National Research Centre for Environmental Toxicology Publications - UQ eSpace

Consumption-based approach for assessing the contribution of hospitals towards the load of pharmaceutical residues in municipal wastewater

2012-06-26T15:12:10Z

Hospitals are considered as major sources of pharmaceutical residues discharged to municipal wastewater, but recent experimental studies showed that the contribution of hospitals to the loads of selected, quantifiable pharmaceuticals in sewage treatment plant (STP) influents was limited. However such conclusions are made based on the experimental analysis of pharmaceuticals in hospital wastewater which is hindered by a number of factors such as access to suitable sampling sites, difficulties in obtaining representative samples and availability of analytical methods. Therefore, this study explores a refined and extended consumption-based approach to predict the contribution of six selected Australian hospitals to the loads of 589 pharmaceuticals in municipal wastewater. In addition, the possibility that hospital-specific substances are present at levels that may pose a risk for human health was evaluated. For 63 to 84% of the pharmaceuticals investigated, the selected hospitals are not a major point source with individual contributions likely to be less than 15% which is in line with previous experimental studies. In contrast, between 10 and 20% of the pharmaceuticals consumed in the selected hospitals are exclusively used in these hospitals. For these hospital-specific substances, 57 distinct pharmaceuticals may cause concerns for human health as concentrations predicted in hospital effluents are less than 100-fold lower than effect thresholds. However, when concentrations were predicted in the influent of the corresponding STP, only 12 compounds (including the antineoplastic vincristine, the antibiotics tazobactam and piperacillin) remain in concentration close to effect thresholds, but further decrease is expected after removal in STP, dilution in the receiving stream and drinking water treatment. The results of this study suggest that risks of human exposure to the pharmaceuticals exclusively administered in the investigated hospitals are limited and decentralised wastewater treatment at these sites would not have a substantial impact on pharmaceutical loads entering STPs, and finally the environment. Overall, our approach demonstrates a unique opportunity to screen for pharmaceuticals used in hospitals and identifying priority pollutants in hospital wastewater explicitly accounting for site-specific conditions. Being based on consumption and loads discharged by hospitals into municipal wastewater, it is not limited by 1) the big effort to obtain representative samples from sewers, 2) the availability of sensitive chemical analysis or 3) a pre-selection of consumption data (e.g. consumption volume).

Contaminant bioavailability and bioaccessibility - Part 1: A scientific and technical review

2011-03-14T00:00:00Z

Contaminant bioavailability and bioaccessibility - Part 2: Guidance for industry

2011-03-14T00:00:00Z

Contaminant dietary exposure assessment for a coastal community in Moreton Bay, Queensland: Persistent organic pollutants in local seafood

2012-06-01T00:00:00Z

Contaminants in the Antarctic Environment. The Combined Effects of Cantamination and UV irradiation

2008-06-06T00:00:00Z

Contaminants in the Antarctic Environment VII. Linking Contamination to Ecological Risk

2008-06-06T00:00:00Z

Contaminants in the Antarctic Environment XII. Use of the Gammarid Paramorea walkeri as Potential Biological Indicator of Marine Environmental Contamination

2008-06-06T00:00:00Z

Contamination of Organochlorines Pesticides in Coastal Marine Environmental of Karachi (Pakistan)

2007-08-24T00:00:00Z

Coper chaperones: function, structure and copper-binding properties

2008-06-10T00:00:00Z

Copper is an absolute requirement for living systems and the intracellular trafficking of this metal to copper-dependent proteins is fundamental to normal cellular metabolism. The copper chaperones perform the dual functions of trafficking and the prevention of cytoplasmic exposure to copper ions in transit. Only a small number of copper chaperones have been identified at this time but their conservation across plant, bacterial and animal species suggests that the majority of living systems utilise these proteins for copper routing. The available data suggest that each copper-dependent protein in the cell is served by a specific copper chaperone. Although copper chaperones cannot be substituted for one another in a given cell type, copper chaperones that deliver to the same protein in different cell types appear to be functionally equivalent. The majority of the copper chaperones identified thus far have an "open-faced β-sandwich" global fold with a conserved MXCXXC metal-binding motif. Specificity for a given copper-dependent protein appears to be mediated by the residues surrounding the copper-binding motif. Copper binds to such proteins as Cu(I) in a trigonal complex with three sulfur ligands. Only the copper chaperone specific for cytochrome-c-oxidase, Cox17, deviates from this design.

