Relationship between chronic toxicity and bioaccumulation of copper,cadmium and zinc as affected by water hardness and humic acid

Using daphnids, we have evaluated the effects of water hardness and humic acid (HA) on the chronic toxicity and bioaccumulation of Cu, Cd and Zn. Although changes in water hardness and HA concentration changed bioaccumulation or chronic toxicity, or both, of each of the three metals, there was no consistent relationship between changes in toxicity and changes in bioaccumulation. Only for Cu in hard water was there a positive correlation between toxicity and bioaccumulation. The uptake of ⁶⁵Zn by molted exoskeletons suggests that changes in water chemistry do indeed modify the bioavailability of metals as would be expected. That is, an increase in the concentration of Ca²⁺ or Mg²⁺ or the increased chelation of metals by HA should decrease bioavailability. The complex storage, transformation and excretion processes in multicellular animals, however, result in there being a poor correlation among bioavailability, bioaccumulation and toxicity.     

Mechanism of the toxicity induced by natural humic acid on human vascular endothelial cells

Humic acid (HA), a group of high‐molecular weight organic compounds characterized by an ability to bind heavy metals, is normally found in natural water. Although the impairment of vascular endothelial cells in the presence of humic substances has been reported to be involved in some diseases, the mechanisms responsible for this involvement remain unclear. In this study, we examined the cytotoxicity of HA obtained from peatland in Central Kalimantan, Indonesia, to human vascular endothelial cells, as well as the mechanisms behind these effects. It was found that 50 mg/L HA showed cytotoxicity, which we considered to be mediated by apoptosis through the mitochondrial pathway because of an increase in the expression of caspases 6 and 9 in response to HA administration. In addition, this cytotoxicity was enhanced when cells in this experimental system were exposed to oxidative stress, while it was decreased by the addition of vitamin C. Thus, we conclude that the apoptosis induced by HA depends upon oxidative stress. Furthermore, an iron chelator, DFO, showed a tendency to decrease HA‐induced cytotoxicity, suggesting that iron may potentially mediate HA‐induced oxidative stress. In conclusion, long‐term consumption of HA‐rich water obtained from our study area may cause damage to endothelial cells and subsequent chronic health problems. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 916–925, 2014.     

Acute toxicity and bioaccumulation of arsenic in freshwater clam Corbicula fluminea

Arsenic is a potent human carcinogen of skin, lung, and urinary bladder. Freshwater clam Corbicula fluminea is a commercially important native species in Taiwan. C. fluminea is also a suitable biomonitoring test organism. Little is known, however, about the actual effects of arsenic on C. fluminea. The objectives of this study were to provide information on the acute toxicity and bioaccumulation kinetics of arsenic in C. fluminea. We carried out a 14-day exposure experiment to obtain bioaccumulation parameters. Uptake was very rapid when C. fluminea was first exposed and then slightly decayed during the uptake phase of the experiment and an uptake rate constant of 1.718 +/- 6.70 (mean +/- SE) mL g(-1) d(-1) was estimated. The elimination of arsenic from C. fluminea obeyed first-order depuration kinetics (r(2) = 0.85, p < 0.05) with a calculated half-life of 6.80 days. The derived bioaccumulation factor of 16.84 suggests that arsenic has a high potential for bioaccumulation in C. fluminea. This had important implications for dietary exposure of arsenic to humans who eat contaminated clams, because the soft tissue usually constitutes the majority of tissue consumed. The 96-h LC50 value was estimated to be 20.74 (95% CI: 11.74-30.79) mg L(-1) obtained from a 7-day acute toxicity bioassay. We also kinetically linked an acute toxicity model and a Hill sigmoid model to reconstruct an internal effect concentration based dose-response profile to assess the effect of soft tissue arsenic burden on the C. fluminea mortality. This result could be used to support the establishment of an ecological risk assessment to prevent possible ecosystem and human health consequences.     

