Grand Rounds: Nephrotoxicity in a Young Child Exposed to Uranium from Contaminated Well Water

Abstract

Private wells that tap groundwater are largely exempt from federal drinking-water regulations, and in most states well water is not subject to much of the mandatory testing required of public water systems. Families that rely on private wells are thus at risk of exposure to a variety of unmeasured contaminants.
A family of seven--two adults and five children--residing in rural northwestern Connecticut discovered elevated concentrations of uranium in their drinking water, with levels measured at 866 and 1,160 microg/L, values well above the U.S. Environmental Protection Agency maximum contaminant level for uranium in public water supplies of 30 microg/L. The uranium was of natural origin, and the source of exposure was found to be a 500-foot well that tapped groundwater from the Brookfield Gneiss, a geologic formation known to contain uranium. Other nearby wells also had elevated uranium, arsenic, and radon levels, though concentrations varied widely. At least one 24-hr urine uranium level was elevated (> 1 microg/24 hr) in six of seven family members (range, 1.1-2.5 microg/24 hr). To assess possible renal injury, we measured urinary beta-2-microglobulin. Levels were elevated (> 120 microg/L) in five of seven family members, but after correction for creatine excretion, the beta-2-microglobulin excretion rate remained elevated (> 40 microg/mmol creatinine) only in the youngest child, a 3-year-old with a corrected level of 90 microg/mmol creatinine. Three months after cessation of well water consumption, this child's corrected beta-2-microglobulin level had fallen to 52 microg/mmol creatinine.
This case underscores the hazards of consuming groundwater from private wells. It documents the potential for significant residential exposure to naturally occurring uranium in well water. It highlights the special sensitivity of young children to residential environmental exposures, a reflection of the large amount of time they spend in their homes, the developmental immaturity of their kidneys and other organ systems, and the large volume of water they consume relative to body mass.

Full text

Groundwater is the principal source of drink-
ing water for 14–15 million (14%) of the
105.5 million homes in the United States and
for approximately 42 million people [Centers
for Disease Control and Prevention (CDC)
2003; U.S. Census Bureau 2000; U.S.
Environmental Protection Agency (EPA)
2006].
Groundwater is at risk of contamination
by a wide variety of industrial pollutants and
naturally occurring toxic chemicals. Industrial
chemicals that have been identified in ground-
water include benzene, methyl tert-butyl
ether, nickel, perchlorate, perchloroethylene,
pesticides, phenol, and trichloroethylene
[Agency for Toxic Substances and Disease
Registry (ATSDR) 1996, 1997a, 1997b,
1998, 2005b, 2005c; Baker et al. 1978; U.S.
EPA 2006]. These contaminants are most
commonly found near chemical and pesticide
production facilities, hazardous waste sites,
roads, and railways. Naturally occurring toxic
chemicals that have been documented in
groundwater include arsenic, manganese,
radon, and uranium (ATSDR 1999, 2005a;
U.S. EPA 2006). These materials may be pre-
sent in especially high concentrations in min-
ing districts, but also occur widely in certain
geologic formations, especially in mountain-
ous areas of the United States (U.S. EPA
2006; Walsh 2003).
Private wells that tap groundwater have
been associated with episodes of human expo-
sure to toxic chemicals (U.S. EPA 2006).
Private wells in the United States are largely
exempt from state and federal drinking water
regulations, and thus in most states they are
not subject to much of the mandatory testing
that is required of public water supplies under
the provisions of the Safe Drinking Water Act
Amendments of 1996 (1996). In most loca-
tions, well water is routinely tested only for
pH, bacteria, and a small number of chemical
contaminants. Uranium is not commonly
among the chemicals tested. Because of
increasing urban sprawl with continuing
movement of populations from urban centers
to previously rural areas that lack public water
supplies (Frumkin et al. 2004), a growing
number of private wells are being drilled in the
United States. Unless changes are mandated in
current testing requirements, the number of
people at risk of exposure to toxic chemicals in
groundwater will therefore likely increase.
