Alteration in bone geometric and mechanical properties,histomorphometrical parameters of trabecular bone,articular cartilage,and growth plate in adolescent rats after chronic co-exposure to cadmium and lead in the case of supplementation with green,black, red and white tea

Adolescent male Wistar rats were used to check whether regular consumption of black, red, white, or green tea would have a protective effect on femur development during 12-week exposure to Cd and Pb (7 mg Cd and 50 mg Pb in 1 kg of the diet). The animals were randomly divided (n = 12) into a positive control (without Cd, Pb and teas), a negative control group (Cd and Pb), and groups supplemented additionally with green (GT), black (BT), red (RT), and white tea (WT). Heavy metals reduced the geometric and densitometric parameters and the total thickness of articular cartilage irrespective of tea administration and influenced mechanical endurance, growth plate thickness, and trabecular histomorphometry depending on the tea type. It is difficult to indicate which tea has the best protective effects on bone and hyaline cartilage against heavy metal action.     

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.     

Lead accumulation and metallothionein content in female rats of different ages and generations after daily intake of Pb-contaminated food

Female Wistar rats of different ages (45, 90 and 140 days) and generations (mothers and offspring) were fed a feed containing 2.0 mg of Pb kg⁻¹ daily from weaning and the Pb accumulation was determined in different organs and in maternal milk, in addition metallothioneins (MTs) content was determined in the liver and kidneys. The results showed that Pb accumulation exhibited the following pattern: bone > liver > kidney > gut > blood cells > muscle > brain > ovary. Bones accumulated the most Pb in all animals, with its concentration increasing with age and prenatal exposure. Pb accumulation in the liver, kidney and blood cells, did not follow a consistent pattern with increasing age and our data did not indicate a relationship between the presence of MTs in liver and kidney and metal accumulation in these organs. However, in the offspring and with increasing age, Pb accumulated in more organs. Mothers fed with Pb produced contaminated milk, exposing their offspring to the metal via nursing Thus, increasing age and prenatal exposure increases susceptibility to Pb toxicity-induced damage.     

Dyslipdemia induced by chronic low dose co-exposure to lead,cadmium and manganese in rats: the role of oxidative stress

Lead (Pb), cadmium (Cd) and manganese (Mn) have many potential adverse health effects in vitro and in animal models of clinical toxicity. The current study investigated the dyslipidaemic and oxidative stress effects of chronic low-dose oral exposure to Pb, Cd and Mn and the combination (Pb + Cd + Mn) in rats for 15 weeks. Chronic exposure to the metals did not significantly (P > 0.05) alter serum lipid profiles. However, the atherogenic index decreased by 32.2% in the Pb + Cd + Mn group, relative to the control. The triglyceride/high-density lipoprotein cholesterol ratio decreased by 39.4% in the Pb + Cd + Mn group, relative to the control, and elevated by 81.8, 94.8 and 20.8%, relative to the Pb, Cd and Mn groups, respectively. While the serum concentrations of malondialdehyde significantly increased in the Mn and Pb + Cd + Mn groups, that of glutathione peroxidase-1 decreased in the Pb + Cd + Mn group, and metallothionein-1 and zinc concentrations markedly decreased in all the metal treatment groups.The results suggest that long-term exposure of rats to Pb + Cd + Mn may result in hypolipidaemia, mediated via oxidative stress and metal interactions. Individuals who are constantly exposed to environmentally relevant levels of the metals may be at risk of hypolipidaemia.     

Safety evaluation of metal exposure from commonly used moisturizing and skin-lightening creams in Nigeria

