Bioaccumulation of trace metals in the Antarctic amphipod Paramoera walkeri (Stebbing, 1906): comparison of two-compartment and hyperbolic toxicokinetic models

Bioaccumulation of Cd, Pb, Cu and Zn in the Antarctic gammaridean amphipod Paramoera walkeri (Stebbing, 1906) was investigated at Casey station (Australian Antarctic Territory). The main goals were to provide information on accumulation strategies of the organisms tested and to verify toxicokinetic models as a predictive tool. The organisms accumulated metals upon exposure and it was possible to estimate significant model parameters of two-compartment and hyperbolic models. These models were successfully verified in a second toxicokinetic study. However, the application of hyperbolic models appears to be more promising as a predictive tool for metals in amphipods compared to compartment models, which have failed to adequately predict metal accumulation in experiments with increasing external exposures in previous studies. The following kinetic bioconcentration factors (BCFs) for the theoretical equilibrium were determined: 150-630 (Cd), 1600-7000 (Pb), 1700-3800 (Cu) and 670-2400 (Zn). We find decreasing BCFs with increasing external metal dosing but similar results for treatments with and without natural UV radiation and for the combined effect of different exposure regimes (single versus multiple metal exposure) and/or the amphipod collective involved (Beall versus Denison Island). A tentative estimation showed the following sequence of sensitivity of P. walkeri to an increase of soluble metal exposure: 0.2-3.0 microg Cd l(-1), 0.12-0.25 microg Pb l(-1), 0.9-3.0 microg Cu l(-1) and 9-26 microg Zn l(-1). Thus, the amphipod investigated proved to be more sensitive as biomonitor compared to gammarids from German coastal waters (with the exception of Cd) and to copepods from the Weddell Sea inferred from literature data.     

Bioaccumulation of trace metals in the brown shrimp Crangon crangon (Linnaeus, 1758) from the German Wadden Sea

The objective of the present study is to evaluate the suitability of the brown shrimp Crangon crangon (Linnaeus, 1758) from the German Wadden Sea as a biomonitor for the trace metals Cd, Pb, Cu, and Zn and to analyse whether the two-compartment model sensu OECD could be used as a predictive tool to assess environmental quality. The tested decapods accumulated Cd and Pb upon exposure and it was possible to estimate significant model parameters of two-compartment models, while they did not respond to waterborn Cu and Zn. Kinetic BCFs at theoretical equilibrium were 860 for Cd and 750 for Pb. A tentative estimation showed the following sensitivity of C. crangon to an increase of soluble metal exposure: 0.4 microg Cd l(-1) and 0.9 microg Pb l(-1). Available information can be used to quantify a measure of agreement or disagreement between bioaccumulation in various decapods. This can be regarded as an important step in the calibration of biomonitors, which is necessary to assess the potential for bioaccumulation on different temporal and geographical scales.     

Expression of glutathione S-transferase (GST) genes in the marine copepod Tigriopus japonicus exposed to trace metals

The intertidal copepod, Tigriopus japonicus has been recognized as a potential model species for marine pollution toxicity testing. Toxicity ranges of several biocides, endocrine-disrupting chemicals (EDCs), and trace metals are known in T. japonicus. A large number of expressed sequence tags (ESTs) and genomic DNA are also sequenced from T. japonicus. In this study, expression of ten glutathione S-transferase (GST) genes was studied in the copepods exposed to trace metals. Expression of these genes was also studied against exposure to hydrogen peroxide (H(2)O(2)) used as a positive control with prooxidant activity. Of all genes, expression of GST-Sigma (GSTS) was highly upregulated in H(2)O(2) as well as trace metal-exposed copepods. In the time-course study, expression of GSTS mRNA was more consistent compared to other GSTs such as GST-Omega, GST-Delta1, GST-Theta3 or microsomal GST1 (mGST1). GSTS is predominantly reported from the insects. Coupled with the previous study of the in vitro antioxidant role of T. japonicus GSTS, these findings imply an antioxidant role for GSTS and highlight its importance as a biomarker of exposure to trace metals in T. japonicus. However, further validation and field trials would be necessary to propose GSTS gene expression as biomarker of exposure to trace metals, as for some trace metals such as silver the response was not consistent in concentration and time-series exposure experiments.     

