Radiation Dose Reduction for Computed Tomography Localizer Radiography Using an Ag Additional Filter.

OBJECTIVE: This study aimed to assess the potential of an Ag additional filter attached to the bow tie filter of a computed tomography (CT) scanner to reduce the radiation dose in CT localizer radiography. METHODS: Radiation doses in CT localizer radiography with Cu and Ag additional filters were evaluated based on dose measurements and Monte Carlo simulations. Image quality evaluations of an adult torso phantom were performed, and the automatic exposure control performance was evaluated in terms of the water-equivalent thickness estimated from CT localizer radiographs. RESULTS: With the Ag additional filter, effective doses were approximately 72% to 75% lower than those with the Cu additional filter. The image quality and water-equivalent thickness with the Ag additional filter were similar to those with the Cu additional filter. CONCLUSIONS: The Ag additional filter helped significantly reduce radiation doses in CT localizer radiography while maintaining image quality and performance.

Reversal of heavy metal-induced antibiotic resistance by dandelion root extracts and taraxasterol.

Introduction. Metal exposure is an important factor for inducing antibiotic resistance in bacteria. Dandelion extracts have been used for centuries in traditional Chinese and Native American medicine.Aim. We assessed the effects of dandelion water extracts and taraxasterol on heavy metal-induced antibiotic resistance in Escherichia coli as well as the underlying mechanisms.Methodology. Dandelion extracts were obtained through 4 h of boiling in distilled water. Bacterial growth was monitored with a spectrophotometer. Biochemical assays were performed to assess the activities and gene transcriptions of ß-lactamase and acetyltransferase. Oxidative stress was determined using an oxidation-sensitive probe, H2DCFDA.Results. The present study demonstrated that higher concentrations of nickel (>5 µg ml-1), cadmium (>0.1 µg ml-1), arsenic (>0.1 µg ml-1) and copper (>5 µg ml-1) significantly inhibited the growth of E. coli. Lower concentrations of nickel (0.5 µg ml-1), cadmium (0.05 µg ml-1) and arsenic (0.05 µg ml-1) had no effect on bacterial growth, but helped the bacteria become resistant to two antibiotics, kanamycin and ampicillin. The addition of dandelion root extracts and taraxasterol significantly reversed the antibiotic resistance induced by these heavy metals. The supplements of antibiotics and cadmium generated synergistic effects on the activities of ß-lactamase and acetyltransferase (two antibiotic resistance-related proteins), which were significantly blocked by either dandelion root extract or taraxasterol. In contrast, oxidative stress was not involved in the preventative roles of dandelion root extracts and taraxasterol in heavy metal-induced antibiotic resistance.Conclusion. This study suggests that heavy metals induce bacterial antibiotic resistance and dandelion root extracts and taraxasterol could be used to help reverse bacterial resistance to antibiotics.

Assessment of Copper Nanoclusters for Accurate in Vivo Tumor Imaging and Potential for Translation.

Nanoparticles have been widely used for preclinical cancer imaging. However, their successful clinical translation is largely hampered by potential toxicity, unsatisfactory detection of malignancy at early stages, inaccurate diagnosis of tumor biomarkers, and histology for imaging-guided treatment. Herein, a targeted copper nanocluster (CuNC) is reported with high potential to address these challenges for future translation. Its ultrasmall structure enables efficient renal/bowel clearance, minimized off-target effects in nontargeted organs, and low nonspecific tumor retention. The pH-dependent in vivo dissolution of CuNCs affords minimal toxicity and potentially selective drug delivery to tumors. The intrinsic radiolabeling through the direct addition of 64Cu to CuNC (64Cu-CuNCs-FC131) synthesis offers high specific activity for sensitive and accurate detection of CXCR4 via FC131-directed targeting in novel triple negative breast cancer (TNBC) patient-derived xenograft mouse models and human TNBC tissues. In summary, this study not only reveals the potential of CXCR4-targeted 64Cu-CuNCs for TNBC imaging in clinical settings, but also provides a useful strategy to design and assess the translational potential of nanoparticles for cancer theranostics.

