Standardization of Sandwich-Structured Cu-Glass Substrates Embedded in a Flexible Diode Laser-Plasma Interface for the Detection of Cholesterol.

This study introduced sandwich-structured copper-glass substrates for standardization of laser desorption and plasma ionization. For standardized quantitative analysis, cavities were constructed which allow better reproducibility in droplet deposition and for laser application. Applying the diode laser, molten substrate material is incorporated into the glass, being trapped inside. Therefore, this method can be separated from laser ablation, achieving high ion signals without ablating material from the surface. Flexible microtube plasma (FµTP) was selected as the ionization source, this being the first time that laser desorption and FµTP ionization are coupled. This laser-plasma interface was applied to the detection of cholesterol, which showed a significantly improved limit of detection of 0.46 ng and linear dynamic range of 3 orders of magnitude in positive ion mode compared to other (ambient air mass spectrometry) methods. The main reason was the change of phase on the copper surface. The dehydrated molecule [M-H2O+H]+ was the base peak of the spectrum and no further dissociation or fragmentation was observed. Blood plasma was spiked with cholesterol. In a 1:100 chloroform dilution, the presence of the plasma was neglectable and led to the same detection limits and linear dynamic range as in the cholesterol standard. No sample preparation or internal standards were needed for calibration. The physical effects of the surface modification were investigated, including the calculation of the laser beam waist to simplify the comparison and reproducibility of results.

A new anion exchange purification method for Cu stable isotopes in blood samples.

The isotopic composition of iron, zinc, copper, and cadmium (δ56Fe, δ66Zn, δ65Cu, and δ114Cd) are novel and promising tools to study the metabolism and homeostasis of trace metals in the human body. Serum δ65Cu has been proposed as a potential tool for diagnosis of cancer in liquid biopsy, and other metals may have similar utility. However, accurate analysis of trace metal isotopes is challenging because of the difficulties in purifying the metals from biological samples. Here we developed a simple and rapid method for sequential purification of Cu, Fe, Zn, and Cd from a single blood plasma sample. By using a combination of 11 M acetic acid and 4 M HCl in the first steps of column chemistry on AG-MP1 resin, we dramatically improve the separation of Cu from matrix elements compared to previous methods which use concentrated HCl alone. Our new method achieves full recovery of Cu, Fe, Zn, and Cd to prevent column-induced isotope fractionation effects, and effectively separates analytes from the matrix in order to reduce polyatomic interferences during isotope analysis. Our methods were verified by the analysis of isotope standards, a whole blood reference material, and a preliminary sample set including five plasma samples from healthy individuals and five plasma samples from cancer patients. This new method simplifies preparation of blood samples for metal isotope analysis, accelerating multi-isotope approaches to medical studies and contributing to our understanding of the cycling of Fe, Zn, Cu, and Cd in the human body. Graphical abstract ᅟ.

Water-effect ratio of copper and its application on setting site-specific water quality criteria for protecting marine ecosystems of Hong Kong.

Generic water quality criteria (WQC) of a chemical are usually set based on results generated from toxicity tests which were conducted using standard laboratory water with well-controlled physiochemical properties. However, in natural aquatic environments, physiochemical characteristics, such as salinity, total suspended solid, total organic carbon and the co-existence of chemical contaminants, often vary spatially and temporally. These parameters can, in turn, alter the bioavailability of target chemicals and, thus, influence their toxicity to marine organisms. To account for site specificity, the US Environmental Protection Agency's water-effect ratio (WER = site water-LC50 / laboratory water-LC50) procedure can be applied to derive site-specific WQC. Most past studies, however, were conducted for freshwater systems. Here, for the first time, the WER of copper (Cu) was determined for three marine water control zones (WCZs) in Hong Kong: Victoria Harbour, Deep Bay and Southern WCZs. Samples of water were collected from three locations within each WCZ, while acute toxicities to the marine diatom Skeletonema costatum, intertidal copepod Tigriopus japonicus and larvae of marine medaka Oryzias melastigma were determined in site or laboratory (artificial seawater) waters. Results of this study showed that conservative final WER relative coefficients for Cu ranged from 0.57 to 0.73 for the three WCZs, and water from some locations caused >30% mortality in the fish larvae in the controls (without Cu addition). These results suggested that current generic WQC for Cu are likely under-protective for marine organisms in the three areas, and it should be tightened by multiplying it with site-specific WER to offer better protection to marine biodiversity and integrity of the ecosystem.