Exposures to chemical contaminants in
groundwater have caused disease and disabil-
ity in exposed populations. The prevalence
and severity of these effects reflect the inten-
sity, the duration, and the developmental
timing of exposure. Reported health effects
have included diminished intelligence after
prenatal exposures to lead and manganese;
peripheral vascular disease and skin cancer
after childhood exposure to arsenic; and fatal
methemoglobinemia after exposure in infancy
to nitrates (Ahsan et al. 2006; Campbell
1952; Needleman et al. 1979).
Infants and young children are especially
vulnerable to chemical contaminants in drink-
ing water. This heightened vulnerability reflects
the disproportionately great water consumption
of young children, who drink 7 times as much
water per kilogram body weight per day as the
average adult (Ershow and Cantor 1989)
(Figure 1). It also reflects the inherent biologi-
cal vulnerability of the young, which is a conse-
quence of their rapid growth and development
and their relative inability to detoxify and
excrete many exogenous chemicals [National
Research Council 1993].
We present a case of a family who was
exposed to naturally occurring uranium in
groundwater from their private well in
Connecticut. Although all family members
Environmental Health Perspectives
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VOLUME 115 |NUMBER 8 |August 2007
1237
Research
|
Environmental Medicine
Address correspondence to P.J. Landrigan,
Department of Community and Preventive
Medicine, Mount Sinai School of Medicine, One
Gustave L. Levy Place, Box 1057, New York, NY
10029 USA. Telephone: (212) 241-4804. Fax: (212)
996-0407. E-mail: phil.landrigan@mssm.edu
This work was supported by the Association of
Occupational and Environmental Clinics/Agency for
Toxic Substances and Disease Registry Pediatric
Environmental Health Specialty Unit contract
(U50/ATU300014-13), and by the Mount Sinai
Center for Children’s Environmental Health and
Disease Prevention Research supported by the U.S.
Environmental Protection Agency (EPA-RD-
83171101) and the National Institute of Environmental
Health Sciences (ES009584).
The authors declare they have no competing
financial interests.
Received 11 September 2006; accepted 22 May
2007.
Grand Rounds: Nephrotoxicity in a Young Child Exposed to Uranium from
Contaminated Well Water
H. Sonali Magdo,
1
Joel Forman,
2,3
Nathan Graber,
2,3
Brooke Newman,
3
Kathryn Klein,
2,3
Lisa Satlin,
2
Robert W. Amler,
4
Jonathan A. Winston,
5
and Philip J. Landrigan
2,3
1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, California, USA; 2Department of
Pediatrics, and 3Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA;
4School of Public Health, New York Medical College, New York, New York, USA; 5Department of Medicine, Mount Sinai School of
Medicine, New York, New York, USA
CONTEXT: Private wells that tap groundwater are largely exempt from federal drinking-water
regulations, and in most states well water is not subject to much of the mandatory testing required
of public water systems. Families that rely on private wells are thus at risk of exposure to a variety
of unmeasured contaminants.
CASE PRESENTATION: A family of seven—two adults and five children—residing in rural northwest-
ern Connecticut discovered elevated concentrations of uranium in their drinking water, with levels
measured at 866 and 1,160 µg/L, values well above the U.S. Environmental Protection Agency
maximum contaminant level for uranium in public water supplies of 30 µg/L. The uranium was of
natural origin, and the source of exposure was found to be a 500-foot well that tapped groundwater
from the Brookfield Gneiss, a geologic formation known to contain uranium. Other nearby wells
also had elevated uranium, arsenic, and radon levels, though concentrations varied widely. At least
one 24-hr urine uranium level was elevated (> 1 µg/24 hr) in six of seven family members (range,
1.1–2.5 µg/24 hr). To assess possible renal injury, we measured urinary beta-2-microglobulin.
Levels were elevated (> 120 µg/L) in five of seven family members, but after correction for creatine
excretion, the beta-2-microglobulin excretion rate remained elevated (> 40 µg/mmol creatinine)
only in the youngest child, a 3-year-old with a corrected level of 90 µg/mmol creatinine. Three
months after cessation of well water consumption, this child’s corrected beta-2-microglobulin level
had fallen to 52 µg/mmol creatinine.
