RoC Review of Haloacetic Acids Found as Water Disinfection By-products
Water treatment removes contaminants and disease-causing agents from drinking water. Although water disinfection is a significant public health advancement, an unintended consequence of the process is the formation of many chemical by-products, some of which may be hazardous to health.
Haloacetic acids (HAAs) are chemical compounds consisting of an acetic acid backbone and one or more halogen atoms such as chlorine, bromine, and iodine. HAAs are formed during the disinfection of water from a reaction between chlorine-based disinfection agents and organic matter in the source water.
Why is it important to study HAAs?
Approximately 250 million U.S. residents are potentially exposed to HAAs from using disinfected water from community drinking-water systems. People can also be exposed to HAAs by drinking beverages prepared with treated water and from eating food cooked in, or in contact with, chlorinated water. Exposure may also occur from bathing or coming into contact with water treated with chlorine for disinfection in swimming pools, hot tubs, or spas.
Several human studies, including studies conducted by the National Cancer Institute, have reported an excess risk of urinary bladder cancer associated with ingestion of, or contact with, chlorinated water. A recent publication estimates that 6,800 new urinary bladder cancer cases per year may be due to disinfection by-products present in U.S. community drinking water. Epidemiological studies have difficulty separating the effects of different types of water disinfection by-products; therefore, providing toxicological information on specific by-products, including HAAs, can help inform public health decisions.
Thirteen HAAs have been identified in chlorinated drinking water and are formed as by-products as a result of the water disinfection process:
- Bromoacetic acid (BA)
- Bromochloroacetic acid (BCA)
- Bromodichloroacetic acid (BDCA)
- Bromoiodoacetic acid (BIA)
- Chloroacetic acid (CA)
- Chlorodibromoacetic acid (CDBA)
- Chloroiodoacetic acid (CIA)
- Dibromoacetic acid (DBA)
- Dichloroacetic acid (DCA)
- Diiodoacetic acid (DIA)
- Iodoacetic acid (IA)
- Tribromoacetic acid (TBA)
- Trichloroacetic acid (TCA)
A systematic review of scientific literature on HAAs and cancer studies in experimental animals and humans was conducted using standard methods for the Report on Carcinogens, or RoC (see also, HAA protocol). NTP applied established criteria to determine the level of evidence for carcinogenicity from studies in experimental animals and considered mechanistic and other relevant information to determine whether a substance should be listed in the RoC.
What did the evaluation find?
NTP concluded that six HAAs are reasonably anticipated to be human carcinogens: BCA, BDCA, CDBA, DBA, DCA, and TBA.
BCA, BDCA, DBA, and DCA are listed based on sufficient evidence of carcinogenicity from studies in experimental animals. CDBA and TBA are listed based on convincing relevant information indicating the HAAs would likely cause cancer in humans, including rodent studies showing the HAA is broken down in the body to a known carcinogen, and mechanistic studies demonstrating possibility of its carcinogenicity in humans.
Q: Will drinking chlorinated tap water with HAAs give me cancer?
A: A listing in the RoC identifies a substance or exposure circumstance as known or reasonably anticipated to be a human carcinogen, thus indicating that it can cause cancer under certain circumstances. The listing does not estimate cancer risks to individuals associated with exposures in their daily lives. Many factors affect whether a person will or will not develop cancer, including the carcinogenic potency of the substance, the level and duration of exposure, and an individual’s susceptibility to the carcinogenic action of the substance.
Q: What are prevention strategies to decrease health effects from exposure to HAAs?
A: Public water supplies are monitored for HAAs and other contaminants to reduce risk from excess exposure; other sources of water that are disinfected with chlorine should be monitored for HAAs to reduce possible exposure risk.
The U.S. Environmental Protection Agency (EPA) regulates five HAAs, including two that are recommended for listing in the RoC. The Fourth Unregulated Contaminant Monitoring Rule (2016) requires EPA to monitor four unregulated HAAs in addition to the five regulated HAAs. The nine HAAs include all six HAAs that NTP recommends for listing in the report.
Improvements in disinfection technology, such as filtration methods, can reduce the levels of HAAs in the drinking water. Clean up of HAAs and other disinfection by-products can occur by:
- Removal of natural organic precursors prior to disinfection.
- Altering disinfectant dose and type or application point in the water treatment process.
- Removal of the by-products after formation.
For more information on disinfection by-product remediation methods, see Report on Carcinogens Monograph on Haloacetic Acids, Section 2.3 and Table 2-3.
Q: How can I reduce my exposure to HAAs in tap water?
