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Volume 19, No.3 - 2000Position Paper
Safe Drinking Water: A Public Health Challenge
Donald T Wigle
Abstract
Disinfection of drinking water through processes including filtration
and chlorination was one of the major achievements of public health,
beginning in the late 1800s and the early 1900s. Chloroform and other
chlorination disinfection by-products (CBPs) in drinking water were
first reported in 1974. Chloroform and several other CBPs are known to
cause cancer in experimental animals, and there is growing epidemiologic
evidence of a causal role for CBPs in human cancer, particularly for
bladder cancer. It has been estimated that 14-16% of bladder cancers in
Ontario may be attributable to drinking water containing relatively high
levels of CBPs; the US Environmental Protection Agency has estimated the
attributable risk to be 2-17%. These estimates are based on the
assumption that the associations observed between bladder cancer and CBP
exposure reflect a cause-effect relation. An expert working group (see
Workshop Report in this issue) concluded that it was possible (60% of
the group) to probable (40% of the group) that CBPs pose a significant
cancer risk, particularly of bladder cancer. The group concluded that
the risk of bladder and possibly other types of cancer is a moderately
important public health problem. There is an urgent need to resolve this
and to consider actions based on the body of evidence which, at a
minimum, suggests that lowering of CBP levels would prevent a
significant fraction of bladder cancers. In fact, given the widespread
and prolonged exposure to CBPs and the epidemiologic evidence of
associations with several cancer sites, future research may establish
CBPs as the most important environmental carcinogens in terms of the
number of attributable cancers per year.
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Disinfection of Drinking Water: Historical Perspective
In the 19th century, major outbreaks of waterborne diseases were common
in Canada, the United States and other developed nations. Beginning in
the early years of the 20th century, the provision of chlorinated
drinking water virtually eliminated typhoid fever, cholera and other
waterborne diseases, representing one of the great achievements of
public health.
Chlorine was discovered in 1774 by the Swedish chemist Karl Wilhelm
Scheele and confirmed to be an element in 1810 by Sir Humphry Davy.1 Use
of chlorine as a disinfectant was first introduced by Semmelweis on the
maternity ward of the Vienna General Hospital in 1846 to clean the hands
of medical staff and prevent puerperal fever. In 1881 Koch showed that
pure cultures of bacteria were destroyed by hypochlorites.1
The first continuous usage of chlorination in the US began in 1908 for
the water supply to Jersey City, New Jersey, and at a site that served
the Chicago Stockyards to control sickness in livestock caused by
sewage-contaminated water.1 In Canada, the earliest use of chlorination
found by this author was in Peterborough, Ontario, in 1916.2
Chlorination has been the main method of disinfecting drinking water in
Canada, the United States and many other countries for several decades
and has proven effective against most waterborne pathogens.
Health Effects of Chlorination Disinfection By-products
Chlorine's potent oxidizing power causes it to react with naturally
occurring organic material in raw water to produce hundreds of
chlorinated organic compounds, referred to generically as chlorination
disinfection by-products (CBPs). One of the most commonly occurring
groups of CBPs, the trihalomethanes (THMs), was first identified at
higher concentrations in chlorinated drinking water than in natural raw
water by Rook3 and by Bellar et al.4
Raw drinking water supplies were found to have low background levels of
mutagenic activity with relatively large increases in mutagenicity after
chlorination.5 The mutagenic activity of chlorinated water is caused
mainly by reactions of chlorine with natural humic substances released
by the breakdown of vegetation in the source waters.6 Recently, the
chlorinated hydroxyfuranones (e.g. MX) have been shown to be responsible
for a major part of the mutagenic activity. Other CBPs, including
brominated THMs and haloacetic acids, are also mutagenic. The
concentration of THMs correlates strongly with the amount of organic
precursors in raw water and, although imperfect, it can be a useful
indicator of the level of total CBPs in treated water.
Although numerous CBPs have been identified in chlorinated drinking
water, very few have been subjected to carcinogenicity bioassays.