SIGNIFICANCE: This case underscores the hazards of consuming groundwater from private wells. It
documents the potential for significant residential exposure to naturally occurring uranium in well
water. It highlights the special sensitivity of young children to residential environmental exposures,
a reflection of the large amount of time they spend in their homes, the developmental immaturity
of their kidneys and other organ systems, and the large volume of water they consume relative to
body mass.
KEY WORDS: beta-2-microglobulin, drinking water, drinking water standards, groundwater,
nephrotoxicity, private wells, uranium. Environ Health Perspect 115:1237–1241 (2007).
doi:10.1289/ehp.9707 available via http://dx.doi.org/ [Online 22 May 2007]

had evidence of exposure, the only family
member with evidence of nephrotoxicity was
the youngest child.
Case Presentation
In September 2000 a family of seven—two
adults and five children 3, 5, 7, 9, and 12
years of age—living in a development in rural
northwestern Connecticut discovered highly
elevated levels of uranium in the drinking
water of the home where they had resided for
5 years. The home water was supplied by a
private well that tapped groundwater at a
depth of approximately 500 feet. The family
had used water from this well for cooking,
drinking, and bathing from the time that they
had moved into the home until discovery of
the contamination.
The family first became aware of the pos-
sibility of uranium exposure after a neighbor
was found to have markedly elevated levels of
uranium in her hair. This neighbor had had
her hair tested for a range of metals because
she was concerned that she had been exposed
to mercury from her dental fillings; mercury
levels in the neighbor’s hair were not elevated.
After the discovery of elevated levels of
uranium in her hair, the neighbor had the
water from her well tested for uranium. Her
well water was found to contain uranium at a
level of 41 pCi/L. Applying the U.S. EPA
conversion factor of 0.9 pCi/µg (an estimate
based on the ratio of uranium species found
typically by the U.S. EPA in well water) this
translates to 46 µg/L, a value above the
U.S. EPA maximum contaminant level
(MCL) for uranium in public water supplies
of 30 µg/L (National Primary Drinking
Water Regulations 2001a). In response to
their neighbor’s discovery of uranium in her
well water, the index family had their well
water tested. Initial testing in a private labora-
tory (RSA Laboratories, Inc., Hebron, CT)
on 28 September 2000 returned a level of 866
µg/L (779 pCi/L), a value also above the U.S.
EPA MCL. Repeat measurement by the State
of Connecticut Department of Public Health
Laboratory (Hartford, CT) on 12 October
2000 returned a level of 1,160 µg/L (1049
pCi/L). Investigation for other contaminants
revealed that arsenic was present at a concen-
tration of 0.104 mg/L (above the current U.S.
EPA MCL of 0.01 mg/L) (U.S. EPA 2001b)
and radium 226 and 228 combined activity
was measured at 15.61 pCi/L (above the U.S.
EPA MCL for combined activity of 5 pCi/L).
The family was advised to immediately stop
consuming water from their home well.
Environmental assessment. Environmental
investigation was undertaken by the State of
Connecticut Department of Public Health
(Hartford, CT). Agency staff collected samples
from the index family, as described above,
and from other nearby homes in the develop-
ment where the family resided. The State of
Connecticut Department of Public Health
Laboratory analyzed the water samples for
uranium and radon and air samples for radon.
Environmental assessment revealed that
four of 11 homes tested in the development
where the index family resided had elevated
levels of uranium in their well water. The
level of uranium contaminations was quite
variable, with very high levels occurring in
some homes and almost none in adjoining
homes (Table 1).
