Single Metal Exposure Research Articles

Combined exposure to lead, inorganic mercury and methylmercury shows deviation from additivity for cardiovascular toxicity in rats.

Environmental exposure to metal mixtures in the human population is common. Mixture risk assessments are often challenging because of a lack of suitable data on the relevant mixture. A growing number of studies show an association between lead or mercury exposure and cardiovascular effects. We investigated the cardiovascular effects of single metal exposure or co-exposure to methylmercury [MeHg(I)], inorganic mercury [Hg(II)] and lead [Pb(II)]. Male Wistar rats received four different metal mixtures for 28 days through the drinking water. The ratios of the metals were based on reference and environmental exposure values. Blood and pulse pressure, cardiac output and electrical activity of the heart were selected as end-points. While exposure to only MeHg(I) increased the systolic blood pressure and decreased cardiac output, the effects were reversed with combined exposures (antagonism). In contrast to these effects, combined exposures negatively affected the electrical activity of the heart (synergism). Thus, it appears that estimates of blood total Hg levels need to be paired with estimates of what species of mercury dominate exposure as well as whether lead co-exposure is present to link total blood Hg levels to cardiovascular effects. Based on current human exposure data and our results, there may be an increased risk of cardiac events as a result of combined exposures to Hg(II), MeHg(I) and Pb(II). This increased risk needs to be clarified by analyzing lead and Hg exposure data in relation to cardiac electrical activity in epidemiological studies.

Three novel superoxide dismutase genes identified in the marine polychaete Perinereis nuntia and their differential responses to single and combined metal exposures

To identify superoxide dismutase (SOD) genes and evaluate their usefulness as potential markers for monitoring metal toxicity in aquatic environment, we cloned, sequenced, and characterized 3 SOD genes (Cu/Zn-SOD1, Cu/Zn-SOD2, and Mn-SOD) from the marine polychaete Perinereis nuntia. The accumulated metal contents and expressions of 3 SOD genes were compared after exposure to single and combinations of heavy metals, As, Ni, and Pb. The deduced amino acid sequences of the 3 SODs had evolutionary conserved domains, such as metal binding sites, and signature sequences. The phylogenetic analysis revealed that Cu/Zn-SOD1, Cu/Zn-SOD2, and Mn-SOD were clustered with extracellular Cu/Zn-SOD, intracellular Cu/Zn-SOD and mitochondrial Mn-SOD, respectively, of other species. The accumulated contents of Ni and Pb increased significantly in a time - dependent manner after exposure to both single and combination of the metals. However, the concentration of As did not change significantly in the exposure test. The quantitative real-time polymerase chain reaction (PCR) array showed that the 3 SOD genes had differential expression patterns depending on the exposure condition. The expression of all SODs mRNAs was significantly elevated in response to Pb alone and in combination with As. The mRNA level of Cu/Zn-SOD1 was the highest after exposure to Pb alone, while that of Mn-SOD was remarkably enhanced after exposure to a combination of As and Pb. Exposure to Ni alone rapidly elevated the expression of Cu/Zn-SOD1 and Mn-SOD mRNA, which then gradually decreased. Exposure to As had no significant effect on the modulation of any of the SOD genes of P. nuntia. These results suggest that all SOD genes might play important roles in cellular protection as antioxidant enzymes against heavy metal toxicity via different modes of action in P. nuntia and might have the potential to act as indicators in an environment containing a mixture of metals.

Histopathology related to cadmium and lead bioaccumulation in chronically exposed wood mice, Apodemus sylvaticus, around a former smelter