Nitrite bioaccumulation in Salmo gairdneri rich. and hematological consequences

Salmo gairdneri Rich. exposed to 450 μg/l (NO₂N) of environmental nitrite, and examined after various periods of treatment, possess methemoglobin levels neither correlatable to their physiological conditions, nor proportional to their hematic nitrite concentration. Also, functional hemoglobin content (total Hb minus metHb) can be connected to a physiological state only in the early stages of intoxication. Nitrite accumulates in blood and tissues of fish to a surprisingly high extent (up to 60 times the environmental concentration) against increasing concentration gradients. The nitrite concentration in blood seems to be linked to exposure time more than to physiological conditions, while in the liver and brain of treated specimens, much greater differences exist between apparently unstressed animals and torpid, unreactive trout. Further evidence is given, therefore, that death following acute intoxication depends on nitrite toxic action in vital organs rather than on methemoglobinemia.     

Acute toxicity and bioaccumulation of aqueous and sediment-bound metals in the estuarine amphipod Melita plumulosa

The sensitivities of juvenile and adult amphipods to metals (Cd, Cu, Ni, Pb, and Zn) in whole sediment and water-only exposures were compared using a newly developed acute test with the estuarine species Melita plumulosa. Endpoints included survival and bioaccumulation in adults, and survival and growth (body length) in juveniles over 96 h water-only and 10 day sediment exposures. Juveniles were more sensitive than adults to metals, either bound to sediments or in the aqueous phase. Although LOEC values for copper and zinc in juvenile whole-sediment tests (820 and 2290 mg/kg dry weight, respectively) were high in comparison with interim sediment quality guideline values for individual metals (270 and 410 for copper and zinc respectively), they were generally within the range of concentrations found in contaminated sediments in local estuaries. Accumulation of metals, together with the low porewater metal concentrations in whole-sediment tests, indicated that the ingestion of sediment is an important source of zinc and copper and cause of toxicity in this species.     

Toxicological assessment of combined lead and cadmium: Acute and sub-chronic toxicity study in rats

The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90 day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD₅₀ value of Pb(NO₃)₂ and CdCl₂ mixture by the oral route was 2696.54 mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague–Dawley (SD) rats with dose–response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96 mg/(kg bw day) when administered orally for 90 consecutive days.     

Acute toxicity and bioaccumulation of arsenic in tilapia (Oreochromis mossambicus) from a blackfoot disease area in Taiwan

The general objective of our work was to determine the acute toxicity and bioaccumulation of arsenic (As) in tilapia (Oreochromis mossambicus) from the blackfoot disease (BFD) area in Taiwan. The average concentration of As in pond water ranged from 17.8 to 49 microg L(-1). Acute toxicity tests showed that the As concentration that caused toxicity to tilapia ranged from 69 060 microg As L(-1), in the 24-h toxicity test, to 28 680 microg As L(-1), in the 96-h toxicity test. We measured As concentrations in various tissues of tilapia to identify the affinities of tissues for As. Significant correlations were found among the As concentrations in all tissues. The highest bioconcentration factor (BCF) was found in the intestine (maximum value: 2270). The order of BCFs was: intestine > stomach > liver approximately gill > muscle. Arsenic concentrations in all tissues were allometric, negatively correlating with fish body weight [r(2) = 0.63 +/- 0.045 (mean +/- SE), p < 0.05]. Our results also revealed that As concentrations in muscle tissue were positively correlated with As accumulation in the viscera (r(2) = 0.85, p < 0.05). Significantly higher concentrations of As were obtained in the viscera of tilapia [12.65 +/- 10.17 microg g(-1) dry wt (mean +/- SD)] than in the muscle tissue (3.55 +/- 0.42 microg g(-1) dry wt). Our results suggest that a simple way of reducing the health risk associated with consuming tilapia is to trim and cook the fish properly, that is, removing the viscera of tilapia can greatly reduce the amount of As ingested and consequently reduce the health risks.     

