Mutation Research/Reviews in Mutation Research
ReviewOccurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research
Introduction
Water disinfection is one of the most important public health advances of the last century; its introduction in the U.S. reduced cholera incidence by 90%, typhoid by 80%, and amoebic dysentery by 50% [1]. Millions of people worldwide receive quality drinking water every day from their public water systems. However, chemical disinfection has also raised a public health issue: the potential for cancer and reproductive/developmental effects associated with chemical disinfection by-products (DBPs).
Chemical disinfectants are effective for killing harmful microorganisms in drinking water, but they are also powerful oxidants, oxidizing the organic matter, anthropogenic contaminants, and bromide/iodide naturally present in most source waters (rivers, lakes, and many groundwaters). Chlorine, ozone, chlorine dioxide, and chloramines are the most common disinfectants in use today; each produces its own suite of DBPs in drinking water, with overlapping constituents [2]. Most developed nations have published regulations or guidelines to control DBPs and minimize consumers’ exposure to potentially hazardous chemicals while maintaining adequate disinfection and control of targeted pathogens.
Scientists first became aware of DBPs only in the early 1970s. In 1974, Rook and others reported the identification of the first DBPs in chlorinated drinking water: chloroform and other trihalomethanes (THMs) [3], [4]. In 1976, the U.S. Environmental Protection Agency (U.S. EPA) published the results of a national survey that showed that chloroform and the other THMs were ubiquitous in chlorinated drinking water [5]. In the same year, the National Cancer Institute published results showing that chloroform was carcinogenic in laboratory animals [6]. In addition, the first reports appeared in the late 1970s showing that organic extracts of drinking water were mutagenic in the Salmonella mutagenicity assay [7]. As a result of these observations, an important public health issue was recognized.
In the 30 years since the THMs were identified as DBPs in drinking water, significant research efforts have been directed toward increasing our understanding of DBP formation, occurrence, and health effects [2], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. Although more than 600 DBPs have been reported in the literature [2], [18], only a small number has been assessed either in quantitative occurrence or health-effects studies.
The DBPs that have been quantified in drinking water are generally present at sub-μg/L (ppb) or low- to mid-μg/L levels. However, more than 50% of the total organic halide (TOX) formed during the chlorination of drinking water [19] and more than 50% of the assimilable organic carbon (AOC) formed during ozonation of drinking water has not been accounted for as identified DBPs [20]; furthermore, nothing is known about the potential toxicity of many of the DBPs present in drinking water.
Here we review 30 years of results of occurrence, genotoxicity, and carcinogenicity studies of DBPs regulated by the U.S. Government and those that are not named specifically in regulations. The compounds in these two categories, and a qualitative assessment of the results, are shown in Table 1. Although most of the research has been performed on the regulated DBPs, there is a growing literature on the unregulated DBPs. The results of our analyses in this paper offer an opportunity to assess the value and completeness of the current literature on the regulated DBPs and to consider how the emerging literature on the unregulated DBPs might inform future research needs and assessments of drinking water.
To provide a historical context for this work, we begin with an overview of U.S. DBP regulations, followed by a brief summary of the epidemiology of drinking water and cancer. We have not reviewed the literature on reproductive/developmental effects associated with DBPs or drinking water. We then review the occurrence, genotoxicity, and carcinogenicity literature for the regulated and then the unregulated DBPs, ending with our conclusions regarding research needs.