The ceasing of industrial activities often reduces the emission of pollutants but also often leaves disturbed areas without remediation and with persistent pollutants that can still be transferred along the food chain. This study examines the potential relationships between non-essential trace metals and histopathology in target tissues of wood mice (Apodemus sylvaticus) collected along a gradient of contamination around the former smelter, Metaleurop Nord (northern France). Cadmium and lead concentrations were measured, and histological alterations attributable to chronic trace metal exposure were assessed in the liver and the kidneys of 78 individuals. Metal concentrations quantified in the present study were among the highest observed for this species. Some histological alterations significantly increased with Cd or Pb concentrations in the soil and in the organs. Sixteen mice from polluted sites were considered at risk for metal-induced stress because their Cd and/or Pb tissue concentrations exceeded the LOAELs for single exposure to these elements. These mice also exhibited a higher severity of histological alterations in their organs than individuals with lower metal burdens. These results indicate that the Metaleurop smelter, despite its closure in 2003, still represents a threat to the local ecosystem because of the high levels and high bioavailability of Cd and Pb in the soil. However, among the mice not considered at risk for metal-induced stress based on the metal levels in their tissues, a large percentage of individuals still exhibited histological alterations. Thus, the present study suggests that the evaluation of toxic effects based only on the LOAELs for single metal exposure may result in the underestimation of the real risks when specimens are exposed to multiple stressors.

Comparison of Chelating Agents DMPS, DMSA and EDTA for the Diagnosis and Treatment of Chronic Metal Exposure

Aims: Several chelating agents are presently used among environmental physicians to diagnose and treat a chronic metal overexposure. We evaluated and compared the binding capacity of the most common chelating agents DMPS (2, 3-dimercapto-1propanesulfonic acid), DMSA (dimercaptosuccinic acid), also called Succimer) and EDTA (ethylene diamine tetraacetic acid) for the potentially toxic metals Antimony (Sb), Arsenic (As), Cadmium (Cd), Lead (Pb) and Mercury (Hg). Secondly, we evaluated how the nutrient elements Calcium (Ca), Copper (Cu) and Zinc (Zn) are affected by the chelating agents tested. Study Design: Through ICP-MS (Inductively Coupled Plasma Mass Spectroscopy) analysis of urine from environmentally burdened patients, we determined which chelating agent in oral or injectable form has the best potential to be used as a provocation test for the diagnosis of multiple metal over exposure, and which chelating agent is best used for the detoxification treatment of a single metal exposure. Place and Duration of Study: Micro Trace Minerals and Friedle Laboratories, Hersbruck/Regensburg, Germany, between January 2011 and February 2013. Methodology: Data utilized is based on urine samples from chronically exposed Original Research Article British Journal of Medicine & Medical Research, 4(9): 1821-1835, 2014 1822 patients, male and female adults, received from chelation therapists. Acutely intoxicated patients were not included. Results: The intravenous application of DMPS is most suitable for the diagnosis and treatment of a single or multiple metal exposure, involving the metals Sb, As and Hg. Both EDTAs (NaCaEDTA and NaEDTA), administered intravenously, are the agents of choice for Cd, while Pb can be chelated using DMSA, DMPS, or the EDTAs. Both EDTAs have a strong Zn binding ability, but only NaEDTA is suitable for binding appreciable amounts of Ca. DMPS best binds Cu. Conclusion: The intravenous application of DMPS is most useful for the diagnosis of multiple metal overexposure. It is also the treatment of choice for Sb, As and Hg and has the strongest Cu binding ability of the chelators tested.

The Response of Metallothionein and Malondialdehyde after Exclusive and Combined Cd/Zn Exposure in the Crab Sinopotamon henanense

The purpose of this paper is to show the interactions of Cd and Zn in the freshwater crab Sinopotamon henanense through metallothionein (MT) and malondialdehyde (MDA) level measurements. Laboratory acclimated S.henanense were exposed to Cd (50 µg/L, 100 µg/L, 500 µg/L ), and Zn (100 µg/L, 1000 µg/L) alone and in combined treatments (100 µg/L Zn+50 µg/L Cd, 100 µg/L Zn+100 µg/L Cd, 100 µg/L Zn+500 µg/L Cd, 1000 µg/L Zn+50 µg/L Cd, 1000 µg/L Zn+100 µg/L Cd, 1000 µg/L Zn+500 µg/L Cd) for 7, 14, 21, 28, 35 days. The results demonstrated that the MDA contents increased with exposure time and dose and showed time- and dose-dependence in both gills and hepatopancreas of S.henanense after single Cd exposure, while the changes of MDA levels were not significant with single Zn exposure. The MDA levels decreased when the crabs were exposed to metal mixtures compared to Cd exposure alone, indicating that Zn mediated the cellular toxicity of Cd. MT contents increased after single Cd exposure and also showed a time- and dose-dependence, in a tissue-specific way. Zn showed a limited ability of MT induction both in gills and hepatopancreas of S.henanense. The MT contents represented not a simple addition of single metal exposures but were enhanced at a higher concentration of Zn combined with different Cd concentrations compared to single metal exposure. Whether MT can be used as a biomarker for complex field conditions need to be considered cautiously since different induction patterns of MT were found among single Zn, Cd and combined groups. It is suggested that several biomarkers together as a suite should be used in the monitoring of heavy metal pollution in the aquatic environment.