Geologic assessment by the Connecticut
Department of Public Health determined
that this housing development had been built
in the Appalachian foothills of northern
Connecticut and that it sat above the
“Brookfield Gneiss,” a metamorphic rock for-
mation common throughout the Appalachian
ridges of western New England. Geologic for-
mations similar to the Brookfield Gneiss have
been shown to contain concentrated pockets
of natural uranium (Robinson and Kapo
2003; Walsh 2003). The Connecticut
Department of Public Health considered nat-
urally occurring metals in the Brookfield
Gneiss to be the most likely source of the ura-
nium and other minerals detected in the
index family’s well water. Review of town and
county records and of business directories
revealed no evidence of any current or past
metal mining or other industrial source of
uranium or other toxic metals in the area.
Clinical assessment. To assess the uranium
exposure of family members, a 24-hr meas-
urement of urine uranium was obtained by a
pediatric nephrologist in our group (L.S.)
from all family members in October 2000, 4
weeks after cessation of well water consump-
tion, an event that had occurred on 28
September 2000 (Table 2). An additional
24-hr collection was obtained from the par-
ents in November 2000, 6 weeks after cessa-
tion of well water consumption. At least one
urine uranium measurement was found to be
elevated in six of the seven family members.
Levels ranged from < 1 µg/L to 6.2 µg/L, well
above the mean concentration in the U.S.
population of 0.009 µg/L (CDC 2005).
When adjusted for urinary volume, uranium
excretion was 1.1–2.5 µg uranium/24 hr (val-
ues above the < 1 µg uranium/24 hr expected
in an unexposed population). Although ele-
vated levels of radon, radium, and arsenic were
found in the family’s water, biological measures
were not pursued because these substances are
not known to have chemical nephrotoxic
effects. The MCLs for these substances are
designed to protect against the elevated risk of
cancer that exposure confers.
Magdo et al.
1238
VOLUME 115 |NUMBER 8 |August 2007
•
Environmental Health Perspectives
Table 1. Well water uranium in homes, suburban development, northwestern Connecticut, October–November 2000.
Case family
Water uranium (Home 1) Home 2 Home 3 Home 4 Home 5 Home 6 Home 7 Home 8 Home 9 Home 10 Home 11
pCi/L 1049.00 41.00 0.19 12.50 7.50 12.20 7.50 469.00 14.70 32.00 19.00
µg/L
a
1165.56 45.56 0.21 13.89 8.33 13.56 8.33 521.11 16.33 35.56 21.11
Testing done by CT DOH Lab.
a
Mass calculated from activity measurements using EPA conversion factor of 0.9 pCi/µg.
Figure 1. Mean daily intake of total water per unit of body weight by age group and sex. Figure reprinted
from Ershow and Cantor (1989), with permission from Life Sciences Research Office.
< 0.5 < 0.5–0.9 1–3 4–6 7–10 11–14 15–19 20–44 45–64 65–74 ≥ 75
225
200
175
150
125
100
75
50
25
0
Water intake (g/kg/day)
Age (years)
Female
Male

To assess the possible occurrence of renal
tubular injury, measurements were made (by
L.S.) in family members of urine beta-2-
microglobulin levels (Table 2). Beta-2-
microglobulin is a low-molecular-weight
(11.8 kD) protein that is freely filtered at the
glomerulus and avidly taken up and catabo-
lized by the proximal tubule (Brenner 2004).
Elevation of urine beta-2-microglobulin is a
nonspecific marker of proximal tubule dam-
age. Elevated beta-2-microglobulin levels
(normal reference range in adults is < 120
µg/L) were found in five of the seven family
members and ranged from 89 to 530 µg/L,
thus suggesting the possible presence of proxi-
mal tubular injury. To adjust the beta-2-
microglobulin for urine volume and body
mass in children, a urinary beta-2-microglob-
ulin excretion rate (micrograms beta-2-
microglobulin per gram creatinine) is
commonly calculated (Tomlinson 1992). The
beta-2-microglobulin excretion rate was nor-
mal (< 40 µg/mmol creatinine) in all family
members except for the youngest child. In
this 3-year-old, who unlike other family
members had spent virtually all of her life in
the house, the urinary beta-2-microglobulin
excretion rate was 90 µg/mmol creatinine, a
value more than twice the reported upper
limit of normal. Three months after the fam-
ily had ceased consuming water from the
home well (January 2001), this child’s urinary
beta-2-microglobulin excretion rate had fallen
to 52 µg/mmol creatinine. There was no evi-
dence of other proximal tubule dysfunction,
as evidenced (in January 2001) by the absence
of glucosuria, phosphate wasting (with nor-
mal values for the tubular reabsorption of
phosphate), bicarbonate wasting, or metabolic
acidosis (Table 3).