Copper chaperones - Investigating how structure affects the metal binding properties

Cobine, P. A. og Dameron, C. — 2008-06-06T00:00:00Z

Copper chaperones - The key to understanding copper ion transport and delivery

2008-06-06T00:00:00Z

Copper (I) regulation of the repressor CopY: Novel metal replacements leading to structural rearrangements

2008-06-06T00:00:00Z

Copper salicylate and copper phenylbutazone as topically applied anti-inflammatory agents in the rat and horse

2011-02-09T00:00:00Z

Topically applied copper phenylbutazone, phenylbutazone, copper salicylate, salicylate and dimethylsulfoxide glycerol (80:20) were investigated as antiinflammatory agents in rats and horses. Dimethylsulfoxide and glycerol (80:20) or dimethylsulfoxide, ethanol and glycerol (60:20:20) were used as the drug solvents. Subcutaneously administered carrageenin was used to induce inflammatory oedema, either in the paws of rats or the alar fold of the horse. The severity of the oedema and the anti-inflammatory effect of the drugs were assessed by measuring changes in the paw or alar-fold diameters. Copper salicylate and copper phenylbutazone were effective inhibitors of the inflammatory oedema in both species, but dimethylsulfoxide:glycerol (80:20) was not. In the rat, copper salicylate and copper phenylbutazone were superior antiinflammatory agents compared to either salicylate or phenylbutazone, respectively. Following the topical application of four times the recommended daily dose of copper phenylbutazone to the horse for 5 days, minor skin irritation occurred and trace concentrations of phenylbutazone (maximum 0.6 μg/ml) and negligible concentrations of oxyphenbutazone and ß-hydroxyphenylbuta-zone were detected in the plasma.

CopZ and Chaperoning: The intracellular routing of copper by the CopZ Chaperone of Enterococcus hirae

2008-06-06T00:00:00Z

Correction of deployment specific chemical uptake rates for chlorinated pesticides accumulated by SPMD and PDMS passive sampling devices using a passive flow monitor

O'Brien, D. og Mueller, J. — 2013-04-15T12:13:30Z

Corrigendum to: Use of simple pharmacokinetic modeling to characterize exposure of Australians to perfluorooctanoic acid and perfluorooctane sulfonic acid (vol 36, pg 390, 2010)

2010-07-25T00:00:00Z

Coumarin 7-hydroxylase in inbred strains of mice: Comparison with other microsomal monooxygenase activities and induction by pyrazole

2009-11-30T00:00:00Z

This study was carried out in order to find out the effects of pyrazole on liver drug metabolism in several inbred mice: D2, B6, BALB, and AKR and in the outbred mouse NMRI. Compared to control pyrazole treatment decreased the microsomal cytochrome P-450 content of liver to 60-70% and benzo(a)pyrene hydroxylase and ethylmorphine N-demethylase activities to 40-55% and increased 7-ethoxycoumarin O-deethylase activity to 100-200% in AKR, BALB, B6, and NMRI mice and 300% in D2 mouse. Coumarin 7-hydroxylase was increased only 200-300% in B6, AKR, and BALB mice and as much as 700% in D2 and 900% in NMRI mice compared to control. Coumarin 7-hydroxylase is under different genetic control from other monooxygenase activities and differently expressed in various strains of mice.