Effects of Cd, Zn and Cd + Zn Combination on ATPase Activitiy in the Gill and Muscle of Tilapia (Oreochromis niloticus)

This study investigated the responses of Na(+)/K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase in the gill and muscle of a freshwater fish Oreochromis niloticus exposed to 1 μg/mL of Cd and Zn and their mixture for different periods (0, 7, 14, 21 and 28 days). At the end of experimental periods, the activities Na(+)/K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase in gill tissues and only Ca(2+)-ATPase activity in muscle tissues were measured. Gill Na(+)/K(+)-ATPase activity generally decreased following single metal exposures, whereas their combinations increased its activity. Gill Ca(2+)-ATPase activity decreased relative to the control at most exposure times for single exposures of Zn and Cd, as well as for the combined exposure. There was no gill Ca(2+)-ATPase activity after 28 days of exposure to Zn and Cd combined. Mg(2+)-ATPase activity was not affected significantly in gill tissue by exposure to Zn and Cd individually or in combination. Muscle Ca(2+)-ATPase activity also decreased significantly following metal exposure, but not as greatly as in the gill tissue. Tissue protein levels were mostly unaffected by metal exposures. This study showed that certain ATPases are highly sensitive to metal exposure whether the metals are essential or non essential, and suggests using gill tissue Na(+)/K(+)-ATPase and Ca(2+)-ATPase as sensitive biomarkers in metal contaminated waters.

Time-response relationships for the accumulation of Cu, Ni and Zn by seven-spotted ladybirds (Coccinella septempunctata L.) under conditions of single and combined metal exposure

Accumulation, and therefore toxicity, of trace metals in invertebrates may be affected by potential interactive effects that can occur amongst different metallic elements. However, there is little data on the nature and effects of such interactions in terrestrial systems. This work reports the interactions among Cu, Ni and Zn during accumulation by the beetle Coccinella septempunctata. Test animals were treated with 500mgkg−1 of each metal singularly and in combination for 15d. The effects of treatment with a single metal had no effect on the baseline concentrations of the other two. Time-response relationships for Cu and Ni after treatment with one metal were curvilinear, demonstrating that the metals were initially accumulated, but after ∼8d regulatory mechanisms became effective. This resulted in decreasing concentrations in test animals despite continued treatment. In contrast, the time-response relationship for Zn was linear. Treatment with metals in combination markedly altered the time-response relationships with all three metals showing a linear trend and the slope of the Zn relationship increasing significantly. After 15d of exposure this had the effect of increasing the metal concentration in animals exposed in combination compared to those exposed singularly by 144% to 38.3mgkg−1 for Cu, 141% to 27.5mgkg−1 for Ni and 55% to 311mgkg−1 for Zn. For all metals, differences amongst treatments were significant, indicating that inter-element interactions can enhance the concentration of trace metals in C. septempunctata.