An inductively coupled plasma mass spectrometry method for relative free copper determination and generation of a paediatric reference interval.

Background Diagnosis of Wilson's disease is currently performed using caeruloplasmin as a first-line screening test; however, this test has well-described limitations. Monitoring of known Wilson's disease patients often uses 24-h urine collection; however, this is inaccurate in children. Methods for directly measuring plasma free copper have been described, but no reference interval data exist for a paediatric population. Methods An inductively coupled plasma mass spectrometry method for measuring free copper was developed and validated, using ultracentrifugation. A paediatric reference interval was generated using 85 plasma samples from children attending outpatient clinics at University Hospital Southampton. Results Results showed no significant contamination of copper using the ultracentrifugation technique, and validation showed the method was accurate and precise with an analytical coefficient of variation between 5 and 7% depending on the concentration of free copper. Conclusions We describe the use and validation of an ultrafiltration inductively coupled plasma mass spectrometry method for plasma free copper with the first published paediatric reference interval. Free copper could provide much needed assistance for the monitoring of Wilson's disease in children and also for adults.

Artificial Leaks in Container Closure Integrity Testing: Nonlinear Finite Element Simulation of Aperture Size Originated by a Copper Wire Sandwiched between the Stopper and the Glass Vial.

Container closure integrity (CCI) testing is required by different regulatory authorities in order to provide assurance of tightness of the container closure system against possible contamination, for example, by microorganisms. Microbial ingress CCI testing is performed by incubation of the container closure system with microorganisms under specified testing conditions. Physical CCI uses surrogate endpoints, such as coloration by dye solution ingress or gas flow (helium leakage testing). In order to correlate microbial CCI and physical CCI test methods and to evaluate the methods' capability to detect a given leak, artificial leaks are being introduced into the container closure system in a variety of different ways. In our study, artificial leaks were generated using inserted copper wires between the glass vial opening and rubber stopper. However, the insertion of copper wires introduces leaks of unknown size and shape. With nonlinear finite element simulations, the aperture size between the rubber stopper and the glass vial was calculated, depending on wire diameter and capping force. The dependency of the aperture size on the copper wire diameter was quadratic. With the data obtained, we were able to calculate the leak size and model leak shape. Our results suggest that the size as well as the shape of the artificial leaks should be taken into account when evaluating critical leak sizes, as flow rate does not, independently, correlate to hole size. Capping force also affected leak size. An increase in the capping force from 30 to 70 N resulted in a reduction of the aperture (leak size) by approximately 50% for all wire diameters. From 30 to 50 N, the reduction was approximately 33%. LAY ABSTRACT: Container closure integrity (CCI) testing is required by different regulatory authorities in order to provide assurance of tightness of the container closure system against contamination, for example, by microorganisms. Microbial ingress CCI testing is performed by incubation of the container closure system with microorganisms under specified testing conditions. Physical CCI uses surrogate endpoints, such as coloration by dye solution ingress or gas flow. In order to correlate microbial ingress CCI and physical CCI test methods and to evaluate the methods' capability to detect a given leak, artificially created defects (artificial leaks) are being introduced into the container closure system in a variety of different ways. In our study, artificial leaks were generated using inserted copper wires between the glass vial opening and rubber stopper. Up to date, the insertion of copper wires introduced leaks of unknown size and shape. With nonlinear finite element simulations, the effective aperture size between the rubber stopper and the glass vial was calculated, depending on wire diameter and capping force, and the leak shape was modelled. Our results suggest that the size as well as the shape of the artificial leaks should be taken into account when evaluating critical leak sizes, as flow rate does not, independently, correlate to the hole size.

Evaluation of current copper bioavailability tools for soft freshwaters in Sweden.

The Water Framework Directive (WFD) in Europe calls for an improved aquatic ecological status. Biotic ligand models (BLM) have been suggested as a possible tool assisting in the regulatory process. The aim of this study was therefore to investigate the applicability of BLM under the WFD to set environmental quality standards (EQS), in particular regarding copper in Swedish freshwaters of which many are softer than those used for model calibration. Three different BLMs, one acute and two chronic, were applied to water chemistry data from 926 lakes and 51 rivers (1530 data entries) and evaluated with respect to their calibration range for input parameters. In addition, the predicted no-effect concentration (PNEC) for copper was calculated. From the 1530 data entries, 750 ended up outside of the BLM calibration range, when looking at the chemical parameters Ca(2+), alkalinity, pH and DOC, primarily due to low carbonate alkalinity. Furthermore, the calculated Cu PNECs were higher than the suggested Swedish limit for Cu (4µgL(-1)) in surface waters for 98% and 99% of the cases concerning lakes and rivers, respectively. To conclude, our findings show that water chemical characteristics outside of the calibration ranges are quite common in Sweden and that the investigated models differ in how they calculate toxicity concerning Cu under these conditions. As a consequence, additional work is required to validate the BLMs by use of bioassays with representative species of soft waters. Such results will show if these models can be used outside of their calibration ranges and also which of the models that gives the most reliable results.

