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Richland, WA, United States

Bull R.J.,MoBull Consulting | Crook J.,Environmental Consulting Engineer | Whittaker M.,ToxServices LLC | Cotruvo J.A.,Joseph Cotruvo and Associates LLC
Regulatory Toxicology and Pharmacology | Year: 2011

The detection of drugs in drinking water sources has raised questions related to safety. In the absence of regulatory or other official guidance, water utilities are faced with a problem of which drugs should be monitored and the detection limits that should be required. The US FDA summarizes data required for drug approval and post marketing adverse reaction reporting. The use of these data as a means of arriving at concentrations in water where adverse health effects are minimal or non-existent was explored. The minimum therapeutic dose was assumed an appropriate point of departure. Appropriate uncertainty factors could be applied depending upon the qualitative and quantitative nature of the data that are available. Assumptions inherent in US FDA's approval of drugs for use in subsets of the population relative to the broader concerns that arise for exposures of the entire population had to be considered. Additional questions are; whether the drug under consideration is carcinogenic, carries pregnancy and lactation warnings, approval for limited vs. chronic use, exposures to multiple compounds that could act in additive or synergistic ways, and the seriousness of toxicities that are observed. Aside from these considerations, a combined uncertainty factor of 1000 appeared adequate. © 2011 WateReuse Research Foundation.


Zhao Y.,University of Alberta | Anichina J.,University of Alberta | Lu X.,University of Alberta | Bull R.J.,MoBull Consulting | And 3 more authors.
Water Research | Year: 2012

Consumption of chlorinated drinking water has shown somewhat consistent association with increased risk of bladder cancer in a series of epidemiological studies, but plausible causative agents have not been identified. Halobenzoquinones (HBQs) have been recently predicted as putative disinfection byproducts (DBPs) that might be of toxicological relevance. This study reports the occurrence frequencies and concentrations of HBQs in plant effluents from nine drinking water treatment plants in the USA and Canada, where four common disinfection methods, chlorination, chloramination, chlorination with chloramination, and ozonation with chloramination, are used. In total, 16 water samples were collected and analyzed for eight HBQs: 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), 2,6-dichloro-3-methyl-1,4-benzoquinone (2,6-DC-3-MBQ), 2,3,6-trichloro-1,4-benzoquinone (2,3,6-TriCBQ), 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ), 2,3-dibromo-5,6-dimethyl-1,4-benzoquinone (2,3-DB-5,6-DM-BQ), tetrabromo-1,4-benzoquinone (TetraB-1,4-BQ), and tetrabromo-1,2-benzoquinone (TetraB-1,2-BQ). Of these, 2,6-DCBQ, 2,6-DBBQ, 2,6-DC-3-MBQ and 2,3,6-TriCBQ were detected in 16, 11, 6, and 3 of the 16 samples with the method detection limit (DL) of 1.0, 0.5, 0.9 and 1.5 ng/L, respectively, using a solid phase extraction and high performance liquid chromatography-tandem mass spectrometry method. The concentrations were in the ranges of 4.5-274.5 ng/L for 2,6-DCBQ, below DL to 37.9 ng/L for 2,6-DBBQ, below DL to 6.5 ng/L for 2,6-DC-3-MBQ, and below DL to 9.1 ng/L for 2,3,6-TriCBQ. These authentic samples show DCBQ and DBBQ as the most abundant and frequently detectable HBQs. In addition, laboratory controlled experiments were performed to examine the formation of HBQs and their subsequent stability toward hydrolysis when the disinfectants, chlorine, chloramine, or ozone followed by chloramines, reacted with phenol (a known precursor) under various conditions. The controlled reactions demonstrate that chlorination produces the highest amounts of DCBQ, while pre-ozonation increases the formation of DBBQ in the presence of bromide. At pH < 6.8, 2,6-DCBQ was observed to be stable, but it was easily hydrolyzed to form mostly 3-hydroxyl-2,6-DCBQ at pH 7.6 in drinking water. © 2012 Elsevier Ltd.