Chloroform induced significant increases in kidney tumours in male rats
when administered in high concentrations in drinking water.7 Chloroform
also produced kidney tumours in male rats and liver tumours in male and
female mice when administered by gavage in corn oil.8 Unlike the
brominated THMs, chloroform appears not to be carcinogenic through a
direct DNA reactive mechanism, acting instead through regenerative cell
proliferation, possibly with an exposure threshold.9 In studies of the
three other THMs, bromoform administered by corn oil gavage induced
intestinal tumours in male and female rats; chlorodibromomethane by corn
oil gavage produced liver tumours in both sexes of mice; and
bromodichloromethane by corn oil gavage induced intestinal and kidney
tumours in male and female rats, kidney tumours in male mice and liver
tumours in female mice.10-12
After the THMs, the most commonly occurring group of CBPs in drinking
water is the haloacetic acids (HAAs). Comparing published results from
the two most studied HAAs, dichloroacetate in drinking water induced
hepatic tumours in both rats and mice, but trichloroacetate induced
hepatic tumours only in mice.13-17 Both compounds appear to act as
tumour promoters, but likely via different mechanisms: trichloroacetate
has been shown to be a peroxisome proliferator, whereas dichloroacetate
affects cell cycle kinetics.18 While none of the brominated HAAs have
been tested in carcinogenicity bioassays, preliminary screening tests
have indicated a potential for the induction of liver tumours by
bromochloroacetate, dibromoacetate and bromodichloroacetate; lung
tumours by bromodichloroacetate; and colonic tumours by
dibromoacetate.18,19
MX (3-chloro-4-(dichloromethyl)-5- hydroxy-2(5H)-furanone) is a CBP and
is one of the most potent known mutagens as determined by the Ames
assay.20 MX is reported to occur at much lower concentrations than the
THMs or HAAs, yet it appears to account for about one third of the
mutagenicity of chlorinated drinking water.21 DeMarini et al.22 found
that MX produced 50-70% hotspot 2-base deletions and 30-50% complex
frameshifts; no other compound or mixture is known to induce such high
frequencies of complex frameshifts. MX caused several types of cancer or
benign tumours in rats, including thyroid, liver, adrenal gland, lung,
pancreas, breast, lymphomas and leukemias.23
As noted in the following report, results of the epidemiologic studies
of cancer have been most consistent in showing an association between
exposure to THMs and bladder cancer. Conflicting results have been
observed with respect to cancers of the colon and rectum. In 1996, King
and Marrett24 reported the results of a large population-based
case-control study of bladder cancer conducted in Ontario. Persons
exposed to chlorinated surface water for 35 or more years had an
increased risk of bladder cancer compared with those exposed for less
than 10 years (odds ratio = 1.41, confidence interval [CI] =
1.10-1.81)). Persons exposed to THM levels of at least 50 µg/L for 35 or
more years had 1.63 times the risk of those exposed for less than 10
years (CI = 1.08-2.46). The authors concluded that the risk of bladder
cancer increases with both duration and concentration of exposure to
chlorination by-products, with population-attributable risks of about
14-16% for Ontario. Approximately 1150 persons in Ontario will be
diagnosed with bladder cancer in 1998.25 If CBPs do cause bladder
cancer, then roughly 160-185 cases of bladder cancer per year in Ontario
are attributable to such exposure.
There have been about 20 case-control and cohort epidemiologic studies
of CBPs and cancer risk since 1978. The US Environmental Protection
Agency (EPA) reviewed these studies26 and identified 5 case-control
studies (including the King and Marrett study) that met the criteria of
being population-based, well designed and having adequate exposure
assessment. The EPA concluded that, based on the entire cancer
epidemiology database, bladder cancer studies provide better evidence
than other types of cancer for an association between exposure to
chlorinated surface water and cancer.
The EPA recognized that a causal relationship between chlorinated
surface water and bladder cancer has not yet been demonstrated
conclusively by epidemiologic studies, but concluded that the assumption
of a potential causal relationship is supported by the weight of
evidence from toxicology and epidemiology. Based on this assumption, the
EPA estimated that the attributable risk of bladder cancer due to
exposure to chlorinated water in the US is in the range of 2-17%; the
annual number of bladder cancer cases attributable to such exposure was
estimated to be in the 1100-9300 range. The EPA also stated that it
believes that the overall evidence from available epidemiologic and
toxicologic studies on chlorinated surface water continues to support a
hazard concern and a prudent public health protective approach for
regulation.26
The expert working group convened by the Laboratory Centre for Disease
Control (see Workshop Report in this issue) observed that the few
available epidemiologic studies of CBP exposure and pregnancy outcome
indicated associations between exposure to THMs and spontaneous
abortion, growth retardation and birth defects. However, these studies
were weak in exposure assessment and control of potential confounders.