Incorporating bioavailability into management limits for copper in sediments contaminated by antifouling paint used in aquaculture.

Although now well embedded within many risk-based sediment quality guideline (SQG) frameworks, contaminant bioavailability is still often overlooked in assessment and management of contaminated sediments. To optimise management limits for metal contaminated sediments, we assess the appropriateness of a range methods for modifying SQGs based on bioavailability considerations. The impairment of reproduction of the amphipod, Melita plumulosa, and harpacticoid copepod, Nitocra spinipes, was assessed for sediments contaminated with copper from antifouling paint, located below aquaculture cages. The measurement of dilute acid-extractable copper (AE-Cu) was found to provide the most useful means for monitoring the risks posed by sediment copper and setting management limits. Acid-volatile sulfide was found to be ineffective as a SQG-modifying factor as these organisms live mostly at the more oxidised sediment water interface. SQGs normalised to %-silt/organic carbon were effective, but the benefits gained were too small to justify this approach. The effectiveness of SQGs based on AE-Cu was attributed to a small portion of the total copper being present in potentially bioavailable forms (typically<10% of the total). Much of the non-bioavailable form of copper was likely present as paint flakes in the form of copper (I) oxide, the active ingredient of the antifoulant formulation. While the concentrations of paint-associated copper are very high in some sediments, as the transformation of this form of copper to AE-Cu appears slow, monitoring and management limits should assess the more bioavailable AE-Cu forms, and further efforts be made to limit the release of paint particles into the environment.

Development of a certified reference material (NMIJ CRM 7531-a) for the determination of trace cadmium and other elements in brown rice flour.

A certified reference material (CRM) for trace cadmium and other elements in brown rice flour was developed at the National Metrology Institute of Japan (NMIJ). The CRM was provided as a dry powder after drying and frozen pulverization of fresh brown rice obtained from a Japanese domestic market. Characterization of the property value for each element was carried out exclusively by NMIJ with at least two independent analytical methods, including inductively coupled plasma mass spectrometry (ICP-MS), ICP high-resolution mass spectrometry, isotope-dilution ICP-MS, ICP optical emission spectrometry, and graphite-furnace atomic-absorption spectrometry. Property values were provided for six elements (Mn, Fe, Cu, Zn, As, and Cd). The concentration range of the property values was from 0.280 mg kg(-1) of As to 31.8 mg kg(-1) of Zn. The combined relative standard uncertainties of the property values were estimated by considering the uncertainties of the homogeneity, characterization, difference among analytical methods, dry-mass correction factor, and calibration standard. The range of the relative combined standard uncertainties was from 1.1% of Zn to 1.6% of As.

Defining reference values of trace elements in the tear film: diagnostic methods and possible applications.

The study has been performed on tears of apparently healthy subjects who live and work in urban and rural areas, respectively. After the collection the following elements were investigated: chromium (Cr); arsenic (As); copper (Cu); zinc (Zn); selenium (Se); rubidium (Rb); barium (Ba); lead (Pb) and cobalt (Co). Significantly higher values of As were found in subjects living and working in rural areas as compared to those found in urban area residents (0.290 vs. 0.025; p<0.001). Conversely, Ba and Pb were significantly lower in rural area residents (1.10 vs. 2.50, p=0.027 and 1.70 vs. 1.10, p=0.057, respectively). Our data show that trace elements analysis in tears is possible; further studies could define if it could be a reliable biomarker in persons exposed to high concentration of trace elements due to working or environmental reasons.

Relationship between biotic ligand model-based water quality criteria and avoidance and olfactory responses to copper by fish.

