Environmental Health Perspectives Volume
103, Supplement 6, September 1995
[Citation
in PubMed]
Elevated Incidence of Childhood Leukemia in Woburn, Massachusetts: NIEHS
Superfund Basic Research Program Searches for Causes
John L. Durant, Jia Chen, Harold F. Hemond, and William G. Thilly
Center for Environmental Health Sciences, Massachusetts Institute of
Technology, Cambridge, Massachusetts
Abstract
Between 1966 and 1986, the childhood leukemia rate in Woburn, Massachusetts,
was 4-fold higher than the national average. A multidisciplinary research
team from MIT, which is being supported by the NIEHS Superfund Basic Research
Program, has explored the possible importance of a temporal correlation
between the period of elevated leukemia and a previously unrecognized mobilization
of toxic metals from a waste disposal site in north Woburn. Residents of
Woburn may have been exposed to arsenic (70 µg/l) and chromium (240
µg/l) at levels in excess of federal drinking water standards (50
µg/l for each metal) by consuming municipal groundwater contaminated
with these metals. Research is currently underway a) to elucidate
the mechanisms and the pathways by which these metals were transported from
the waste disposal site to the drinking water supply; b) to determine
the identity of the principal human cell mutagens in samples of aquifer
materials collected from the site of the municipal supply wells; and c)
to measure the extent of exposure and genetic change in residents who consumed
the contaminated well water. -- Environ Health Perspect 103(Suppl
5):00-00 (1995)
Key words: childhood leukemia, chromium(VI), hazardous waste,
Aberjona River, Woburn, MA
This paper was presented at the Symposium on Preventing
Child Exposures to Environmental Hazards: Research and Policy Issues held
18-19 March 1993 in Washington, DC.
This research was supported by NIEHS Superfund Basic Research
Program grant 1-P42-ESO4675 and the MIT Center for Environmental Health
Sciences grant 2-P30-ESO2109.
Address correspondence to Dr. John L. Durant, Center for
Environmental Health Sciences, Massachusetts Institute of Technology, 50
Ames Street, E18-666, Cambridge, MA 02139. Telephone (617) 253-6062. Fax
(617) 253-1626.
Introduction
To better understand the relationships between chemicals in the environment
and genetic diseases in humans, toxicologists, analytical chemists, and
environmental engineers at Massachusetts Institute of Technology (MIT) have
undertaken a study of the presence, movement, and historical use of organic
and inorganic toxins in the Aberjona River basin in eastern Massachusetts
(Figure 1). This watershed, which contains two U.S. Environmental Protection
Agency (U.S. EPA) Superfund sites and over 20 state-identified hazardous
waste sites, is home to the Woburn neighborhood, infamous for what the federal
Centers for Disease Control called "the most persistent leukemia cluster
in the United States" (1). From 1966 to 1986, 28 cases of childhood
leukemia were reported in Woburn, while only six cases were expected (Figure
2). MIT's multidisciplinary collaboration, which is being funded by the
National Institute of Environmental Health Sciences' Superfund Basic Research
Program, has considered the correlation between the timing of use of certain
municipal drinking water wells, the period of heightened leukemia incidence,
and a previously unrecognized major mobilization of toxic metals from waste
disposal sites upstream of the wells' water supply. Our goal now is to join
with members of the community to test this hypothesis by searching for evidence
of actual human exposure.
Figure 1. Aberjona watershed.
Figure 2. Incidence
of childhood leukemia cases in Woburn, Massachusetts, between 1960 and 1992.
The expected number of cases in Woburn (population approximately 36,000)
for persons 0 to 19 years of age was 0.3 per year (2).
Background
The upper reaches of the Aberjona watershed have long been home to a
variety of industries which have used and/or produced chemicals known to
cause mutations (mutagens), cancer (carcinogens), and birth defects (teratogens).
Machine degreasers, dry cleaners, and manufacturers have used chlorinated
and aromatic solvents; tanneries used chromium as a tanning agent; pesticide
manufacturers produced lead arsenate; and sulfuric acid production generated
large quantities of arsenic-laden wastes. We have detected high levels of
some of these substances in the sediments of streams and ponds on the watershed.
The distributions of arsenic and chromium in surface sediments are shown
in Figures 3 and 4, respectively. An example of the distribution of organic
chemicals in the basin is given for polycyclic aromatic hydrocarbons in
Table 1. Using human cell mutation assays, we have found that as much as
half the mutagenicity in organic extracts of pond sediments is due to benzo[a]pyrene
(3), a ubiquitous combustion product which has been known since the
earliest days of chemical carcinogenesis research to be a potent animal
carcinogen.
Figure 3. Distribution
of arsenic in surface sediments in the Aberjona watershed.
Figure 4. Distribution
of chromium in surface sediments in the Aberjona watershed.
