Memories of a friend and colleague - Takashi Sugimura.

Takashi Sugimura, M.D., Honorary President of the National Cancer Center in Tokyo, and former President of The Japan Academy, is regarded by many as a pre-eminent contributor to the field of environmental genotoxicology. His pioneering spirit led to many key discoveries over a long and distinguished scientific career, including the first preclinical models for gastric cancer, identification of novel mutagens from cooked food, and the development of fundamental concepts in environmental chemical carcinogenesis. With his passing on September 6, 2020, many will reflect on the loss of an astute and engaging "Scientific Giant," who with warmth and good humor maintained lasting friendships both at home and abroad, beyond his many important scientific contributions.

Polycyclic aromatic hydrocarbons in traditionally smoked meat products from the Baltic states.

A total of 77 traditionally smoked meat samples produced in Latvia, Lithuania, and Estonia were tested for the occurrence of four EU regulated polycyclic aromatic hydrocarbons (PAHs). Levels of PAHs exceeding the EU maximum levels for benzo[a]pyrene and for the sum of four PAHs (PAH4) were detected in 46% and 48% of the samples originating from Latvia. The detected BaP levels in smoked meats ranged from 0.05 to 166 µg kg-1, while the PAH4 content ranged from 0.42 to 628 µg kg-1. The mean dietary exposure to PAHs was estimated at the levels of 5.4 ng BaP/kg bw/day and 36 ng PAH4/kg bw/day. The margin of exposure (MOE) approach was utilised to assess the risks to Latvian consumers due to PAHs and the obtained MOEs were in a range of 7205-24,434, thus indicating a potential concern for consumer health for specific population groups.

Polycyclic aromatic hydrocarbons in teas using QuEChERS and HPLC-FLD.

Polycyclic aromatic hydrocarbons (PAHs) are food-processing contaminants considered to be carcinogenic and genotoxic. Due to its drying process stage, teas may be contaminated with PAHs. The aim of the study was to validate an analytical method involving QuEChERS and HPLC-FLD for the determination of PAH4 in teas and evaluate the contamination levels in 10 different types of teas from Brazil. Recoveries varied from 54% to 99% and relative standard deviations from 1% to 21%. Limits of detection and quantification were from 0.03 to 0.3 µg/kg and 0.1 to 0.5 µg/kg, respectively. Mate tea presented the highest PAH levels, with PAH4 varying from 194 to 1795 µg/kg; followed by black (1.8-186 µg/kg), white (24-119 µg/kg), and green teas (3.1-92 µg/kg). Teas with lowest PAH4 were strawberry, lemongrass, peppermint, and boldo. Only trace levels of PAHs were detected in tea infusions, so apparently it would not affect PAH intake by Brazilian population.

When alcohol is the answer: Trapping, identifying and quantifying simple alkylating species in aqueous environments.

Alkylating agents are a significant class of environmental carcinogens as well as commonly used anticancer therapeutics. Traditional alkylating activity assays have utilized the colorimetric reagent 4-(4-nitrobenzyl)pyridine (4NBP). However, 4NBP based assays have a relatively low sensitivity towards harder, more oxophilic alkylating species and are not well suited for the identification of the trapped alkyl moiety due to adduct instability. Herein we describe a method using water as the trapping agent which permits the trapping of simple alkylating electrophiles with a comparatively wide range of softness/hardness and permits the identification of donated simple alkyl moieties.

Hexavalent chromium removal from aqueous solutions by a novel powder prepared from Colocasia esculenta leaves.

In this study, batch removal of hexavalent chromium from aqueous solutions by powdered Colocasia esculenta leaves was investigated. Batch experiments were conducted to study the effects of adsorption of Cr(VI) at different pH values, initial concentrations, agitation speeds, temperatures, and contact times. The biosorbent was characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectrometer analysis. The biosorptive capacity of the adsorbent was dependent on the pH of the chromium solution in which maximum removal was observed at pH 2. The adsorption equilibrium data were evaluated for various adsorption isotherm models, kinetic models, and thermodynamics. The equilibrium data fitted well with Freundlich and Halsey models. The adsorption capacity calculated was 47.62 mg/g at pH 2. The adsorption kinetic data were best described by pseudo-second-order kinetic model. Thus, Colocasia esculenta leaves can be considered as one of the efficient and cheap biosorbents for hexavalent chromium removal from aqueous solutions.