The U.S. Environmental Protection Agency's (U.S. EPA) water quality criteria for Cu were tested to determine whether they protect fish against neurophysiological impairment. From published studies with rainbow trout (Oncorhynchus mykiss), Chinook salmon (Oncorhynchus tshawytscha), coho salmon (Oncorhynchus kisutch), and fathead minnows (Pimephales promelas), 20% inhibition concentrations (IC20s) were calculated for avoidance of Cu-containing water and for impairment of electroencephalogram (EEG) and electro-olfactogram (EOG) responses to natural odorants in Cu-containing water. Additionally, a Cu-olfactory biotic ligand model (BLM) that fits the coho salmon EOG data was parameterized by changing the sensitivity parameter in the ionoregulatory-based BLM. The IC20s calculated from reported Cu avoidance, EEG, and EOG data and IC20s predicted by the olfactory BLM were compared with acute and chronic Cu criteria calculated using U.S. EPA's BLM 2007 or hardness-adjustment equations. The BLM-based chronic criteria were protective in all 16 exposure water-species combinations used in avoidance and olfaction experiments. Additionally, the BLM-based acute criteria were protective in all 11 exposure water-species combinations in which comparisons could be made with olfactory BLM-predicted IC20s but not in two of the 16 exposure water-species combinations in which comparisons could be made with the reported IC20s (which were < or =8% lower than but did not differ significantly from the BLM-based acute criteria; p > 0.05). In effect, the olfactory BLM factored out the relatively high variability in the reported IC20s. It is concluded that the U.S. EPA's BLM-based water quality criteria for Cu protect against these types of neurophysiological impairment in the six species-endpoint combinations analyzed in this paper. However, the U.S. EPA's hardness-based criteria for Cu sometimes were considerably underprotective and sometimes were much less protective than the BLM-based criteria.

New use of polypyrrole-chloride for selective preconcentration of copper prior to its determination of flame atomic absorption spectrometry.

Polypyrrole-chloride was studied as a new sorbent for preconcentration of copper(II) using solid-phase extraction prior to determination by flame atomic absorption spectrometry. The sorbent showed an extremely high selectivity towards copper(II) as an anionic chelate, i.e. Cu (pyrocatechol violet)(2)(2-) in the pH range of 4-7. Copper(II) as Cu (pyrocatechol violet)(2)(2-) was selectively retained on a column containing 1.0 g of polypyrrole-chloride and quantitatively eluted by 3 mL of 2.0 mol L(-1) nitric acid. The calibration graph was linear with a correlation coefficient of 0.999 at levels near the detection limit and up to at least 50 microg L(-1). When applied for preconcentration and determination of copper in tap water, waste water and hot spring water, the recoveries were found to be 96, 101 and 95%, respectively, with high precision (% relative standard deviation <4%) and low detection limit (0.87 microg L(-1)). Verification of the accuracy was carried out by the analysis of a standard reference material (BCR 715 wastewater-SRM). The relative error was +3.33%. The proposed method was successfully applied to the determination of copper in tap water, waste water and hot spring water samples.

Copper and zinc water quality standards under the EU Water Framework Directive: the use of a tiered approach to estimate the levels of failure.

Environmental quality standards are an important tool for assessing the chemical quality of water bodies under the Water Framework Directive. However, there must be confidence in assessments of any failure to avoid disproportionate investment in unnecessary risk reduction. Metals present a number of unique challenges for environmental regulators in that they are naturally occurring and their ecotoxicology is driven, in part, by the physico-chemical conditions of the water body in which they are present. This paper describes the use of a tiered approach that could be adopted to assess compliance with any future environmental quality standards for metals under the Water Framework Directive. Through this approach, the use of background concentrations is considered and also bioavailability via the use of biotic ligand models. This assessment is based on an analysis of routine Environment Agency chemical monitoring data combined with biological indices to support results of the approach. Using copper and zinc as examples, it is shown that it is important to take account of background concentrations and the bioavailability of metals, otherwise the risk of impact from metals may be significantly overestimated. The approach presented here provides a methodology by which regulators and the regulated community may implement surface water standards for metals under the Water Framework Directive.

Simultaneous determination of nickel and copper by H-point standard addition method-first-order derivative spectrophotometry in plant samples after separation and preconcentration on modified natural clinoptilolite as a new sorbent.

