Sex-specific Profiles of Blood Metal Levels Associated with Metal–Iron Interactions

Lee, Byung Kook; Kim, Yangho

doi:10.1016/j.shaw.2014.06.005

Cited by 57 publications

(32 citation statements)

References 87 publications

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“…A strong dose-dependence, with greater gastrointestinal uptake and retention of cadmium at higher doses, is known from animal experiments [43]. In humans, uptake from the diet has been shown to be influenced by iron status, with up to four-fold higher uptake when serum ferritin was below 20 μg L −1 [44][45][46][47][48], leading to higher cadmium values in blood or urine in women with low iron stores [49][50][51]. Women often have lower iron stores than men, explaining a higher fractional intestinal uptake of cadmium and higher cadmium concentrations in biomonitoring media.…”

Section: Ingestionmentioning

confidence: 99%

Risk assessment of effects of cadmium on human health (IUPAC Technical Report)

Nordberg

Bernard

Diamond³

et al. 2018

Pure and Applied Chemistry

168

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Chemistry and Human Health, Division VII of the International Union on Pure and Applied Chemistry (IUPAC), provides guidance on risk assessment methodology and, as appropriate, assessment of risks to human health from chemicals of exceptional toxicity. The aim of this document is to describe dose-response relationships for the health effects of low-level exposure to cadmium, in particular, with an emphasis on causation. The term “cadmium” in this document includes all chemical species of cadmium, as well as those in cadmium compounds. Diet is the main source of cadmium exposure in the general population. Smokers and workers in cadmium industries have additional exposure. Adverse effects have been shown in populations with high industrial or environmental exposures. Epidemiological studies in general populations have also reported statistically significant associations with a number of adverse health effects at low exposures. Cadmium is recognized as a human carcinogen, a classification mainly based on occupational studies of lung cancer. Other cancers have been reported, but dose-response relationships cannot be defined. Cardiovascular disease has been associated with cadmium exposure in recent epidemiological studies, but more evidence is needed in order to establish causality. Adequate evidence of dose-response relationships is available for kidney effects. There is a relationship between cadmium exposure and kidney effects in terms of low molecular mass (LMM) proteinuria. Long-term cadmium exposures with urine cadmium of 2 nmol mmol−1creatinine cause such effects in a susceptible part of the population. Higher exposures result in increases in the size of these effects. This assessment is supported by toxicokinetic and toxicodynamic (TKTD) modelling. Associations between urine cadmium lower than 2 nmol mmol−1creatinine and LMM proteinuria are influenced by confounding by co-excretion of cadmium with protein. A number of epidemiological studies, including some on low exposures, have reported statistically significant associations between cadmium exposure and bone demineralization and fracture risk. Exposures leading to urine cadmium of 5 nmol mmol−1creatinine and more increase the risk of bone effects. Similar associations at much lower urine cadmium levels have been reported. However, complexities in the cause and effect relationship mean that a no-effect level cannot be defined. LMM proteinuria was selected as the critical effect for cadmium, thus identifying the kidney cortex as the critical organ, although bone effects may occur at exposure levels similar to those giving rise to kidney effects. To avoid these effects, population exposures should not exceed that resulting in cadmium values in urine of more than 2 nmol mmol−1creatinine. As cadmium is carcinogenic, a ‘safe’ exposure level cannot be defined. We therefore recommend that cadmium exposures be kept as low as possible. Because the safety margin for toxic effects in kidney and bone is small, or non-existent, in many populations around the world, there is a need to reduce cadmium pollution globally.

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Section: Ingestionmentioning

confidence: 99%

Risk assessment of effects of cadmium on human health (IUPAC Technical Report)

Nordberg

Bernard

Diamond³

et al. 2018

Pure and Applied Chemistry

168

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“…It is thought that the positive correlation between age and blood lead level may be attributed to a cumulative effect, owing to the long half-life of heavy metals in human body [28, 29]. Meanwhile, the higher blood lead level among the male subjects may be explained by the fact that in the female body, lead is deposited in the marrows due to the action of female hormones [30]. Notably, at a low level of exposure, age and gender differences in blood lead levels were greater than the differences resulting from subjects’ degree of exposure (residence) to lead.…”

Section: Discussionmentioning

confidence: 99%

Levels of blood lead and urinary cadmium in industrial complex residents in Ulsan