A Single Metal, Metal Mixture, and Whole-Effluent Approach to Investigate Causes of Metal Mine Effluent Effects on Fathead Minnows (Pimephales promelas)

Although many studies have examined effects of metal mine effluents (MMEs) on receiving environments, few have compared the roles of individual and mixed metals relative to whole effluents. The objective of the present set of studies was to examine whether Cu, Ni, or Se, alone or in a mixture, causes comparable effects to those observed in fathead minnows (Pimephales promelas) exposed to an environmentally relevant MME (45 % process water effluent [PWE]). Metal bioaccumulation, fathead minnow (FHM) morphometrics, and egg production were compared between treatments over a 21-day exposure. FHMs were exposed to similar waterborne concentrations and species of metals in single and mixed metal treatments relative to 45 % PWE. FHMs were also exposed to similar concentrations of metals in single and mixed metal treatments relative to 45 % PWE through the diet (Chironomus dilutus — a representative prey species). However, only FHMs exposed to 45 % PWE had reduced egg production (60–80 % less than controls). Our findings indicate that Cu, Ni, and Se exposures and bioaccumulation did not contribute to decreased reproductive output in FHMs under the conditions that were examined. We also found no evidence to believe that these metals were responsible for decreased egg production in PWE. It is therefore reasonable to suggest that these metals have limited potential to cause reproductive effects in MMEs with similar composition and water chemistry conditions. Overall, this study highlights the importance of examining single and mixed metal exposures prior to suggesting that adverse effects in fish exposed to MMEs occur due to bioaccumulation of metal(s).

Behavioural and physiological responses of Gammarus pulex exposed to cadmium and arsenate at three temperatures: individual and combined effects.

This study aimed at investigating both the individual and combined effects of cadmium (Cd) and arsenate (AsV) on the physiology and behaviour of the Crustacean Gammarus pulex at three temperatures (5, 10 and15°C). G. pulex was exposed during 96 h to (i) two [Cd] alone, (ii) two [AsV] alone, and (iii) four combinations of [Cd] and [AsV] to obtain a complete factorial plane. After exposure, survival, [AsV] or [Cd] in body tissues, behavioural (ventilatory and locomotor activities) and physiological responses (iono-regulation of [Na+] and [Cl−] in haemolymph) were examined. The interactive effects (antagonistic, additive or synergistic) of binary mixtures were evaluated for each tested temperature using a predictive model for the theoretically expected interactive effect of chemicals. In single metal exposure, both the internal metal concentration in body tissues and the mortality rate increased along metallic gradient concentration. Cd alone significantly impaired both [Na+] and [Cl−] while AsV alone had a weak impact only on [Cl−]. The behavioural responses of G. pulex declined with increasing metal concentration suggesting a reallocation of energy from behavioural responses to maintenance functions. The interaction between AsV and Cd was considered as ‘additive’ for all the tested binary mixtures and temperatures (except for the lowest combination at 10°C considered as “antagonistic”). In binary mixtures, the decrease in both ventilatory and locomotor activities and the decline in haemolymphatic [Cl−] were amplified when respectively compared to those observed with the same concentrations of AsV or Cd alone. However, the presence of AsV decreased the haemolymphatic [Na+] loss when G. pulex was exposed to the lowest Cd concentration. Finally, the observed physiological and behavioural effects (except ventilation) in G. pulex exposed to AsV and/or Cd were exacerbated under the highest temperature. The discussion encompasses both the toxicity mechanisms of these metals and their interaction with rising temperature.

Antagonistic toxicity of arsenate and cadmium in a freshwater amphipod (Gammarus pulex)

Because toxicants rarely occur alone in the environment, a major challenge in risk assessment is to address the combined effects of chemicals on aquatic organisms. This work is aimed at investigating the joint toxicity action of binary mixtures of cadmium and arsenate on Gammarus pulex. Individuals were exposed during 240 h to four single arsenate or cadmium concentrations and binary mixtures of these metals according to a complete factorial plane. Observed mortality in binary mixtures was compared to observed mortality in single arsenate or cadmium exposures. In addition, interactive effects (antagonistic, additive or synergistic) were evaluated using a predictive model for the theoretically expected interactive effect of chemicals. For all the tested concentration combinations, we observed an antagonist 'between-metals' interaction on G. pulex mortality. This antagonistic effect was more marked for the lowest than for the highest (i.e. 1502.0 μg(AsV) L(-1) and 28.5 μg(Cd) L(-1)) tested concentrations of individual metals in binary mixtures. Metal concentrations in body tissues were evaluated and were significantly lower in binary mixtures than in single metal exposures at similar concentration, especially for combinations corresponding to the highest concentrations of both metals (1502.0 μg(AsV) L(-1) and 28.5 μg(Cd) L(-1)). Results were discussed in terms of (1) mechanisms of uptake and bioconcentration and (2) relationships between metal concentration in gammarid body and observed toxicity.

