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.

Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: a review and roadmap for research.

The relationship between antioxidant activity and antimutagenicity of various tea extracts (green tea, pouchong tea, oolong tea, and black tea) was investigated. All tea extracts exhibited markedly antioxidant activity and reducing power, especially oolong tea, which inhibited 73.6% peroxidation of linoleic acid. Tea extracts exhibited a 65-75% scavenging effect on superoxide at a dose of 1 mg and 30 - 60% scavenging effect on hydrogen peroxide at a dose of 400 microgram. They scavenged 100% hydroxyl radical at a dosage of 4 mg except the black tea. Tea extracts also showed 50 - 70% scavenging effect on alpha, alpha-diphenyl-beta-picrylhydrazyl radical. The antioxidant activity and the scavenging effects on active oxygen decreased in the order semifermented tea > nonfermented tea > fermented tea. Tea extracts showed strong antimutagenic action against five indirect mutagens, i.e., AFB1, Trp-P-1, Glu-P-1, B[a]P, and IQ, especially oolong and pouchong teas. The antioxidant effect of tea extracts was well correlated to their antimutagenicity in some cases but varied with the mutagen and antioxidative properties.

Antioxidant activity of various tea extracts in relation to their antimutagenicity

Guidelines for Canadian Drinking Water Quality

http://jmclachlan.tulane.edu/PDFs/wetherilletal2007.pdf

In vitro molecular mechanisms of bisphenol A action.

Toxicological profile for arsenic

The comparative cytogenetic effects on the synthesis of DNA, RNA and protein in cultured mammalian cells of trivalent and pentavalent arsenic were investigated. The chromosome-breaking activity in cultured leukocytes was significantly higher for the compounds with trivalent (NaAsO 2 , AsCl 3 and As 2 O 3 ) than with pentavalent arsenic (Na 2 HAsO 4 , H 3 AsO 4 and As 2 O 5 ). The activity in cultured human skin fibroblasts was similar to that in leukocyte cultures. The colony-forming capacity after exposure to arsenicals indicated that trivalent was more toxic than pentavalent arsenic. In the response of DNA, RNA and protein synthesis, both trivalent and pentavalent arsenic inhibited DNA and protein synthesis in leukocytes.

Comparative studies of chromosomal aberration induced by trivalent and pentavalent arsenic

Estrogen receptor α in mouse splenic lymphocytes: possible involvement in immunity

The comparative cytogenetic and mutagenic effects between trivalent and hexavalent chromium were investigated. Five chromium compounds, K 2 Cr 2 O 7 and K 2 CrO 4 containing Cr 6+ , and Cr(CH 3 COO) 3 , Cr(NO 3 ) 3 and CrCl 3 containing Cr 3+ , were examined for their ability to induce chromosomal damage in cultures of human leukocytes, for their reactivity with DNA by a rec-assay system and for mutagenicity in the E. coli Hs30R test system. Chromosome-breaking activity was significantly higher for the compounds with hexavalent than trivalent chromium, the efficiency being in the decreasing order K 2 Cr 2 O 7 > K 2 CrO 4 >> Cr(CHCOO) 3 > Cr(NO 3 ) 3 , CrCl 3 . In the rec-assay and mutation assay, hexavalent (K 2 Cr 2 O 7 and K 2 CrO 4 ) and trivalent Cr(CH 3 COO) 3 ) compounds gave positive results, their mutagenic potential being higher in the same order of clastogenic magnitude.

Comparative studies of chromosomal aberration and mutagenicity of trivalent and hexavalent chromium

Disinfection by-products in the chlorination of organic nitrogen compounds: By-products from kynurenine

Comparative metabolic fate of labelled chromium chloride and sodium chromate and interaction of these compounds in the rat liver and blood were investigated after their oral and intravenous administration. Gastrointestinal absorption of both compounds was below 1% of the oral dose, but trivalent chromium showed higher radioactivity than the hexavalent form in rats (biological half-life : CrCl3 91.79 days, Na2CrO4 22.24 days). The higher residual activity of the trivalent chromium was also observed after intravenous administration. Both forms of chromium were excreted more in the urine via the kidney than in the intestinal tract after intravenous administration. When 51CrCl3 and Na251CrO4 were injected into rats, in the time-distribution patterns of 51Cr in the organs, a significant difference was shown between oxidation states of the two compounds, especially in subcellular fractions of the liver and blood constituents. This significant difference mainly observed in the rat blood came from the fact that trivalent chromium possessed a high binding activity for transferrin in plasma, while hexavalent chromium was permeable into red cells and bound with hemoglobin.

Katsuhiko Nakamuro

Papers

Comparative studies of chromosomal aberration induced by trivalent and pentavalent arsenic

Estrogen receptor α in mouse splenic lymphocytes: possible involvement in immunity

Comparative studies of chromosomal aberration and mutagenicity of trivalent and hexavalent chromium

Disinfection by-products in the chlorination of organic nitrogen compounds: By-products from kynurenine

Metabolic fate of chromium compounds. I. Comparative behavior of chromium in rat administered with Na251CrO4 and 51CrCl3.