Carcinogenicity of consumption of red and processed meat: What about environmental contaminants?

In October 26, 2015, the International Agency for Research on Cancer (IARC) issued a press release informing of the recent evaluation of the carcinogenicity of red and processed meat consumption. The consumption of red meat and processed meat was classified as "probably carcinogenic to humans", and as "carcinogenic to humans", respectively. The substances responsible of this potential carcinogenicity would be generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures (N-nitroso-compounds, polycyclic aromatic hydrocarbons and heterocyclic aromatic amines). However, in its assessments, the IARC did not make any reference to the role that may pose some carcinogenic environmental pollutants, which are already present in raw or unprocessed meat. The potential role of a number of environmental chemical contaminants (toxic trace elements, polycyclic aromatic hydrocarbons, polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls, polybrominated diphenyl ethers, polychlorinated diphenyl ethers, polychlorinated naphthalenes and perfluoroalkyl substances) on the carcinogenicity of consumption of meat and meat products is discussed in this paper. A case-study, Catalonia (Spain), is specifically assessed, while the influence of cooking on the concentrations of environmental pollutants is also reviewed. It is concluded that although certain cooking processes could modify the levels of chemical contaminants in food, the influence of cooking on the pollutant concentrations depends not only on the particular cooking process, but even more on their original contents in each specific food item. As most of these environmental pollutants are organic, cooking procedures that release or remove fat from the meat should tend to reduce the total concentrations of these contaminants in the cooked meat.

Graphene oxide coated coordination polymer nanobelt composite material: a new type of visible light active and highly efficient photocatalyst for Cr(VI) reduction.

A visible light active photocatalyst was synthesized successfully by coating graphene oxide (GO) on a coordination polymer nanobelt (CPNB) using a simple colloidal blending process. Compared with neat CPNB, the resulting graphene oxide coated coordination polymer nanobelt composite material (GO/CPNB) exhibits excellent photocatalytic efficiency in the reduction of K2Cr2O7 under visible light irradiation. In the composite material, GO performs two functions. Firstly, it cuts down the band gap (E(g)) of the photocatalyst and extends its photoresponse region from the ultraviolet to visible light region. Secondly, GO exhibits excellent electron transportation ability that impedes its recombination with holes, and this can enhance photocatalytic efficiency. For GO, on its surface, the number of functional groups has a great influence on the photocatalytic performance of the resulting GO/CPNB composite material and an ideal GO"coater" to obtain a highly efficient GO/CPNB photocatalyst has been obtained. As a photocatalyst that may be used in the treatment of Cr(VI) in wastewater, GO/CPNB exhibited outstanding stability during the reduction of this pollutant.

Multi-commutated fluorometric optosensor for the determination of citrinin in rice and red yeast rice supplements.

Citrinin is a toxic secondary metabolite first isolated from Penicillium citrinum, although is also produced by other species of Penicillium and Aspergillus. It has highly toxic, mutagenic, teratogenic and carcinogenic properties and is often found in crops, vegetables and fruit. To our knowledge there is no specific legislation on maximum levels permitted for citrinin, so no official analytical method is currently available for its determination. Our laboratory developed a fluorometric flow-through optosensor using Sephadex SPC-25 as solid support. Multi-commutated flow injection analysis was used for the construction of the manifold and for handling solutions. In this way, we minimised waste generation and human intervention, which are critical aspects when dealing with highly toxic compounds such as citrinin. The optimum excitation/emission wavelengths were set at 330/494 nm; the calibration curve was linear in the concentration range 35-900 ng ml⁻¹. A detection limit of 10.5 ng ml⁻¹ and relative standard deviations (RSDs) lower than 3% were obtained. The developed optosensor was applied to the determination of citrinin in rice and dietary supplements containing red yeast rice.

