by the American Dental Association
[21].) Mercury(0) is the principal component of
amalgam, usually accounting for about 50% by
weight. Other metals include silver, copper, tin, and
zinc. In general, patients with amalgam fillings show
a small but statistically significant increase in blood
and urine mercury levels. The median blood mercury
concentration in 239 patients with amalgam fillings
was 6.2 µg/L (25-75 percentile 4.0-8.0, maximum
22.1) versus 5.3 µg/L (2.0-8.0, 16.1) for 36 patients
without amalgam fillings [22].
Adverse reactions to dental amalgams are
infrequent [22]. The majority of evidence does not
support the contention that amalgams contribute
to amyotrophic lateral sclerosis, Alzheimer’s disease,
multiple sclerosis, Parkinson’s disease, or similar
degenerative disorders [8]. In contrast, contact
hypersensitivity is an uncommon but well-
recognized adverse reaction [23,24]. Its presentation
is often characterized by lichen planus of the oral
mucosa adjacent to amalgam restorations [24].
Some authors advocate the removal of dental
amalgams in symptomatic patients when mercury
patch testing is positive [24]; chelation challenge
tests are not useful for diagnosis [25]. In a Norwegian
study of patients referred for symptoms attributed
to dental materials, patch testing was positive to
mercury in 6% (11 of 181); reactions to at least one
allergen were also seen in 28% to nickel, 23% to
gold, 14% to cobalt, 9% to palladium, and 8% to
components of resin-based dental materials [22].
When mercury is responsible, remission is expected
about 3 months after the last amalgam filling is
removed [24].
Patient Factors
It has been recognized for some time that mercury
concentrations in blood and urine show little
correlation with the symptoms of mercury poisoning
[2]. Some individuals are particularly sensitive to
the toxic effects of mercury, while others are resistant.
Adults are generally more resistant to mercury, where
children are more susceptible [8]. The fetus is
particularly sensitive. Genetic factors are especially
important, although environmental and dietary
influences also exert effects. An example of a well-
characterized effect is the reduced toxicity to
mercury(0) inhalation associated with consumption
of alcoholic beverages [26]. Many influences are not
intuitively obvious or well-characterized.
Acrodynia. An example of mercury sensitivity is seen
with acrodynia, also known as ‘pink disease’ (see
Reports #15, #16 and #17). Acrodynia is primarily
a disease of children but it can also occur in adults.
Although rare at the present time, acrodynia was a
common disease in the first half of the twentieth
century when exposures to mercury-containing
products were widespread. Warkany [27] estimated
that for every 500 children exposed to mercury, only
1 developed the disorder. In acrodynia and similar
disorders, it is impossible to differentiate between
affected and unaffected individuals on the basis of
blood and urine mercury concentrations, and
diagnostic confirmation requires an appropriate
response to the cessation of mercury exposure.
Immune-based reactions. Allergic reactions such as
contact dermatitis can be caused by exposure to
mercury, as well as to other metals such as nickel,
cobalt, chromium, and copper [28]. Allergic-type

reactions include tattoo reactions associated with
mercury(II) sulfide [16,29], cutaneous granulomas
caused by mercury(0) [16], and lichen planus of the
oral mucosa caused by dental amalgams [23,24].
Patch testing has been used to confirm a diagnosis
of contact allergy [28], although the usefulness of
this approach has been questioned [22,29].
Mercury can induce membranous glomerulo-
nephritis in rare individuals (see Report #12) [30].
This is an autoimmune disorder and related
conditions include a scleroderma-like disorder and
the induction of antinuclear antibodies [31].
Exposures to metals such as mercury and gold in
experimental animals lead to disorders similar to that
observed in humans. Studies of inbred mice and rats
showed that a few strains are susceptible to the
autoimmune effects, whereas the majority of inbred
strains are resistant. These findings emphasize the
genetic factors in metal-associated autoimmunity.
Metabolism
The metabolic rates of selected mercury species are
summarized in Table 1 and discussed below.
Inorganic forms follow a similar metabolic path,
while organic compounds show more complexity.
In general, mercury undergoes relatively little
bioaccumulation in humans [32].
Mercury(II). When ingested, about 90% of
mercury(II) remains bound to alimentary mucosa
and intestinal contents [5]. It is divided about equally
between plasma and red cells in the blood.
Mercury(II) does not cross the blood-brain barrier
or the placenta, so neurologic abnormalities are not
Table 1. Approximate metabolic rates of selected mercury species in humans.
Mercury species Blood half-life (days)
Inorganic mercury 5 19
Methylmercury ion c 44
Ethylmercury ion 18 d
7e
Phenylmercury ion f 5
Merbromin rapid
a Brief exposure [33]. b Long-term exposure [34]. c Single iv dose in adults [35]. d Adults [38]. e Low-dose thiomersal in infants
[40]. f Releases and behaves like mercury(II) [41].
Interpreting mercury levels in individual patients 239
prominent. Bile and feces are the major routes of
excretion, although excretion also occurs in urine.
The highest tissue accumulation of mercury is in
the kidneys and urine mercury comes mainly from
kidney deposits. The metabolic half-life is similar
to that described for mercury(0) below.