Coupling of cyclooctyne with carbon monoxide on divalent molybdenum and tungsten. Crystal and molecular structure of a bis(hexamethylene)cyclopentadienonetungsten complex, W(S2CNMe2)2(CO){(C8H12)2CO}

2009-11-10T00:00:00Z

Cowal Gold Project: Comments on the Environmental Impact Statement

Noller, B. N. — 2007-08-14T00:00:00Z

Critical review of the environmental fate of TBT and its toxicological effect on the Pacific oyster Crassostrea gigas including at Georges Bay and other locations

Noller, B. N. — 2007-08-14T00:00:00Z

Cutaneous hypersensitivity reactions to freshwater cyanobacteria - human volunteer studies

2007-08-15T00:00:00Z

Cyanide Use, Wildlife Protection and the International Cyanide Management Code: An Industry Brokered Partnership Approach

2007-08-23T00:00:00Z

Cyanobacterial lipopolysaccharides and human health - a review

2007-08-15T00:00:00Z

Cyanobacterial lipopolysacchariedes and human illness - An alternative hypothesis

2007-08-24T00:00:00Z

Cyanobacterial poisoning in livestock, wild mammals and birds - an overview.

2009-02-10T00:00:00Z

Poisoning of livestock by toxic cyanobacteria was first reported in the 19th century, and throughout the 20th century cyanobacteria–related poisonings of livestock and wildlife in all continents have been described. Some mass mortality events involving unrelated fauna in prehistoric times have also been attributed to cyanotoxin poisoning; if correct, this serves as a reminder that toxic cyanobacteria blooms predate anthropogenic manipulation of the environment, though there is probably general agreement that human intervention has led to increases in the frequency and extent of cyanobacteria blooms. Many of the early reports of cyanobacteria poisoning were anecdotal and circumstantial, albeit with good descriptions of the appearance and behaviour of cyanobacteria blooms that preceded or coincided with illness and death in exposed animals. Early necropsy findings of hepatotoxicity were subsequently confirmed by experimental investigations. More recent reports supplement clinical and post–mortem findings with investigative chemistry techniques to identify cyanotoxins in stomach contents and tissue fluids.

Cyanobacterial toxins and drinking water guidelines

Wickramasinghe, Wasantha A. og Shaw, Glen R. — 2009-11-30T00:00:00Z

The occurrence of toxic cyanobacterial blooms has been reported worldwide and pose a threat to human health through drinking water exposure. The toxins they produced are highly water soluble and can leach into the water body. To eliminate any risk of drinking water exposure, removal of these toxins is essential before the water is consumed. Conventional water treatment techniques such as chlorination, if managed well, can be effectively used to remove some of these toxins, however, saxitoxin and derivatives pose a problem. Little toxicological data are available to evaluate the real threat of these toxins.

Cyanobacterial toxins, drinking water and human health

Wickramasinghe, Wasantha A. og Shaw, Glen R. — 2009-11-24T00:00:00Z

Cyanobacterial Toxins in Drinking Water, Extraction Using Carbograph Cartridges

2007-08-23T00:00:00Z

Cylindrospermopsin, A cyanobacterial alkaloid: Evaluation of its toxicologic activity

2008-06-10T00:00:00Z

This paper describes the natural occurrence of the toxin, cylindrospermopsin, in two species of cyanobacteria found in Australia. The structure and chemical properties of this compound are described along with a nontoxic analog of cylindrospermopsin. The results of both intraperitoneal (IP) and oral dosing of mice show that hepatotoxicity is the main effect of cylindrospermopsin in vivo, but that a thrombo-hemorrhagic phenomenon is observed in a proportion of dosed animals. It has been shown that the toxin can be metabolized in vivo and that a bound metabolite occurs in the liver. Cytotoxicity experiments using cell cultures show that cylindrospermopsin is more cytotoxic to isolated rat liver hepatocytes than to other cell types. Risk assessment calculations show that guideline values for cylindrospermopsin in drinking water should lie in the low microgram per liter range.