To reconstruct the time of release of these organic and inorganic chemicals
on the watershed, we have dated and analyzed sediment cores from lakes and
ponds. In the Upper Mystic Lake--the body of water into which all surface
waters of the watershed drain--the deposition rates of benzo[a]pyrene
and other polycyclic aromatic hydrocarbons (PAH) were found to correlate
well with the rates of coal burning (Figure 5). Deposition rates dropped
off after the 1940s as coal was replaced by oil and natural gas for home
heating. In contrast, when cores were analyzed for toxic metals, a different
picture emerged. As seen in Figures 6 and 7, large quantities of arsenic
and chromium were deposited in sediments between about 1920 and 1930. The
source of these metals appears to be the Industri-Plex Superfund Site, which
lies at the headwaters of the Aberjona River (Figure 1) and contains hundreds
of metric tons of both arsenic and chromium (5,6). Over the years
tens of tons of these and other toxic elements have been transported by
the Aberjona River to the sediments of the Mystic Lakes (7). A second
metals mobilization episode, which occurred in the 1960s, appears to have
been caused by earth-moving activities aimed at reclaiming the Industri-Plex
site for commercial use. Figure 8 is a photograph of this area from 1921
showing one of the "lagoons" used to hold industrial wastewater.
Figure 5. Profiles
for selected PAH in a sediment core from Upper Mystic Lake (JM MacFarlane
and PM Gschwend, unpublished data). Coal consumption data for the United
States is from Hottle and Howard (4).
Figure 6. Profiles
for arsenic in Upper Mystic Lake from three sediment cores (7).
Figure 7. Profiles
for chromium in Upper Mystic Lake from two sediment cores. The insert shows
the estimated temporal variation of chromium in wastewater discharged by
tanneries operating on the watershed (7).
Exposure Pathways
Although a relationship between land redevelopment at the Industri-Plex
site, toxic metals deposition in sediments, and childhood leukemia was suggested
by these facts, there was no evidence linking the contaminated river water
to children living in Woburn. As it meanders through Woburn, the Aberjona
River cuts through tracts of commercial and industrial land and several
large wetland areas. Since these places typically were not used for recreational
activities, Woburn residents would have received little direct exposure
to the Aberjona River and its contaminated sediments. However, exposure
to Aberjona River water may have occurred after the mid-1960s when two municipal
drinking water wells, G and H, were drilled in a wetland area adjacent to
the river. The wells were brought on line to supplement water supplies during
summer months when water demand was highest. Although residents immediately
complained about the foul odor of the water and its brown color, the wells
were used until 1979 when chlorinated solvents, including chloroform, trichloroethene,
and tetrachloroethene, were detected in well-water samples at levels above
federally mandated limits. The area surrounding the wells was subsequently
found to be widely contaminated with solvents, pesticides, plasticizers,
and toxic metals. As a result, in 1980 the "Wells G and H Site"
was added to the National Priorities List of sites eligible for remediation
under Superfund. When high numbers of childhood leukemia cases were reported
in Woburn between the mid-1970s and early 1980s, the contaminated well water
was blamed and the immediate assumption of cause and effect resulted in
a series of lawsuits and a widely publicized trial.
Chemicals of Concern
Although organic solvents were identified as the most hazardous pollutants
in the water samples collected from wells G and H in 1979, the abundance
of toxic metals at waste disposal sites near the Aberjona River and findings
of high levels of metals in river water and sediments raised concerns that
toxic metals may also have been present in the well water. Interestingly,
wells G and H water samples collected in 1979 did not contain elevated concentrations
of toxic metals (9). However, in reviewing data from a pump test
performed in 1986 (10), it has become evident that the aquifer from
which wells G and H drew water and the river were hydraulically connected
and that during the operation of these wells--between 1964 and 1979--as
much as 60% of the water supplying the wells came from the Aberjona River
as induced inflow. This means that chemicals in river water could also have
infiltrated the aquifer and reached the wells The spatial relationship between
wells G and H, the Aberjona River, and the wetland is illustrated in Figure
9.
Figure 8. Discharge
of wastewater from the Merrimac Chemical Company (8).
Figure 9. Possible
pathways of recharge from the Aberjona River to the sand and gravel aquifer
and municipal wells G and H.
To learn more about the transport pathways linking the Aberjona River
to the wells, we have begun a hydraulic investigation of the wetland in
the vicinity of wells G and H. We are also studying sorptive properties
of peat material to determine the extent to which metals in recharging river
water may have been retarded by the peat and thereby removed from the passing
water. When our hydraulic and chemical transport studies are complete, we
expect to generate estimates of the amounts of toxic metals that would have
been present in well water while the wells were in use. To date our study
of peat cores has shown that huge quantities of toxic metals (g/kg amounts)
were deposited in the wetland. Using data collected by H Solo (unpublished)
we estimate that between the early 1960s and the 1970s on the order of hundreds
of µg/l of chromium and arsenic may have been mobilized in the river
water passing the wells G and H area.
