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.     

Co-exposure of cadmium and lead on bone health in a southwestern Chinese population aged 40-75 years

Both cadmium (Cd) and lead (Pb) are associated with bone health, but studies exploring the effects of Cd and Pb co-exposure on bone health are rare. This study aimed to assess the interactive effects of Cd and Pb co-exposure on bone health. In total, 799 participants, living in the targeted areas (located in southwestern China) for more than 15 years, aged 40-75 years, and subsisted on homegrown rice and vegetables were investigated. Cd and Pb levels in urine and blood samples, as well as bone mineral density, T- and Z-score were determined. After being adjusted for covariates, the T-score was negatively correlated with blood Pb in men (P < .05); for women and non-smoking women, the T-score was negatively correlated with urinary Pb (P < .05). Moreover, after being adjusted for covariates, the Z-score was negatively correlated with urinary Pb in non-smoking women (P < .05). No positive association of prevalence of osteoporosis with Cd and Pb exposure was found. However, at an additive scale, positive interactions of urinary Cd and Pb on the prevalence of osteoporosis for women and non-smoking women, and the same interactions to blood Cd and Pb for men were found. There was also a positive interaction of urinary Cd and Pb for women at a multiplicative scale. This study suggests Cd and Pb exposure could exert detrimental effects on bone health, with possible underlying interactions. Nevertheless, more studies are needed to explore the interactive effects of heavy metal co-exposure.     

Background exposure to toxic metals in women adversely influences pregnancy during in vitro fertilization (IVF)

Low-level environmental exposure to Hg, Pb and Cd may interfere with pregnancy during in vitro fertilization (IVF). The aim of this study was to generate hypotheses concerning associations between background exposures and pregnancy. In modified Poisson regression models including 24 women and adjusted for urine Cd and creatinine, blood Pb, age, race and smoking, 1μg/L increases in blood Hg are associated with decreases of 35% (P=0.03) and 33% (P=0.01) in clinical and biochemical pregnancies, respectively. In alternate Poisson models including 26 women and adjusted for blood Pb, blood Hg, age, race and smoking, 1μg/L increases in blood Cd are associated with decreases of 94% (P=0.01) and 82% (P=0.04) in clinical and biochemical pregnancies, respectively. No effects are detected in 15 men, although inverse associations are suggested for urine cadmium and pregnancy. These data suggest that low-level, background exposures to Hg and Cd may interfere with pregnancy following IVF.     

Comprehensive study of the effects of age, iron deficiency, diabetes mellitus, and cadmium burden on dietary cadmium absorption in cadmium-exposed female Japanese farmers

The absorption rate of dietary cadmium (Cd) was investigated among 38 female farmers who had been exposed to Cd at levels close to the current provisional tolerable weekly intake (PTWI); these levels were much higher than those examined in previous studies. The study group composed of 7 diabetics and their 13 age-matched controls and 6 anemic subjects and their 12 controls. With their informed consent, the study participants were confined in an inn for 7 nights and 8 days to collect all feces and urine and duplicates of all food consumed. The dietary Cd absorption rate was calculated for each subject from her total Cd intake and fecal excretion. The means and 95% confidence intervals (CI) of the diabetic group and the anemic group did not differ significantly from those of their respective controls. By individual analysis using all 38 subjects, however, significant Pearson's correlation coefficients were observed between Cd absorption rate and age, serum ferritin, serum iron, and blood and urine Cd levels. Among these, multiple regression analysis revealed that only age was a significant factor contributing to Cd absorption rate. The actual Cd absorption rate in the youngest age group (20-39 years) was 44.0%, which was highly accelerated compared with the rate in the total subject group of 6.5%, while zero to negative balance was observed in the older subjects. These results demonstrate that age, rather than iron deficiency, diabetes mellitus (DM), or Cd burden, is the only independent factor affecting the Cd absorption rate, suggesting that young women are always at high risk.     

Exposure of citizens in China and in Japan to lead and cadmium: a comparative study.