Chronic toxicity and bioaccumulation of mercuric chloride in the fathead minnow (Pimephales promelas)

Fathead minnows (Pimephales promelas) were exposed to various concentrations of mercuric chloride in water to determine its acute and chronic (including reproduction) toxicity and to measure bioaccimulalion. Mean LC₅₀ values of HgCl₂ for juvenile fatheads were 168, 112, 84, and 74 μg Hg/l at 4, 5, 6, and 7 days, respectively. Following 41 wk of exposure to 0.26 to 3.69 μg/l, females were significantly smaller than controls at all concentrations except 0.50 μg/l and males showed reduced growth at 3.69 μg/l. Over half of the fish at 2.01 and 3.69 μg/l were severely stunted and scoliosis was prevalent among these stunted fish. No spawning occurred at and above 1.02 μg/l and the number of spawning pairs was reduced at 0.26 and 0.50 μg/l resulting in total egg production of 46 and 54%, respectively, of control. Thirty-day growth of second-generation larvae (from transferred control embryos at and above 1.02 μg/l) was significantly reduced at all mercury concentrations tested. No effects on hatchability or larval survival were detected. Chronically-exposed fish accumulated mean whole body total mercury residues of 1.36 to 18,80 μg/g of tissue (wet weight) from 0.26 to 3.69 μg/l, respectively. Uptake appeared proportional to water concentration; bioconcentration factors varied between 4380 and 5680.The influence of diet on mercury toxicity and bioaccumulation was studied during two 60-day larval fathead exposures. Overall recuccd growth and possibly enhanced toxic effects occurred in larvae on the dry trout starter diet compared to larvae fed on Artemia. Mercury uptake appeared influenced by the severity of toxic effects.     

Effect of silver nanoparticle surface coating on bioaccumulation and reproductive toxicity in earthworms (Eisenia fetida)

Abstract

The purpose of this study was to investigate the effect of surface coating on the toxicity of silver nanoparticles (Ag NPs) soil. Earthworms (Eisenia fetida) were exposed to AgNO₃ and Ag NPs with similar size ranges coated with either polyvinylpyrrolidone (hydrophilic) or oleic acid (amphiphilic) during a standard sub-chronic reproduction toxicity test. No significant effects on growth or mortality were observed within any of the test treatments. Significant decreases in reproduction were seen in earthworms exposed to AgNO3, (94.21 mg kg^-1) as well as earthworms exposed to Ag NPs with either coating (727.6 mg kg^-1 for oleic acid and 773.3 mg kg^-1 for polyvinylpyrrolidone). The concentrations of Ag NPs at which effects were observed are much higher than predicted concentrations of Ag NPs in sewage sludge amended soils; however, the concentrations at which adverse effects of AgNO₃ were observed are similar to the highest concentrations of Ag presently observed in sewage sludge in the United States. Earthworms accumulated Ag in a concentration-dependent manner from all Ag sources, with more Ag accumulating in tissues from AgNO₃ compared to earthorms exposed to equivalent concentrations of Ag NPs. No differences were observed in Ag accumulation or toxicity between earthworms exposed to Ag NPs with polyvinylpyrrolidone or oleic acid coatings.     

Toxicity and bioaccumulation of the insecticide "Raid" in Wister rats

Toxicity and bioaccumulation of the insecticide "Raid" was determined to assess total animal dietary exposures in a nonoccupational environment. The study focused primarily on dietary exposure concentrations (25-960 microg/g) of the ingredients of Raid administered to rats for 10 days. Tissue concentrations of the insecticide were determined by a high-pressure liquid chromatography method, whereas established methods were used to assess the tissue levels of glucose-6-phosphate and lactic acid dehydrogenase. Results show that animal mortality progressively increased with increasing concentrations while growth (in weight) decreased. Bioaccumulation of the insecticide in the tissues was in the order of lipid > muscle > liver > brain. The indices of toxicity showed no significant effect in brain, but significant reduction of glucose-6-phosphatase and lactic acid dehydrogenase levels were observed in muscle and liver. These results suggest an inhibition of some key metabolic enzymes resulting from accumulation of the insecticide components in the tissues.     