Cylindrospermopsin, A cyanobacterial alkaloid toxin - Evaluation of its pharmacological activity

2008-06-06T00:00:00Z

CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: Regional and inter-individual variation in expression and relevance to nitrosamine metabolism

2009-11-30T00:00:00Z

CYP2A6 genotypes and coumarin-oxidation phenotypes in a Thai population and their relationship to tobacco smoking

2009-09-03T00:00:00Z

CYP2A5-mediated activation and early ultrastructural changes in the olfactory: Studies on 2,6-dichlorophenyl methylsulfone

2009-11-30T00:00:00Z

2,6-Dichlorophenyl methylsulfone (2,6-diClPh-MeSO2) is a potent olfactory toxicant reported to induce endoplasmic reticulum (ER) stress, caspase activation, and extensive cell death in mice. The aim of the present study was to examine cytochrome P450 (P450)- dependent bioactivation, nonprotein sulfhydryl (NP-SH) levels, and early ultrastructural changes in mouse olfactory mucosa following an i.p. injection of 2,6-diClPh-MeSO2 (32 mg/kg). A high covalent binding of 2,6-diClPh-14C-MeSO2 in olfactory mucosa S9 fraction was observed, and the CYP2A5/CYP2G1 substrates coumarin and dichlobenil significantly decreased the binding, whereas the CYP2E1 substrate chlorzoxazone had no effects. An increased bioactivation was detected in liver microsomes of mice pretreated with pyrazole, known to induce CYP2A4, 2A5, 2E1, and 2J, and addition of chlorzoxazone reduced this binding. 2,6-DiClPh-14CMeSO2 showed a marked covalent binding to microsomes of recombinant yeast cells expressing mouse CYP2A5 or human CYP2A6 compared with wild type. One and 4 h after a single injection of 2,6-diClPh-MeSO2, the NP-SH levels in the olfactory mucosa were significantly reduced compared with control, whereas there was no change in the liver. Ultrastructural studies revealed that ER, mitochondria, and secretory granules in nonneuronal cells were early targets 1 h after injection. We propose that lesions induced by 2,6-diClPh-MeSO2 in the mouse olfactory mucosa were initiated by a P450-mediated bioactivation in the Bowman’s glands and depletion of NP-SH levels, leading to disruption of ion homeostasis, organelle swelling, and cell death. The high expression of CYP2A5 in the olfactory mucosa is suggested to play a key role for the tissue-specific toxicity induced by 2,6- diClPh-MeSO2.

Cytochrome P4502A-mediated coumarin 7-hydroxylation and testosterone hydroxylation in mouse and rat lung

2009-11-30T00:00:00Z

Pulmonary coumarin 7-hydroxylase, testosterone hydroxylase and other P450-mediated activities were compared in the mouse and rat. Coumarin 7-hydroxylase activity was 20 pmol/mg/min. in mouse and 4 pmol/mg/min. in rat lung microsomes. Liver values were 180 (mouse) and 1 (rat) pmol/mg/min. K(m) values of rat and mouse lung coumarin 7-hydroxylase were about 1 μM whereas the rat liver k(m) value was > 100 μM. Phenobarbital and 3-methylcholanthrene did not affect rat lung (or liver) coumarin 7-hydroxylase activity. Anti-Cyp2A-5 antibody effectively inhibited mouse and rat lung coumarin 7-hydroxylase and testosterone 15α-hydroxylations but failed to block these activities in the rat liver. In immunoblot analysis anti-Cyp2a-5 antibody recognized the 50-kDa Cyp2a-4/5 protein in mouse lung microsomes. A P450 protein co-migrating with Cyp2a-5 was also detected in rat lung microsomes. Cyp2a-5 cDNA probe hybridized with a 1.8-kb mRNA species in rat lung RNA fraction. The hybridization signal was not increased by 3-methylcholanthrene or phenobarbital. These data suggest that the mouse lung expresses CYP2A-5 which differs from the liver enzyme only in its regulation and that the rat lung contains a P450 isoform(s) belonging to the 2A subfamily which may be orthologous with the moue Cyp2a-4/5 catalyzing coumarin 7-hydroxylase and testosterone 15α-hydroxylase activities. The recently reported rat lung CYP2A3 (Kimura et al.) gene product is a candidate for the observed coumarin 7-hydroxylase activity in the rat lung.