NMR-based metabolomic studies on the toxicological effects of cadmium and copper on green mussels Perna viridis

Traditional toxicology studies have focused on selected biomarkers to characterize the biological stress induced by metals in marine organisms. In this study, a system biology tool, metabolomics, was applied to the marine mussel Perna viridis to investigate changes in the metabolic profiles of soft tissue as a response to copper (Cu) and cadmium (Cd), both as single metal and as a mixture. The major metabolite changes corresponding to metal exposure are related to amino acids, osmolytes, and energy metabolites. Following metal exposure for 1 week, there was a significant increase in the levels of branched chain amino acids, histidine, glutamate, glutamine, hypotaurine, dimethylglycine, arginine and ATP/ADP. For the Cu + Cd co-exposed mussels, the levels of lactate, branched chain amino acid, succinate, and NAD increased, whereas the levels of glucose, glycogen, and ATP/ADP decreased, indicating a different metabolic profile for the single metal exposure groups. After 2 weeks of exposure, the mussels showed acclimatization to Cd exposure based on the recovery of some metabolites. However, the metabolic profile induced by the metal mixture was very similar to that from Cu exposure, suggesting that Cu dominantly induced the metabolic disturbances. Both Cu and Cd may lead to neurotoxicity, disturbances in energy metabolism, and osmoregulation changes. These results demonstrate the high applicability and reliability of NMR-based metabolomics in interpreting the toxicological mechanisms of metals using global metabolic biomarkers.

Transcriptomic signatures in Chlamydomonas reinhardtii as Cd biomarkers in metal mixtures

In the natural environment, toxicant effects can be monitored by the signature mRNA expression patterns of genes that they generate in test organisms. The specificity and sensitivity of these transcriptome-based bioassays to a given toxicant can be confounded by temporal changes in biomarker mRNA expression, effects of other toxicants and hardness ions, and non-linear mRNA expression responses of genes. This study provides the foundation for the development of a transcriptomic-based bioassay for bioavailable Cd in the freshwater alga, Chlamydomonas reinhardtii. It characterizes: (1) the Cd regulation of nine genes with respect to their mRNA induction kinetics; (2) the effects of two additional metals common to freshwaters, Cu 2+ and Pb 2+, and (3) the relationships between metal bioaccumulation and the transcriptomic responses. Quantitative real time PCR was used to monitor mRNA levels of nine Cd-induced genes following an exposure to 0.01, 0.11 and 1.16 μM Cd 2+. Several distinct mRNA expression patterns were observed with time. While the presence of Cu 2+ and Pb 2+ decreased Cd biouptake, mRNA levels increased for six genes, showing lack of Cd 2+ specificity. Nonetheless, the transcriptomic effects of binary metal exposures rarely adhered to a simple additive model based on single metal exposures; rather most exhibited synergistic or antagonistic interactions. While none of these genes could be used as a specific Cd biomarker, the signature mRNA expression profile obtained from a select subset of Cd sensitive genes was a useful biomarker of sublethal effects.

Effect of a polymetallic mixture on metal accumulation and metallothionein response in the clam Ruditapes decussatus