Bioaccumulation of algal toxins and changes in physiological parameters in Mediterranean mussels from the North Adriatic Sea (Italy)

The Northwestern Adriatic Sea is a commercially important area in aquaculture, accounting for about 90% of the Italian mussel production, and it was subjected to recurring cases of mussel farm closures due to toxic algae poisoning. A spatial and temporal survey of four sites along the North Adriatic Sea coasts of Emilia Romagna (Italy) was undertaken to study the possible impairments of physiological parameters in Mytilus galloprovincialis naturally exposed to algal toxins. The sites were selected as part of the monitoring network for the assessment of algal toxins bioaccumulation by the competent Authority. Samples positive to paralytic shellfish toxins and to lipophilic toxins were detected through the mouse bioassay. Lipophilic toxins were assessed by HPLC. Decreasing yessotoxins (YTX) levels were observed in mussels from June to December, while homo‐YTX contents increased concomitantly. Lysosome membrane stability (LMS), glutathione S‐transferase and catalase activities, and multixenobiotic resistance (MXR)‐related gene expressions were assessed as parameters related to the mussel health status and widely utilized in environmental biomonitoring. Levels of cAMP were also measured, as possibly involved in the algal toxin mechanisms of action. Low LMS values were observed in hemocytes from mussels positive to the mouse bioassay. MXR‐related gene expressions were greatly inhibited in mussels positive to the mouse bioassay. Clear correlations were established between increasing homo‐YTX contents (and decreasing YTX) and increasing cAMP levels in the tissues. Similarly, significant correlations were established between the increase of homo‐YTX and cAMP levels, and the expressions of three MXR‐related genes at submaximal toxin concentrations. In conclusion, YTXs may affect mussel physiological parameters, including hemocyte functionality, gene expression and cell signaling. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 451–470, 2013.     

Baseline trace metals in bivalve molluscs from the Beagle Channel,Patagonia (Argentina)

In order to test the aptitude of individuals of Mytilus chilensis as biomonitors of heavy metals pollution in seawater, several samples of this mollusk together with surrounding seawater samples were collected along 170 km of the coastal area of the Beagle Channel (Tierra del Fuego, Argentina) in 2005 and 2007. The study, performed in seven locations strategically selected, involved the determination of Cd, Cr, Cu, Ni, Pb and Zn in seawaters and mollusks by atomic absorption spectrometry (AAS) and the calculation of the respective concentration factors (CFs). Obtained data were standardized and analyzed by multivariate techniques in order to establish differences between sampling sites and periods. Obtained results will be shown and the bioaccumulation ability of M. chilensis will be evaluated by comparison with results obtained for Mytilus species in different geographical marine areas. A fully discussion on the possibility of employing the results as background levels for comparative purposes in other marine waters of the world will be provided. The possible harm derived from human consumption of these mollusks will be also assessed.     

Toxic trace metals and human oocytes during in vitro fertilization (IVF)

Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each μg/dL increase in blood Pb concentration (relative risk (RR) = 0.25, 95% confidence interval (CI) 0.03–2.50, P = 0.240). For 15 male IVF partners, each μg/L increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR = 0.19, 95% CI 0.03–1.35, P = 0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses.     