Mercury(0). With inhalation, about 80% of
mercury(0) vapor is retained in the body. Dissolved
vapor accumulates in the red blood cells and is
subsequently carried to all tissues. Because it crosses
the blood-brain barrier and the placenta, exposure
can be associated with neurologic abnormalities [8].
Upon entering cells, mercury(0) is oxidized to
mercury(II) with a half-life of about 2 days, and
thereafter behaves like the +2 oxidation state. The
highest tissue accumulation for mercury(0) remains
the kidney, where it is deposited as mercury(II).
After 3 days of exposure to mercury(0) vapor in
8 adult males, blood mercury showed a half-life of
3.1 days (95% CI 2.5-4.0) for a fast phase and 18
days (CI 11-42) for a slow phase [33]. The fast phase
corresponds to the redistribution of mercury to the
kidneys and other tissues, whereas the slow phase is
related to the fecal loss of mercury(II). Median peak
urine excretion occurred 19 days after exposure and
thereafter showed a median half-life of 40 days (CI
35-78). The peak corresponds to the maximum
kidney accumulation. In contrast to brief contact,
years of occupational exposure in 7 adults produced
a longer average half-life in urine of 90 days (range
69-109) [34].
The 2-compartment model described above for
blood mercury can be approximated with a 1-
compartment model using a half-life (τ) of 5 days
Urine peak (days) Urine half-life (days)
40 a
90 b
limited excretion
limited excretion
rapid rapid
240 Annals of Clinical & Laboratory Science
[33], and the equation N = No 0.5t/τ, where No is
blood mercury at time zero, N is at time t, and t is
time in days.
Methylmercury ion. About 95% of methylmercury
in foodstuffs is absorbed in the gastrointestinal tract
and transported to the liver [8]. Methylmercury then
undergoes an enterohepatic cycle with excretion in
the bile, reabsorption in the GI tract, and return by
portal circulation to the liver. A small portion is
converted by intestinal flora to mercury(II) which
is reabsorbed to a limited extent. Thus, most methyl-
mercury is eliminated by demethylation and
excretion of inorganic mercury(II) in the feces. After
a single intravenous dose, the average half-life of
methylmercury in blood was 44 days (range 32-60)
in 7 adult men [35]. About 1.6% (range 1.3-2.1)
was excreted daily in the feces. In the blood,
methylmercury ion concentrates in the red cells at
about 20 times that in plasma.
In the body, methylmercury is present largely
as water soluble complexes with sulfhydryl
compounds such as cysteine [8]. Transport across
cell membranes proceeds through specific
mechanisms such as the large neutral amino acid
carrier, and methylmercury complexes cross the
blood-brain barrier and the placenta. Less than 10%
of methylmercury in blood is normally excreted in
urine, although more would presumably be excreted
if the kidney tubules were not reabsorbing amino
acids appropriately. N-acetylcysteine (mucomyst)
can markedly increase urinary excretion and appears
to be a good therapeutic agent for use in methyl-
mercury poisoning when started early after exposure
[8,36,37].
Thimerosal and ethylmercury ion. Sodium
ethylmercury thiosalicylate (proprietary names
include thimerosal, thiomersal, methiolate sodium,
and merthiolate) is a water-soluble compound used
as a preservative [38]. It is added to many com-
mercial products of human plasma, immuno-
globulins, and vaccines, usually to a final
concentration about 10 mg/L [39]. Toxicity is
generally low, although allergic reactions occur, and
symptomatic and fatal poisonings have been
reported.
Thimerosal rapidly breaks down in the body to
release the ethylmercury ion (CH 3CH 2-Hg + ).
Ethylmercury appears to be less toxic than methyl-
mercury in part because metabolism is more rapid
[38]. The blood half-life in adults is about 18 days.
Low dose ethylmercury derived from thimerosal in
vaccines had a blood half-life of 7 days (95% CI 4-
10) in 40 full-term infants [40].
Phenylmercury ion. The carbon-mercury bond in
the phenylmercury ion (C6H5-Hg+) is relatively
weak and rapidly breaks down to release inorganic
mercury(II). After inhalation of volatile phenyl
mercury acetate, mercury(II) is released and follows
the kinetics of the +2 oxidation state [41].
Merbromin. Merbromin (mercurochrome) is an
organic mercury compound that was formerly
widely used as a topical antiseptic for minor skin
injuries. Accidental ingestion is usually associated
with minimal toxicity. Absorption through normal
skin in negligible but absorption through an
omphalocele is described in Report #21 [42]. Its
metabolism is determined by two characteristics: (a)
merbromin is freely soluble in water and (b) the
compound remains essentially intact. Because of
these characteristics, merbromin is rapidly cleared
in the urine. Compounds that share these
characteristics may be expected to behave similarly.
Published Reports
To put mercury results into an appropriate context,
a limited number of literature reports are
summarized in Table 2 and described briefly below
(comments by the author are in parentheses). The
literature review helps to emphasize that there is no
clear correlation between patient symptoms and
mercury concentrations in blood and urine. It is also
evident that mistakes in units and concentrations
are not uncommon in the mercury literature; see
Report #5 [43], Report #15 [44], and Weinstein
[45] for examples. Since such mistakes are more
likely to occur when an analyte is unfamiliar and
the magnitude of a typical result is unknown, a
literature review is also useful to characterize the
range of expected results. One aspect that may be
 Interpreting mercury levels in individual patients 241

Table 2. Published reports discussed in text.