The concentrations of ten metals (Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, Zn and Al) were measured in some commonly used moisturizing and skin-lightening creams in Nigeria with a view to providing information on the risk of exposure to metals from the use of these products. The metal concentrations in these products were measured by atomic absorption spectrometry after acid digestion of the samples. The measured concentrations of metals in the skin moisturizing creams ranged from <0.15 to 6.3 μg/g Cd, <0.02 to 17.5 μg/g Cu, 2.25 to 6.25 μg/g Cr, <0.25 to 124.3 μg/g Al, 0.2 to 7.3 μg/g Pb, <0.03 to 10.7 μg/g Ni, 17.3 to 372.0 μg/g Zn, <0.02 to 1.0 μg/g Co, 17.75 to 28.8 μg/g Mn, <0.1 to 89.8 μg/g Fe while the concentrations of metals in the skin-lightening products ranged from <0.15 to 16.5 μg/g Cd, <0.02 to 10.0 μg/g Cu, 4.25 to 8.0 μg/g Cr, <0.25 to 128.0 μg/g Al, 0.5 to 4.5 μg/g Pb, <0.03 to 1.65 μg/g Ni, 24.7 to 267.5 μg/g Zn, <0.02 to 2.5 μg/g for Co, 19.3 to 31.8 μg/g Mn, 9.5 to 211.63 μg/g Fe. In a significant number (>93%) of the samples investigated the concentrations of Pb, Cd, Ni and Co were below the specified limit, or the maximal limit for impurities in colour additives in cosmetics for external use. However, Cr was found at concentrations above the allergenic limit of 1 μg/g. The results also showed that skin-lightening creams contained higher concentrations of the studied metals than the moisturizing creams, except for Ni, which indicates that persons who uses skin-lightening creams in preference to moisturizing ones, are exposed to higher concentrations of metals.     

Sensitive biomarkers identification for differentiating Cd and Pb induced toxicity on zebrafish embryos

Cadmium (Cd) and lead (Pb) are naturally existing heavy metals that pose significant health risks. The present study aims to identify sensitive biomarkers for differentiating the toxicities induced by Cd and Pb and for providing clues for the early prediction of toxicity and environmental risk assessment. Indicators related to oxidative stress and inflammatory responses in zebrafish treated with Cd and Pb over time (from 24 hpf to 96 hpf) were compared. Furthermore, endpoints such as embryo lethality and teratogenicity were detected. Then, several related genes involved in oxidative stress and inflammatory responses characterizing both Cd and Pb exposure, along with key molecules in the MAPKs pathway, were compared at the mRNA level, allowing the selection of the most sensitive and informative biomarkers. Significant increases in reactive oxygen species (ROS) production were observed in zebrafish exposed to Cd and Pb. Cd and Pb exposure induced developmental toxicity, influencing survival rate, hatching rate, larval growth, and heart rate and causing abnormal embryonic development. Similar trends in SOD1 and SOD2 gene expression were induced by Cd and Pb, while nuclear factor erythroid-2 related factor 2 (Nrf2) gene expression responded differently to each metal. In addition, Cd and Pb induced a delayed activation of the CAT and HO-1 genes, with no apparent change in the 24 hpf and 48 hpf groups. Genes related to immunotoxicity were activated significantly in a time-dependent manner, and these genes exhibited different sensitivities to Cd and Pb. MAPKs pathway genes were also activated in a time-dependent manner, and the expression of these genes showed different effects under Cd and Pb treatment. In summary, the present works have identified some potential sensitive biomarkers. The Nrf2 gene is a potential biomarker to differentiate Pb-induced toxicity from that of Cd, and the IFN-γ gene may be used as a sensitive biomarker for evaluating the risk of Pb contamination. We found that the timeline of MAPKs pathway activation helped to differentiate these two metals toxicities. Furthermore, Pb induced the early activation of ERK2/3 and JNK1, while p38 MAPKs showed delayed activation with no apparent change in the 24 hpf group. Cd induced an early activation of ERK2 and a delayed activation of p38a, p38b, ERK3 and JNK1, indicating that the JNK1 pathway is sensitive to Pb exposure, while the p38 pathway may be susceptible to Cd. This work contributes to sensitive biomarker identification and early environmental risk evaluation for chemicals as well as toxicity prediction.     