Influence of humic substances on the toxic effects of cadmium and SDBS to the green alga Scenedesmus obliquus

The joint toxicity of chemicals mixture in the aquatic environment was still not well clear. To clarify the joint toxicity of the mixtures of metals and organic pollutants, as well as the influence of dissolved organic matter (DOM) in field water-body on their toxic effects, we conducted the toxicity tests with cadmium (Cd) and sodium dodecyl benzene sulfonate (SDBS) on Scenedesmus obliquus (S. obliquus) with or without the presence of fulvic acid (FA), a typical of DOM. Our results showed Cd was more toxic to S. obliquus than SDBS, and the effects of fulvic acid on SDBS were greater than Cd. The joint toxicity of Cd and SDBS expressed a synergistic effect on S. obliquus, which was observed to be increased with the presence of FA. Our results gave an example for the joint toxicity investigations of organics and metals, aiding to understanding the toxicity of pollutant mixtures in field water bodies containing DOM.     

Relationship between the development of hepato-renal toxicity and cadmium accumulation in rats given minimum to large amounts of cadmium chloride in the long-term: preliminary study

We wished to clarify the relationship between the sensitivity to induce hepato-renal toxicity and the level of cadmium (Cd) in the organs of rats exposed to minimum to large amounts of cadmium chloride (CdCl₂). For this purpose, groups of female Sprague-Dawley (SD) rats, each consisting of 24 animals, were fed diet containing CdCl₂ at concentrations of 0, 8, 40, 200, and 600 ppm for 2, 4, and 8 months from 5 weeks of age. All surviving rats given 600 ppm Cd were killed at 4␣months because of deterioration of their general condition. Animals of this group showed anemia and decreased hematopoiesis in the bone marrow, in addition to reduction of cancellous bone in their femurs. Hepatotoxicity was observed after 2 months in the groups treated with 200 ppm. By 4 months, the rats in the 600 ppm group had developed periportal liver cell necrosis. Renal toxicity characterized by degeneration of proximal tubular epithelia was apparent in the groups treated with 200 ppm from 2 months, becoming more prominent in the high-dose rats at 4 months. Hepatic accumulation of Cd increased linearly with the duration of treatment. In contrast, the concentration of Cd in the renal cortex of rats treated with 600 ppm reached a plateau level of ∼250 μg/g within the first 2 months. The renal concentration of Cd in the 200 ppm group when renal toxic lesions were first detected at 2 months ranged from 104 to 244 μg/g. No renal lesions were observed in the 40 ppm group after 8 months, despite the presence of 91–183 μg/g of Cd in the kidneys. The results thus suggest that renal toxicity would not be induced by treatment with minimum amounts of CdCl₂ for periods longer than 8 months, although accumulation of Cd might gradually progress. A further 2-year feeding study of CdCl₂ and Cd-polluted rice is now in progress. Received: 26 January 1998 / Accepted: 26 May 1998     

Copper bioaccumulation and hepatoprotein synthesis during acclimation to copper by juvenile rainbow trout

Rainbow trout were exposed for 3 wk to copper at 0.09, 0.18, 0.29, 0.40, or 0.59 of the mean control incipient lethal level (ILL) of copper. Whole body copper concentration increased with both exposure concentration and time. Mean residues stabilized in the range of 34 to 37 μg/g dry weight after 2 to 3 wk of exposure at 0.29 to 0.59 ILL.After 3 wk at 0.29 ILL of copper, most fish survived a subsequent exposure at 1.7 ILL, during which their elevated body concentration of copper did not change appreciably (35 to 33 μg/g). In contrast, control fish died rapidly, their body concentration rising from 3.8 to 7.4 μg/g).Sublethal copper exposure increased the protein content of a low-molecular-weight hepatoprotein fraction. There was also greater incorporation into that protein of ¹⁴C from intraperitoneally administered [¹⁴C]leucine. Fish exposed to cadmium showed a similar increase in hepatoprotein but not increased ¹⁴C incorporation. This suggests different, metal-specific proteins. Results are discussed with respect to a previously reported acclimation to copper by the fish, acclimation which significantly altered lethal tolerance of copper.     