Report Dosing Patients Blood Urine Notes

pattern age (yr) & mercury mercury
gender (µg/L) (µg/L)

1 acute 23 F 10,000 death on day 6 [11]

2 acute 40 M 15,580 discharged [47]
3 acute 70 F 590 death on day 28 [48]
4 acute 31 M 130 2,220 discharged [49]
5 acute 41 M 0.8 a 21 a death on day 23 [43]
6 acute 48 M 152 joint pain [50]
7 acute adult M 85 asymptomatic [33]
8 subacute 15 M 329 2,037 asymptomatic [51]
9 chronic 29 M 237 610 severe symptoms [52]
10 chronic 22 M 680 140 mild symptoms [53]
11 chronic 41 M 160 mild symptoms [15]
12 chronic 47 M 41 158 nephropathy [30]
13 chronic adults 3-60 subtle symptoms [54]
13.1 - adults 0.2-13 background [54]
14 remote adults 0-9.0 background [32]
15 chronic 1.9 M 43 73 acrodynia [44]
16 chronic 14 M 22 80 acrodynia [57]
17 chronic 0.9 F 12.6 acrodynia [58]
18 latent 48 F 4,000 234 dimethylmercury [7]
19 acute 20 M 2,800 dimethylmercury [37]
20 acute 44 M 14,000 10,700 thimerosal [39]
21 acute newborn 252 1,105 merbromin [42]
22 chronic adults 6-19 seafood rash [59]
23 - adults 0.8-112 dietary extreme [60]
24 - adults 0.4-16 background [61]

a Concentration inaccurate.

obscured by the literature is that cases involving
benign outcomes are probably more frequent than
the dramatic presentations that tend to reach print.
When comparing results generated in different
laboratories using different assays, it is probably
reasonable to compare relatively high concentrations
to within one significant figure, that is, 150-249
µg/L is about 200 µg/L. Uncertainties are likely to
be larger for lower concentrations. Use of colori-
metric assays was common at one time [46] and
results from such assays can only be regarded as
approximate; reports based on colorimetric assays
were excluded from those discussed here.
Report #1: acute ingestion fatal on day 6. Three hr
after ingesting 7 g of mercury(II) chloride, a 23-yr-
old female chemistry student presented with
abdominal pain [11]. Gastric lavage produced blood-
stained fluid. Her condition deteriorated rapidly
with hypotension, respiratory failure, rectal bleeding,
and renal failure. Initial blood mercury was 10,000
µg/L. Treatment included chelation and dialysis.
Hypotension remained severe even with fluid and
pressor support, presumably from intra-abdominal
fluid shifts and leaky capillary syndrome. Serial X-
rays showed progressive adult respiratory distress
syndrome and on day 6 she suffered fatal cardio-
respiratory arrest. (Report illustrates progression of
massive mercury(II) ingestion.)
Report #2: acute ingestion discharged on day 50.
Two hr after ingesting 1 g of mercury(II) sulfate
powder, a 40-yr-old male developed a burning
sensation in his throat [47]. Shortly after, he
experienced hematemesis and respiratory failure
requiring intubation and ventilation. Initial blood
242 Annals of Clinical & Laboratory Science
mercury collected 3 hr after ingestion was 15,580
µg/L. Within 12 hr of ingestion, he became anuric.
Treatment included chelation and continuous veno-
venous hemodiafiltration. The patient developed no
neurologic features and was discharged on day 50
with a normal creatinine clearance. (Report describes
significant mercury(II) ingestion that responded to
aggressive treatment. Because the initial blood
mercury was collected before the distribution phase
was complete, the degree of exposure was probably
exaggerated. Neurologic features would not be
expected because mercury(II) does not typically cross
the blood-brain barrier.)
Report #3: acute ingestion fatal on day 28.
Approximately 24 hr after ingesting unidentified
pills, a 70-yr-old female presented with nausea,
vomiting, cramping abdominal pain, melena, and
hematemesis [48]. Creatinine was 2.8 mg/dl and
hematocrit 47% on admission. Within 48 hr,
creatinine was 7.5 mg/dl, hematocrit 27%, and she
became anuric. Three days after ingestion, the pills
were identified as containing 1.4 g of mercury(II)
chloride and the blood mercury was found to be
590 µg/L. Hemodialysis and chelating agents were
started at that time. Delayed treatment may have
contributed to the fatal outcome 28 days after
poisoning. (Report illustrates that a relatively
moderate elevation of blood mercury can be
associated with a fatal outcome. Using a 1-
compartment model [33], blood mercury on the
initial day is estimated at 760 µg/L.)
Report #4: acute ingestion discharged on day 7.
About 45 min after ingesting 40 g of mercury(II)
oxide, a 31-yr-old male presented with nausea,
vomiting, and abdominal cramping [49]. Initial
mercury was 130 µg/L in blood and 2,220 µg/L in a
24-hr urine collection. He was treated with activated
charcoal, whole-bowel irrigation, and chelation.
