Disinfection by-products (DBPs) are formed when disinfectants (chlorine, ozone, chlorine
dioxide, or chloramines) react with naturally occurring organic matter, anthropogenic
contaminants, bromide, and iodide during the production of drinking water. Here we
review 30 years of research on the occurrence, genotoxicity, and carcinogenicity of
85 DBPs, 11 of which are currently regulated by the U.S., and 74 of which are considered
emerging DBPs due to their moderate occurrence levels and/or toxicological properties.
These 74 include halonitromethanes, iodo-acids and other unregulated halo-acids, iodo-trihalomethanes
(THMs), and other unregulated halomethanes, halofuranones (MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone]
and brominated MX DBPs), haloamides, haloacetonitriles, tribromopyrrole, aldehydes,
and N-nitrosodimethylamine (NDMA) and other nitrosamines. Alternative disinfection
practices result in drinking water from which extracted organic material is less mutagenic
than extracts of chlorinated water. However, the levels of many emerging DBPs are
increased by alternative disinfectants (primarily ozone or chloramines) compared to
chlorination, and many emerging DBPs are more genotoxic than some of the regulated
DBPs. Our analysis identified three categories of DBPs of particular interest. Category
1 contains eight DBPs with some or all of the toxicologic characteristics of human
carcinogens: four regulated (bromodichloromethane, dichloroacetic acid, dibromoacetic
acid, and bromate) and four unregulated DBPs (formaldehyde, acetaldehyde, MX, and
NDMA). Categories 2 and 3 contain 43 emerging DBPs that are present at moderate levels
(sub- to low-mug/L): category 2 contains 29 of these that are genotoxic (including
chloral hydrate and chloroacetaldehyde, which are also a rodent carcinogens); category
3 contains the remaining 14 for which little or no toxicological data are available.
In general, the brominated DBPs are both more genotoxic and carcinogenic than are
chlorinated compounds, and iodinated DBPs were the most genotoxic of all but have
not been tested for carcinogenicity. There were toxicological data gaps for even some
of the 11 regulated DBPs, as well as for most of the 74 emerging DBPs. A systematic
assessment of DBPs for genotoxicity has been performed for approximately 60 DBPs for
DNA damage in mammalian cells and 16 for mutagenicity in Salmonella. A recent epidemiologic
study found that much of the risk for bladder cancer associated with drinking water
was associated with three factors: THM levels, showering/bathing/swimming (i.e., dermal/inhalation
exposure), and genotype (having the GSTT1-1 gene). This finding, along with mechanistic
studies, highlights the emerging importance of dermal/inhalation exposure to the THMs,
or possibly other DBPs, and the role of genotype for risk for drinking-water-associated
bladder cancer. More than 50% of the total organic halogen (TOX) formed by chlorination
and more than 50% of the assimilable organic carbon (AOC) formed by ozonation has
not been identified chemically. The potential interactions among the 600 identified
DBPs in the complex mixture of drinking water to which we are exposed by various routes
is not reflected in any of the toxicology studies of individual DBPs. The categories
of DBPs described here, the identified data gaps, and the emerging role of dermal/inhalation
exposure provide guidance for drinking water and public health research.