When tested in rats, rabbits and mice, chloroform was not teratogenic,
but both bromodichloromethane and chlorodibromomethane have shown
evidence of fetotoxicity. Other CBPs have produced adverse effects on
the testes and on sperm production in male rats and congenital heart
defects in rats exposed in utero.
Recently, a prospective study27 that included concurrent trihalomethane
sampling data showed that women who drank at least five glasses per day
of cold tap water containing at least 75 µg/L total THMs had an adjusted
odds ratio of 1.8 for spontaneous abortion (CI = 1.1-3.0). Of the four
individual THMs, only high bromodichloromethane exposure (consumption of
at least five glasses per day of cold tap water containing at least 18
µg/L of bromodichloromethane) was associated with spontaneous abortion,
both alone (adjusted OR = 2.0, CI = 1.2-3.5) and after adjustment for
the other trihalomethanes (adjusted OR = 3.0, CI = 1.4-6.6).
The expert group concluded that it was possible (60% of the group) to
probable (40% of the group) that CBPs pose a significant cancer risk,
particularly of bladder cancer. The group concluded that the risk of
bladder and possibly other types of cancer is a moderately important
public health problem. They also determined that there was insufficient
evidence to establish a causal relationship between CBPs and adverse
reproductive outcomes in humans, but that confirmation of the available
limited data could establish CBPs as an important health problem.
Finally, the group concluded that there were not enough data available
to conduct a quantitative risk/benefit/cost evaluation and recommended
that developing health risk data be monitored to determine when such an
evaluation would be possible.
To the extent that epidemiologic studies randomly misclassify individual
exposures to CBPs, the resulting risk estimates may be lower than the
true risks. It is likely that many of the epidemiologic studies
published to date have misclassified individual exposures to chlorinated
water or CBPs. To lessen the impacts of this type of misclassification,
Lynch et al.28 recommended that future epidemiologic studies of this
type should quantify exposures more extensively.
Next Steps
In most areas of Canada, the provinces, territories and local
governments are responsible for providing safe drinking water. The
Federal-Provincial Subcommittee on Drinking Water (DWS) of the Committee
on Environmental and Occupational Health establishes and publishes
Guidelines for Canadian Drinking Water Quality.29 Health Canada acts as
the secretariat for DWS and provides health and safety advice with
regard to drinking water health risks in Canada. In 1993, DWS lowered
the Canadian drinking water guideline for THMs from a maximum level at
any one time of 350 ug/L to a maximum annual average, based on at least
quarterly measurements, of 100 ug/L and recommended that THM levels be
reduced as much as possible whenever treatment plants are expanded or
upgraded. The THM guideline was based on a combination of risk
assessment and risk management considerations, as is the case for all
drinking water guidelines.
The Guidelines for Canadian Drinking Water Quality have no legal weight
per se; however, they are used by the provinces and territories to
establish their own drinking water regulations. In the US, the EPA
promulgates drinking water standards that are legally binding on water
supplies throughout the US that serve more than 10,000 persons.
The supporting document for the THM drinking water guideline states that
the preferred method for controlling disinfection by-products is
precursor removal, i.e. use of methods such as flocculation and
filtration to remove organic material prior to disinfection. For surface
waters in particular, use of filtration and postchlorination greatly
reduces CBP levels.
Other options for reducing CBPs include ozone, chloramine and charcoal
filters. Ozone has been used for water treatment in Europe for over 90
years, particularly in France and Switzerland.1 If a sufficient dose of
ozone is applied, its use does not lead to the creation of mutagenic
compounds in drinking water and can even eliminate the initial
mutagenicity of the water.30 Combined treatment of ozone and activated
carbon also decreases the chlorine consumption of treated water and
reduces the formation of CBPs. DeMarini et al.22 compared water treated
by different methods: chlorination, chloramination or ozonation alone
and ozonation followed by chlorination or chloramination. Ozone alone
produced the lowest levels of mutagenic activity in treated water, and
chlorine alone, the highest levels. However, ozonation disinfection
by-products include bromate, a genotoxic carcinogen. Also, the
effectiveness of ozonation in reducing microbial and CBP risks varies
with the characteristics of raw water (e.g. pH, temperature, particulate
matter, bromide concentration) and ozonation alone does not give
residual disinfective capacity in distribution systems.