Urine output remained normal and he was asympto-
matic at discharge on day 7. (Report illustrates a
potentially fatal poisoning which responded to
prompt treatment. Since the oxide is much less water
soluble than the chloride or sulfate salts [4],
mercury(II) oxide responded to intestinal evacuation
and only a small fraction of the dose was absorbed.)
Report #5: acute inhalation fatal on day 23. After
silver was recovered from dental amalgam in a
basement workshop, all four family members living
in a home died within 9 to 23 days [43]. Patient 4
was a 41-yr-old male who presented with nausea,
shortness of breath, and chills. The initial chest X-
ray was normal, but subsequent studies showed
bilateral infiltrates consistent with adult respiratory
distress syndrome. Mercury was reported as 0.8 µg/
L (4.0 nmol/L) in blood and 21 µg/L (105 nmol/L)
in urine on day 5 (concentrations clearly inaccurate).
Mechanical ventilation was necessary to maintain
oxygenation and the patient died on day 23
following cardiac arrest. No renal or neurologic
deterioration was evident clinically. On autopsy,
mercury was 1,000 µg/g (5,230 nmol/g) in kidney
tissue and 19 µg/g (95 nmol/g) in brain. The kidney
showed focal acute tubular necrosis on microscopy.
(Report illustrates progression of massive mercury(0)
inhalation. Since the blood and urine mercury were
inaccurate, tissue results are included to confirm that
the poisonings were caused by mercury.)
Report #6: acute inhalation with recovery.
Mercury(0) boiled in a kitchen pot produced a blood
mercury of 152 µg/L in a 48-yr-old male 12 days
after exposure [50]. The night of exposure, the
patient, wife, and son all had chest pain and difficulty
breathing. The following day the patient presented
with swollen eyelids, itchy red spots over his body,
difficulty breathing, and nausea. Mercury was not
mentioned and the condition was diagnosed as an
allergic reaction. A few days later, the patient
developed arthralgia that became progressively more
severe. Mercury exposure was considered on day 12.
The patient was treated with a nonsteroidal anti-
inflammatory drug and symptoms resolved about 3
weeks after the initial event. (Report illustrates
progression of symptoms associated with a moderate
degree of mercury(0) inhalation. Assuming a 1-
compartment model [33], blood mercury is
estimated at 800 µg/L on the initial day.)
Report #7: acute inhalation at low dose. After a brief
occupational exposure to low dose mercury(0) vapor,
blood mercury was 85 µg/L (425 nmol/L) in an adult
male described as subject 1 [33]. Random urine

mercury was 32 µg/g (18.2 nmol/mmol) on day 14.
(Report describes kinetics of low-dose exposure with
multiple specimens collected over time.)
Report #8: subacute inhalation in a community.
Several liters of mercury(0) were stolen by teenagers
who played with it and took it home [51]. A 15-yr-
old male (patient 1) showed a blood mercury of 329
µg/L on day 8, although exposure was probably
ongoing. He was hospitalized and treated with
DMPS (no symptoms were reported). Urine
mercury peaked at 2,037 µg/L on day 22. A 17-yr-
old male (patient 2) showed a blood mercury of 111
µg/L on day 8. He had a rash and felt unwell, but
was uncooperative and not fully evaluated. A 37-
yr-old female (patient 3) showed a blood mercury
of 178 µg/L on day 15, although exposure probably
occurred after the initial event. She was
asymptomatic but treated with chelation as an out-
patient. Afterwards, she required hospitalization for
paresthesias, tremor, and flu-like symptoms,
probably due to side-effects of chelation. (Report
describes several individuals with moderate, short-
term exposure to mercury(0) inhalation, and is an
example of treating based on laboratory values rather
than patient symptoms.)
Report #9: chronic inhalation with severe symptoms.
A 29-yr-old Chinese male with occupational
exposure to mercury(0) vapor in a lamp socket
manufacturing factory (worker 1) presented with
nervousness, irritability, gingivitis, blurred vision,
tremor, stuttering and slurred speech, ataxic gait,
and transient involuntary movement in the past 4
mo [52]. Mercury was 237 µg/L in blood and 610
µg/L in a 24-hr urine collection. No proteinuria was
present and renal function appeared normal. (Report
describes severe neurologic symptoms from chronic
mercury(0) inhalation. Mercury(II) is the chemical
form measured in blood and urine.)
Report #10: mercury(0) injection at 6 months. A
22-yr-old male attempted suicide by injecting
approximately 8 g of mercury(0) into the left cubital
fossa [53]. The patient presented 6 mo later
complaining of an increasing lack of concentration
and tremor. Radiographs showed widespread
Interpreting mercury levels in individual patients 243
densities in the lungs, abdomen, and subcutaneous
tissue of the elbow. Mercury concentration was 680
µg/L in blood and 140 µg/L in a random urine
sample. Renal function and nerve conduction studies
were normal. (Report describes remarkably mild
symptoms for the degree of exposure; see also Report
#11. Report emphasizes that liquid mercury(0) in
the blood is considerably less available metabolically
than dissolved mercury(0) vapor. Mercury(II) is the
chemical form measured in blood and urine.)
