Could alterations in disinfection practice intended to reduce THM4 ultimately increase the toxicity of disinfected water? For example, one laboratory study indicated that the cytotoxicity of a drinking water with elevated bromide and iodide was higher when chloraminated than when chlorinated. Disinfection Optimization and Toxicity Drivers. An initial response to this challenge is to target a more complex optimization of the disinfectant combinations to simultaneously control pathogens, the traditional regulated DBPs, and the emerging DBPs of interest e.
For example, combining ozone for primary disinfection with chloramines to maintain a residual in the distribution system can effectively inactivate pathogens and reduce formation of regulated THM4 and HAA5. However, the ozone exposure must be optimized because the benefits of increasing ozone exposure in terms of reducing pathogens and NDMA come at the expense of enhanced production of bromate, halonitromethanes, and haloacetaldehydes when followed by chlorination or chloramination. This optimization necessitates that we prioritize which DBPs to control, and re-emphasizes the need to identify toxicity drivers.
The DBP field has been blessed with strong collaborations between chemists and toxicologists. For example, over DBPs have been subjected to quantitative cytotoxicity and genotoxicity assays on a Chinese hamster ovary CHO cell platform. However, until recently the focus has remained on meeting specific regulatory targets.
EPA has been considering whether to promulgate nationwide regulatory limits on nitrosamines.
Strategies for Minimizing the Disinfection By-Products Trihalomethanes and Haloacetic Acids
Are these the proper DBP targets to minimize exposure to toxicity drivers? While DBP chemists frequently cite high toxic potency as a rationale for focusing on emerging DBP classes, the contribution of a DBP to toxicity is really a function of both their concentrations and toxic potency. By these calculations, a water featuring higher concentrations of some of the more toxic unregulated DBPs but lower concentrations of regulated DBPs may be considered to represent a higher risk, provided the sum of the toxicity-weighted concentrations of DBPs in the complex mixture is greater Figure 1.
When applied to conventional European drinking waters, 37 chlorinated or chloraminated high salinity groundwaters, 38 or chloraminated potable reuse effluents, 39 these calculations indicate that unregulated halogenated DBP classes, particularly haloacetonitriles, may be greater contributors to the DBP-associated toxicity of disinfected waters than the THM4, HAA5, and nitrosamines of current regulatory interest.
High Resolution Image. Identifying the toxicity drivers requires advances in analytical chemistry and toxicology. Frontiers in these areas are discussed below. The application of high performance liquid chromatography HPLC and high-resolution mass spectrometry technologies is revealing the important contribution of polar DBPs to the uncharacterized TOX, and is suggesting a dynamic transformation of the TOX pool over time scales relevant to drinking water distribution.
Its application has demonstrated that chlorination of NOM targets polyphenolic structures, generating products in the range of — Da containing 1—3 halogens with relatively high oxygen-to-carbon ratios and high double bond equivalents. The DBP elemental formulas occurred in series separated by mass units corresponding to CH 2 groups, and many were common across different waters. The application of LC-MS has demonstrated the release of hydroxybenzaldehydes, hydroxybenzoic acids, and phenols within 1 h of NOM chlorination.
However, while these transformations continue over a week, a significant portion occurs within a day. Although additional research is needed, these initial results suggest that the contribution of DBP classes to TOX is not static Figure 2. The transformation of lignins in leaves and other allochthonous sources to humic substances by microorganisms, photochemical reactions, and other processes in watersheds can occur over time scales of months.
Research has validated this approach with respect to anthropogenic contaminants in EfOM.
While the ultimate precursors for NDMA remain unclear, application of chloramine reaction chemistry to pharmaceutical structures containing dimethylamine functional groups has demonstrated that the antacid ranitidine 50 and the opioid methadone 51 form NDMA at high yield. The occurrence of N -nitrosodiethanolamine was predicted based on the widespread use of triethanolamine in personal care products.
Other research is characterizing some intermediates, which could constitute some of the polar constituents of the unidentified TOX. During chlorination of the antibacterial triclosan, the initial DBPs formed by chlorine addition to aromatic rings were converted to chlorophenols and eventually to chloroform. The biomolecules likely to constitute the bulk of AOM and EfOM protein, lipids, carbohydrates, and nucleic acids consist of a limited array of well-characterized monomers.
For example, there are 20 common amino acids, but research has demonstrated that they occur fold more frequently within polypeptides than as free amino acids in water supplies. This process has been applied to demonstrate the conversion of methionine to methionine sulfoxide, tyrosine to 3-chlorotyrosine and 3,5-dichlorotyrosine, and lysine to lysine nitrile during chlorination of model proteins and MS2 bacteriophage. The prediction of DBPs could be expanded to other biomolecules. For example, one would expect halohydrins to form during chlorination of unsaturated fatty acid precursors in source waters.
U.S. Food and Drug Administration
Frontiers in DBP Toxicology. Toxicological evidence is critical for regulatory decisions on DBPs. A scheme for prioritizing DBPs for in vivo testing is needed. Highlighting the need for in vivo testing, CHO cells lack certain metabolic features that may be important for the activation of DBPs to mutagens.
For example, the marine polychaete Platynereis dumerilii , which can survive the high salinity of water concentrates, has been applied to demonstrate the developmental toxicity of more than 20 halogenated aromatic DBPs. In vitro assays can also be useful to demonstrate toxic modes of action, including the identification of enzyme systems associated with DBP metabolism. Environmental Protection Agency, and the Food and Drug Administration, that has advanced high throughput in vitro toxicology assays to characterize modes of action.