Section snippets
Overview of DBP regulations in the United States
Based on the discoveries of DBPs described in the Introduction, the U.S. EPA issued a regulation in 1979 to control total THMs at an annual average of 100 μg/L (ppb) in drinking water; THMs here are defined as chloroform, bromodichloromethane, dibromochloromethane, and bromoform [21]. In 1998, the U.S. EPA issued the Stage 1 Disinfectants (D)/DBP Rule, which lowered permissible levels of total THMs to 80 μg/L and regulated for the first time five haloacetic acids (HAAs) (60 μg/L), bromate (10
Summary of epidemiology studies of cancer and drinking water
Some epidemiologic studies have shown that a life-time exposure to chlorinated water is associated with an increased risk for cancer, especially of the urinary bladder and colorectum [17], [30]. Besides DBPs, drinking water may contain other potential carcinogens, such as arsenic and radionuclides; however, the bladder cancer risk has generally been associated with THM levels [31], [32]. One study showed that both bladder and kidney cancer risks were associated with the mutagenicity of the
Occurrence
The halomethanes make up one class of the approximately 600 drinking-water DBPs that have been identified. Within the halomethane class are the THMs (chloroform, bromoform, bromodichloromethane, and chlorodibromomethane), which are currently regulated by the U.S. EPA at a level of 80 μg/L for total trihalomethanes [24]. The THMs were the first DBPs identified [3], [4]. Together, the THMs and HAAs are the two most prevalent classes of DBPs formed in chlorinated drinking water, accounting for
Summary of the occurrence of the regulated DBPs
In chlorinated drinking water, the THMs and HAAs are generally present at the highest levels of the DBPs measured (mid-ppb levels), with chloroform generally being the dominant THM (mean of 23 μg/L in the ICR, with some samples above 100 μg/L) and dichloroacetic acid and trichloroacetic acid being the dominant HAAs (mean of 11 and 10 μg/L in the ICR, respectively). The sum of the four regulated THMs (THM4) are generally present at levels higher than the sum of the five regulated HAAs (HAA5);
Emerging unregulated DBPs
Although more than 600 DBPs have been reported in the literature, only 11 are currently regulated in the United States. Some of the unregulated chemicals are similar to those that are regulated, such as the haloacetic acids, whereas others are unique. Most of these unregulated DBPs have been found in chlorinated drinking water, but many of them are also formed by alternative disinfectants, such as chlorate from chlorine dioxide treatment or formaldehyde from ozonation. For the most part, there
Summary of the occurrence of the emerging unregulated DBPs
The unregulated DBPs that occur at the highest levels include chlorate (in chlorine dioxide-treated waters); the four remaining HAAs (bromochloro-, bromodichloro-, dibromochloro-, and tribromoacetic acid); trichloronitromethane (chloropicrin); and trichloroacetaldehyde (chloral hydrate). Chlorate is generally present at high ppb levels (and sometimes ppm levels), and the others are generally present at low ppb levels. It is no surprise that these DBPs are commonly measured, along with the
DBPs formed from anthropogenic contaminants
All of the DBP studies discussed above involve primarily the DBPs formed from natural organic matter found in drinking-water source waters. However, source waters are also impacted by municipal and industrial emissions [231], [232], and recent investigations have shown that some of these water contaminants can also react with disinfectants used in drinking-water treatment to form their own by-products. Chlorination in swimming pools has also been shown to transform active compounds used in
Mutagenicity of organic extracts or concentrates of drinking water
As discussed above, alternatives to chlorination, such as ozonation and chloramination, have generally accomplished the intended reduction in the levels of regulated THMs and HAAs compared to the levels produced by chlorination. However, these alternative methods have also produced higher levels of other DBPs and even new classes of DBPs, some of which appear to be more toxic or genotoxic than those currently regulated. Despite the presence of these newly identified DBPs in water prepared by
Carcinogenicity of raw waters or organic extracts of drinking water or mixtures of DBPs
Unlike for mutagenicity, only a few carcinogenicity studies of drinking water or concentrates/extracts of drinking water have been performed, and all were negative. All exposures were done as drinking water. However, inhalation and dermal exposure to DBPs must also be considered major exposure routes because showering or bathing typically entails larger volumes of water than drinking. It must also be noted that higher concentrations of some volatile DBPs are found in the blood or breath after
Risk assessment of DBPs
It has been 30 years since research on DBPs began in earnest, and not surprisingly, there are as many scientific questions as there are accepted answers. Some of these questions are on the types of data and evaluations needed to demonstrate that DBPs are controlled to an acceptable level while maintaining the needed degree of protection against microbial disease that water disinfection provides. The U.S. EPA and other groups have used the tools of risk assessment in their analysis of potential
Categories of DBPs to prioritize testing and aid in decision-making
Our analysis identifies three categories of DBPs for priority testing and decision-making based on the combination of occurrence, genotoxicity, and carcinogenicity data reviewed here. These categories contain those DBPs that (1) have some or all of the toxicologic characteristic of human carcinogens, (2) occur at moderate concentrations and are genotoxic, and (3) occur at moderate concentrations but for which little or no toxicology data are available. The DBPs in these categories are described
Acknowledgments
We would like to thank Dr. Said Hilal of the U.S. EPA's National Exposure Research Laboratory for the Henry's Law and hydration calculations on formaldehyde and acetaldehyde and for helpful discussions. We also thank two anonymous reviewers and our colleagues, Rex Pegram, Don Delker, Larry Claxton, and Anthony DeAngelo, for the helpful comments on this paper. We appreciate the support by the Center of Advanced Materials for the Purification of Water with Systems, a National Science Foundation
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