Analytic methods for key environmental
and biological tests are reported in Table 4.
Discussion
This case underscores the potential hazards of
consuming groundwater from private wells. It
emphasizes the need to test drinking water for
a wide range of potential contaminants.
Specifically, it documents the potential for
significant residential exposure to naturally
occurring uranium in well water. The case
also highlights the special sensitivity of young
children to environmental exposures in the
home—a reflection of the large amount of
time young children spend in their homes,
their developmental immaturity, and the large
volume of water they consume relative to
their body mass.
Uranium is a commonly occurring
radioactive mineral. It is found naturally in
geologic formations such as the Brookfield
Gneiss. In the formation of metamorphic
rock, uranium is distributed very unevenly. It
typically deposits in areas of low pressure and
irregular cracks. Therefore, concentrations
can vary significantly within a small area. The
level of uranium that appears in drinking
water depends on the flow of water through
complicated fracture networks within the
rock, as well as on the pH, calcium content
and other characteristics of groundwater. For
these reasons, concentrations of uranium in
closely adjoining wells may be quite different,
as was seen in this case. This pattern of signif-
icant local variability in concentrations of ura-
nium has been observed in various locations
across North America (Natural Resources
Uranium in well water
Environmental Health Perspectives
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VOLUME 115 |NUMBER 8 |August 2007
1239
Table 2. Urine measurements of uranium, β2-microglobulin (β2-M), and creatinine.
Uranium β2-M
Uranium Urine volume Uranium excretion excretion rate
in 24 hr in 24 hr excretion (ng/mmol β2-M Creatinine (µg β2-M/mmol
Subject Age [years (sex)] Test date (µg/L) (L) (µg/24 hr)
a
creatinine) (µg/L)
b
(mmol/L) creatinine)
c
1 3 (F) Oct 2000 6.2 0.4 2.5 1,062 532 5.84 90.8
Jan 2001 267 5.13 52
2 5 (M) Oct 2000 4.9 0.475 2.3 690 100 7.1 14.1
Jan 2001 174 9.08 19.2
3 7 (M) Oct 2000 < 1 0.7 < 1 NA 140 7.4 18.9
Jan 2001 343 12.24 28
4 9 (M) Oct 2000 4.1 0.5 2.1 532 90 7.7 11.7
Jan 2001 89 11.12 8
5 12 (M) Oct 2000 1.2 1.4 1.7 97 280 12.4 22.6
Jan 2001 167 9.8 17
6 34 (M) Oct 2000 < 1 0.85 < 1 NA 100 18.5 5.4
Nov 2000 1.2 1.1 1.3
7 37 (F) Oct 2000 1.3 0.65 0.8 92 130 14.1 9.2
Nov 2000 1.1 1.025 1.1
Abbreviations: F, female; M, male; NA, cannot be calculated. Oct and Nov 2000 samples are 24-hr collections; Jan 2001 sample is a random sample. Conversion factor: 1,000 ng = 1 µg.
β2-M excretion rate = urinary β-2-M:creatinine ratio.
a
Uranium reference level < 1.0 µg/24 hours unexposed population.
b
β2-M reference level ≤120 µg/L (adults 21–57 years of age).
c
β2-M excretion rate reference level in children: < 40 µg
β2-M/g creatinine.
Table 3. Urine analysis and electrolyte measurements of the five children (1–5).