Report #11: mercury(0) injection at 5 yr. A 41-yr-
old male attempted suicide by injecting mercury(0)
[15]. More than 5 yr after the incident, radiographs
showed widespread opacities in the lungs, abdomen,
and subcutaneous tissue at the injection site.
Mercury concentration was 160 µg/L (800 nmol/
L) in blood and 470 µg/g creatinine (263 nmol/
mmol) in urine. Neurologic examination was normal
and no biochemical evidence of toxicity was found.
(Report illustrates that the findings in Report #10
are not unique; significant, chronic mercury
exposure occurs in some individuals without the
development of obvious symptoms.)
Report #12: chronic inhalation in a susceptible
individual. A 47-yr-old male employee with
exposure to mercury(0) vapor at a fluorescent-tube-
recycling factory was admitted with nephrotic
syndrome [30]. Mercury concentration was 41 µg/
L in blood and 158 µg/L in urine. Urine protein
excretion was 12.3 g/d (reference limit <0.10 g/d)
and renal biopsy showed membranous glomerulo-
nephritis with granular IgG and C3 deposits along
the glomerular basement membrane. Two yr after
withdrawal from mercury exposure, urine protein
excretion was 0.32 g/d. (Report illustrates an
autoimmune disorder induced in a susceptible
person. Although this phenomenon occurs rarely
[31], most individuals would never develop
membranous glomerulonephritis regardless of the
type and intensity of mercury exposure.)
Report #13: chronic inhalation in a group. Chronic
exposure of 89 Swedish chloralkali workers to
mercury(0) vapor produced an average blood
mercury concentration of 11 µg/L (55 nmol/L) with
244 Annals of Clinical & Laboratory Science
a range of 3-60 µg/L (15-299 nmol/L) [54]. In
morning urine specimens, average mercury
concentration was 25 µg/g creatinine(14.3 nmol/
mmol) with a range of 0.5-83 µg/g (0.3-46.9 nmol/
mmol). Kidney function [55], performance on
psychometric tests, and tremor frequency were
normal, although subtle central nervous system
deficits were identified [56]. Self-reported symptoms
and scores for tiredness, confusion, and neuroticism
were significantly higher compared to the control
group. (Studies describe chronic low-dose exposure
in a group. Subtle symptoms are difficult to
quantitate even in group studies.)
In 75 controls lacking occupational exposure,
average blood mercury was 3 µg/L (15 nmol/L) with
a range of 0.2-13 µg/L (1-65 nmol/L) [54]. The
average morning urine mercury was 1.9 µg/g
creatinine (1.1 nmol/mmol), range 0-7.6 µg/g (0-
4.3 nmol/mmol). Blood mercury was best correlated
with fish consumption and urine mercury was
weakly correlated (r=0.54) with the number of dental
amalgam surfaces. Fish and amalgam fillings were
important sources of exposure among occupationally
unexposed individuals, but these sources were
overshadowed by occupational exposure. (Control
group illustrates typical background concentrations,
and the influences of fish and dental amalgams.)
Report #14: remote inhalation. Exposure to
mercury(0) vapor at a chloralkali plant was not
associated with elevated urine mercury level assayed
years later [32]. Urine mercury (mean ± SD) was
3.37 ± 2.51 µg/L (95% interval 0-9.0, maximum
18.2) in 24-hr collections from 119 previously
exposed individuals. Mean duration of exposure was
7.0 yr and mean time since last exposure was 6.1 yr.
These values were not statistically different from
specimens collected from 101 workers without prior
exposure. Urine mercury increased after DMSA
challenge but was not significantly different in
exposed versus unexposed workers. (Study illustrates
that mercury does not undergo significant bio-
accumulation and that chelation challenge does not
add additional information. Report also illustrates
a small reference interval study, keeping in mind
that studies based on more individuals show wider
intervals.)
Report #15: chronic inhalation in child (acrodynia).
A 23-mo-old infant was well until 1 mo prior to his
referral for anorexia, weight loss, and rash [44]. He
perspired excessively, was irritable, had undergone
a personality change, and had become progressively
less active. An erythematous, papular rash developed
over his trunk 2 weeks before referral; a week later
erythema and peeling of the finger tips occurred.
Blood pressure and catecholamine metabolites were
elevated, although further evaluation for a
catecholamine-secreting tumor was cancelled after
mercury results became available. Mercury in blood
was 43 µg/L (43 ng/mL, listed as ng/dL most likely
in error) and urine was 73 µg/L (73 ng/mL). After
extensive search, the source was discovered to be
mercury(0) vapor from broken fluorescent light
bulbs. Symptoms disappeared rapidly after
discharge, and neurologic and developmental
findings were normal 6 weeks later. (Report
illustrates features of acrodynia. Recovery was
complete, in so far as determined. Report also
provides an example of confusion concerning units,
and the difficult task often encountered when trying
to identify the source of mercury exposure.)
Report #16: acrodynia in a teen. A 14-yr-old male
complaining of back pain was discovered to have
tachycardia and elevated blood pressure [57].