A toxicokinetic comparison of norditerpenoid alkaloids from Delphinium barbeyi and D. glaucescens in cattle

Cattle are poisoned by N‐(methylsuccinimido) anthranoyllycoctonine type (MSAL‐type) and 7,8‐methylenedioxylycoctonine type (MDL‐type) norditerpenoid alkaloids in Delphinium spp. Alkaloids in D. glaucescens are primarily of the MSAL‐type, while D. barbeyi is a mixture of MSAL and MDL‐types. The objectives of this study were to determine and compare the toxicokinetics of selected alkaloids from D. glaucescens and D. barbeyi in cattle. The two species of larkspur were dosed to three groups of Angus steers via oral gavage at doses of 8 mg kg^?1 MSAL‐type alkaloids for D. barbeyi and either 8.0 or 17.0 mg kg^?1 MSAL‐type alkaloids for D. glaucescens. In cattle dosed with D. barbeyi, serum deltaline (MDL‐type) concentrations peaked at 488 ± 272 ng ml^?1 at 3 h and serum methyllycaconitine (MSAL‐type) concentrations peaked at 831 ± 369 ng ml^?1 at 6 h. Deltaline was not detected in the serum of cattle dosed with D. glaucescens. Serum methyllycaconitine concentrations peaked at 497 ± 164 ng ml^?1 at 18 h, and 1089 ± 649 ng ml^?1 at 24 h for the 8 mg kg^?1 and 17 mg kg^?1 doses of D. glaucescens respectively. There were significant differences between the maximum serum concentrations and the area under the curve for the two doses of D. glaucescens but not D. barbeyi. Results from this experiment support the recommendation that approximately 7 days are required to clear 99% of the toxic alkaloids from the serum of animals orally dosed with D. barbeyi or D. glaucescens, and that MDL‐type alkaloids play an important role in the toxicity of Delphinium spp. in cattle. Published in 2010 by John Wiley & Sons, Ltd.     

Toxic trace metals and embryo quality indicators during in vitro fertilization (IVF)

Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may interfere with in vitro fertilization (IVF). The aim of this study is to explore biologically plausible hypotheses concerning associations between metals and embryo quality indicators during IVF. For 24 female patients, a multivariable ordinal logistic regression model suggests a 75% reduction in the odds for higher embryo cell cleavage per μg/dL increase in blood Pb (adjusted odds ratio (aOR) 0.25, 95% confidence interval (CI) 0.07-0.86). For 15 male partners, each μg/L increase in blood Hg (aOR 0.60, 95% CI 0.45-0.79) and μg/dL increase in blood Pb (aOR 0.58, 95% CI 0.37-0.91) is associated with a decrease in the analogous odds. Embryo fragmentation is reduced by higher blood Hg (aOR 0.85, 95% CI 0.72-1.00), but increased by higher blood Pb (aOR 1.47, 95% CI 1.11-1.94) in men. The magnitude of these suggested effects warrants confirmation in a larger study.     

Baseline trace metals in gastropod mollusks from the Beagle Channel,Tierra del Fuego (Patagonia,Argentina)

With the aim to evaluate the mollusk Nacella (P)magellanica as biomonitor of elemental pollution in seawater of the Beagle Channel, more than one hundred individuals of the gastropod were sampled, separated in viscera and muscle, and then examined with respect to the accumulation of Cd, Cr, Cu, Ni, Pb and Zn. Collection was performed in seven strategic locations along 170 km of the coastal area of the Beagle Channel (Tierra del Fuego, Argentina) in two campaigns during 2005 and 2007. Samples of surrounding seawater in the different sites were obtained and tested for the same metals as well. The accumulation capacity of Nacella (P)magellanica and thus its aptitude as biomonitor, was evaluated through the calculus of the preconcentration factors of the metals assayed. A discussion involving the comparison with other mollusks previously tested will be given. Several statistical approaches able to analyze data with environmental purposes were applied. Non parametric univariate tests such as Kruskal–Wallis and Mann–Whitney were carried out to assess the changes of the metal concentrations with time (2005 and 2007) in each location. Multivariate methods (linear discriminant analysis on PCA factors) were also applied to obtain a more reliable site classification. Johnson’s probabilistic method was carried out for comparison between different geographical areas. The possibility of employing these results as heavy metals′ background levels of seawater from the Beagle Channel will be debated.     

Bioaccumulation and effects of metals on oxidative stress and neurotoxicity parameters in the frogs from the Pelophylax esculentus complex

Ecotoxicology - Metals are involved in the formation of reactive oxygen species and can induce oxidative stress. The aim of this study was to assess the effects of several metals on oxidative...     