Eggshell membrane-based biotemplating of mixed hemimicelle/admicelle as a solid-phase extraction adsorbent for carcinogenic polycyclic aromatic hydrocarbons.

A new solid-phase extraction (SPE) format was demonstrated, based on eggshell membrane (ESM) templating of the mixed hemimicelle/admicelle of linear alkylbenzenesulfonates (LAS) as an adsorbent for the enrichment of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in environmental aqueous samples. The LAS mixed hemimicelle/admicelle formation and SPE of the target PAHs were conducted simultaneously by adding the organic target and LAS through a column filled with 500 mg of ESM. The effect of various factors, including LAS concentration, solution pH, ionic strength, and humic acid concentration on the recoveries of PAHs were investigated and optimized. The results showed that LAS concentration and solution pH had obvious effect on extraction of PAHs, and the recoveries of PAHs compounds decreased in the presence of salt and humic acid. Under the optimized analytical conditions, the present method could respond down to 0.1-8.6 ng/L PAHs with a linear calibration ranging from 0.02 to 10 µg/L, showing a good PAHs enrichment ability with high sensitivity. The developed method was used satisfactorily for the detection of PAHs in environmental water samples. The mixed hemimicelle/admicelle adsorbent exhibited high extraction efficiency to PAHs and good selectivity with respect to natural organic matter and was advantageous over commercial C18 adsorbent, for example, high extraction yield, high breakthrough volume, and easy regeneration.

Fabrication and characterization of microelectromechanical systems-based gas chromatography column with embedded micro-posts for separation of environmental carcinogens.

In this paper, a micro gas chromatography (µGC) column with embedded micro-posts was developed for increasing overall surface area of the columns which is able to support more of the stationary phase and reducing the effective width of the column, leading to higher separation efficiency. The proposed columns have a higher sample capacity as the overall surface area is about 3 times larger than that of open columns with the same dimensions. In order to achieve an even flow velocity in the channels, the location of the micro-posts in the linear channels and the configuration of curved channels were optimized by numerical simulation. The results have indicated that the proposed column separated 5 environmental carcinogens in less than 50s, achieved a separation efficiency of about 9500plates/m and eluted highly symmetrical Gaussian peaks.

Isotope dilution-GC-MS/MS analysis of 16 polycyclic aromatic hydrocarbons in selected medicinal herbs used as health food additives.

Medicinal herbs have a very important role in health protection and disease control, and have been used in health foods. Polycyclic aromatic hydrocarbons (PAHs) have carcinogenic, biological and mutagenic effects. In this paper, the content of 16 PAHs as representative contaminants in nine Chinese medicinal herbs, as additives for health foods, was investigated in order to ensure food safety from this source. A highly sensitive isotope dilution-gas chromatography-tandem mass spectrometry (ID-GC-MS/MS) method combined with gel permeation chromatography (GPC) and solid-phase extraction (SPE) was developed. Calibration curves showed good linearity for all PAHs (R² > 0.999), and the limit of quantification (LOQ) ranged from 0.42 to 2.7 µg kg⁻¹. Average recoveries for these compounds were in the range of 52.5-117%, 52.6-119% and 81.4-108% at the concentrations of 10, 50 and 250 µg kg⁻¹ with RSD of 1.8-15%, 0.9-15% and 1.0-15%, respectively. The proposed method was used for the analysis of nine Chinese medicinal herbs. Total levels of PAHs varied from 98.2 µg kg⁻¹ (cassia seed) to 2245 µg kg⁻¹ (eucommia bark). The highest level was found for phenanthrene (Phe) in liquorice root (631.3 µg kg⁻¹), indigowoad leaf (551.0 µg kg⁻¹), rose flower (435.2 µg kg⁻¹) and eucommia bark (432.3 µg kg⁻¹). The proposed method could provide a useful basis for safety monitoring of herbs and risk management for PAHs in the health food industry.

Kinetic and isotherm of hexavalent chromium adsorption onto nano hydroxyapatite.