Cytochrome P450 2a of nasal epithelium: Regulation and role in carcinogen metabolism

2009-11-30T00:00:00Z

In this study, we found that rat nasal coumarin-7–hydroxylase (a) activity was two orders of magnitude higher than rat hepatic COH activity and could be induced by adding coumarin to the rats' drinking water. In western blot analysis, an anti-cytochrome P450 (a) 2a-5 (mouse liver COH) antibody recognized a sharp band in the microsomal fraction of rat nasal epithelium but not of the liver; the band comigrated with Cyp2a-5. The intensity of the band was increased by the coumarin treatment. Similarly, in northern blot analysis, a cDNA probe specific for Cyp2a-5 recognized an mRNA in the nasal epithelium having the same size as mouse liver Cyp2a-5 mRNA; however, no hybridizable mRNA was recognized in liver preparations. Unlike the protein level, the level of the mRNA was not increased by coumarin. When northern blot analyses were performed with two oligoprobes specific for rat lung CYP2A3, an mRNA of similar size to Cyp2a-5 mRNA was recognized. In immunoinhibition analysis, anti-Cyp2a-5 antibody inhibited rat nasal COH activity and aflatoxin B1 (AFB1) metabolism completely. It inhibited N-nitrosodiethylamine (a) and 4- (a) -1-(3-pyridyl)-1-butanone (a) metabolism by 80–90%. In contrast, the hepatic metabolism of the four compounds was not affected by the antibody. When coumarin instead of anti-Cyp2a-5 antibody was used, a strong but variable inhibition of the nasal metabolism of AFB1, NDEA, and NNK was seen. The results suggest that an enzyme or enzymes similar to mouse liver Cyp2a-5, one of which may be CYP2A3, is expressed at high levels in rat nasal epithelium but not in the liver and that its expression is increased by coumarin, an odorant and a substrate of Cyp2a-5. The increase probably occurs by protein stabilization or stimulation of translation. The results also show that the enzyme has a key role in the nasal metabolism of three well-known carcinogens, AFB1, NDEA, and NNK and may therefore be an important contributing factor in nasal carcinogenesis.

Cytochrome P450 isozyme protein verified in the skin of southern hemisphere humpback whales (Megaptera novaeangliae): Implications for biochemical biomarker assessment

2012-02-20T00:00:00Z

D-2-dopaminergic receptor-linked pathways: critical regulators of CYP3A, CYP2C, and CYP2D

2012-11-25T00:00:00Z

Decision process for comparison of partial and complete XANES spectra

2010-03-13T00:00:00Z

Decision support for the management of circulatory shock

2009-11-26T00:00:00Z

Decline of maternal blood lead concentrations in Glasgow

2007-08-13T00:00:00Z

Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9)

2007-08-15T00:00:00Z

One of seven poor metabolizers of coumarin found in Thai subjects was previously genotyped as heterozygote for the CYP2A6*4 (whole deletion) and CYP2A6*9. Thus, we aimed to investigate the relationship between the genetic polymorphism in the TATA box of the CYP2A6 gene (CYP2A6*9), expression levels of CYP2A6 mRNA and coumarin 7-hydroxylase activities in human livers. Levels of CYP2A6 mRNA were quantified by real-time quantitative reverse transcriptase-polymerase chain reaction. The mean expression levels of CYP2A6 mRNA in individuals with CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 58%, 71% and 21% of the individuals genotyped as CYP2A6*1/*1, respectively. The mean in-vitro coumarin 7-hydroxylase activities in subjects carrying CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 41%, 71% and 12%, respectively, compared to those of the subjects judged as wild-type. Vmax values for coumarin 7-hydroxylation in the liver microsomes from human subjects with genotypes of CYP2A6*1/*1, CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 0.58, 0.26, 0.44 and 0.13 nmol/min/nmol total P450, respectively. CYP2A6 protein levels in human liver microsomes with the CYP2A6*4 and the CYP2A6*9 alleles were markedly decreased. These results suggest that the genetic polymorphism in the promoter region of the CYP2A6 gene (CYP2A6*9) reduced the expression levels of CYP2A6 mRNA and protein in human livers, resulting in the decrease of coumarin 7-hydroxylase activities. Individuals judged as CYP2A6*4/*9 were expected to be poor metabolizers, having extremely low activity of CYP2A6.