Behavioural responses of the supralittoral amphipod Talitrus saltator (Montagu) to trace metals contamination

We investigated behavioural responses (locomotor activity and substrate selection) of the amphipod Talitrus saltator after laboratory exposure to different concentrations of Hg, Cu and Cd. Locomotor activity, measured with a microwave radar device, was assessed in animals exposed to contaminated sand and in sandhoppers previously kept for 48 h in contaminated seawater and tested in clean sand. The contents of Hg, Cu and Cd in T. saltator tissues were measured at the end of pre-exposure to contaminated seawater and after 7 days of exposure to contaminated sand. Substrate selection tests were carried out in a binary choice arena. Tests in contaminated sand showed that sandhopper locomotor activity varied in a dose-dependent manner in the presence of Cu and Hg (at lower Hg concentration they were more active during daytime) but did not show significant changes in Cd-exposed animals except for disappearance of the typical circadian activity pattern. Pre-exposure to trace metals in seawater induced a significant decrease of movements for all metals, although the effects varied according to the toxicity of the metal. Trace metals analyses showed that tissue concentrations of Hg, Cu and Cd were related to their concentrations in the test medium. Substrate selection tests showed avoidance of contaminated sand only when sandhoppers were tested in the presence of both concentrations of Hg and at the higher concentration of Cu. In conclusion, locomotor activity and avoidance behaviour of T. saltator could be used as behavioural biomarkers of trace metals exposure.     

Comparative toxicity and toxicokinetic studies of oxiracetam and (S)-oxiracetam in dogs

1. Oxiracetam (ORT) is known as a derivative of piracetam in the family of nootropics for treating memory impairment and cognition disorders.

2. Given the chiral toxicological concerns surrounding ORT and the absence studies of (S)-ORT, the toxicity and toxicokinetics of (S)-ORT, and comparative toxicology of oxiracetam were systematically investigated in dogs following acute and 13-week repeated oral dosing.

3. The animal toxicity mainly manifested as loose stools in both the acute and the 13-week studies. The no-observed-adverse-effect level is proposed to be 100?mg/kg. The 13-week toxicokinetics study indicated that, in the (S)-ORT group, the time to peak concentration was delayed, elimination half-life extended, and apparent volume of distribution increased compared with the ORT group. The clearance rate increased at low- and mid-doses, but decreased in the high-dose group and was accompanied by drug accumulation. Compared with the same dose of ORT, (S)-ORT had a lower clearance rate and longer elimination half-life.

     

Heavy metals concentrations in fish and shellfish from eastern Mediterranean Sea: Consumption advisories

The present study evaluate concentrations of arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), nickel (Ni), vanadium (V) and zinc (Zn) in fish and shellfish from the Gulf of Catania. Heavy metal analysis was carried on with an ICP-MS, and consumption rates advisory for minimizing chronic systemic and non cancer endpoints in child and adults have been estimated. Among metals investigated, only Cd and Pb have a limit set by European Community for human consumption, and the thresholds were not been exceeded in analyzed species. The As, toxic in its inorganic form, have not a regulatory limit yet, but the Environmental Protection Agency and the World Health Organization provide a reference dose, a cancer slope factor and a tolerable intake, applicable in the risk factors assessment. Arsenic target hazard quotient (THQ) values, suggest that human should minimizing meals/week of analyzed species to avoid deleterious effect during lifetime, furthermore, with As cancer risk assessment, for most of the fish, the risk for cancer is greater than the acceptable lifetime risk of 10^–5. Our results give important finding about the consumption limits on certain metals, especially for As, all for minimizing potential health risks in population.     