Characteristic 1 2 3 4 5
Age [years (sex)] 3 (F) 5 (M) 7 (M) 9 (M) 12 (M)
Test date Jan 2001 Jan 2001 Jan 2001 Jan 2001 Jan 2001
Serum [HCO3–] (mmol) 21.9 23.0 24.4 28.1 27.7
TRP (%)
a
92 92 95 92 91
pH 6 7 6 7 6.5
Specific gravity 1.015 1.025 1.020 1.025 1.020
Glucose dip Negative Negative Negative Negative Negative
Protein dip Negative Negative Negative Negative Negative
a
TRP (%) = tubular reabsorption of phosphate = [1 – (
Up
×
SCr
)/(
Sp
×
UCr
)] ×100, where
Up
,
SCr
,
Sp
, and
UCr
are urine phos-
phate, serum creatinine, serum phosphate, and urine creatinine concentrations, respectively. Normal values are > 85%.
Table 4. Uranium and β2-microglobulin analytic methods.
Analysis Method
Uranium in water (RSA Laboratories, CT) Ion exchange separation with alpha-spectrometry detection
(APHA 1992)
Uranium and radium in water (Connecticut Gas proportional analysis; EPA Method 908-0 (U.S. EPA 1980)
State Department of Public Health Laboratory)
Uranium in urine (quest diagnostics sent out to Inductively coupled plasma/mass spectrometry
Medtox Laboratories, St. Paul, MN)
β2-microglobulin in urine (quest diagnostics, Fixed rate time nephelometry
Medtox Laboratories, St. Paul, MN)
Creatinine in urine (quest diagnostics, Spectrophotometry
Medtox Laboratories, St. Paul, MN)

Magdo et al.
1240
VOLUME 115 |NUMBER 8 |August 2007
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Environmental Health Perspectives
Canada 2005). Given the unpredictability of
uranium concentrations in at-risk areas, test-
ing of well water for the presence of uranium
at the time of drilling a new well or the sale or
transfer of a property with an existing well is a
reasonable measure (ATSDR 1999).
Uranium can enter the body via inhala-
tion as well as through consumption of conta-
minated food or water (Mao et al. 1995).
Dermal absorption is seen principally in the
instance of military veterans who have been
exposed to munitions containing depleted
uranium and suffered puncture wounds
(Bleise et al. 2003). Ingested uranium is
absorbed from the digestive tract and appears
initially in the blood, bound to red blood
cells. Most is excreted via urine and feces, and
experimental studies in humans have shown
that about two-thirds of an injected dose of
uranium is excreted within the first 24 hr and
75% within 5 days (Taylor and Taylor 1997).
Retained uranium accumulates initially in the
kidneys and liver and then in the skeleton (Li
et al. 2005). Approximately 50–60% of
stored uranium in the human body is found
in the skeleton (Fisenne and Welford 1986).
The biological half-life of uranium in the
skeleton is approximately 300 days. The
amount of uranium present in skeletal tissue
is proportional to cumulative absorption
(Hursh and Spoor 1973).
Uranium has the potential to be both
chemically and radiologically toxic, but of
principal concern in the context of ground-
water exposure are the chemical toxic effects of
uranium on the kidneys. The most extensive
data on the human toxicity of uranium come
from studies conducted on workers occupa-
tionally exposed in the nuclear industries
(Thun et al. 1985); these studies demon-
strated increased excretion of beta-2-
microglobulin with increasing duration of
exposure to uranium. Investigations of Gulf
War veterans exposed to depleted uranium
did not find clinically significant abnormali-
ties in renal function, but did demonstrate
that mean concentrations of microalbumin
were significantly elevated in the group
exposed to high levels of uranium (Harley
et al. 1999; Squibb et al. 2005). There is also
evidence that uranium may cause toxic effects
in bone (Kurttio et al. 2005).
Within the kidneys, the proximal tubules
are the structures principally damaged by ura-
nium (Mao et al. 1995; Zamora et al. 1998).