Assessing exposure to metals using biomonitoring: Achievements and challenges experienced through surveys in low- and middle-income countries.

In this narrative account based on a keynote presentation on exposure biomonitoring of metals in low- and middle-income countries (LMIC), we first briefly address practical issues that have arisen from our experience during the conduct of various surveys in LMIC. These have included the statistical handling of multiple pollutants in the same subject, the problem of correctly adjusting for urinary flow in spot samples of urine, and the possible external contamination of samples when doing field surveys in challenging environments. We then review and present selected results from surveys conducted in the mining area of Katanga in the Democratic Republic of Congo (DR Congo), where we documented high urinary levels of cobalt and other trace metals (arsenic, uranium) in people living close (<3 km) to mining or smelting operations (Banza et al., 2009). Consumption of contaminated foodstuffs (maize, legumes, fish) and, especially among children, dust ingestion proved to be the main sources of exposure to cobalt (Cheyns et al., 2014). Urinary biomonitoring studies among artisanal workers involved in mining cobalt, craftsmen working malachite, and workers processing gold ore revealed high to extremely high values of cobalt (largely exceeding the Biological Exposure Index of 15 µg/L), as well as other trace metals such as uranium, manganese, lead or mercury, depending on the type of jobs. This abundant biomonitoring data has been valuable to argue for improved enforcement of legislation to protect workers and citizens against the hazards posed by the mining activities in the area. Epidemiological studies have been undertaken and are ongoing to assess the human health impact of this pollution.

Testing hypotheses on the resistance to metals by Daphnia longispina: differential acclimation, endpoints association, and fitness costs.

Pollution by metals may lead to an increased tolerance in the exposed population through adaptive microevolution, with resistant genotypes becoming more abundant than in reference sites. This work investigated the outcomes associated with selection for resistance by testing three hypotheses to assess the following: Do resistant versus sensitive clonal lineages of Daphnia longispina differentially acclimate to metals during a long-term sublethal exposure, is there a significant correlation between lethal and sublethal responses, and does resistance to metals entail costs to fitness under uncontaminated conditions? No evidence of acclimation was observed. The median effective dilutions of acid mine drainage for reproduction were similar for successive broods within clones during long-term exposures. Lethal and sublethal responses were not correlated, indicating that mechanisms regulating the two types of response were more than likely different. Finally, fitness costs associated with the resistance to lethal levels of metals were not detected, but resistance to sublethal levels of Cu was found to be correlated with a lower intrinsic growth rate under control conditions.

Essentiality and toxicity in copper health risk assessment: overview, update and regulatory considerations.

Copper (Cu), an essential element required as a cofactor and/or structural component of numerous metalloenzymes, is uniquely positioned as a case study for issues associated with the essential metals health risk assessment, because of its extensive database. Essential elements pose distinct challenges when establishing regulatory guidelines because too little as well as too much intake can produce adverse health consequences and the dose-response curve is roughly U-shaped. Thus, conventional health risk assessment paradigms do not apply to essential elements; the dose-response assessment needs to define an acceptable range of oral intake (AROI) which prevents deficiency by meeting nutritional requirements while avoiding toxicity due to high intakes. The conceptual framework for this type of risk assessment includes consideration of biological processes that are unique to essential elements-homeostasis, basal and normative nutritional requirements, bioavailability, and nutrient-nutrient interactions. In this paper, the Cu database on physiology, deficiency, and excess is briefly reviewed in order to establish the range of potential health hazards associated with varying levels of intake. Issues discussed include the (1) development of suitable dose-response methodologies, including appropriate dose and response metrics, for Cu; (2) categorization of severity of response and functional significance; (3) use of endpoints of similar severity and functionality for deficiency and excess in dose-response assessment; (4) development of valid biomarkers for subclinical effects, exposures and susceptibilities. Guideline values for Cu intake have been established by nutritional and toxicologic regulatory or advisory boards. Although regulators are more concerned with the potential human toxicity arising from excessive Cu intake, the preponderance of evidence suggests that deficiency is more of a public health concern than excess.

Is copper-silver ionisation safe and effective in controlling legionella?

