Water Disinfection By-Products: Trihalomethanes and Carcinogenicity – Should DCs Care?

David P. Gilkey, DC, DABCO, DACBOH, FICC and Holly A. Williams, DC, DABCO

"The presence of trihalomethanes in drinking water has been the subject of increasing public concern since the 1970s."1 Specific concerns over the potential adverse effects related to cancer and developmental abnormalities have been the point of public and scientific debate.2 As a consequence of public concern, the Environmental Protection Agency (EPA) is taking action. The EPA has prepared an 85-page summary of proposed drinking water regulations related to disinfectants and disinfection byproducts (DBPs) containing 122 references and available off the Internet.2 The following is a brief overview of the topic of DBPs and trihalomethanes, using selected examples. In doing so, a basic review of the facts is presented regarding their sources, routes of exposure, toxicology and epidemiological relationship to carcinogenicity. The authors are intending to inform and educate treating doctors of chiropractic on yet another health issue that may adversely effect their patients, families and themselves. The next time you advise a patient to drink eight glasses or more of water a day, you might think of adding the words "filtered" first.

Sources

Chlorine is the principal disinfectant used to purify 98% of the drinking water in the modern world.3,7,8 Bromine may alternatively be used in water disinfection with or without chlorine.5 Disinfection of water against waterborne disease is achieved through chlorination. "Chlorination starts at the point where pH >5 and Cl concentration in the mg 1-1 range, complete and instantaneous disassociation is observed."9 Free chlorine is toxic

Basic water treatment methods include coagulation, sedimentation, filtration, chemical oxidation and disinfection.4 Critical to the formation of DBPs is the total organic compounds (TOCs) in the water; this varies depending on the location of chlorination in that process and treatment methods used. Chlorine or bromine is added to the water at potentially multiple points in the disinfection treatment process. Free chlorine or bromine may then interact with TOCs to produce a wide array of organo-compounds: trihalomethanes (THMs), halogenated acetic acids (HAAs), halogenated acetonitriles, haloketones, halophenols, aldehydes, chlorinated furones, and others (see table 1).4,5,10,11 As a consequence of water treatment methods, DBPs have been identified in variable concentrations in different communities.2

Table 1: Potential Disinfection Byproducts (DBPs).

Haloacetic Acids
Monochloroacetic acid
Trichloroacetic acid
Monobromoacetic acid
Dibromoacetic acid
Haloacetonitriles
Dichloroacetonitrile
Trichloroacetonitrile
Bromochloroacetonitrile
Dibromoacetonitrile

Exposure Routes

Humans are primarily exposed to DBPs, specifically THMs, through consumption of drinking water.2,12 Other routes of exposure include dermal and respiratory pathways from bathing and swimming pool use.13,14

Toxicokinetics

DBPs are rapidly absorbed and distributed by the blood compartment to many tissues.15,16 Mathews et al. (1990) found radioactively™tagged DBPs within 24 hours of their ingestion, in blood, plasma, adipose, intestine, kidney, liver, muscle, skin and stomach. The highest levels were found in the liver. Biotransformation varies with the chemical characteristic of the DBP. THMs, such as chloroform, follow two pathways: one, first-order kinetics withÔ metabolism in the liver by P450 enzyme oxidation, and to a lesser extent in the kidney and other tissues.13

Toxic metabolites may be formed by P450 enzyme reaction and then induce glutathione and other phase II enzymes to conjugate and detoxify hepatic and nephrotic cells, or result in additional activation and cell injury.17 THMs such as chloroform and bromodichloromethane (BDCM) are eliminated via respiration, urine and feces.13,16,17

Toxicodynamics

Toxic metabolites may be formed during biotransformation of a number of DBPs and induce cell injury. Pegram and colleagues17 reported that rodent and bacterium studies revealed evidence that chloroform and BDCM both induce cytotoxicity through glutathione (GSE) mediated pathways. In two-year rodent studies, cytochrome P450 enzyme induced reactive metabolites such as phosgene to be formed. Those same researchers also concluded, "Chloroform hepatotoxicity has been associated with covalent binding of reactive metabolites to tissue macromolecules."16,18