BACKGROUND: Hexavalent chromium (Cr (VI)) is an important contaminant in surface and groundwater and its removal from contaminated water and wastewater has received interest in recent years. This study aimed to explain the removal process of Cr (VI) from aqueous solution using nano hydroxyapatite (n-HAp) as an adsorbent material. METHODS: Cr (VI) removal experiments with the prepared n-HAp were carried out as the batch test in 100 ml flask while agitating on the shaker. The influence of pH (3 toll), contact time (3-60 min), Cr (VI) concentration (1 to 2 mg/L) and adsorbent dosage (0.025 to 1 g/L) were explored. Three isotherms models and eight kinetics models were used to evaluate the experimental data, respectively. For validation of kinetic and isotherm data, correlation coefficient, sum of square errors (SSE) and normalized deviation were used. RESULTS: The removal efficiency of Cr (VI) was improved an increase in Cr (VI) and n-HAp concentration. The results best fitted with Langmuir model and the pseudo-second-order rate reaction. Analysis of data with Dubinin Radushkevich isotherm showed that the adsorption of Cr (VI) onto synthetic n-HAp is a chemisorption process. CONCLUSION: The n-HAp as an ecofriendly compound is effective adsorbent for the removal of Cr (VI) from aqueous solution. Accordingly, n-HAp is feasible and promise adsorbent for treating polluted Cr (VI) groundwater.

Hexavalent chromium reduction and plant growth promotion by Staphylococcusarlettae strain Cr11.

Cr(VI), a mutagenic and carcinogenic pollutant in industrial effluents, was effectively reduced by an indigenous tannery effluent isolate Staphylococcus arlettae strain Cr11 under aerobic conditions. The isolate could tolerate Cr(VI) up to 2000 and 5000 mg L(-1) in liquid and solid media respectively. S. arlettae Cr11 effectively reduced 98% of 100 mg L(-1) Cr(VI) in 24h. Reduction for initial Cr(VI) concentrations of 500 and 1000 mg L(-1) was 98% and 75%, respectively in 120 h. The isolate was also positive for siderophore, indole acetic acid, ammonia and catalase production, phosphate solubilization and biofilm formation in the presence and absence of Cr(VI). The isolate showed halotolerance (10% NaCl) and cross tolerance to other toxic heavy metals such as Hg(2+), Ni(2+), Cd(2+) and Pb(2+). Bacterial inoculation of Triticum aestivum in controlled petri dish and soil environment showed significant increase in percent germination, root and shoot length as well as dry and wet weight in Cr(VI) treated and untreated samples. This is the first report of simultaneous Cr(VI) reduction and plant growth promotion for a S. arlettae strain.

Impact of beta-naphthoflavone on genotoxicity of food-derived carcinogens.

OBJECTIVES: Benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogens, which frequently occur in the human diet. Their metabolic activation to reactive species binding to DNA is mediated by cytochromes P450 (CYPs) 1A1 and 1A2. Thus, levels and activities of these CYPs are crucial for initiation of BaP- and PhPI-mediated carcinogenesis. Here, the effect of CYP1A1/2 induction due to their prototype flavonoid inducer, ß-naphthoflavone (BNF), on BaP- and PhPI-derived DNA adduct formation in rats was examined. METHODS: Male rats pretreated with BNF were treated with a single dose of either carcinogen by oral gavage. Nuclease P1 version of 32P-postlabeling assay and online column-switching liquid chromatography-electrospray ionization-tandem mass spectrometry were used to detect and quantify covalent DNA adducts formed by BaP and PhIP in-vivo, respectively. Expression of CYP1A1/2 enzymes was examined by Western blot. Enzymatic activities of CYP1A1/2 were assessed using their marker substrates (ethoxyresorufin and methoxyresorufin). RESULTS: Treatment of rats with a single dose of BNF produced an increase in levels CYP1A1/2 and CYP1A1 proteins in liver and small intestine, respectively. An increase in CYP1A1 protein expression found in both organs correlated well with specific activities of these CYPs. The CYP1A1 expression levels and its specific activity in small intestine decreased along the length of the organ, being highest in its proximal part and lowest in its distal part. The BNF induction of CYP1A1/2 resulted in a significant increase in the formation of BaP- and PhIP-DNA adducts in liver and in the distal part of the small intestine, respectively. Thus, pretreatment of rats with BNF did not prevent the PhIP and BaP activation, but vice versa, enhanced their genotoxicity. CONCLUSIONS: The results of this study demonstrate that the administration of only a single dose of CYP-inducing flavonoid prior to the intake of food carcinogens may increase the risk of a tumor formation.

