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.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2892%2980911-Y

Biologically relevant metal ion-dependent hydroxyl radical generation. An update.

Toxicological profile for arsenic

Plant cyanogenic glycosides.

http://ssu.ac.ir/cms/fileadmin/user_upload/Mtahghighat/tfood/ARTICLES/chemical_safety/Food_processing_a_tool_to_pesticide_residue_dissipation.pdf

Food processing a tool to pesticide residue dissipation : A review

Simultaneous determination of thiols and disulfides by high-performance liquid chromatography with fluorescence detection

Active oxygen species derived from the interaction of potassium bromate (KBrO3), a rat renal carcinogen, with cells from rat kidney and other organs were examined by electron spin resonance spectrometry using the spin trapping agents 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2,2,6,6-tetramethylpiperidine (TEMP). DMPO-OH, an indicator of hydroxyl radical production, was generated from KBrO3 by kidney cells or homogenate, but not by liver preparations and to only a limited extent by heart and brain homogenates, suggesting relative kidney specificity. To assess what chemical components are responsible for production of DMPO-OH, several physiologically related materials were examined. Glucose, saccharose, albumin and methyl linolate were found not to be involved in the KBrO3 reaction, but reduced glutathione and also ferric ions participated to produce DMPO-OH. In addition, DMPO-OH production derived from the reaction of KBrO3 with kidney homogenate was not affected by superoxide dismutase, catalase or hydroxyl radical scavengers such as DMSO or ethanol, but was effectively inhibited by singlet oxygen scavengers such as histidine and NaN3, implying singlet oxygen production. To assess this possibility, TEMP was used as a trapping agent, and TEMPO, derived from singlet oxygen, was found to be produced by the reaction of KBrO3 with homogenates of kidney, but not of liver. Furthermore, singlet oxygen production was confirmed by studies of chemiluminescence using 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2a]pyrazine-3-one. As a control, DMPO-OH was also demonstrated to be produced by a known singlet oxygen source, toluidine blue plus light. The results thus indicate that singlet oxygen is a very probably candidate for the active oxygen species generated in the specific interaction of KBrO3 with rat kidney cells in vitro. This raises the question of its concern with renal carcinogenicity in vivo.

Sadao Uchiyama

Papers

Simultaneous determination of thiols and disulfides by high-performance liquid chromatography with fluorescence detection

Generation of active oxygen species in vitro by the interaction of potassium bromate with rat kidney cell.

Hydride generation-flame atomic-absorption spectrometry as an arsenic detector for high-performance liquid chromatography

Fluorescence enhancement in thin-layer chromatography by spraying viscous organic solvents

Protein-binding Potential of Ochratoxin A in vitro and Its Fluorescence Enhancement