Subsequently a pruritic, erythematous, maculo-
papular rash developed with desquamation on the
palms and soles. The patient began to have
paroxysmal sweating with chills and tremor, became
increasingly irritable, and lost weight. A diagnosis
of pheochromocytoma appeared to be confirmed by
increased basal plasma and urinary catecholamines
with no evidence of clonidine suppression, although
no adrenal or extra-adrenal tumor could be
identified. His condition deteriorated and he began
to have hallucinations. At a third review of history
and in response to a direct question, he admitted
playing with mercury(0) at home. Mercury
concentration was 22 µg/L (110 nmol/L) in blood
and 80 µg/L (400 nmol/L) in urine. The home
required extensive cleaning to prevent further
exposure. (Report describes acrodynia in a slightly
older individual. Lower blood mercury compared
to Report #15 could reflect less exposure over the

previous few days or could reflect measurement in a
different laboratory.)
Report #17: acrodynia with ‘normal’ mercury. An
11-mo-old girl was admitted because of drowsiness,
malaise, and anorexia [58]. She had been well until
6 weeks before, when she lost her appetite, began
sweating profusely, and stopped crawling or standing
up. On examination, she had a generalized pruritic
rash, and swollen, red hands and feet with desquam-
ation. After a 6-yr-old sister presented with less severe
symptoms, the mother reported mercury from a
broken thermometer had been dropped on the
carpet in the children’s room 2 weeks before
symptoms started. Urine mercury in the 11-mo-old
was 12.6 µg/L, slightly above the reference limit of
< 10 µg/L. After 3 mo of DMSA treatment, the
symptoms had disappeared and urine mercury was
<1 µg/L. Several months later, both children were
in good health. (Report emphasizes that mercury
can appear virtually normal in acrodynia. Although
not needed for diagnosis, blood mercury analysis
would have added supportive information.)
Report #18: fatal dimethylmercury with latent onset.
A 48-yr-old chemistry professor was admitted with
5 days of progressive deterioration in balance, gait,
and speech [7]. Examination showed moderate
upper-extremity dysmetria (voluntary muscle
movement overreaching or falling short of the
intended goal), dystaxic handwriting, a widely based
gait, and ‘scanning speech’ (speech with syllables
separated by pauses). While working in a hood 5
mo previously (154 days before the onset of
symptoms), the patient reported accidentally spilling
several drops of dimethylmercury from the tip of a
pipet onto the dorsum of her latex-gloved hand.
Blood mercury was 4,000 µg/L and urine 234 µg/L
on admission. The patient’s neurologic deterioration
continued and she died 298 days after exposure.
(Report describes exposure to an extremely toxic
form of organic mercury with a long latent period;
compare to Report #19.)
Report #19: acute dimethylmercury ingestion. A 20-
yr-old male ingested several gulps of a fungicide
containing ‘methylmercury’ [37]. (Methylmercury
Interpreting mercury levels in individual patients 245
in this context refers to dimethylmercury [6]). Blood
mercury was 2,800 µg/L at 2 hr after ingestion and
declined to less than half that value at 12 hr; the
rapid decline corresponded to the distribution phase
during which the blood concentration is dispersed
to tissues. Chelation was started 4-5 hr after the
episode and hemodialysis with N-acetylcysteine
infusion started at 1.5 days. Neurologic examination
remained normal at 4 days, 6 weeks, and 1 yr.
(Report illustrates prompt treatment of dimethyl-
mercury poisoning; compare to Report #18.
Dimethylmercury poisoning is usually not
recognized until symptoms develop, at which point
treatment is ineffective.)
Report #20: acute thimerosal ingestion. After
drinking an aqueous solution containing 5 g of
thiomersal, a 44-yr-old male developed nausea and
vomiting [39]. Blood mercury was 14,000 µg/L at
4 hr after ingestion and 84 µg/L on day 19. Urine
mercury was 10,700 µg/L on day 3. DMPS and
DMSA did not increase mercury excretion. Polyuric
acute renal failure began on day 1 with a maximum
proteinuria of 9.4 g/d on day 14. Gingivitis and a
maculopapulous rash developed on day 4, poly-
neuropathy on day 6, and delirium on day 11
progressing to coma. Neurologic symptoms
improved after day 19 and renal function returned
to normal by day 40. The patient subsequently
recovered completely. (Report illustrates progression
of thimerosal poisoning. Thiomersal releases
ethylmercury ion which is cleared rapidly relative
to methylmercury ion.)
Report #21: acute merbromin exposure. A 3,498 g
newborn with a large omphalocele was treated with
topical 2% merbromin twice daily on days 5 through
10 [42]. Blood mercury was 252 µg/L on day 9 and
1.0 µg/L on day 15. Urine mercury was 1,105 µg/L
on day 10 and 270 µg/L on day 11. The newborn
developed no symptoms and received no treatment
for mercury exposure, although similar exposures
have been reported to result in symptoms and
fatalities. (Report illustrates rapid clearance of
merbromin relative to other organic forms.)