An additional source of chemicals to wells G and H was the wetland material
itself. In hindsight it may have been organic material from the wetland,
which was carried by water flowing into the wells, that offended the local
residents when the wells were first used. To determine whether mutagenic
substances are present in the wetland, we are now testing extracts of peat
samples for mutagenicity in human cells. If the peat samples are mutagenic,
we will use mutagenicity assay-directed chemcial analysis methods to identify
the principal human cell mutagens.
Measurement of Human Exposure
What will toxicologists do with this information? The data in hand suggest
that public exposure occurred from drinking water possibly containing 70
µg/l of arsenic and 240 µg/l of chromium (the federal drinking
water quality standard for both arsenic and chromium is 50 µg/l).
Since ingested arsenic tends to accumulate in hair, analysis for arsenic
in hair growing during the period that wells G and H were being used (1964-1979)
should help determine whether exposure occurred. We are in the process of
obtaining such samples. If the hair analyses indicate that Woburn children
were exposed to high concentrations of arsenic and/or chromium, we will
use neutron activation analysis for the set of all metals (except lead)
that may have been incorporated in teeth and bones growing during the period
of confirmed arsenic solidus chromium exposure.
Although these measurements may tell us whether Woburn residents were
exposed to high concentrations of toxic metals, demonstration of exposure
is not demonstration of cause and effect. In terms of scientific proof,
the evidence linking metal exposure--if indeed we do find such evidence--to
leukemogenesis would be speculative. Furthermore, by simply analyzing hair
samples for the presence of a suite of metals, we would not learn which
metal(s), if any, actually caused the biological damage. To deal with this
central issue we will use the newly developed technology mutational spectrometry,
which allows elucidation of the location, frequency, and nature of mutations
in the genetic code. It has been demonstrated that if exposure to a chemical
or radiation mutates human cells, mutations are not caused in a random way.
On the contrary, a very reproducible and idiosyncratic set of mutations
is induced along any DNA sequence by any particular mutagen. Figure 10 shows
how the sets of the mutations produced by different mutagens, including
chromate, are distributed along a piece of the human X chromosome.
Figure 10. Mutagenicity
and toxicity induced in human lymphoblastoid B-cells (TK6) by 5-hr exposure
to K2Cr2O7. Each response represents the
mean of three independent cultures. Error bars represent 99% confidence
levels (10).
We have devised methods to measure mutations such as those that chromate
causes in human cell cultures and human tissue and blood samples. Based
on experiments involving very low dose rates in human cell mutation assays
and the data of Figure 11, we estimate that the concentration of chromate
(as K2Cr2O7) necessary to double the rate
of mutation in human cells would be about 1 µg/l. This means that
a 15-kg child ingesting one liter of water with a total chromium content
of 240 µg/l would have an internal concentration of 16 µg/l,
an amount which, if present as chromate, is considerably greater than that
needed to double the mutation rate. These numbers suggest that continuous
exposure over several years to chromium in the water supply could have made
chromium mutagenesis a dominant pathway of genetic change in exposed persons.
If this is true, we should still be able to find evidence of that exposure
in the form of chromium-induced mutations in blood cell samples taken today.
Figure 11. Kinds,
positions, and frequencies of 6TGr mutations induced by K2Cr2O7,
O2, H2O2, X-rays in the low melting domain
of exon 3 on the hgprt gene in human lymphoblastoid B-cells (TK6)
(10).
Summary
We are exploring the possibiliy that the elevated levels of childhood
leukemia observed in Woburn over the 21-year period between 1966 and 1986
may have been caused by exposure to toxic metals introduced into the city's
drinking water supply from contaminated groundwater. To test this hypothesis
we are developing new field measurement techniques to determine the pathways
by which these metals entered the city's groundwater aquifers, we are testing
aquifer materials to determine whether they contain human cell mutagens,
and we are collecting hair samples from Woburn residents to analyze the
extent of toxic metals exposure. If evidence of exposure is found, we will
use mutational sepctrometry to measure the patterns of mutations in the
DNA of exposed individuals. Mutational spectrometry has not been used in
human population studies before; therefore, we have made efforts to establish
a dialogue with the community about what we are trying to do and why, and
to address concerns raised by community members. We realize that the success
of our research depends on the support of Woburn residents, and thus it
is incumbent upon us to explain fully the nature of our experimental methods
and what the results can and cannot tell us. With community support, the
resolving power of mutational spectrometry, and the essential contributions
of the analytical chemists, environmental engineers, and other members of
our multidisciplinary initiative, we hope to find a cause for the elevated
incidence of childhood leukemia in Woburn. In doing so, we further hope
our effort will help bring the field of environmental health science to
the point where it can provide scientifically sound answers to many other
public health questions that we are presently unable to answer.
REFERENCES
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