Snyder and Andrews18 discuss an indirect theory of carcinogenesis from recurrent injury to hepatic cells. The kidney was also identified as a target organ for phosgene generated from BDCM. Genotoxic metabolites derived from GSE-transferase interactions are believed to exert injury if generated intracellularly.17 Daniel and colleagues19 found increased organ weights in rats exposed to BDCM in their subchronic 90-day study. Overall reduced body weights were seen in treated rats; liver and kidney weights increased while brain weight decreased. Histopathologic evaluation revealed fatty changes, inflammation, and slight necrosis in hepatic cells and tubular necrosis in the kidneys. Dunnick & Melnick20 reported DBPs, chlorodibromomethane, BDCM, and bromoform induced base-pair substitution mutations in bacterium studies. Evidence from their chronic two-year study on rats revealed P450 mediated oxidation to toxic dihalocarbonyl intermediates causing cellular injury and regenerative hyperplasia. Itoh & Matsuoka21 found evidence that DBP compounds containing nitro and carbonyl groups could induce chromosomal aberrations in hamster cells.

Epidemiology

Numerous investigators have looked into the association of DBPs to adverse health effects in the areas of carcinogenesis and reproductive and developmental effects. Koivusalo and colleagues22 found that "statistically significant risk" was observed for women to develop cancers of the bladder (relative risk RR: 1.48), rectum (RR 1.38), esophagus (RR 1.90), and breast (RR 1.11 – see Figure 3). Stocker1 reported, "These trihalomethanes have shown evidence of genotoxicity in bacterial and mammalian cell systems in vitro and some evidence of carcinogenicity in rodents." King & Marrett23 found evidence of increasing risk for bladder cancer withÔ and colleagues24 found minimal to significant increasing risk of cancers of the liver, pancreas, soft-tissue, Hodgkin's disease, non-Hodgkin's lymphoma, and leukemia due to drinking chlorinated water. McGeehan25 in Colorado found increased risk of bladder cancer with prolonged exposure to chlorinated surface water compared with no exposure.

Table 2: Cancers potentially related to DBPs. Koivusalo, et al., 1997.

Site

Soft Tissue

Melanoma`
Breast
Bladder

Non©Hodgkins

Glioma
Leukemia

Conclusions

While the jury is still partially out, the evidence is growing, both epidemiologically and mechanistically, to identify and understand the relationship between THMs and other DBPs and their role in increased cancer rates. Researchers have been quick to admit that ecological and environmental studies are fraught with difficulty when attempting to establish a clear cause-effect relationship of DBPs to cancer. The confounders are numerous and very difficult, if not impossible, to adjust for entirely. Increasing interest has been focused on alternative water disinfection methods; however, they too are not without drawbacks. It is clear that the risk of not using proper disinfection methods far outweighs the immediate consequences of waterborne infectious disease. The real risk of disease from chlorinated or bromonated water is not known. The EPA2 has estimated that "Cancer risks due to DBPs range from less than 1 case per year to over 10,000 cases per year," while cost estimates to reduce these risks range from $400,000 to $8 billion per case! Chiropractic doctors should advise their patients and families to drink water that has been filtered, distilled, or at least left open to volatilize organics and increase the purity of the water. Water is essential to life, and disinfection methods are being adapted to minimize DBP formation in most communities. Everyone shares environmental health issues. Stand up and be educated on the risks to which your patients are exposed; give good advice and take pride in being a multitalented health practitioner.