Bioaccumulation and the effects of organochlorine pesticides, PAH and heavy metals in the Eel (Anguilla anguilla) at the Camargue Nature Reserve, France

Pesticides (organochlorines-OC), polycyclic aromatic hydrocarbons (PAH) and heavy metals are toxic to fish and may be taken in through gills, skin and contaminated foods. Here we measure concentrations of OC, PAH and heavy metals, and their effects in the eel Anguilla anguilla from three locations in the Camargue Reserve in southern France. The Camargue Biosphere Reserve is the largest coastal wetland in Western Europe, and A. anguilla is a common predator at the top of the food chain. Livers and spleens were analyzed for histopathological, chemical and organo-somatic (HSI and SSI) effects. Gill, liver and spleen samples were collected for histopathological studies. Livers and muscles were sampled for metabolic parameters and persistent organic pollutant analysis. Total lipids were estimated by spectrophotometry and lipid-free residues were used in protein and glycogen analysis. OC pesticides were extracted from lipids of muscles and livers, analyzed by gas chromatography, and PAH from bile were analyzed by fixed wavelength fluorescence spectrofluorimetry. Heavy metals were measured by inductively coupled plasma with optical or with mass spectrometers. High concentrations of contaminants were found in eel tissues. La Capelière had the greatest OC and PAH concentrations; unexpected lesions in gills, livers and spleens were more common at the other sites. Liver and spleen tumors and lipidosis in livers were associated with chronic, and gill lesions with acute exposure. High pesticide and PAH concentrations and lesions in eels from the Camargue reserve demonstrate the contamination of the area. A more complete study in the Camargue reserve is necessary to better understand the impact on wildlife and humans. Also, this study suggests that eel biology must be better understood before continued use of this species as a biomonitor of polluted areas.     

Oral and IV dosing: a method to determine the compartment of drug elimination for two-compartment models

It has been shown previously that it is impossible to measure the volume of distribution at steady state conclusively for a multicompartment system from an iv bolus dose only. The problem lies in deciding from which compartment elimination of the drug occurs in the compartmental model. In this paper a new modelling strategy is examined whereby the compartment of elimination may be identified uniquely for the case of two-compartment models. The two models examined predict different profiles in the absorption phase of an oral profile. An in vivo data set is provided that favours a peripheral elimination explanation of its observed pharmacokinetics, based on the 'goodness of fit'.     

Toxicological and toxicokinetic analysis of angiotensin (1-7) in two species

The objectives of this study were to determine the potential systemic and local toxicity, as well as evaluate the toxicokinetic (TK) profile of angiotensin (1-7) [A(1-7)] when administered daily via subcutaneous injection for 28 days to Sprague-Dawley rats and Beagle dogs. A(1-7) is a member of the renin-angiotensin system and has undergone clinical evaluation for the treatment of chemotherapy-induced myelosuppression. In this present study, A(1-7) was given at 10 mg/(kg day) for 28 days to rats and canines. At day 27, blood was harvested to evaluate the TK parameters. On day 28, systemic toxicology was evaluated. Following A(1-7) administration for 27 days, no plasma A(1-7) accumulation was detected in canines; however, increased A(1-7) plasma concentrations were detected in rats. Despite the accumulation observed in rats, no detectable toxicity was found following A(1-7) administration for 28 days. The TK analysis of A(1-7) revealed a plasma half-life of 20-30 min in both rats and canines. The time to maximum plasma concentration was found to be 15 and 26.25 min in rats and canines, respectively. This study shows that subcutaneous administration of A(1-7) at 10 mg/(kg day) for 28 days did not lead to any detectable toxicities in either rats or canines.     

Single administration toxicokinetic studies of decalin (decahydronaphthalene) in rats and mice.