Kim¹,

Kim²,

An³

et al. 2017

Ann of Occup and Environ Med

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BackgroundPopulations neighboring industrial complexes are at an increased health risk, due to constant exposure to various potentially hazardous compounds released during industrial production activity. Although there are many previous studies that focus on occupational exposure to heavy metals, studies that focused on environmental exposure to lead and cadmium are relatively rare. The purpose of this study is to evaluate the extent of the environmental exposure of heavy metals in residents of industrial area.MethodsFour areas in close proximity to the Ulsan petrochemical industrial complex and the Onsan national industrial complex were selected to be included in the exposure group, and an area remotely located from these industrial complexes was selected as the non-exposure group. Among the residents of our study areas, a total of 1573 subjects aged 20 years and older were selected and all study subjects completed a written questionnaire. Blood and urine samples were obtained from about one third of the subjects (465 subjects) who provided informed consent for biological sample collection. Total 429 subjects (320 subjects from exposure area, 109 subjects from non-exposure area) were included in final analysis.ResultsThe geometric mean blood lead level among the subjects in the exposed group was 2.449 μg/dL, which was significantly higher than the non-exposure group’s level of 2.172 μg/dL. Similarly, the geometric mean urine cadmium levels between the two groups differed significantly, at 1.077 μg/g Cr. for the exposed group, and 0.709 μg/g Cr. for the non-exposure group.In a multiple linear regression analysis to determine the relationship between blood lead level and related factors, the results showed that blood lead level had a significant positive correlation with age, the male, exposure area, and non-drinkers. In the same way, urine cadmium level was positively correlated with age, the female, exposure area, and smokers.ConclusionsThis study found that blood lead levels and urine cadmium levels were significantly higher among the residents of industrial areas than among the non-exposure area residents, which is thought to be due to the difference in environmental exposure of lead and cadmium. Furthermore, it was clear that at a low level of exposure, differences in blood lead or urine cadmium levels based on age, gender, and smoking status were greater than the differences based on area of residence. Therefore, when evaluating heavy metal levels in the body at a low level of exposure, age, gender, and smoking status must be adjusted, as they are significant confounding factors.

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“…The body absorbs iron and cadmium by similar mechanisms [6,22], and animal experiments have shown there may be metabolic interactions between cadmium and iron [6,22]. In particular, animals with low iron stores have increased cadmium uptake [18,20,51].…”

Section: Cadmiummentioning

confidence: 99%

“…The gastrointestinal absorption of these divalent metals appears to be mediated by intestinal iron transporters, such as apical divalent metal transporter 1 (DMT1), which also mediates the uptake of other divalent metals [21]. There is up-regulation of DMT1 in the presence of low iron stores [22], and this explains the increased uptake of divalent metals [13,14] and the higher blood concentrations of these metals in iron-deficient individuals. New evidence indicates that the iron exporter ferroportin 1 (FPN1) also transports these divalent metal ions [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Effect of Iron Deficiency on the Increased Blood Divalent Metal Concentrations

Kim¹

2019

Iron Deficiency Anemia

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The apical divalent metal transporter 1 (DMT1) and the iron exporter ferroportin 1 (FPN1) are responsible for the absorption of iron and other divalent metals (manganese, lead, and cadmium). Thus, an iron-deficient diet can lead to excess absorption of manganese, lead, and cadmium, and high blood concentrations of these metals. Relative to males, females of childbearing age have higher blood concentrations of manganese because of their lower blood concentrations of ferritin. Moreover, relative to premenopausal women, menopausal women have lower blood manganese levels because their higher concentrations of ferritin. There is also a significant increase in the whole blood manganese level throughout pregnancy due to the upregulation of iron absorption at this time. Several previous studies reported a temporal relationship between iron deficiency and increased blood lead concentrations in children. However, this association does not occur in postmenarcheal or postmenopausal women because estrogen promotes bone mineralization and redistributes blood lead into the bone, overshadowing the effect of ferritin on blood lead level. Although blood cadmium concentrations are higher in females of childbearing age because of their lower ferritin concentrations, there is no association of blood cadmium and iron levels in infants and postmenopausal women.

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Sex-specific Profiles of Blood Metal Levels Associated with Metal–Iron Interactions

Cited by 57 publications

References 87 publications

Risk assessment of effects of cadmium on human health (IUPAC Technical Report)

Risk assessment of effects of cadmium on human health (IUPAC Technical Report)

Levels of blood lead and urinary cadmium in industrial complex residents in Ulsan

Effect of Iron Deficiency on the Increased Blood Divalent Metal Concentrations

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