[Treatment of Cr( VI) in deoxygenated simulated groundwater using nanoscale zero-valent iron].

Laboratory experiments and theoretical modeling studies were performed to investigate the mechanisms of Cr( VI) removal from deoxygenated simulated groundwater using nanoscale zero-valent iron, and to evaluate influencing factors and kinetics based on zeta potential, redox potential, ferrous concentrations, and the pe-pH diagram of Fe-Cr-H2O system. Experimental results demonstrate that the removal efficiency of Cr(VI) decreases with the increasing Cr( VI)/Fe mass ratio. When the Cr(VI)/Fe mass ratios are 0.025, 0.050, 0.075, and 0.100, the corresponding Cr(VI) removal rates are 100.0%, 85.6%, 72.7% and 39.6%, respectively. The Cr( VI) removal is favorable at acidic pH with fixed Cr(VI)/Fe mass ratio of 0.100. When pH are 3.0, 5.0, 7.0, 9.0 and 11.0, the Cr(VI) removal rates are 73.4%, 57.6%, 39.6%, 44.1%, and 41.2%, accordingly. The Cr(VI) removal follows the pseudo second-order kinetics. When pH is 7.0 and Cr(VI)/nZVI mass ratio is 0.025, the rate of Cr(VI) removal is the highest with rate constant at 9.76 x 10(-3) g x (mg x min)(-1). The conversion from Cr2O7(2-) to Cr3+ should be instantaneous when Cr2O7(2-) is absorbed on the surface of Fe. The Cr(VI) was reduced to Cr(III), which was subsequently incorporated into the FeOOH shell and formed a Cr-Fe film. The film once formed could further inhibit the electron transfer between Cr2O7(2-) and Fe. Then Cr(V) removal was primary controlled by the adsorption process.

Ice phase as an important factor on the seasonal variation of polycyclic aromatic hydrocarbons in the Tumen River, Northeastern of China.

BACKGROUND, AIM AND SCOPE: The climatic characteristic is a major parameter affecting on the distribution variation of organic pollutants such as polycyclic aromatic hydrocarbons (PAHs). The Tumen River is located in Northeastern of China. The winter era lasts for more than 5 months in a year, and the river water was frozen and covered by ice phase. Coal combustion is an essential heating source in the Tumen River Basin. The objective of this research is to study ice phase effect on the seasonal variation of PAHs in the Tumen River environment. MATERIALS AND METHODS: Samples were collected from 13 sites along the River in March, July, October, and December of 2008. In addition, the ice sample, under ice water and air particulate were also collected in winter. The samples were analyzed for 16 PAHs (naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, beazo[a]anthene, chrysene, beazo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indeno(1,2,3-cd)pyrene, dibenz(a,h)anthracene, and benzo(ghi)perylene). The compounds were extracted from the water samples and solid samples using LLE and Soxhlet extraction technique, respectively, and it is determined by gas chromatography-mass spectrometry. RESULTS AND DISCUSSION: Among 16 PAHs, fluorene, phenanthrene, and pyrene were found to be present in high concentrations and at high detection frequencies. The total concentration of PAHs in the water, particulate, sediment and ice phase ranged from 35.1-1.05 x 10(3) ng L(-1), 25.4-817 ng L(-1), 117-562 ng g(-1)and 62.8-136 ng g(-1), respectively. The levels of PAHs were generally higher in spring than other seasons. The ice phase in winter acts like a major reservoir of the pollutants and it is major contributor on the seasonal variation of PAHs in Tumen River. The PAHs found in water, particulate, and sediment in the Tumen River were possibly derived from similar pollution sources a proposition based on the compositions and isomer ratios of PAHs. CONCLUSIONS: The distribution of PAHs was showed clear seasonal variation in the Tumen River environment, the ice phase and air pollution look like an important factor affecting on the seasonal variation. RECOMMENDATIONS AND PERSPECTIVES: The ice phase as an important factor affecting on the seasonal variation of PAHs in Tumen River environment. Further studies regarding the effects of air pollution on the river and the mechanisms of migration and transformation of them in the environment are currently being conducted in our laboratory.