Copper-silver ionisation is gaining popularity worldwide as a water disinfection method. We review the literature that supports the effectiveness and safety of the copper-silver ionisation pertaining to legionella control in water distribution systems. A search between January 1997 and January 2007 was conducted in relevant health databases: Medline, Embase, NHS CRD, Cochrane Library Plus, Web of Knowledge, IME (Spanish Medical Index) and IBECS (Health Sciences Bibliographic Index). Ten published studies were selected according to inclusion and exclusion criteria previously established; most of these were experimental. Legionella levels decrease with the application of any of the procedures used in these studies and the procedures can be combined to obtain better outcomes. No studies containing an economic evaluation were found. We conclude that copper-silver ionisation is an effective method to control legionella, bearing in mind that eradication cannot be achieved by any method in isolation. Maintaining high temperatures in the water system can maximise effectiveness of the method. Copper-silver appears to be safe, as long as ion levels are monitored and kept within international recommended levels. More studies with concurrent control group, long follow-up and economic evaluation are required to properly assess this procedure.

An assessment of the safety of copper heptonate for parenteral therapy in sheep.

OBJECTIVE: To investigate any adverse effects of an intramuscular injection (i.m.) of copper heptonate (CuHep) in sheep. PROCEDURE: Merino wethers about 9 months old were retained in pens and given 1 or 2 mg Cu/kg body weight as CuHep or no Cu treatment. Sheep were weighed and samples of blood for haematology, Cu and enzyme assay and tissues for Cu and Fe assay were collected before and at intervals over 21 days after treatment. RESULTS: CuHep was removed from the injection site within 7 days of treatment and most of it was retained in the liver. Wethers had adequate liver Cu reserves before treatment and the higher dosage of CuHep raised liver Cu to values associated with Cu toxicity. No clinical signs of Cu toxicity were evident. Transient increases in plasma activity of the liver enzyme glutamate dehydrogenase suggested mild liver necrosis due to CuHep, but there was no histopathological evidence of liver necrosis 7 days after treatment. CONCLUSIONS: I.m. injection of Cu as CuHep appears to be readily transferred to the liver. No significant necrosis is caused at the injection site.

Assessment of copper-nickel industry impact on a subarctic lake ecosystem.

The Kuetsjärvi lake ecosystem has been subject to intensive pollution generated by the Pechenganickel Company activities for more than 50 years. This article considers the effects of emissions from the copper-nickel smelter, that uses out-of-date technology, on a subarctic lake ecosystem. Six years of investigations revealed changes occurring at all ecosystem levels. It was found that the content of heavy metals (Cu, Ni, etc.) in lake sediments was dozens of times higher than the background values. Phyto- and zooplankton communities were in an unstable condition, while fish had pathologies of functionally important organs (gill, liver and kidney). The concentration of nickel in zoobenthos and fish was correlated its accumulation in sediments.

Health assessment of a marine bivalve Ruditapes decussatus from the Gulf of Gabès (Tunisia).

Metallothioneins (MTs), malonedialdehyde (MDA), and glycogen concentrations were determined in order to assess the health status of Ruditapes decussatus exposed to in situ contamination, showing the effects of time, site, and metal contamination on these three biomarkers. Metallothionein was positively correlated with Cd and Zn. If introduced in a multiple model, the factors site and time were shown to decrease significantly MT concentrations. MDA was inversely correlated with size of the animals and was affected by the factor time. Glycogen was inversely correlated with zinc and was affected by both site and time.This study constitutes a field-based validation of a multiparametric approach using specific and nonspecific biomarkers.

Human health risk assessment case study: an abandoned metal smelter site in Poland.