There is no evidence for glomerular injury
(Kurttio et al. 2002). Evidence for dose-
related proximal tubular injury has been
observed after both ingestion and injection of
uranium in animal (Diamond et al. 1989;
Gilman et al. 1998) as well as in human
(Zamora et al. 1998) studies. The histopatho-
logic damage to the proximal tubules is mani-
fest as cytoplasmic vacuolation, interstitial
scarring, and destruction of the basal lamina
(Gilman et al. 1998).
The pathophysiologic consequences of the
proximal tubular injury associated with expo-
sure to uranium include decreased ability to
reabsorb water and small molecules, as is
evidenced by the presence of elevated levels of
the low-molecular-weight protein beta-2-
microglobulin in the urine (Kurttio et al.
2002; Mao et al. 1995; Zamora et al. 1998;).
Another marker for proximal tubule dam-
age—increased fractional excretion of calcium
and phosphate—has been observed to increase
in dose-related manner after chronic ingestion
of water containing uranium; this change has
been observed in the absence of any increase
in urinary beta-2-microglobulin to creatinine
ratio (Kurttio et al. 2002). There appears to be
no clear threshold for these pathophysiologic
changes, and they typically become evident
before any histopathologic evidence of injury
is manifest (Kurttio et al. 2002). The severity
of the tubular injury caused by uranium expo-
sure has been shown in rat experiments involv-
ing relatively high-dose exposures to range
from mild proximal tubular dysfunction to
tubular necrosis (Haley 1982).
Although specific studies on the nephro-
toxic effects of uranium in children have not
been conducted, it is reasonable to assume that
children would be at increased risk for adverse
effects from exposure compared with adults.
Children consume more water and food per
kilogram of body weight than do adults
(Figure 1) (Ershow and Cantor 1989; National
Research Council 1993). Thus children will
ingest proportionately greater quantities of any
contaminants that are present in the water or
food that they consume. For example, the
3-year-old girl in this case series who mani-
fested elevated urinary excretion of beta-2-
microglobulin was reported to derive a major
portion of her nutritional intake from infant
formula that was prepared by mixing pow-
dered formula with contaminated well water.
Terminal differentiation and maturation
of the kidneys and other organ systems occur
postnatally, and these developing organs are
especially vulnerable to the effects of toxic
chemical exposures (National Research
Council 1993). Recent studies suggest that
chronic uranium exposure is associated with
increases in blood pressure (Kurttio et al.
2006). The long-term significance of these
changes is unclear. However, children’s long
future life expectancy further places them at
increased risk of delayed adverse health effects
that may develop years or decades after expo-
sure in early life to uranium or other chemical
contaminants in drinking water.
Because of its radioactivity, concern has
arisen about the possible carcinogenicity of
uranium. However, the levels of uranium that
have been observed to induce nephrotoxicity
are much lower than those that increase risk
of cancer, and uranium intake from contami-
nated water has not been associated with
increased risk of human cancer (Auvinen
et al. 2002, 2005; Boice et al. 2003; Kim
et al. 2004; Kurttio et al. 2002). A recent
study that examined a cluster of childhood
leukemia cases in Fallon, Nevada, found that
the town had levels of uranium above or
greatly above the maximum contaminant
level. However, the children in Fallon with
leukemia did not have a higher exposure to
uranium than children without leukemia
(Seiler 2004).
Although levels of arsenic, radium, and
radon were elevated in the index family’s
water supply, none of these substances are
known to have nephrotoxic effects.
In summary, this case series demonstrates
the potential for significant residential expo-
sure to naturally occurring uranium in
groundwater. It underscores the hazards of
consuming groundwater from untested pri-
vate wells (U.S. EPA 2006). It confirms previ-
ous epidemiologic studies showing that
chronic, low-level exposure to uranium in
drinking water may result in mild injury to
the proximal renal tubule (Kurttio et al.
2002). It highlights the special sensitivity of
young children to environmental exposures
(National Research Council 1993). Public
health organizations should take the unique
exposures and the special vulnerability of chil-
dren into consideration when setting stan-
dards for uranium and other chemical
contaminants in drinking water.
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Uranium in well water
Environmental Health Perspectives
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