Effective nitrosamines trap derived from the in situ carbonized mesoporous silica MCM-41.

A new route to modify the mesoporous silica MCM-41 with carbon, using the inherent surfactant template in the as-synthesized sample as the carbon precursor, is reported in this article. Apart from the advantage of omitting energy and time required for removal of template, the resulting silica-carbon composites exhibit a high efficiency in adsorption and catalytic decomposition of N-nitrosopyrrolidine (NPYR), the typical carcinogenic pollutant in environment. The influence of carbonization temperature on the structure and performance of the resulting carbon-silica composite was investigated by use of XRD, N(2) adsorption-desorption, FTIR and TG-DSC techniques, and the instantaneous adsorption and the temperature-programmed surface reaction (TPSR) of NPYR as well as the reduction of nitrosamines level of cigarette smoke were also utilized to assess the actual function of these composites. The carbonization performed in the range of 773-973 K enabled the resulting composites to possess a higher activity than parent MCM-41 in eliminating volatile nitrosamines, which is beneficial for controlling carcinogenic pollutants in environment.

Treatment of groundwater contaminated with gasoline components by an ozone/UV process.

In this paper, the treatment of real groundwater samples contaminated with gasoline components, such as benzene, toluene, ethylbenzene, and xylene (BTEX), methyl tert-butyl ether (MTBE), tert-butyl alcohol (TBA), and other gasoline constituents in terms of total petroleum hydrocarbons as gasoline (TPHg) by an ozone/UV process was investigated. The treatment was conducted in a semi-batch reactor under different experimental conditions by varying ozone gas dosage and incident UV light intensity. The groundwater samples contained BTEX compounds, MTBE, TBA, and TPHg in the ranges of 5-10000, 3000-5500, 80-1400, and 2400-20000 microgl(-1), respectively. The ozone/UV process was very effective compared to ozonation in the removal of the gasoline components from the groundwater samples. For the various gasoline constituents, more than 99% removal efficiency was achieved for the ozone/UV process and the removal efficiency for ozonation was as low as 27%. The net ozone consumed per mol of organic carbon (from BTEX, MTBE, and TBA) oxidized varied in the range of 5-60 for different types of groundwater samples treated by the ozone/UV process. In ozonation experiments, it was observed that the presence of sufficient amount of iron in groundwater samples improved the removal of BTEX, MTBE, TBA, and TPHg.

Characterization of Cr(VI) removal from aqueous solutions by a surplus agricultural waste--rice straw.

The removal of Cr(VI) from aqueous solution by rice straw, a surplus agricultural byproduct was investigated. The optimal pH was 2.0 and Cr(VI) removal rate increased with decreased Cr(VI) concentration and with increased temperature. Decrease in straw particle size led to an increase in Cr(VI) removal. Equilibrium was achieved in about 48 h under standard conditions, and Cr(III), which appeared in the solution and remained stable thereafter, indicating that both reduction and adsorption played a part in the Cr(VI) removal. The increase of the solution pH suggested that protons were needed for the Cr(VI) removal. A relatively high level of NO(3)(-) notably restrained the reduction of Cr(VI) to Cr(III), while high level of SO(4)(2-) supported it. The promotion of the tartaric acid modified rice straw (TARS) and the slight inhibition of the esterified rice straw (ERS) on Cr(VI) removal indicated that carboxyl groups present on the biomass played an important role in chromium remediation even though were not fully responsible for it. Isotherm tests showed that equilibrium sorption data were better represented by Langmuir model and the sorption capacity of rice straw was found to be 3.15 mg/g.

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

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.