To compare the background exposure of general urban populations to lead (Pb) and cadmium (Cd) in China and Japan, 250 adult women in five Chinese cities and 72 women in three Japanese cities were surveyed by means of collection and analyses of food duplicate and blood samples. The results show that the geometric mean dietary Pb intake and Pb level in blood were significantly higher among Chinese (24.6 microg/day and 45.8 ng/ml) than their counterparts in Japan (14.6 microg/day and 32.2 ng/ml). In contrast, Cd exposures were significantly higher among Japanese women (34.1 microg/day and 1.91 ng/ml) than among Chinese women (8.8 microg/day and 0.61 ng/ml). Thus, the public health concern should be focussed on Pb exposure for Chinese population and Cd for Japanese people.     

Cumulative rate and distribution of Cd and Pb in the organs of adult male Wistar rats during oral exposure

The degree of accumulation of Cd and Pb in the brains, spleens, lungs, hearts, livers and kidneys of adult Wistar rats was compared both for separate (Cd or Pb) and combined (Cd + Pb) oral exposure. In addition, the metals were administered either with liquids or with solid feed. Rats were exposed to low doses of metals (7 mg Cd and 50 mg Pb/kg feed or L of distilled water) over 6 or 12 weeks. In total the organs of rats accumulated about 0.3–0.5% Cd and 0.4–0.6% Pb supplied with food or drink. The presented studies demonstrated that the distribution of Cd and Pb in the organs is affected by: the type of exposure (separate or combined), the source of metals (feed or drinks) and the duration of exposure. It was found that simultaneous exposure to low doses of Cd and Pb supplied with food is much more hazardous than exposure to such metals supplied with water.     

Normal levels of cadmium in diet, urine, blood, and tissues of inhabitants of the United States

Cd was measured in the feces, urine, blood, and hair of U.S. inhabitants without known high Cd exposure in Chicago, Illinois, and Dallas, Texas, and in autopsy tissues of accident victims in Dallas. The average intake of Cd in food was estimated to be 13-16 microgram/d and was higher for males than females. The average levels of Cd were 0.59-0.77 microgram/l in urine, 0.09-0.11 microgram per 100 ml in blood, 0.83-1.10 microgram/g in hair, 21 microgram/g in kidney cortex, 1.2 microgram/g in liver, 0.067 microgram/g in muscle, 0.58 microgram/g in pancreas, and 0.040 microgram/g in fat. Hair Cd was higher for males than females. Cd levels increased with age in urine and all tissues and were higher in cigarette smokers than nonsmokers in urine, blood, and all tissues.     

Heavy metals (Pb,Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na⁺ − K⁺ ATP-ase pump (Cd, MeHg), biological Ca⁺² (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals.     

Evaluation of factors associated with cadmium exposure and kidney function in the general population

Cadmium (Cd) is a nonessential toxic metal which is widely distributed in the environment. The general population is exposed to low levels of Cd and the kidney is the organ most sensitive to Cd toxicity. This study was performed to simultaneously evaluate Cd exposure, kidney function, and oxidative stress biomarkers in the general population. A total of 643 adults were interviewed to document demographic characteristics, lifestyles, past‐medical history, and diet during the last 24 h. We estimated daily Cd intake based on the diet of study subjects who had not been exposed to Cd occupationally. Whole blood and urine samples were collected and analyzed to determine Cd concentrations and kidney function indices (β₂‐microglobulin [β₂‐MG], N‐acetyl‐β‐D ‐glucosaminidase [NAG], metallothionein [MT]). The oxidative stress index (malondialdehyde [MDA]) was determined from the urine. The daily Cd intake from diet was established as 7.07 μg/day. The mean concentration of Cd measured in the blood was 1.22 μg/L and urine was 0.95 μg/g creatinine. The concentrations of Cd in blood and urine were higher in females than in males. The blood levels of Cd were affected by sex, age, and smoking, and urine Cd was influenced by sex, age, and blood Cd. The urine Cd was positively correlated with MT, NAG activity, and MDA in females, but with NAG only in males. The blood Cd was associated with MT in males. Increased NAG activity was observed when Cd in urine reached 1.0 μg Cd/g creatinine and was also affected by age, hypertension, and diabetes mellitus. Urinary MT only responded to Cd in urine or blood. In summary, exposure to Cd in the general population was influenced by various factors including sex, age, and smoking habits. Such exposure might eventually cause tubular damage in the kidneys through the oxidative stress mechanism, and females might be more susceptible than males to Cd exposure under the environment. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 563–570, 2013.     