For the simultaneous determination of nickel(ll) and copper(ll) in plant samples, a rapid and accurate method was developed. In this method, solid-phase extraction (SPE) and first-order derivative spectrophotometry (FDS) are combined, and the result is coupled with the H-point standard addition method (HPSAM). Compared with normal spectrophotometry, derivative spectrophotometry offers the advantages of increased selectivity and sensitivity. As there is no need for carrying out any pretreatment of the sample, the spectrophotometry method is easy, but because of a high detection limit, it is not so practical. In order to decrease the detection limit, it is suggested to combine spectrophotometry with a preconcentration method such as SPE. In the present work, after separation and preconcentration of Ni(ll) and Cu(ll) on modified clinoptilolite zeolite that is loaded with 2-[1-(2-hydroxy-5-sulforphenyl)-3-phenyl-5-formaza-no]-benzoic acid monosodium salt (zincon) as a selective chromogenic reagent, FDS-HPSAM, which is a simple and selective spectrophotometric method, has been applied for simultaneous determination of these ions. With optimum conditions, the detection limit in original solutions is 0.7 and 0.5 ng/mL, respectively, for nickel and copper. The linear concentration ranges in the proposed method for nickel and copper ions in original solutions are 1.1 to 3.0 x 10(3) and 0.9 to 2.0 x 10(3) ng/mL, respectively. The recommended procedure is applied to successful determination of Cu(ll) and Ni(ll) in standard and real samples.

An assessment of the application factor used to derive the saltwater acute ambient water quality copper criterion.

The basis for all US Environmental Protection Agency (USEPA) acute ambient water quality criteria is the chemical specific final acute value (FAV; an estimate of the concentration of the chemical corresponding to a cumulative probability of 0.05 of acute toxicity values for all genera with which acceptable acute tests have been conducted). The acute criterion for all chemicals is equal to the chemical's FAV divided by an application factor of 2. The intention of dividing the FAV by a factor of 2 is to convert the acute toxicity value to an incipient acute toxicity value, resulting in an acute criterion concentration that will protect against toxic effects to aquatic organisms. In the case of copper (Cu) in saltwater, the FAV is reduced from the normal 0.05 probability to equal to the genus mean acute value (GMAV; the geometric mean of copper effect concentration 50% [EC50] values) of the economically important marine bivalves of the genus Mytilus. Analyses to determine an application factor specific to Mytilus and copper were performed to assess the adequacy of the application factor of 2. An estimate of a dissolved copper application factor that is specific to and protective of Mytilus was determined using the results of sixty-four 48-h embryo survival and shell development copper toxicity tests of natural water samples collected from sites around the United States. A variety of point-estimate effects concentrations (EC1, EC5, EC10, EC20, and chronic values [ChV]) and statistical toxic-effect endpoints (no observed effect concentration [NOEC] and lowest observed effect concentration [LOEC]) were derived from the test results and compared. The most similar toxic effect endpoint estimates were EC1 approximately equal to NOEC, EC10 approximately equal to ChV, and EC20 approximately equal to LOEC. Probabilistic methods were used to determine a specific application factor with a high probability of providing protection. This analysis suggests that an application factor of 1.5 (rather than 2) is adequate to provide a high degree of protection against acute effects of dissolved copper to Mytilus. In context, this translates to an acute saltwater dissolved copper criterion of 6.4 microg Cu/L compared to the current acute criterion of 4.8 microg Cu/L.

An evaluation of freshwater mussel toxicity data in the derivation of water quality guidance and standards for copper.

The state of Oklahoma has designated several areas as freshwater mussel sanctuaries in an attempt to provide freshwater mussel species a degree of protection and to facilitate their reproduction. We evaluated the protection afforded freshwater mussels by the U.S. Environmental Protection Agency (U.S. EPA) hardness-based 1996 ambient copper water quality criteria, the 2007 U.S. EPA water quality criteria based on the biotic ligand model and the 2005 state of Oklahoma copper water quality standards. Both the criterion maximum concentration and criterion continuous concentration were evaluated. Published acute and chronic copper toxicity data that met American Society for Testing and Materials guidance for test acceptability were obtained for exposures conducted with glochidia or juvenile freshwater mussels. We tabulated toxicity data for glochidia and juveniles to calculate 20 species mean acute values for freshwater mussels. Generally, freshwater mussel species mean acute values were similar to those of the more sensitive species included in the U.S. EPA water quality derivation database. When added to the database of genus mean acute values used in deriving 1996 copper water quality criteria, 14 freshwater mussel genus mean acute values included 10 of the lowest 15 genus mean acute values, with three mussel species having the lowest values. Chronic exposure and sublethal effects freshwater mussel data available for four species and acute to chronic ratios were used to evaluate the criterion continuous concentration. On the basis of the freshwater mussel toxicity data used in this assessment, the hardness-based 1996 U.S. EPA water quality criteria, the 2005 Oklahoma water quality standards, and the 2007 U.S. EPA water quality criteria based on the biotic ligand model might need to be revised to afford protection to freshwater mussels.