The toxic effects of metals are related to changes in natural physiological and biochemical processes in organisms, which are not easily detected. Marine invertebrates developed strategies to survive in the presence of toxic metal levels, by the removal of these compounds from the soluble fraction of the cell through different processes, including the synthesis of metallothionein (MT). To better understand the effect of Cd, Cu and Zn in MT response it is important to consider that in their natural environment these metals are normally mixed. The exposure to a metal mixture result in toxicological interactions that produce different biological responses when compared to the effects of a single metal exposure. The aim of this study was to assess metal accumulation and MT response in different tissues of the clam Ruditapes decussatus exposed to a mixture of sublethal Cd, Cu and Zn concentrations. Kinetic models were applied to determine metal uptake and loss to better predict and understand the detoxification mechanisms in this species. The kinetic model showed that the effect of this polymetallic exposure compared to a single exposure to these metals caused different metal uptake and loss rates in several tissues. Moreover, the exposure of R. decussatus to a polymetallic mixture caused an increase in MT induction compared to a single metal exposure. This is probably related to the interaction between the different metals and their different affinity to this protein. Metal interactions within aquatic organisms are very important in MT synthesis and the effect of polymetallic mixtures in the environment must be taken into account in field studies.

Validation of the Biotic Ligand Model in Metal Mixtures: Bioaccumulation of Lead and Copper

The biotic ligand model (BLM) has the potential to predict biological effects and bioaccumulation in metal mixtures. Pb and Cu uptake by the green alga Chlamydomonas reinhardtii have been quantified in single-metal exposures and in metal mixtures in order to test some of the key assumptions of the BLM. Stability constants for the interaction of the metals with biological uptake sites were determined from measured short-term internalization fluxes. In the absence of competition, a value of 10(5.8) M(-1) was obtained for Cu, while 10(5.9) M(-1) was obtained for Pb. Competition experiments did not show a straightforward antagonistic competition as would be predicted by the BLM. Only at high Cu(2+) concentrations (>1 microM) did Cu behave as a competitive inhibitor of Pb transport. Surprisingly, low concentrations of Cu(2+) had a synergistic effect on Pb uptake. Furthermore, Cu uptake was independent of Pb when Cu concentrations were below 10(-7) M. In order to explain the observed discrepancies with the BLM, membrane permeability and Cu transporter expression levels were probed. The expression of ctr2, a gene coding for a Cu transporter, increased significantly in the presence of Pb, indicating that bioaccumulation is much more dynamic than assumed in the equilibrium models.

Monitoring the sensitivity of the oligochaete Tubifex tubifex in laboratory cultures using three toxicants

Acute toxicity tests were conducted to assess the sensitivity of laboratory cultured Tubifex tubifex (Annelida, Clitellata), as an intralaboratory quality assurance requirement for the test organisms used in sediment chronic bioassays. Worms were exposed to cadmium, copper, and chromium in water-only 96-h tests, in single metal exposure, over a three-year period. The lethal concentration for the x% of the exposed population (LCx), the No-Observable-Effect Concentration (NOEC) and the Lowest-Observable-Effect Concentration (LOEC) were estimated. Based on LC50 values, the rank of toxicity was Cu+2>Cd+2>Cr+6. Sensitivity remained relatively constant during the research period and was comparable with the sensitivity of the same culture stock examined more than 10 years ago. This observed consistency in sensitivity indicates that comparisons between different sediment chronic bioassays conducted during the study period, using T. tubifex worms from the same culture stock, was appropriate. It is necessary to control both worm biomass and age for the acute test in order to standardize the test-organism conditions in intralaboratory quality assurance programs.

Single and joint effects of Zn and Cd on Porcellio scaber (Crustacea, Isopoda) exposed to artificially contaminated food

This study aimed at determining effects of Zn, Cd and their equitoxic mixtures on metal assimilation and food consumption of the terrestrial isopod Porcellio scaber, in relation to metal availability in the food. Cd was four times less water-extractable than Zn. Cd or Zn extractability was affected neither by metal concentration nor by the presence of the other metal. In single metal exposures, assimilation efficiency (AE) was up to five times higher for Cd than for Zn. In a mixture, AE of Cd significantly increased at low mixture concentrations and decreased at high mixture concentrations. AE of Zn significantly increased at intermediate mixture concentrations. Effects of the Zn and Cd mixture on food consumption were additive (28-day EC50,total=1.10TU; EC50,water-extractable=1.18TU) when based on total and water-extractable concentrations but antagonistic when related to internal metal concentrations in the isopods (EC50,internal=1.40TU).