Decalin (decahydronaphthalene) is an industrial solvent known to cause alpha2u-globulin nephropathy in male rats. Studies were conducted using decalin (mixture of cis and trans isomers) to (1) characterize systemic elimination of decalin in rats and mice and (2) evaluate disposition of decalin, its metabolites, and kidney alpha2u-globulin in young and old rats of both sexes following a single 6-h whole-body inhalation exposure at up to 400 ppm decalin. Additionally, a separate group of young male F344/N rats were administered either cis- or trans-decalin iv at doses up to 20 mg/kg to assess disposition of each isomer, its metabolites, and kidney alpha2u-globulin. Decalin was eliminated from blood in a dose-dependent manner, regardless of sex, age, or species. C0 and AUC infinity increased supra-proportionally with exposure concentration. Mice were more efficient in eliminating decalin than rats at lower exposure concentrations, but nonlinear elimination kinetics were more noticeable at 400 ppm. Sex differences in blood decalin elimination were observed in rats; females had a consistently higher AUC infinity at all exposure concentrations. There was a dose-dependent increase in kidney decalin, decalone, and alpha2u-globulin in male rats exposed to decalin. Kidney alpha2u-globulin and decalone concentrations in old male rats were substantially lower than those in young males, but were similar to those observed in all (young and old) females. Compared to old males and all females, young male rats had significantly lower urinary decalol concentrations, but higher kidney decalin, decalone, and alpha2u-globulin concentrations. Administration of decalin to male rats as either the cis or trans isomer revealed that more cis -decalone is produced per unit dose as compared to trans-decalone, and that more trans-decalin accumulated in the kidney (as alpha2u-globulin-ligand complexes) compared to cis-decalin. These patterns of isomer-specific metabolism were also reflected in the cis/trans ratios of decalin in blood, as well as urinary decalol metabolites. The ratio of alpha2u-globulin to the total amount of decalin plus decalone measured in the male rat kidney was approximately 1.0. Therefore, alpha2u-globulin was a key factor in the accumulation of decalin and decalone in kidneys of young male rats, decalin and decalone were practically absent in all females and in old males.     

Purification of a proteinase (Ac5-proteinase) and characterization of hemorrhagic toxins from the venom of the hundred-pace snake (Agkistrodon acutus)

Ac5-Proteinase (15.2 mg) was isolated from Agkistrodon acutus venom (1 g) by column chromatography on Sephadex G-75, CM-Sephadex C-50 and CM-Cellulose. Ac5-Proteinase was homogeneous by disc electrophoresis on polyacrylamide gel at pH 4.3 and also by SDS-disc polyacrylamide gel electrophoresis. Ac1-, Ac2-, Ac3- and Ac5-proteinases possessed lethal and hemorrhagic activities, but Ac4-proteinase had no lethal activity. These activities were inhibited completely by ethylenediaminetetraacetic acid (EDTA), 1,10-phenanthroline or cysteine. The molecular weights of Ac1-, Ac2-, Ac3-, Ac4- and Ac5-proteinases were approximately 24,500, 25,000, 57,000, 33,000 and 24,000, respectively. Ac1-, Ac2-, Ac4- and Ac5-proteinases did not contain any carbohydrates, but Ac3-proteinase contained 0.1% carbohydrate by weight.     

Bioaccumulation and biochemical effects of mercury in the plant Bacopa monnieri (L)

Plants of Bacopa monnieri were treated with six different concentrations of Hg (0.01, 0.5, 1.0, 2.0, 3.0, and 5.0 μg mL⁻¹) for 4, 7, and 14 d under laboratory conditions. The metal accumulation in the root tissues was about five times more than in the shoots. At all the concentrations of Hg, cysteine, total -SH, reduced glutathione, and ascorbic acid contents increased in the roots of B. monnieri up to 7 d of exposure except the ascorbic acid content, which decreased above 2 μg mL⁻¹ Hg. The malondialdehyde content decreased at all the concentrations of Hg; however, protein and sugar contents decreased above 0.1 and 2.0 μg mL⁻¹ Hg, respectively, after 4 d of exposure in the roots of the plant. The chlorophyll content in leaves decreased significantly with an increase in metal concentrations and durations of exposure. The results suggest that an increase in cysteine, total -SH, reduced glutathione, and ascorbic acid content by Hg treatment at the initial exposure period are part of the overall expression of Hg tolerance in the plant, and the decrease in chlorophyll and protein content is a consequence of Hg toxicity at higher metal concentrations and increased period of exposure. © 1996 by John Wiley & Sons, Inc.