Lead,mercury, and cadmium in blood and their relation to diet among Swedish adults

The aim of the present study was to examine the body burden of lead (Pb), mercury (Hg), and cadmium (Cd) in blood among Swedish adults and the association between blood levels, diet and other lifestyle factors.The study was based on a subgroup (n = 273) of the national survey Riksmaten 2010–2011 (4-day food records and questionnaire). Lead, Hg, and Cd were measured in whole blood, and Cd additionally in urine, by mass or fluorescence spectrometry methods.The median values (5–95th percentiles) of the metals in blood were as follows; Pb: 13.4 (5.8–28.6) μg/L, Hg: 1.13 (0.31–3.45) μg/L, and Cd: 0.19 (0.09–1.08) μg/L. All three metals increased with increasing age. Lead levels in blood were positively associated with intakes of game and alcohol, Hg was related to fish intake, and blood Cd related to smoking and low iron stores and to a low meat intake.Body burdens of the studied metals were generally below health based reference values, but several individuals had blood Pb levels above the reference point for possible nephrotoxic and developmental neurotoxic effects. As health effects cannot be excluded, individuals with high Pb exposure should aim at decreasing their body burden, both from food and from other exposure routes.     

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.     

Simultaneous assessment of zinc,cadmium, lead and copper in poultry feeds by differential pulse anodic stripping voltammetry

In the present work four metals (Zn, Cd, Pb and Cu) were determined simultaneously in 28 commercial broiler poultry feeds by differential pulse anodic stripping voltammetry (DPASV) using hanging mercury drop electrode (HMDE). The digestion of poultry feeds was carried out with concentrated nitric acid and hydrogen peroxide (2:1) with the help of microwave heating. Acetate buffer of pH 5 was used as a supporting electrolyte. The limit of detection for Zn, Cd, Pb and Cu was 0.69, 0.35, 0.68 and 0.24 μg/kg, respectively. The amount of Zn, Cd, Pb and Cu in the analyzed poultry feeds was ranged between 54.3–482.2, 3.8–33.6, 23.2–32.6 and 12.3–65.8 mg/kg, respectively. In most of analyzed poultry feed samples, the amount of Cd and Pb was found to be greater than the maximum tolerable level (MTL) which could be harmful for the poultry.     

Concentrations of arsenic,cadmium and lead in human hair and typical foods in eleven Chinese cities

Concentrations of arsenic (As), cadmium (Cd) and lead (Pb) were determined in 384 human hair samples and 445 purchased food samples from 11 cities in China. The mean concentrations of hair As, Cd and Pb were 0.23, 0.062 and 2.45 mg kg⁻¹, respectively. The As, Cd and Pb concentrations in different foods were lower than the national maximum allowable contaminant levels. By comparison, males had higher hair As concentrations but lower Cd concentrations than females. When the interaction effects of gender and age were considered, males had the higher hair As, Cd and Pb concentrations in the 51–65 year-old age group. Residents of rural areas had higher hair As, Cd and Pb concentrations than people living in urban areas. Further analysis indicates that hair As, Cd and Pb concentrations and their changes with biological and environmental factors cannot be satisfactorily explained by the estimated intakes from purchased food.     

Role of diallyl tetrasulfide in ameliorating the cadmium induced biochemical changes in rats

Cadmium (Cd) is an ubiquitous environmental and occupational toxic metal concerned with a variety of adverse effects. The present study was undertaken to evaluate the role of diallyl tetrasulfide (DTS), an organosulfur compound in alleviating the Cd induced biochemical changes in male Wistar rats. During the experiment, rats were injected with Cd (3 mg/(kg day)) subcutaneously alone or with oral administration of DTS at different doses (10, 20 and 40 mg/(kg day)) for 3 weeks. In Cd treated rats, the activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) were significantly increased in serum with elevated levels of bilirubin, urea and creatinine. The hemoglobin level and creatinine clearance were also significantly decreased in Cd treated rats. In addition, the levels of plasma lipid peroxidation markers: thiobarbituric acid reactive substances and lipid hydroperoxides were significantly increased while the levels of plasma reduced glutathione (GSH), Vitamins C and E were significantly decreased in Cd administered rats. Administration of DTS along with Cd significantly decreased the serum, liver and kidney markers towards near normal level in a dose dependent manner. DTS at a dose of 40 mg/(kg day) was highly effective when compared to other doses (10 and 20 mg/(kg day)). DTS also significantly reduced the accumulation of Cd in blood and tissues as well as decreased the level of lipid peroxidation markers with elevation of antioxidants in plasma. All these changes were accompanied by histological observations in liver. The obtained results demonstrated the beneficial effect of DTS in reducing the harmful effects of Cd.     