Laingam S.,Australian Water Quality Center | Froscio S.M.,Australian Water Quality Center | Bull R.J.,MoBull Consulting | Humpage A.R.,Australian Water Quality Center
Environmental and Molecular Mutagenesis | Year: 2012

Disinfection by-products (DBPs) are of concern to both water industries and health authorities. Although several classes of DBPs have been studied, and there are regulated safe levels in disinfected water for some, a large portion of DBPs are not characterized, and need further investigation. Organic N-chloramines are a group of DBPs, which can be formed during common disinfection processes such as chlorination and chloramination, but little is known in terms of their toxicological significance if consumed in drinking water. Only a few in vitro studies using bacterial assays have reported some genotoxic potential of organic N-chloramines, largely in the context of inflammatory processes in the body rather than exposure through drinking water. In this study, we investigated 16 organic N-chloramines produced by chlorination of model amino acids and amines. It was found that within the drinking water-relevant micromolar concentration range, four compounds were both cytotoxic and genotoxic to mammalian cells. A small reduction of cellular GSH was also observed in the treatment with these four compounds, but not of a magnitude to account for the cytotoxicity and genotoxicity. The results presented in this study demonstrate that some organic N-chloramines, at low concentrations that might be present in disinfected water, can be harmful to mammalian cells. © 2011 Wiley Periodicals, Inc.


Kolisetty N.,University of Georgia | Delker D.A.,University of Utah | Muralidhara S.,University of Georgia | Bull R.J.,MoBull Consulting | And 3 more authors.
Archives of Toxicology | Year: 2013

Bromate (BrO3 -), a by-product of ozonation of drinking water, induces nephrotoxicity in male rats at much lower doses than in female rats. This difference appears to be related to the development of α-2u-globulin nephropathy in males. To determine sex-dependent changes in mRNA and protein expression in the renal cortex attributable to α-2u-globulin nephropathy, we performed microarray and immunohistochemical analyses in proximal renal tubules of male and female F344 rats treated with KBrO3 for 28 days. Particular attention was paid to molecular biomarkers of renal tubular injury. Microarray analysis of male and female rats treated with BrO3 - at low doses (125 mg/L KBrO3) displayed marked sex-dependent changes in renal gene expression. The greatest differences were seen in genes encoding for cellular differentiation, apoptosis, ion transport, and cell proliferation. Differences by sex were especially prominent for the cell cycle checkpoint gene p21, the renal injury protein Kim-1, and the kidney injury and cancer biomarker protein osteopontin. Dose-related nephrotoxicity, assessed by hematoxylin and eosin staining, was greater in males compared to female rats, as was cellular proliferation, assessed by bromodeoxyuridine staining. The fraction of proximal renal cells with elevated 8-oxodeoxyguanosine (8-OH-dG) was only increased at the high dose and did not differ by sex. Dose-dependent increases in the expression of osteopontin were detected immunohistochemically only in male rats and were localized in proximal tubule cells. Similarly, BrO3 - treatment increased clusterin and Kim-1 staining in the proximal tubules; however, staining for these proteins did not differ appreciably between males and females. These data demonstrate both qualitative and quantitative differences in the response of male versus female kidneys to BrO3 --treatment. These sex-dependent effects likely contribute to renal carcinogenesis of BrO3 - in the male rat. © 2013 Springer-Verlag Berlin Heidelberg.


Cotruvo J.A.,Joseph Cotruvo and Associates LLC | Bull R.J.,MoBull Consulting | Pacey G.E.,Miami University Ohio | Gordon G.,Miami University Ohio
Journal / American Water Works Association | Year: 2010

Bromate decomposition kinetics with simulated stomach/gastric juice was studied to contibute to more accurate determination of the risk of environmentally relevant exposures to bromate. Any presystemic reduction in the stomach would yield lower risks. Bromate is rapidly reduced by hydrogen sulfide (H 2S); half-lives were 153 min at zero H 2S and 2,24, and 32 min at 10 -4, 10 -5, and 10 -6 MH 2S, respectively. Half-lives at 10 -4 and 10 -5 Mare biologically relevant for the retention time for water in an empty stomach. Common dietary inorganic reducing agents (ferrous, iodide, and nitrite) generally enhanced bromate reduction with H2S. Oxidizing agents (hypochlorous acid/chlorine, chloramine, and ferric ion) usually modestly reduced decomposition rates with H 2S. Consumption of chlorinated or chloraminated drinking water containing bromate would not materially affect the extent of presystemic brómate reduction. Current studies by the authors are quantifying brómate reduction from the greater systemic liver and blood metabolism, where rapid reactions with glutathione and other reducing agents occur.

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