Validation and update of a model used to predict copper toxicity to the marine bivalve Mytilus sp.

A model was recently published that relates the toxicity of copper to the most sensitive taxa in the U.S. Environmental Protection Agency's criteria database (Mytilus sp.) with dissolved organic carbon concentrations in saltwater. This model was developed for potential use in risk assessment and in the development of site-specific criteria (SSC) for copper in saltwater environments where Mytilus sp. is considered an appropriate indicator species. This manuscript presents the results of a field validation study of that model. Effective concentration 50% (EC(50)) values (n = 21) for seven sites were all predicted by the model within the previously established range of acceptability. Slopes and intercepts of the two data sets were not significantly different. Consequently, the data were pooled, and new equations were developed. Dissolved copper EC(50) values were highly correlated (r(2) = 0.76, n = 75, P < 0.0001) across a wide range of sample dissolved organic carbon (DOC) concentrations (0.3-12 mg C/L) and were explained by the equation EC(50) = 11.22 DOC(0.60). Two updated equations are proposed for consideration as a means of estimating site-specific final chronic criteria (FCC) and final acute criteria (FAC) for copper in marine and estuarine environments (copper FCC(DOC) = 3.59 DOC(0.60); copper FAC(DOC) = 5.61 DOC(0.60)).

Heavy metal levels in fish from coastal waters of Uruguay.

Copper, mercury, and zinc levels were determined in muscle and liver (N = 163) of seven fish species caught in coastal waters off Montevideo and Piriapolis (control site): Odontesthes spp., Mugil platanus, Micropogonias furnieri, Urophycis brasiliensis, Cynoscion guatucupa, Menticirrhus americanus, and Mustelus schmitti. The local population commonly uses these species for consumption. Heavy metal concentrations determined in this study were generally below those obtained for fish caught in Argentinean and Brazilian coastal waters, with some exceptions in the case of mercury and zinc. Based on copper, mercury, and zinc levels in muscle tissue, we conclude that the fish studied here are acceptable for human consumption. Nevertheless, it is recommended not to consume the fish liver (up to 466 microg Zn g(-1) dry weight in liver) nor large specimens of the investigated species. Regional programs involving the neighboring countries should be established to assess the fisheries resources and potential risks for human health.

Effects of dissolved organic carbon on copper toxicity: implications for saltwater copper criteria.

During the past three decades, significant advances have been made in understanding how environmental factors modify the bioavailability and the toxicity of metals such as copper in aquatic environments. Several of these advances have led to the development of guidelines to indirectly account for modifying factors, adjustment of criteria on a site-specific basis, and direct changes to the U.S. Environmental Protection Agency (U.S. EPA) freshwater quality criteria. To date, most of this effort has focused on freshwater systems, although similar modifying factors exist in marine environments as well. This paper focuses on one such modifying factor, dissolved organic carbon (DOC), and describes a method to aid in risk assessments or to refine the saltwater copper criteria on a site-specific basis. The relationship between DOC and toxicity of copper to the most sensitive saltwater genus in the U.S. EPA criteria database, Mytilus, is extensively analyzed. Dissolved copper 50% effective concentrations (EC50s) are highly correlated (r2 = 0.71, n=54, p < 0.001) across a wide range of sample DOC concentrations (0.3-10 mg carbon [C]/L) and are explained by the equation EC50 = 11.53DOC(0.54). Two equations based on DOC are proposed for consideration as a means for deriving site-specific final chronic criteria (FCC) and final acute criteria (FAC) for copper in marine and estuarine environments (Copper FCC(DOC) = 3.71DOC(0.54) and Copper FAC(DOC) = 5.843DOC(0.54).

Toxicity considerations when revising the Nordic nutrition recommendations.

The Nordic countries have issued common nutrition recommendations since 1980. In connection with the 3rd revision, a joint working group of nutritionists and toxicologists assessed the toxicology of selected trace elements. Values for upper limits of intake were established for iron, zinc, iodine and selenium. The safety factors between the lowest intakes at which adverse effects had been reported and the suggested upper limits of intake were small. In the toxicological evaluation of upper safe intake levels of essential trace elements, interactions between trace elements as well as long-term exposure to moderately elevated trace element intakes have to be considered.