Trophic transfer of Cd from larval chironomids (Chironomus riparius) exposed via sediment or waterborne routes,to zebrafish (Danio rerio): Tissue-specific and subcellular comparisons

Zebrafish were fed chironomid larvae (8% wet weight daily ration) for 7 days, followed by 3 days of gut clearance in a static-renewal system. Regardless of whether the chironomids had been loaded with Cd via a waterborne exposure or sediment exposure, they had similar subcellular distributions of Cd, with the largest areas of storage being metal rich granules (MRG) > organelles (ORG) > enzymes (ENZ) except that sediment-exposed chironomids had significantly more Cd in the metallothionein-like protein (MTLP) fraction, and significantly less Cd in the cellular debris (CD) fraction. When zebrafish fed sediment-exposed chironomids (153 ± 11 μg Cd/g dry weight) were compared directly to zebrafish fed waterborne exposed chironomids (288 ± 12 μg Cd/g dry weight), identical whole-body Cd levels were observed, despite the difference in the concentration in the food source. Thus trophic transfer efficiency (TTE) of Cd was significantly greater from sediment-exposed chironomids (2.0 ± 0.5%) than from waterborne-exposed chironomids (0.7 ± 0.2%). Subsequent tests with waterborne exposed chironomids loaded to comparable Cd concentrations, as well as with Cd-spiked manufactured pellets, demonstrated that TTEs were concentration-independent. In all treatments, zebrafish exhibited similar subcellular storage of Cd, with the greatest uptake occurring in the ORG fraction followed by the ENZ fraction. However, neither trophically available metal (TAM) nor metabolically available fractions (MAF) were good predictors for the TTEs found in this study. Tissue Cd concentrations were highest in the kidney and gut tissue, then liver, but lower in the gill, and carcass. Overall, the gut and carcass contributed ≥71% to total body burdens on a mass-weighted basis. This study presents evidence that Cd may be acquired by fish from natural diets at levels of environmental relevance for contaminated sites, and that the exposure route of the prey influences the TTE.     

Evaluation of urinary metal concentrations and sperm DNA damage in infertile men from an infertility clinic

This study aimed to examine associations between urinary metal concentrations and sperm DNA damage. Thirteen metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] were detected in urine samples of 207 infertile men from an infertility clinic using inductively coupled plasma mass spectrometry, and also, sperm DNA damage (tail length, percent DNA tail, and tail distributed moment) were assessed using neutral comet assay. We found that urinary Hg and Ni were associated with increasing trends for tail length (both p for trend < 0.05), and that urinary Mn was associated with increasing trend for tail distributed moment (p for trend = 0.02). These associations did persist even when considering multiple metals. Our results suggest that environmental exposure to Hg, Mn, and Ni may be associated with increased sperm DNA damage.     

Subchronic,reproductive, and maternal toxicity studies with tertiary butyl acetate (TBAC)

Tertiary-butyl acetate (TBAC) was tested for subchronic toxicity in rats and mice and reproductive toxicity in rats at inhalation concentrations of 0, 100, 400 or 1600 ppm. An oral maternal toxicity study was conducted in rats at dose levels of 0, 400, 800, 1000 and 1600 mg kg⁻¹ d⁻¹. In the inhalation studies, hematology, clinical chemistry, urinalysis, gross pathology and the majority of body weight and feed consumption values were unaffected. Exposure to TBAC at concentrations of 400 ppm and higher caused transient hyperactivity in mice and some evidence of increased motor activity counts in male rats at the 1600 ppm exposure level. TBAC caused α₂u-globulin accumulation in male rat kidneys from all exposure groups and increased liver weights in 1600 ppm rats and mice. Levels of thyroxin were decreased in male mice exposed to 1600 ppm TBAC for 4 weeks but otherwise thyroid endpoints were unaffected in rats and mice at either the 4 or 13 weeks time points. There was no evidence or immunotoxicity or reproductive toxicity in rats. Pregnant rats receiving 1000 mg kg⁻¹ d⁻¹ TBAC exhibited severe signs of acute neurotoxicity and decreased feed consumption and body weight gain. Fetal viability and growth were unaffected.     