Report #22: rash from dietary methylmercury. A
246 Annals of Clinical & Laboratory Science
characteristic rash in 11 adults was associated with
modest blood mercury elevations from seafood diets
[59]. The rash consisted of 1-2 mm nonpruritic,
discrete, flesh-colored or slightly erythematous
papules especially on the palms, and occasionally
on the soles of the feet and the arms and trunk. Initial
blood mercury concentrations were 6-19 µg/L (29.9-
94.7 nmol/L). Treatment lasted from 1 to 6 mo,
and consisted of a seafood-free diet or diet with
DMSA chelation. Blood mercury levels decreased
and eruptions cleared in all 11 patients. (Study
illustrates mild symptoms in sensitive individuals.)
Report #23: sea mammal diet. Among 492 Inuit
adults living in the Canadian arctic, blood mercury
concentration averaged 16 µg/L (79.6 nmol/L) with
a range of 0.8-112 µg/L (4-560 nmol/L) [60].
Mercury was primarily methylmercury and was
correlated with sea mammal consumption. (Study
illustrates a probable extreme of dietary exposure.)
Report #24: background. Among 106 elderly
individuals in Sweden, blood mercury
concentrations averaged 3.4 µg/L (17 nmol/L) [61].
The range of blood mercury was 0.4-16 µg/L (2-80
nmol/L) with 5 outliers >5.6 µg/L (>28 nmol/L)
that were excluded from the analysis. No relation
was found between blood mercury level and
cognitive function or blood pressure. (Report
illustrates a typical blood mercury distribution;
mercury outliers are common in population studies.
Study illustrates a common problem– mismatch
between the data collected and the information
sought; the short half-life of blood mercury makes
it unlikely to be correlated with long-term toxicity.)
Evaluating Mercury Results
Blood and urine mercury results should fit into an
understandable metabolic pattern and be consistent
with published reports. Results that do not fit
deserve further scrutiny, such as seeking additional
clinical history or further laboratory testing. When
signs and symptoms of mercury poisoning cannot
be identified in a patient, the assumption is that
toxicity is not present. Contamination from an out-
side source may cause elevated mercury results [62].
When there is sufficient motivation to evaluate
a patient for mercury toxicity, both blood and urine
are often worth collecting. Even when investigating
an issue such as dietary methylmercury, where
methylmercury will not typically be found in urine,
the urine specimen may provide additional
information such as background exposure to other
mercury species. Confidence in the interpretation
of mercury concentrations increases when the results
are concordant among the specimen types and
specimens collected at different times.
Preanalytic specimen collection. Since mercury tends
to accumulate in red blood cells, whole blood
specimens are generally analyzed rather than serum
[62]. Accurate estimation of blood mercury from
serum mercury is difficult, since it depends on the
mercury species involved and the time elapsed since
exposure. The preferred collection device is a
vacutainer-style evacuated blood collection tube for
trace elements (royal blue-top) with EDTA anti-
coagulant, although routine EDTA tubes (lavender-
top) are probably adequate in most cases. Heparin
is a suitable anticoagulant when the specimen is
analyzed within 2-3 days, but the formation of
microclots can render mercury analysis less
reproducible after that time. Blood specimens that
contain visible clots are obviously inhomogeneous
and are impossible to sample adequately. Any
indication that a collection tube was opened prior
to analysis is a risk factor for contamination.
Opinions differ as to what is an appropriate
urine specimen. A 24-hr urine collection is regarded
as superior [62] but it is less convenient and more
expensive, and entails greater opportunity for
collection problems. A random urine specimen is
adequate for most purposes [63], and a plastic,
single-use urine cup with screw-on lid is an
appropriate container. Assay of urine creatinine or
a similar marker can be used to judge if a specimen
is excessively dilute or concentrated; the World
Health Organization’s guidelines for suitable urine
creatinine levels are >30 mg/dl and <300 mg/dl [64].
Collection from a catheterized patient is a risk factor
for mercury contamination, as is any other
indication that the urine specimen has been in
contact with more than a minimum number of

surfaces. Collection at a worksite is a major risk
factor. Addition of ultrapure acid to maximize
mercury solubility may be needed when mercury
concentrations are low and small differences are
important, although the addition may represent
another opportunity for contamination rather than
an improvement in specimen quality.
For 24-hr urine collections, the tendency for
incomplete or excess collections can be partially
evaluated by examining total volume and creatinine.
Inaccurate measurement of the total volume can be
an unrecognized source of error. Collections >2 L
(ie, those received in more than 1 container) are
suspect for: (a) inappropriate aliquoting if not from
a single container that holds the entire well-mixed
specimen, or (b) potential for contamination.
Analytic issues. Adequate analysis of mercury
concentrations in blood or urine requires mass
spectrometry, atomic absorption, neutron activation,
or a similar instrumental method. A limit of
detection of 0.5 µg/L and a CV of 10% at 8.0 µg/L
are characteristic of assays from carefully conducted
research studies [61], although this level of
performance is usually neither required or achieved
in routine practice. Acceptable results are most likely
to come from laboratories that participate in an
interlaboratory comparison program for mercury
assays in blood and urine, such as that offered by
the Centre de Toxicologie du Québec (www.
ctq.qc.ca). Even among such laboratories, however,
assays of blood mercury in a specimen (M03-03)
with a target concentration of 16 µg/L (78 nmol/L)
can show a CV of 83% [65].