葡萄糖酸铜的毒性评价

通过葡萄糖酸铜的食品安全性评价表明,葡萄糖酸铜是中等急性毒性(LD_(50)为41mg/kg)和弱蓄积毒性的化学物质。在小鼠骨髓微核试验和小鼠精子畸变分析中,葡萄糖酸铜均显示阴性结果,并且在Ames试验中对鼠伤寒沙门氏菌株也无基因突变作用。     

The chronic toxicity of equine cadmium metallothionein in the rat

The extensive renal tubular necrosis that results in male rats after the intravenous injection of a single, low dose of equine kidney cadmium (Cd), zinc(Zn)-metallothionein (MT) (0.2 mg MT-bound-Cd/kg body wt.) is followed within 72 h by active regeneration. With repeated administration of the same dose at 3-or 4-day intervals, the lesion resolves although, at least initially, the kidney content of Cd increases progressively. At any time during treatment, about 40% of the accumulated Cd is bound as the endogenous (Cd, Cu)MT. The rate of increase in the renal Cd content is dependent on the ratio of CdZn in the injected metalloprotein, and is appreciably less when the constant dose of protein-bound Cd is given as a (2.4 Cd1 Zn)MT, than as a (3.0 Cd1 Zn)MT. On repeated administration of the latter preparation, however, the concentration of Cd in the kidney does not attain a critical concentration, above which persistant tubular damage occurs, but reaches a maximum of about 150–160 g Cd/g wet wt. (after 16 doses) and then declines. After 19 doses of the (2.4 Cd1 Zn)MT under the same conditions, the renal Cd concentration is submaximal and is less (92 g Cd/g wet wt.) than that after either 16 or 27 doses of the (3.0 Cd1 Zn)MT. In animals that are dosed with either of the heterologous MT preparations, the first dose, although not innocuous, seems to protect the kidneys against further damage by subsequent doses. Repeated doses, however, lead to vascular changes, e.g. lymphoid infiltration, periarteriole oedema and dilation of the arcuate veins, and to dilation of the glomerular spaces.     

Repeated dose and reproductive/developmental toxicity of perfluorododecanoic acid in rats

Perfluoroalkyl carboxylic acids (PFCAs) are a series of environmental contaminants that have received attention because of their possible adverse effects on wildlife and human health. Although many toxicological studies have been performed on perfluorooctanoic acid with carbon chain length C8, available toxicity data on PFCAs with longer chains are still insufficient to evaluate their hazard. A combined repeated dose and reproductive/developmental toxicity screening study for perfluorododecanoic acid (PFDoA; C12) was conducted in accordance with OECD guideline 422 to fill these toxicity data gaps. PFDoA was administered by gavage to male and female rats at 0.1, 0.5, or 2.5 mg/kg/day. The administration of PFDoA at 0.5 and 2.5 mg/kg/day for 42–47 days mainly affected the liver, in which hypertrophy, necrosis, and inflammatory cholestasis were noted. Body weight gain was markedly inhibited in the 2.5 mg/kg/day group, and a decrease in hematopoiesis in the bone marrow and atrophic changes in the spleen, thymus, and adrenal gland were also observed. Regarding reproductive/developmental toxicity, various histopathological changes, including decreased spermatid and spermatozoa counts, were observed in the male reproductive organs, while continuous diestrous was observed in the females of the 2.5 mg/kg/day group. Seven of twelve females receiving 2.5 mg/kg/day died during late pregnancy while four other females in this group did not deliver live pups. No reproductive or developmental parameters changed at 0.1 or 0.5 mg/kg/day. Based on these results, the NOAELs of PFDoA were concluded to be 0.1 mg/kg/day for repeated dose toxicity and 0.5 mg/kg/day for reproductive/developmental toxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1244–1263, 2015.     

Acute and 30-day oral toxicity studies of administered carnosic acid

Purpose

Increasing interest in carnosic acid (CA) is due to its pharmacological properties. The aim of this study was to evaluate the acute and 30-day oral toxicity of CA.