Characterisation and toxicological assessment of Neutral Methacrylate Copolymer for GRAS evaluation

Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance.Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential.An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be “generally recognized as safe” (GRAS).     

Essential trace and toxic element concentrations in organic and conventional milk in NW Spain

Dietary composition and husbandry practices largely determine essential trace element status and toxic element exposure of livestock, and consequently their concentrations in animal products. This study evaluates the main essential trace (Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se and Zn) and toxic (As, Cd, Hg and Pb) element concentrations in milk from organic and conventional farms in NW Spain (n = 50). Milk samples were acid digested and analyzed by ICP-MS. Essential trace element concentrations in organic milk were significantly lower compared to conventional milk, this was especially evident for elements that are routinely supplemented at high concentrations in the conventional concentrate feed: Cu (41.0 and 68.9 μg/L in organic and conventional milk, respectively), Zn (3326 and 3933 μg/L), I (78 and 265 μg/L) and Se (9.4 and 19.2 μg/L). Toxic metal concentrations in milk were in general very low and no statistically significant differences were observed between organic and conventional milk. In addition, the mineral content of organic milk showed a seasonal pattern, the significantly higher As (65%) and Fe (13%) concentrations found in the winter sampling possibly being related to a higher consumption of concentration feed and soil ingestion when grazing.     

Toxic effects and depuration after the dietary lead(II) exposure on the bioaccumulation and hematological parameters in starry flounder (Platichthys stellatus)

Platichthys stellatus (mean length 20 ± 2 cm, mean weight 160.15 ± 15 g) were exposed to the different levels of dietary lead(II) at the concentrations of 0, 30, 60, 120, 240 mg/kg for 4 weeks. Depuration was conducted for 2 weeks after exposure. The lead exposure over 60 mg Pb/kg induced the significant bioaccumulation in tissues of P. stellatus (5–30 μg/g tissue), except for brain and muscle where the exposure to 240 mg Pb/kg caused the bioaccumulation (2–4 μg/g tissue). The hematological parameters such as red blood cell (RBC) counts, hematocrit (Ht) value and hemoglobin (Hb) concentration were substantially decreased over 60 mg Pb/kg, and lasted even after the depuration period. For plasma components, calcium and magnesium levels in plasma were generally decreased over 60 mg Pb/kg, and glucose level was also mainly increased over 60 mg Pb/kg. Total protein was significantly decreased over 120 mg Pb/kg after 4 weeks exposure. Glucose and total protein showed the restoration after the depuration period in groups of fish exposed previously to over 60 and 120 mg Pb/kg, respectively. However, other parameters that changed during the exposure over 60 mg Pb/kg did not recovered. For enzymatic components in plasma, glutamic oxalate transminase (GOT), glutamic pyruvate transminase (GPT) and alkaline phosphatase (ALP) were significantly increased over 120 mg Pb/kg, and there was only restoration observed after the depuration for ALP over 120 mg Pb/kg.     

Regulation of metallothioneins and ZnT-1 transporter expression in human hepatoma cells HepG2 exposed to zinc and cadmium

Essential and non-essential metals can affect vital cellular processes, when over-accumulated within the cells. For this reason, cells have evolved multiple protein sensors, transporters, and other type of proteins to regulate and control free metal homeostasis. Among these, metallothioneins (MT) and ZnT-1 transporter play a key role in the regulation of free Zn concentrations.Herewith, MT expression in Zn (170 μM) and Cd (0.1 and 10 μM) exposed HepG2 cells is analyzed and compared. In addition, the modulation and localization of the membrane transporter ZnT-1 has been investigated. MT-I and MT-II were up-regulated in response to both Zn and Cd exposure and, as expected, Cd represented the most potent inducer. Namely, 0.1 μM Cd was able to up-regulate MT-I, and -II in a way comparable to 170 μM Zn. This is in agreement with MT general function of metal-chelating protein, acting with higher tolerance to essential metals than to non-essential ones. ZnT-1 protein, a plasma membrane specific Zn transporter, was up-regulated as well by both Zn and Cd, although in the same way. Immunofluorescence technique provided evidence that high levels of ZnT-1 measured by biochemical techniques, are related to an increased localization of the transporter at the plasma membrane.