The relation of individual cadmium concentration in urine with total cadmium intake in Kakehashi River basin, Japan

The aim of the present study was to clarify the relationship between urinary cadmium concentration (U-Cd) and total cadmium intake (T-Cd) based on individual data of Cd in urine. Morning urine specimens were collected from 198 persons (100 men with average age of 45.8 years and 98 women with average age of 50.7 years) living in the Kakehashi River basin in Ishikawa Prefecture, Japan. The method used to calculate T-Cd basically mirrored that used in our previous study. Correlation coefficients between U-Cd and T-Cd of 0.879 and 0.835 were obtained in men and women, respectively, with both values statistically significant. Therefore, T-Cd is confirmed to be a useful indicator for external Cd exposure even on the basis of individual data of U-Cd.     

Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers

Purpose

Research on the effect of co-exposure to Cd and Pb on the kidney is scarce. The objective of the present study was to assess the effect of co-exposure to these metals on biomarkers of early renal effect.

Methods

Cd in blood (Cd-B), Cd in urine (Cd-U), Pb in blood (Pb-B) and urinary renal biomarkers, i.e., microalbumin (μ-Alb), beta-2-microglobulin (β₂-MG), retinol binding protein (RBP), N-acetyl-β-d-glucosaminidase (NAG), intestinal alkaline phosphatase (IAP) were measured in 122 metallurgic refinery workers examined in a cross-sectional survey.

Results and conclusions

The median Cd-B, Cd-U, Pb-B were: 0.8 μg/l (IQR = 0.5, 1.2), 0.5 μg/g creatinine (IQR = 0.3, 0.8) and 158.5 μg/l (IQR = 111.0, 219.3), respectively. The impact of Cd-B on the urinary excretion of NAG and IAP was only evident among workers with Pb-B concentrations ≥75th percentile. The association between Cd-U and the renal markers NAG and RBP was also evidenced when Pb-B ≥75th percentile. No statistically significant interaction terms were observed for the associations between Cd-B or Cd-U and the other renal markers under study (i.e., μ-Alb and β2-MG). Our findings indicate that Pb increases the impact of Cd exposure on early renal biomarkers.     

Interactions of lead and cadmium on acetylcholine release at the frog neuromuscular junction

The interactive effects of Cd2+ and Pb2+ on evoked and spontaneous transmitter release were studied in the sciatic nerve-sartorius muscle preparation of the frog (Rana pipiens). Either Pb2+ or Cd2+ competitively inhibited the actions of Ca2+ in bringing about evoked release, as measured by the endplate potential (EPP) amplitude. Combinations of Pb2+ and Cd2+ were additive in their effects on the EPP. The rate of spontaneous transmitter release was measured as the miniature endplate potential (MEPP) frequency. In contrast to their effects on the EPP, exposure of preparations to combinations of Pb2+ and Cd2+ actually increased the MEPP frequency less than exposures of the preparations to Pb2+ alone. The degree of reduction in MEPP frequency produced by Cd2+ depended upon the relative ratio of Pb2+ and Cd2+ ions. These results suggest that Pb2+ and Cd2+ ions competed for a common presynaptic receptor site during evoked release. They also suggest that Pb2+ ions may enter the nerve terminal, possibly through the Ca2+ channel, and that this entry is inhibited by Cd2+.     