United States Environmental Protection Agency methodologies for human health risk assessment (HRA) were applied in a Brownfields Demonstration Project on the Warynski smelter site (WSS), an abandoned industrial site at Piekary Slaskie town, Upper Silesia, Poland. The HRA included the baseline risk assessment (BRA) and the development of risk-based preliminary remedial goals (RBPRGs). The HRA focused on surface area covered with waste materials, which were evaluated with regard to the potential risks they may pose to humans. Cadmium, copper, iron, manganese, lead, and zinc were proposed as the contaminants of potential concern (COPCs) at WSS based on archive data on chemical composition of waste located on WSS. For the defined future land use patterns, the industrial (I) and recreational (II) exposure scenarios were assumed and evaluated. The combined hazard index for all COPCs was 3.1E+00 for Scenario I and 3.2E+00 for Scenario II. Regarding potential carcinogenic risks associated with the inhalation route, only cadmium was a contributor, with risks of 1.6E-06 and 2.6E-07 for Scenario I and Scenario II, respectively. The results of the BRA indicated that the potential health risks at WSS were mainly associated with waste material exposure to cadmium (industrial and recreational scenarios) and lead (industrial scenario). RBPRGs calculated under the industrial scenario were 1.17E+03 and 1.62E+03 mg/kg for cadmium and lead, respectively. The RBPRG for cadmium was 1.18E+03 mg/kg under the recreational scenario. The BRA results, as well as RBCs, are comparable for both scenarios, so it is impossible to prioritize land use patterns for WSS based on these results. For choosing a future land use pattern or an appropriate redevelopment option, different factors would be decisive in the decision-making process, e.g., social, market needs, technical feasibility and costs of redevelopment actions or acceptance of local community.

Development of an improved rapid enzyme inhibition bioassay with marine and freshwater microalgae using flow cytometry.

A rapid toxicity test based on inhibition of esterase activity in marine and freshwater microalgae (Selenastrum capricornutum, Chlorella sp., Dunaliella tertiolecta, Phaeodactylum tricornutum, Tetraselmis sp., Entomoneis cf. punctulata, Nitzschia cf. paleacea) was developed using flow cytometry. Uptake of fluorescein diacetate (FDA) was optimized for each species by varying the substrate concentration, incubation time, and media pH. Propidium iodide (PI) was utilized to assess membrane integrity. The optimized FDA/PI staining procedure was then used to assess the toxicity of copper in short-term exposures (1-24 h). Esterase activity was a sensitive indicator of copper toxicity in S. capricornutum and E. cf. punctulata. As copper concentrations increased, esterase activity decreased in a concentration-dependent manner. The 3- and 24-h EC50 values (based on mean activity states) were 112 microg Cu L(-1) (95% confidence limits 88-143) and 51 microg Cu L(-1) (95% confidence limits 38-70) for S. capricornutum and 47 microg Cu L(-1) (95% confidence limits 43-51) and 9.1 microg Cu L(-1) (95% confidence limits 7.6-11) for E. cf. punctulata, respectively. This enzyme inhibition endpoint showed similar sensitivity to chronic growth rate inhibition in E. cf. punctulata (48-h and 72-h EC50 values of 17 and 18 microg L(-1), respectively) but was less sensitive compared to growth for S. capricornutum (48-h and 72-h EC50 values of 4.9 and 7.5 microg L(-1), respectively). For the other five species tested, inhibition of FDA fluorescence was relatively insensitive to copper, even at copper concentrations that severely inhibited cell division rate. These short-term bioassays that detect sublethal endpoints may provide a more rapid and cost-effective way of monitoring contaminant impacts in natural waters.

Assessment of metal content and toxicity of leachates from teapots.

Metallic teapots traditionally used in Morocco were investigated for release of toxic metals from the teapots and their toxicity, as determined by MetPAD, a bacterial toxicity test that is specific for heavy metal toxicity. Our data show that some teapots were non-toxic while a few others were highly toxic, as shown by MetPAD. Tea addition reduced somewhat heavy metal toxicity due possibly to the complexing ability of tea. Chemical analysis of teapot leachates showed that some contained zinc and copper. Teapot No. 5, which showed the highest toxicity, also displayed the highest Zn concentration (7.39 mg/l), confirming the toxicity data. Based on estimates of tea consumption in Morocco, we showed that the extra daily burden of Zn ranged from 1.75 to 4.2 mg/day, assuming the maximum zinc concentration of 7.4 mg/l, as found in our study. This represents 3.5-8% of the LOAEL for zinc of 50 mg/day and would not be important as compared to other sources zinc intake.