With CRISPR-Cas9 gene-editing technology, 71, 72 engineered cell models may become available to facilitate screening for specific mechanisms of action. Understanding the mechanisms of action can help prioritize DBPs likely to be associated with specific end points e. Additionally, characterizing mechanisms of action can lead to the development of biomarkers of DBP exposure for use in epidemiology studies.
Although DBPs occur within complex mixtures, how individual DBPs interact with respect to the toxicity of the mixture has received little attention.
Disinfection Byproducts | American Water Works Association
The toxicities of DBPs determined in single compound assays generally are assumed to be additive when measured DBP concentrations are weighted by metrics of toxicity to prioritize DBPs. Indeed, researchers have applied bioassays to bulk waters to optimize disinfection schemes without identification of specific toxicity drivers, 33 but methodological improvements are needed.
Toxicological assays generally require concentration of water samples i. Current methods to surmount this challenge include spiking back specific volatile DBPs lost during concentration into the extracts, but this assumes that all volatile DBPs have been characterized. Challenges for Epidemiology. Particularly for the bladder cancer end point, the cancer would result from the accumulated lifetime exposure to DBPs. Most epidemiological studies have relied on THM4 measurements to quantify exposure because of the widespread availability of THM4 data resulting from their early discovery and their collection as part of regulatory compliance.
However, THM4 concentrations can vary seasonally and even diurnally. Furthermore, THM4 measurements are typically infrequent e. Unlike many other contaminants, DBP concentrations also exhibit significant spatial variability since they continue to form within the distribution system. It is important to reiterate that THM4 concentrations have been targeted to measure exposure to DBPs not because they have been demonstrated to be the primary drivers of cancer risk, but because THMs are carcinogens and their concentrations were assumed to correlate with those of other DBPs.
First, the emerging concept of the dynamic transformation of NOM over time scales relevant to drinking water distribution would suggest that the percentage contribution of THM4 to TOX is not static Figure 2. Consumers close to the drinking water facility may consume a different array of DBPs e. Second, the shift in disinfection practices from chlorination to combinations of alternative primary disinfectants and chloramination for secondary disinfection can reduce THM4 while promoting nitrosamines, iodinated DBPs and other DBP classes.
Using the primary toxicity drivers to measure exposure would presumably enhance the resolution of epidemiological studies, highlighting the value of the close collaboration between chemists and toxicologists needed to identify these forcing agents. Initial efforts weighting measured DBP concentrations by metrics of toxic potency obtained from in vitro assays have underscored the potential importance of certain unregulated, low molecular weight DBPs e.
Researchers have evaluated the pharmacokinetics of THMs 77 and demonstrated that exposure via inhalation and dermal contact may be more important than via ingestion. Research is needed regarding the pharmacokinetics of these other DBP classes. THMs are rapidly excreted by exhalation, but is the same true of haloacetonitriles?
shchikarefff.ru/modules/31-comment-acheter.php If haloacetonitriles are not readily excreted, is this because of efficient detoxification? Understanding of adsorption bioavailability , distribution, metabolism, and excretion of different classes of DBPs requires further research using advanced approaches. Even if the toxicity drivers are identified, their incorporation into retrospective cancer epidemiology studies would be challenging due to the lack of concentration measurements over the previous decades and the spatiotemporal variations in concentrations alluded to previously.
However, initiating relevant data collection of toxicologically important DBPs would contribute to epidemiological studies focusing on shorter-term end points, such as developmental toxicity, and would lay the groundwork for future cancer epidemiology studies. Another key factor is analytical cost, particularly given the number of measurements that might be needed to address spatiotemporal variability in concentrations. It is noteworthy that some of the putative toxicity drivers e. Commercially available THM4 analyzers capable of providing results with roughly half-hour frequencies could be modified to include such potential toxicity drivers.
Incorporating consideration of genotypes exhibiting a higher susceptibility to DBP-associated toxicity would also increase the statistical significance of the association of bladder cancer with DBP exposure. For example, an epidemiological study by Cantor et al. However, the adjusted odds ratio for these two THM4 concentration categories increased to 5. Laboratory research had demonstrated that these enzyme systems are involved in the transformation of brominated THMs, HAAs, dibromonitromethane, and potentially other halogenated DBPs, in some cases e.
While the correlation between THM4 concentrations and these genotypes may suggest that brominated THMs are drivers of the cancer risk, the data are insufficient to draw a conclusion regarding the importance of THMs for the cancer risk.
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Research is needed to determine whether these genotypes are involved with the activation of other DBPs, particularly those that correlate with THM4 concentrations in the predominantly chlorinated waters evaluated in that epidemiological study. Determining the DBP classes serving as the drivers of the cancer risk will become increasingly important as changes in disinfection practice alter the relative proportion of the DBP classes in disinfected drinking waters.
Another approach is to identify chemicals excreted in urine or exhaled breath that correlate with DBP exposure. For example, the exhaled concentrations of brominated THMs in swimmers were linked to DBP concentrations in a swimming pool, 79 whereas excretion of trichloroacetic acid and TOX have been measured in urine. Could such byproducts or adducts be used as biomarkers to measure exposure in shorter-term epidemiological studies relevant to bladder cancer?
In light of the trend toward combinations of disinfectants, toxicity-relevant biomarkers reflecting recent exposure to DBPs could foreshadow the results of future epidemiological studies evaluating these changes in disinfectant practice. Translating Research into Practice.
Utilities have attempted to optimize the combination of disinfectants to simultaneously meet pathogen reduction goals and regulatory limits on DBPs. The identification of toxicity drivers will demand close collaboration between chemists, toxicologists, and epidemiologists, but is critical to ensure that efforts toward disinfection optimization do not inadvertently increase exposure to toxicity drivers.