References

1. the potential in vivo of three trihalomethanes: Chlorodibromomethane, bromodichloromethane and bromoform. Mutagenesis 1997;12:169-173.
2. EPA. National primary drinking water regulations: disinfectants and disinfection byproducts; notice of availability; proposed rule. Available online at: http://www.epa.gov/fedrgstr/EPA-WATER/1997/Day-03/w28746.htm.
3. Chlorine Chemistry Council. Drinking water chlorination white paper: a review of disinfection practices and issues. 1997A. Available online at: http://www.c3.org/newsroom.whitepapers/whitepapercl.html.
4. Singer PC. Disinfection byproducts: from the source to the tap. Proceedings. Workshop on disinfection byproducts in drinking water: critical issues in health effects research. Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, 1995.
5. Krasner SW, Sclimenti MJ, Means E. Quality degradation: implications for DBP formation. Journal AWWA 1994;34-45.
6. Summers RS, Hooper SM, Shukairy HU, Solarik G, Owen D. Assessing the DBP yield: uniform formation conditions. Journal AWWA 1996;80-93.
7. Malkin SE, Fumento M. Rachel's folly: the end of chlorine. 1997. Available online at: http://www.cei.org/chlorine.html.
8. Chlorine Chemistry Council. US consumers. 1997B. Available online at: http://www.c3.org/economics.html.
9. Batjer UL, Duszlen JV, Gabel B, Theirman W. Distribution and balance of volatile halogenated hydrocarbons in the water and air of covered swimming pools using chlorine for water disinfection. Water Research 1981;15:803-814.
10. Krewski D. Assessing the health risks of drinking water. Proceedings. Workshop on disinfection by-products in drinking water: critical issues in health effects research. Health Canada & Carelton University. 1995.
11. Singer PC, Oblensky A, Greiner A. DBPs in chlorinated North Carolina drinking water. Journal AWWA 1995;83-92.
12. Roberson JA, Cromwell JE, Krasner SW, McGuire MJ, Owen DM, Regli S, Summers RS. The DBP rule: where did the numbers come from? Journal AWWA 1995;46-57.
13. Aggazzotti G, Fantuzzi G, Righi E, Predieri G. Environmental and biological monitoring of chloroform in indoor swimming pools. Journal of Chromatography 1995A;710:181-190.Ô
14. body burden from showering with chlorinated tap water. Risk Analysis 1990;10:575-580.
15. Aggazzotti G, Fantuzzi A, Righi E, Tartoni P, Cassinardi T, Predieri G. Chloroform in aveolar air individuals attending indoor swimming pools. Archives of Environmental Health 1993;48:250-254.
16. Mathews JM, Troxler PS, Jeffcoat AR. Metabolism and distribution of bromodichloromethane in rats after single and multiple oral doses. Journal of Toxicology and Environmental Health 1990:30,15-22.
17. Pegram RA, Andersen ME, Warren SH, Ross TM, Claxton LD. Glutithione S-transferase-mediated mutagenicity of trihalomethanes in salmonella typhimurium: contrasting results with bromodichloromethane and chloroform. Toxicology and Applied Pharmacology 1997;144:183-188.
18. Snyder R, Andrews LS. Toxic effects of solvents and vapors. In: Klassen CD (ed.) Casarett and Doul's Toxicology. 1996; New York, New York, McGraw-Hill.
19. Daniel FB, Robinson M, Condie LW, York RG. Ninety-day toxicity study of dibromochloromethane in Sprague-Dawley rats. Drug and Chemical Toxicology 1990;13:135-154.
20. Dunnick JK, Melnick RL. Assessment of the carcinogenic potential of chlorinated water: experimental studies of chlorine, chloramine, and trihalomethanes. Journal of National Cancer Institute 1993;85:817-822.
21. Itoh S, Matsuoka Y. Contributions of disinfection byproducts to activity inducing chromosomal aberrations of drinking water. Water Research 1996;30:1403-1410.
22. Koivusalo M, Pukkala E, Vartianien T, Jaakkola JJK, Hakulinen T. Drinking water chlorination and cancer: a historical cohort study in Finland. Cancer Causes and Controls 1997;8:192-200.
23. King WD, Marrett LD. Case-control of bladder cancers and chlorinating byproducts in treated water (Ontario, Canada). Cancer Causes and Controls 1996;7:596-604.
24. Koivusalo M, Vartianien T, Hakulinen T, Pukkala E, Jaakkola J. Drinking water mutagenicity and leukemia, lymphomas, and cancers of the liver, pancreas, and soft tissue. Archives of Environmental Health 1995;50:269-276.
25. McGeehan MA, Reif JS, Becher JC, Mangione EJ. Case-control study of bladder cancer and water disinfection methods in Colorado. American Journal of Epidemiology 1993;138:492-500.

Holly A. Williams, DC, DABCO
Westminster, Colorado