Cadmium and nutritional intake in pregnant Japanese women

A study to clarify the food composition and nutritional factors that contribute to the levels of blood and urinary cadmium (Cd) was conducted on 50 pregnant Japanese women with mean age of 29 years. The mean iron (Fe) intake of subjects was 9.2 mg, which is much lower than the recommended level of 20 mg for pregnant women. Cd in urine samples collected at 30-32 weeks of gestation were correlated (r = 0.354), but urinary Cd was related to age more than blood Cd. Urinary Cd and blood Cd levels were inversely related to total energy (rpartial = -0.325, and -0.334, respectively) and fat intake (rpartial = -0.419, and -0.379, respectively), even after adjustment for age. Blood Cd was also correlated to protein and iron intake (rpartial = -0.299, and -0.353, respectively). These results indicate that Cd exposure levels of pregnant women with low energy intake, especially less fat intake, were higher than those of women with more energy and fat intake. In particular, blood Cd may be affected by protein and iron intake in pregnant women with increased these nutrients demand.     

Biomonitoring of lead exposure-alternatives to blood

Lead ( Pb) is one of the most important models for biomonitoring of exposure, with the blood Pb concentration as a predominant choice in practice and in epidemiology. In this article the alternatives for biomarkers to blood are reviewed. This overview focuses on a number of different qualities that are of importance in the evaluation of a biomarker's usefulness and performance. The qualities scrutinized included: (1) analytical accuracy and precision; (2) cost; (3) practical issues; (4) what is reflected by the biomarker; (5) relationship to exposure; and (6) relationship to effects. Data indicate that the best biomarker in some circumstances may be blood, but bone or teeth (for past exposures), feces (for current gastrointestinal exposure), or urine (for organic Pb) are sometimes more useful. A striking feature is that no generally accepted biomarker of bioavailable Pb exists, though plasma, bone, teeth, urine, and hair have all been discussed. For one of the most used applications of blood Pb, monitoring of lead workers' exposure, blood has important shortcomings in that it shows a poor response to changes in exposure at high levels. The alternative of plasma has not been sufficiently evaluated to be considered an alternative in occupational health services, although previous analytical problems are basically overcome. Possibly, urine deserves also more attention. Almost all biomarkers lack systematic data on variation within and between individuals.     

Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels

Mice were exposed to cadmium (Cd) concentrations ranging from 0 to 100mg CdCl(2)/l in the drinking water for 1, 4, 8, 16 and 23 weeks. Urine samples were taken regularly, Cd content was determined in blood, liver, kidney and urine and histological analyses of the kidney were performed. Kidney cortex Cd content increased linearly with time and dose, while blood levels reached a plateau at 8 weeks and liver at 16 weeks in mice exposed to 100mg CdCl(2)/l after which both started to decrease. Urinary Cd levels were not correlated with the kidney Cd content. A multivariate regression model taking into account the actual Cd intake, calculated from the volume of water taken in by each animal and the exposure concentration, confirmed that blood is an indicator of acute exposure, while kidney Cd content is a reliable indicator of chronic exposure. The urinary protein content was significantly increased from 16 weeks on in mice exposed to 100mg CdCl(2)/l (p<0.05), while other signs of proximal tubular damage (glucosuria, enzymuria) were not detected. Histologically more vacuoles and lysosomes were present in the proximal tubule cells with increasing time and dose. The results indicate that chronic exposure to low doses of Cd induced functional and histological signs of early damage at concentrations in or below the ones generally accepted as safe. Our study does not corroborate the statement that urine Cd levels are a reliable indicator of total Cd body burden, at least when the body burden is low.     

Human and experimental studies on renal eicosanoid response to long-term cadmium exposure.