Chlorine is still the most widely used disinfectant in Canada and the
United States because of its low cost, ability to form a residual and
effectiveness at low concentrations. The continued occurrence of
waterborne disease outbreaks demonstrates that contamination of drinking
water with pathogenic bacteria, viruses and parasites still poses a
serious health risk. A single outbreak of Cryptosporidium in Milwaukee,
Wisconsin, in 1993 resulted from a breakdown in filtration and led to an
estimated 400,000 cases of acute gastroenteritis and 100 deaths.31
Microbiologically contaminated drinking water is a special risk to
children, the elderly and persons with compromised immune systems.
In November 1998, the EPA will promulgate a disinfectants/disinfection
by-products rule originally proposed in 1994. The rule will reduce the
maximum contaminant level (MCL) for total THMs from 100 to 80 µg/L and
establish new MCLs for other by-products such as HAAs, bromate and
chlorite. The new rule will also establish enhanced coagulation
requirements for precursor removal, which should help to reduce both the
number of microbes and the level of CBP precursors. The EPA is also
establishing an extensive national information collection effort on
contaminant occurrence, CBP levels and microbiological contaminants.32
The EPA has requested $1.9 billion to help state, tribal and local
jurisdictions construct the facilities required to comply with federal
requirements. Infrastructure plans include installation of sensors for
real-time monitoring of important distribution system quality indicators
such as disinfectant residual, water pressure, flow direction, microbial
densities and total organic halides.
A 1994 national survey33 showed that 19.5% of households in Canada
reported using a filter or purifier for their drinking water compared
with 13.9% in 1991, while 21.9% of households purchased bottled drinking
water in the month before survey compared with 16.1% of households in
1991. Similarly, in a 1997 survey, one third of US consumers used a home
water treatment device other than bottled water, an increase from 27% in
1995.34 The use of devices such as pour-through water pitchers with
carbon filters grew more than any other type of water treatment device.
These data are consistent with increasing public concern about the
safety and quality of drinking water.
There is an urgent need for co-ordinated epidemiologic and toxicologic
research to seek definitive evidence on the nature of the association
between exposure to CBPs in drinking water and outcomes such as cancer,
spontaneous abortion and related adverse reproductive outcome
conditions. Future epidemiologic studies should focus on associations
between diseases and high potency CBPs identified in animal bioassays,
for example, brominated THMs and HAAs. The effects of CBPs and CBP
metabolites could be examined in vitro with human bladder epithelial
cells.
Biomarkers of susceptibility, exposure and outcome would strengthen
epidemiologic studies of CBP exposures and disease risks. Biomarkers
such as DNA adducts or specific types of mutations may eventually
support the attribution of individual cancer cases to exposure to
specific CBPs, leading to more accurate risk estimates and targeted,
effective control measures. For example, MX reacts with DNA in vitro to
form a unique adduct;35 although the biologic significance of such
adducts is unknown, they may prove to play an important role as
biomarkers of specific exposures.
Despite the undisputed benefits of chlorination in controlling
waterborne infectious diseases, the epidemiologic evidence now available
clearly suggests that CBPs pose a cancer risk to humans, particularly a
risk of bladder cancer. Given the wide and prolonged exposure of
Canadians to this risk, public health authorities must decide if the
available evidence warrants actions to at least reduce public exposure
to CBPs while safer alternatives are sought. In his report of the
Commission of Inquiry on the Blood System in Canada,36 Justice Krever
emphasized the importance of a valuable tenet in the philosophy of
public health, namely, "action to reduce risk should not await
scientific certainty."
In the process of public health risk assessment and risk management,
scientific experts must be satisfied that the "weight of evidence"
exceeds a certain threshold before they can reach consensus and
recommend action. With this end in mind, Health Canada set up the
Chlorination Disinfection By-product Task Group in July 1998. The new
group has multi-stakeholder representation in order to plan and oversee
a co-ordinated effort involving epidemiologic, toxicologic, water
treatment and other types of expertise to estimate the risks from CBPs
and to develop risk management recommendations.
References
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34. Survey shows Americans are concerned about household water quality,
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35. Munter T, Le Curieux F, Sjoholm R, Kronberg L. Reaction of the
potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-
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--------------------------------------------------------------------------------
Author Reference
Donald T Wigle, Bureau of Operations, Planning and Policy, Laboratory
Centre for Disease Control, Health Canada, Tunney's Pasture, AL: 0602E2,
Ottawa, Ontario K1A 0L2; Fax: (613) 941-5497; E-mail: Don_T_Wigle@phac-aspc.gc.ca |
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