In clinical laboratories, mercury levels in blood
and urine are usually determined as total mercury,
without regard to the chemical forms that may be
present. If there is concern about an unusual organic
mercury compound, the assay may need scrutiny to
ensure that it has been validated for that compound.
Mercury speciation, available from a few reference
laboratories, is usually limited to differentiating
between the common inorganic and organic forms.
Elapsed time. Mercury results are obviously influen-
ced by the time that has elapsed between the
individual’s exposure and specimen collection. As a
Interpreting mercury levels in individual patients 247
first approximation, blood mercury concentration
reflects more recent exposure and urine mercury
concentration is indicative of chronic, longer-term
exposure. Concordance between results and the
metabolic pattern is an important aspect of
evaluation. A clue that methylmercury may be
involved is when blood mercury is significantly
elevated but urine mercury is relatively normal.
During acute exposure, the distribution phase
represents rapid uptake before tissue equilibration
[39]. Sampling early in an acute event may
exaggerate the degree of exposure (see Reports #2
and #20). Urine mercury concentrations tend to
underestimate acute exposure until the mercury
excretion peaks at about 2-4 weeks. Since urine
mercury has a longer half-life, it is more useful for
evaluation of chronic exposure. When sufficient time
has elapsed, both blood and urine mercury return
to background concentrations [32] unless further
exposure has occurred.
Reference intervals. A reference interval is a measure
of the mercury distribution in the population studied
and is unrelated to the point at which toxicity
develops. Thus, reference intervals are of limited use
for interpreting analytes such as mercury. A
commonly used reference interval for blood mercury
is 0.6-59.0 µg/L [62], although this is much higher
than the background ranges listed in Table 2 for
Reports #13.1 and #24. Clear signs of mercury
toxicity develop in most individuals only at some
point much higher than the upper reference limit,
although acrodynia is an example of a disorder that
can occur within reference intervals.
Instead of a population-based reference interval,
it may be preferable to select a recommended limit
based on public health concerns. An example of this
is the recommendation by the Environmental
Protection Agency that blood mercury levels be <5.8
µg/L for women who are pregnant or who intend to
become pregnant [66]. This is based on the potential
danger of methylmercury to the developing fetus
and is intended to be well below the concentration
at which fetal effects are expected to occur.
Biologic markers. Additional laboratory tests can be
employed to look for signs of mercury toxicity.
248 Annals of Clinical & Laboratory Science
Analytes in this category include urine porphyrins
[67] and urine proteins such as albumin, β 2-
microglobulin, and N-acetyl-β-D-glucosaminidase
(NAG) [55]. Although elevations of such analytes
support the contention that mercury toxicity is
present, such markers are general indicators and
other causes cannot be excluded. These tests,
however, have the advantage of offering objective
information from the same specimens provided for
mercury analysis.
Urine porphyrin patterns change as early as 1-2
weeks after exposure and remain elevated longer than
urine mercury [68]. Characteristic changes include
elevated levels of 4- and 5-carboxylate porphyrins,
and appearance of an atypical metabolite, precopro-
porphyrin. Following cessation of exposure,
porphyrin concentrations revert to normal levels. For
dentists with subtle changes from low-level occupat-
ional exposure, urine porphyrins were easier to
measure than the associated behavioral changes [69].
Elevated urine NAG is an indication of impaired
function in the renal proximal tubules. Increased
NAG excretion in urine has been used to monitor
the toxic effects of mercury on the kidney in an
occupational setting [55,70]. The NAG isoenzyme
patterns in urine have also been used to monitor
mercury exposure [71].
Chelation challenge tests. Some investigators have
advocated chelation challenge tests to assess the body
burden of mercury [72]. Others have stated that
challenge tests are not useful, particularly for
assessing exposures that occurred years previously
[32]. Unlike lead, mercury undergoes relatively little
bioaccumulation. Chelation challenge increases the
amount of mercury in urine in proportion to the
amount of mercury in kidney tissue. Chelation does
not provide any additional information about the
kidney burden or total body burden [34]. DMPS
challenge was not found to be useful as a diagnostic
tool in patients with symptoms reportedly caused
by mercury from dental amalgam fillings [25].
Future risk. The future risk that may be posed by
past exposure to mercury is a topic of interest. As a
result of chronic, high dose exposure to mercury(0)
vapor, an increased risk of polyneuropathy and
similar neurologic disorders was seen 20 to 35 yr
later [46]. Presumably, the aging process unmasked
subclinical damage that occurred years earlier. This
is similar to the increased risk of developing
Parkinsonian syndrome years after boxing or the late
progression of poliomyelitis. Clinically apparent
effects were not present in most individuals years
after mercury exposure and subtle abnormalities
were identified only by comparing exposed
individuals to unexposed controls. The most
clinically significant subtle abnormality was
increased tremor associated with a peak urine
mercury >600 µg/L. (Urine mercury was determined
by a colorimetric method in wide use at the time
and can only be taken as approximate.) Cognitive
function was not significantly affected. A few
individuals (18 of 247) developed polyneuropathy
as a result of mercury(0) exposure. The severity of
peripheral involvement was comparable to that
found in a random selection of diabetic subjects.
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