In order to assess the effects of long-term exposure to cadmium (Cd) on the renal metabolism of eicosanoids, the urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2) was determined in 37 workers exposed to Cd and in female Sprague-Dawley rats given 100 ppm Cd in drinking water for 10 months. Urinary output of sodium and calcium was also determined. The Cd-exposed workers showed an increased urinary concentration of 6-keto-PGF1 alpha, PGE2, sodium, and calcium. The rise of 6-keto-PGF1 alpha was related to Cd levels in blood and weakly correlated with urinary sodium. Calcium in urine was not related to the concentration of the metal in blood and urine. A slight elevation in urinary TXB2 was also observed in workers with blood Cd higher than 5 micrograms/liter. After 10 months of exposure to Cd, female Sprague-Dawley rats presented an enhanced urinary excretion of albumin, transferrin, beta 2-microglobulin, sodium, and PGE2 in urine. The latter was significantly correlated with albuminuria and transferrinuria. In conclusion the results show that chronic exposure to Cd induces changes in the urinary excretion of some eicosanoids. The possible relation of these changes to Cd-induced kidney dysfunction are discussed.     

Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the population of Santiago (Chile) using a Total Diet Study.

Dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Santiago (Chile) was determined using a Total Diet Study in the market basket modality. After conducting a survey of the foods consumed in the last 24 h, the most consumed food products were included in the basket. Subsequently, they were cooked or prepared according to typical Chilean procedures and grouped into 17 food categories according to their chemical characteristics. The fish and shellfish group had the highest contents of As (1351 ng/g wet weight, ww), Cd (277 ng/g ww), and Hg (48 ng/g ww), while the sugar group had the highest content of Pb (251 ng/g ww). For a person with a body weight of 68 kg, the dietary intakes of As (77 microg/day), Cd (20 microg/day), Hg (5 microg/day), and Pb (206 microg/day) are lower than the provisional tolerable weekly intake values established by the FAO/WHO. Consequently, the total intakes of As, Cd, Hg, and Pb in Santiago (Chile) are within the limits estimated as safe.     

Environmental exposure of the general population to cadmium as a risk factor of the damage to the nervous system: A critical review of current data

Nowadays, more and more attention has been focused on the risk of the neurotoxic action of cadmium (Cd) under environmental exposure. Due to the growing incidence of nervous system diseases, including neurodegenerative changes, and suggested involvement of Cd in their aetiopathogenesis, this review aimed to discuss critically this element neurotoxicity. Attempts have been made to recognize at which concentrations in the blood and urine Cd may increase the risk of damage to the nervous system and compare it to the risk of injury of other organs and systems. The performed overview of the available literature shows that Cd may have an unfavourable impact on the human's nervous system at the concentration >0.8 μg Cd/L in the urine and >0.6 μg Cd/L in the blood. Because such concentrations are currently noted in the general population of industrialized countries, it can be concluded that environmental exposure to this xenobiotic may create a risk of damage to the nervous system and be involved in the aetiopathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as worsening cognitive and behavioural functions. The potential mechanism of Cd neurotoxicity consists in inducing oxidative stress, disrupting the activity of enzymes essential to the proper functioning of the nervous system and destroying the homoeostasis of bioelements in the brain. Thus, further studies are necessary to recognize accurately both the risk of nervous system damage in the general population due to environmental exposure to Cd and the mechanism of this action.     

Dietary exposure to essential and toxic trace elements from a Total diet study in an adult Lebanese urban population

This study assesses, by the Total diet study approach, the adequacy of micronutrient intake (Co, Cu, Fe, Mn, Ni, Zn) and the dietary exposure of a Lebanese adult urban population to two toxic elements (Cd, Pb). The foods that made up the average ‘total diet’ were derived from a previous individual consumption survey. A total of 1215 individual foods were collected, prepared and cooked prior to analysis. Analytical quantification was performed using inductively coupled plasma mass spectrometry. Average daily intakes of Co (11.4 μg/day), Cu (1104.19 μg/day), Fe (13.00 mg/day), Mn (2.04 mg/day), Ni (126.27 μg/day) and Zn (10.97 mg/day) were below toxicological reference values and were found to satisfy nutritional recommendations, except for manganese in men and iron in women. Average dietary exposure to Pb and Cd represented 3.2% and 21.7% of the respective provisional tolerable weekly intakes. Estimates of dietary intakes of iron appeared to be inadequate for 63% of adult women. These findings should constitute a current measure of assessing the adequacy and safety of foods consumed in Lebanon and may be a basis for future monitoring studies.