A: The amounts of by-products including HAAs vary with the water source, time of year, and method of disinfection. Water quality is monitored by local water treatment facilities that also test for certain by-products and other contaminants, including some of the HAAs. It is best to contact your local water treatment facility to determine the amount of HAAs in local tap water and to get information on mitigation methods. Reverse osmosis or charcoal filtration of water at the tap is an efficient way to prevent exposure to most disinfection by-products, including HAAs.
Q: Why were HAAs selected for this report?
A: NTP selected HAAs for review based on public health concerns of widespread exposure and the availability of studies of cancer in animals and mechanisms of cancer. The objective of the review is to provide information on what chemicals are cancer hazards to help inform public health decisions.
Q: Were there any human cancer studies that evaluated exposure to HAAs?
A: The only study available at the time of RoC publication that reported specifically on exposure to HAAs did not find an increased risk for kidney cancer. Several epidemiological studies of exposure to chlorinated water or to other water disinfection byproducts as proxies for mixtures of by-products found an association with increased risk of urinary-bladder cancer. These studies help support the relevance to humans of the cancer studies of HAAs at higher doses in experimental animals.
Q: What other studies did NTP use to determine the listing status?
A: NTP determined there was sufficient evidence of carcinogenicity from studies in experimental animals and supporting evidence from mechanistic studies in cultured cells that demonstrated the possibility of carcinogenicity in humans for four HAAs: BCA, BDCA, DBA, and DCA. All of these HAAs induce liver and other types of tumors in rodents.
|Common tumors across most HAAs|
|Liver||Mice (both sexes)||Mice (both sexes)||Mice (both sexes)||Mice (both sexes) Male rats|
|Mesothelioma||Male rats||Male rats||Male rats|
|Mammary gland||Female rats||Female rats|
|Harderian gland||Male mice|
|Large intestine||Rats (both sexes)|
For two other HAAs, CDBA and TBA, NTP found convincing information indicating the HAA would likely cause cancer in humans. Studies show that CDBA and TBA are metabolized to rodent carcinogens (see below), and mechanistic studies demonstrate the possibility of carcinogenicity in humans.
|HAA||Major metabolite||Predicted tumor sites and species|
|CDBA||BCA||Liver tumors in mice
Mesothelioma in rats
|TBA||DBA||Liver tumors in mice
Mesothelioma in rats
Q: What HAAs weren’t listed in the RoC and why?
A: NTP reviewed and did not list CA and TCA, as there was insufficient evidence of carcinogenicity from studies in experimental animals. In addition, no cancer hazard conclusions were made for BA, BIA, CIA, DIA, and IA because there were no animal cancer studies and few mechanistic studies available.
Q: How are conclusions drawn?
A: Substances are listed in the RoC as known or reasonably anticipated to be a carcinogen using established listing criteria. Conclusions are based on scientific judgment, using systematic review methods, with consideration given to all relevant information.
For a substance to have the status of known to be a human carcinogen, there must be sufficient evidence of carcinogenicity from studies in humans, showing a cause-and-effect relationship between exposure to the substance and human cancer. Occasionally, substances are listed in this category based on human studies showing that the substance causes biological effects known to lead to the development of cancer.
For a substance to have the status of reasonably anticipated to be a human carcinogen, at least one of the following three situations must occur:
- Limited evidence of carcinogenicity from studies in humans, which indicates that causal interpretation is credible but that alternative explanations, such as chance, bias, or confounding factors, could not adequately be excluded.
- Sufficient evidence in experimental animals showing a cause-and-effect relationship between exposure to the substance and cancer.
- Member of a class of substances already listed in the RoC, or the substance acts through mechanisms indicating it would likely cause cancer in humans.
Q: What were the results of the peer review of HAAs?
A: On July 24, 2017, a panel of experts reviewed the draft Report on Carcinogens Monograph on HAAs Found as Drinking Water By-products. The panel unanimously agreed with NTP’s recommended listing status for six HAAs as reasonably anticipated to be human carcinogens. They also agreed that with NTP level of evidence conclusions of not sufficient evidence of carcinogenicity from studies in experimental animals for two HAAs, CA and TCA.
|Oct 07, 2015||Federal Register notice requesting public comment on nominated substances|
|Mar 01, 2016||RoC Concept|
|Mar 23, 2017||RoC Protocol|
|Jun 06, 2017||RoC Monograph - Peer review draft|
|Oct 30, 2017||RoC Monograph - Revised draft|
|Mar 30, 2018||RoC Monograph - Final (correction posted Feb. 23, 2021) (Abstract)
Meetings & Events
|Apr 11, 2016||NTP Board of Scientific Counselors Meeting||Board of Scientific Counselors||
|Jul 24, 2017||Peer Review of the Draft RoC Monograph on Haloacetic Acids Found as Water Disinfection By-Products||Expert Panels - RoC||
|Dec 07, 2017||NTP Board of Scientific Counselors Meeting||Board of Scientific Counselors||
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