Assessing the risk of metal mixtures in contaminated sediments on Chironomus riparius based on cytosolic accumulation

Sediments usually contain mixtures of trace metals introduced via natural geochemical processes and anthropogenic activities. Kinetics and effects of these metals are strongly dependent both on the composition of the mixture and on the physico-chemical characteristics of the sediment. Relating effects to metal concentration may consequently be advised. However, total accumulation may be a poor predictor of metal toxicity for Chironomus riparius exposed to contaminated field sediments. As an alternative, we proposed to relate effects on Chironomus growth with cytosolic metal accumulation, measured in larvae after a short exposure period. Dose–response relationships were derived for zinc, copper, and cadmium through single-metal exposure data analysed with toxicokinetics and toxicodynamics models. They permitted, on the basis of cytosolic accumulation measures, to predict successfully the effects of mixtures of cadmium, zinc, and copper on the growth of larvae exposed to spiked sediments, as well as to field sediments in which zinc and copper were assumed to be predominant.

Modelling Bioaccumulation and Toxicity of Metal Mixtures

ABSTRACT Bioaccumulation of metals in mixtures may demonstrate competitive, anticompetitive, or non-competitive inhibition, as well as various combinations of these and/or enhancement of metal uptake. These can be distinguished by plotting (metal in water)/(metal in tissue) against metal in water and comparison to equivalent plots for single-metal exposure. For the special case of pure competitive inhibition where only one site of uptake is involved, inhibition of metal accumulation in any metal mixture can be predicted from bioaccumulation of the metals when present singly. This is consistent with the commonly used Biotic Ligand Model (BLM) but does not explain bioaccumulation of metals in Hyalella azteca. Options for modelling toxicity of metal mixtures include concentration or response addition based on metal concentrations in either water or tissues. If the site of toxic action is on the surface of the organism, if this is the same as the site of metal interaction for bioaccumulation, if there is only one such type of site, and if metal bioaccumulation interactions are purely competitive (as in the BLM), then metal toxicity should be concentration additive and predictable from metal concentrations in either water or tissues. This is the simplest toxicity interaction to model but represents only one of many possibilities. The BLM should, therefore, be used with caution when attempting to model metal interactions, and other possibilities must also be considered.

Metal accumulation in the polychaete Hediste japonica with emphasis on interaction between heavy metals and petroleum hydrocarbons

The accumulation of cadmium (Cd) and copper (Cu) in the polychaete Hediste japonica exposed to the mixture of Cd (or Cu) and petroleum hydrocarbons (PHCs) was investigated and compared with that exposed to single Cd (or Cu). The increased bioavailability of Cd or Cu with exposure concentrations resulted in an increase in the accumulation and net accumulation rate of Cd or Cu during single metal exposure. The net accumulation rate of Cd increased, but the net accumulation rate of Cu decreased with exposure time during single metal exposure, suggesting that H. japonica could actively regulate Cu burden in their body by inhibition of absolute uptake or promotion of excretion. The interactions between Cd (or Cu) and PHCs had complicated influences on the net accumulation rate of Cd and Cu in H. japonica under the condition of the binary mixture, which are dependent on their concentration combinations and exposure time.

An integrated model describing the toxic responses of Daphnia magna to pulsed exposures of three metals

Some toxicology research in which toxicant exposures are continual (pulsed) rather than continuous have been reported. A number of toxicity models have been developed for pulsed and continuous exposures. Most of these models were developed based on one- or two-compartment, first-order toxicokinetics and were calibrated with organic compounds. In the present study, the relationship between mortality (after 21 d) of Daphnia magna in response to pulsed and continuous exposures to Cu, Zn, and Se was used to develop a model that integrated the effects of single and multiple pulsed metal exposures based on first-order uptake and depuration kinetics. Mortality was a function of exposure concentration, duration, and recovery time between exposures. The model was successfully validated using an independent data set. It is applicable to risk assessment and, potentially, may be incorporated with other models (e.g., the biotic ligand model) to predict the toxicity of pulsed metal exposures under a range of environmental conditions.