Methods

The acute oral toxicity study in Kuming mice design followed the OECD-guidelines 423, and a 30-day chronic oral toxicity study in Wistar rats based on the enhanced OECD test guideline 407 were performed.

Results

The oral lethal dose (LD50) for mice was 7100 mg/kg of body weight in the acute toxicity study. The histopathological changes were observed in the heart, liver and kidney for the survival mice treated with a single dose CA. For the sub chronic toxicity study, CA administered for 30 days produced slightly reductions in the weight gain pattern, which did not reach the significant level when compared with the control values. With respect to serum biochemistry test, decreased total serum protein levels, but conversely increased aspartate aminotransferase (AST) levels were detected in the high-dose and moderate-dose groups. Histopathologically, light pathological changes were observed in the heart, liver, and kidney of rats treated with the high-dose CA.

Conclusion

The present work suggests that a short-term oral administration of CA has a relatively low toxicity profile.     

Acute toxicity of aristolochic acid in rodents

The acute toxic effects of aristolochic acid (AA) were tested in rats and mice of both sexes. Oral or intravenous administration in high doses was followed by death from acute renal failure within 15 days. Histologically, the predominant features were severe necrosis affecting the renal tubules, atrophy of the lymphatic organs and large areas of superficial ulceration in the forestomach, followed by hyperplasia and hyperkeratosis of the squamous epithelium. The LD₅₀ ranged from 56 to 203 mg/kg orally or 38 to 83 mg/kg intravenously, depending on species and sex.Dedicated to Dr. Rolf Madaus on the occasion of his 65th birthday.     

Use of the aquatic oligochaetes Lumbriculus variegatus and Tubifex tubifex for assessing the toxicity of copper and cadmium in a spiked-artificial-sediment toxicity test

A sediment toxicity test using the freshwater oligochaetes Lumbriculus variegatus and Tubifex tubifex was performed. We evaluated acute and chronic toxicity affects of copper and cadmium on reproduction in both species and the bioaccumulation of both metals by L. variegatus using artificial sediment. L. variegatus bioconcentrated copper 22-fold and cadmium 16-fold after a 14-day exposure to spiked artificial sediments with 0.02% organic content. The EC₅₀ for T. tubifex varied depending upon endpoint from 2.7 to 2.8 mg/L for cadmium and from 8.4 to 8.9 mg/L for copper. The EC₅₀ for L. variegatus was 2.2 mg/L for cadmium and 3.9 mg/L for copper. Based on these results, L. variegatus appears to be more sensitive to metal toxicity in artificial sediments than T. tubifex. ©1999 John Wiley & Sons, Inc. Environ Toxicol 14: 271–278, 1999     

Metallothionein protection of cadmium toxicity

The discovery of the cadmium (Cd)-binding protein from horse kidney in 1957 marked the birth of research on this low-molecular weight, cysteine-rich protein called metallothionein (MT) in Cd toxicology. MT plays minimal roles in the gastrointestinal absorption of Cd, but MT plays important roles in Cd retention in tissues and dramatically decreases biliary excretion of Cd. Cd-bound to MT is responsible for Cd accumulation in tissues and the long biological half-life of Cd in the body. Induction of MT protects against acute Cd-induced lethality, as well as acute toxicity to the liver and lung. Intracellular MT also plays important roles in ameliorating Cd toxicity following prolonged exposures, particularly chronic Cd-induced nephrotoxicity, osteotoxicity, and toxicity to the lung, liver, and immune system. There is an association between human and rodent Cd exposure and prostate cancers, especially in the portions where MT is poorly expressed. MT expression in Cd-induced tumors varies depending on the type and the stage of tumor development. For instance, high levels of MT are detected in Cd-induced sarcomas at the injection site, whereas the sarcoma metastases are devoid of MT. The use of MT-transgenic and MT-null mice has greatly helped define the role of MT in Cd toxicology, with the MT-null mice being hypersensitive and MT-transgenic mice resistant to Cd toxicity. Thus, MT is critical for protecting human health from Cd toxicity. There are large individual variations in MT expression, which might in turn predispose some people to Cd toxicity.