Defining the specificity metal transfer ractions from metallochaperones to enzymes

2008-06-06T00:00:00Z

Defining the specificity metal transfer reactions from metallochaperones to enzmyes

2008-06-06T00:00:00Z

Degradation and contamination of land due to economic development: A public health perspective

Ng, J. C. — 2008-06-06T00:00:00Z

Degradation of cylindrospermopsin and chloro-cylindrospermopsin. A kinetic study

2007-08-24T00:00:00Z

Degradation of Land and Its Relation to Public Health

Ng, J. C. — 2007-08-14T00:00:00Z

Degradation of the cyanobacterial toxin cylindrospermopsin from Cylindrospermopsis raciborskii, by chlorination

2008-06-10T00:00:00Z

Cylindrospermopsin, a potent cyanobacterial toxin produced by Cylindrospermopsis raciborskii and other cyanobacteria, is regularly found in water supplies of Queensland, Australia. This study focussed on the e€ectiveness of chlorination as a water treatment procedure for cylindrospermopsin degradation. The results demonstrate that relatively low chlorine doses (<1 mg lÿ1) are sucient for degradation of cylindrospermopsin, when the dissolved organic carbon content is low. However, if organic matter other than cylindrospermopsin is present in the solution, the e€ectiveness of chlorine for cylindrospermopsin degradation is reduced as other organic matter present consumes chlorine. Under the experimental conditions using samples with a solution pH of 6±9, a residual chlorine concentration of 0.5 mg lÿ1 was sucient to degrade >99% of cylindrospermopsin. Toxin degradation via chlorination occurs within the ®rst minute and no di€erence was observable between degradation in an open system and in a closed system. With a decrease of the pH from 6 to 4 a reduction in the eciency of chlorine for degradation of cylindrospermopsin was observable, a possible indication that cylindrospermopsin is more stable to chlorine degradation at lower pH. However, in normal water treatment this is not relevant since the pH is consistently higher than 6.

Degradation of the cyanobacterial toxin cylindrospermopsin using various treatment methods

2008-06-06T00:00:00Z

Dental clinics: A point pollution source, not only of mercury but also of other amalgam constituents

2011-05-06T00:00:00Z

Deoxycylindrospermopsin, an analog of cylindrospermopsin from Cylindrospermopsis raciborskii

2008-06-10T00:00:00Z

Cylindrospermopsin (CYN) is a hepatotoxic alkaloid found in the blue-green alga Cylindrospermopsis raciborskii (C. raciborskii). Data indicating CYN alone does not account for the toxicity of freeze dried cultures of C. raciborskii have been presented recently. In an attempt to explain these data, we have purified and characterized the structure of an analog of CYN, deoxycylindrospermopsin (deoxy-CYN). Three mice dosed intraperitoneally (IP) with 0.8 mg/kg of deoxy-CYN showed no toxicity after 5 days. Comparison with the toxicity of CYN (5 day median lethal dose approximately 0.2 mg/kg IF) and its relative abundance in C. raciborskii suggest deoxy-CYN does not contribute significantly to the toxicity of C. raciborskii. The additional toxicity of freeze dried C. raciborskii over pure CYN, therefore, remains unexplained. (C) 1999 by John Wiley & Sons, Inc.