Intra- and inter-rater agreement in the assessment of occupational exposure to metals.

BACKGROUND: Among the methods of retrospective occupational exposure assessment, expert review is considered the most accurate. Although expert review provides a more objective measure of exposure, depending on the exposure of interest it may still result in a significant degree of misclassification. METHODS: To evaluate the reliability in occupational metal exposure assessment by expert review, we analysed job history data from a case-control study of a neurological disease. First, one industrial hygienist (IH) did an initial exposure assessment of the metals copper, iron and lead, blinded to case-control status, for 608 subjects who had 3033 total jobs. We then compared exposure assessments from the original review with a second blinded review of 60 job histories (306 jobs) by the same IH (intra-rater) and of 64 job histories (361 jobs) by a different IH (inter-rater). RESULTS: The per cent agreements for the intra-IH comparisons were 89.6 for copper, 87.9 for iron and 94.6 for lead, whereas the inter-IH per cent agreements were 86.4 for copper, 81.1 for iron and 76.2 for lead. Based on the assumption that reliability is related to validity, we calculated an estimate of misclassification of metal exposure by one IH. Our exposure misclassification estimates show a sizable attenuation of the odds ratio, with the expected bias similar for copper and iron when using either intra- or inter-reliability results to estimate misclassification. CONCLUSION: Our results suggest that variation in the expert assessment of metal exposure is due mainly to the difficulties involved in transforming an occupational history into an estimate of exposure.

Need to revise the national drinking water regulation for copper.

Copper is an essential micronutrient and a potential toxic metal. The USEPA current maximum contaminant level goal (MCLG, a nonenforceable aspirational health goal) and the required treatment technique action level, both set at 1.3 mg/liter of copper are not adequately protective for infants and children under 10 years of age. Infants and children up to 10 years of age have increased susceptibility to copper toxicity. The two main reasons for the high sensitivity in this population subgroup are the presence of a normally high concentration of copper in the liver during early life and the lack of a fully developed homeostatic mechanism of copper in children under 10 years of age. This sensitive group of infants and children represents approximately 17% of the total U.S. population. The adverse health effects caused by drinking water contaminated with copper are abdominal pain, nausea, vomiting, diarrhea, headache, and dizziness. The proposed drinking water guideline of 0.3 mg/liter for copper was derived by the application of the risk assessment procedures approved by the USEPA. Drinking water containing 0.3 mg/liter of copper will provide approximately 26% of the nutritional requirement of copper. This proposed drinking water guideline (0.3 mg/liter) for copper will adequately protect health of infants, children, and adults.

Assessment of exposure to inorganic arsenic by determining the arsenic species excreted in urine.

Urinary concentrations of inorganic arsenic metabolites (AsIII, AsV, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) and occupational exposure to arsenic were measured in 24 copper smelter and arsenic trioxide refinery workers during a study period consisting of 2 pairs of work days and the 6 (partly 4) days off between them. The correlations between the time-weighted average (TWA) concentrations of arsenic in air (0.8-45 micrograms/m3) and the concentrations of arsenic species in urine 0, 0-8, 8-16 and 16-20 h after the exposure were calculated. The best correlation (r = 0.78, P = 0.0001) was found for the sum of AsIII and AsV concentration in urine collected between 0 and 8 h after the exposure. The DMA concentrations at any time in urine correlated only poorly to the exposure. A reason for this was obviously an increased urinary excretion of DMA due to the ingestion of DMA in the diet. An 8-h TWA exposure of 10 micrograms As/m3 was calculated to lead to an inorganic arsenic concentration of 5 micrograms/l in urine.

[Hygienic assessment of the working conditions for repairmen in the production of pure nickel and copper metals at nickel mills]. / Gigienicheskaia otsenka uslovii truda remontnykh rabochikh v proizvodstve chistykh metallov nikelia i medi na nikelevykh kombinatakh.

Mechanic workers in electrolysis shops of copper and nickel production appear to work in conditions characterized by some occupational hazards, mostly by air pollution with aerosol of nickel sulfate. The study covered influence of work conditions and complexity on the workers' health state, that is demonstrated by higher morbidity and present occupational diseases.