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      Cadmium, Environmental Exposure, and Health Outcomes

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          Abstract

          Objectives

          We provide an update of the issues surrounding health risk assessment of exposure to cadmium in food.

          Data sources

          We reviewed epidemiologic studies published between 2004 and 2009 concerning the bioavailability of cadmium in food, assessment of exposure, and body burden estimate, along with exposure-related effects in nonoccupationally exposed populations.

          Data extraction and synthesis

          Bioavailability of ingested cadmium has been confirmed in studies of persons with elevated dietary exposure, and the findings have been strengthened by the substantial amounts of cadmium accumulated in kidneys, eyes, and other tissues and organs of environmentally exposed individuals. We hypothesized that such accumulation results from the efficient absorption and systemic transport of cadmium, employing multiple transporters that are used for the body’s acquisition of calcium, iron, zinc, and manganese. Adverse effects of cadmium on kidney and bone have been observed in environmentally exposed populations at frequencies higher than those predicted from models of exposure. Increasing evidence implicates cadmium in the risk of diseases that involve other tissues and organ systems at cadmium concentrations that do not produce effects on bone or renal function.

          Conclusions

          Population data raise concerns about the validity of the current safe intake level that uses the kidney as the sole target in assessing the health risk from ingested cadmium. The data also question the validity of incorporating the default 5% absorption rate in the threshold-type risk assessment model, known as the provisional tolerable weekly intake (PTWI), to derive a safe intake level for cadmium.

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          Most cited references76

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          Current status of cadmium as an environmental health problem.

          Cadmium is a toxic metal occurring in the environment naturally and as a pollutant emanating from industrial and agricultural sources. Food is the main source of cadmium intake in the non-smoking population. The bioavailability, retention and toxicity are affected by several factors including nutritional status such as low iron status. Cadmium is efficiently retained in the kidney (half-time 10-30 years) and the concentration is proportional to that in urine (U-Cd). Cadmium is nephrotoxic, initially causing kidney tubular damage. Cadmium can also cause bone damage, either via a direct effect on bone tissue or indirectly as a result of renal dysfunction. After prolonged and/or high exposure the tubular injury may progress to glomerular damage with decreased glomerular filtration rate, and eventually to renal failure. Furthermore, recent data also suggest increased cancer risks and increased mortality in environmentally exposed populations. Dose-response assessment using a variety of early markers of kidney damage has identified U-Cd points of departure for early kidney effects between 0.5 and 3 microg Cd/g creatinine, similar to the points of departure for effects on bone. It can be anticipated that a considerable proportion of the non-smoking adult population has urinary cadmium concentrations of 0.5 microg/g creatinine or higher in non-exposed areas. For smokers this proportion is considerably higher. This implies no margin of safety between the point of departure and the exposure levels in the general population. Therefore, measures should be put in place to reduce exposure to a minimum, and the tolerably daily intake should be set in accordance with recent findings.
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            Toxic metal accumulation, responses to exposure and mechanisms of tolerance in plants.

            S Clemens (2006)
            Over the past 200 years emissions of toxic heavy metals have risen tremendously and significantly exceed those from natural sources for practically all metals. Uptake and accumulation by crop plants represents the main entry pathway for potentially health-threatening toxic metals into human and animal food. Of major concern are the metalloids arsenic (As) and selenium (Se), and the metals cadmium (Cd), mercury (Hg), and lead (Pb). This review discusses the molecular mechanisms of toxic metal accumulation in plants and algae, the responses to metal exposure, as well as our understanding of metal tolerance and its evolution. The main emphasis will be on cadmium, which is by far the most widely studied of the non-essential toxic metals/metalloids. Entry via Zn2+, Fe2+, and Ca2+ transporters is the molecular basis of Cd2+ uptake into plant cells. Much less is known about the partitioning of non-essential metals and about the genes underlying the enormous diversity among plants with respect to Cd accumulation in different tissues. Numerous studies have described symptoms and responses of plants upon toxic metal exposure. Mysterious are primary targets of toxicity, the degree of specificity of responses, the sensing and the signaling events that lead to transcriptional activation. All plants apparently possess a basal tolerance of toxic non-essential metals. For Cd and As, this is largely dependent on the phytochelatin pathway. Not understood is the molecular biology of Cd hypertolerance in certain plant species such as the metallophytes Arabidopsis halleri or Thlaspi caerulescens.
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              A global perspective on cadmium pollution and toxicity in non-occupationally exposed population.

              Cadmium is a non-essential element that has high rates of soil to plant transference compared with other non-essential elements, and certain plant species accumulate large amounts of cadmium from low cadmium content soils. In this paper, levels of cadmium found in major food groups are highlighted together with cadmium levels found in liver and kidney samples from non-occupationally exposed populations. Data on human kidney cadmium levels identified recently, including the study in our own laboratory, are compared with older studies. Human-tissue cadmium contents showed large variations among individuals, but sources of the variation remain unknown. Exposure levels of 30-50 microg per day have been estimated for adults and these levels have been linked to increased risk of bone fracture, cancer, kidney dysfunction and hypertension. Increased mortality was found among individuals showing signs of cadmium renal toxicity compared with those without such signs, suggesting that renal toxicity may be an early warning of complications, sub-clinical or clinical morbidity.

                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                February 2010
                5 October 2009
                : 118
                : 2
                : 182-190
                Affiliations
                Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USA
                Author notes
                Address correspondence to S. Satarug, Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Rd., Grand Forks, ND 58202 USA. Telephone: (701) 777-0389. Fax: (701) 777-3108. E-mail: ssatarug@ 123456medicine.nodak.edu

                The authors declare they have no competing financial interests.

                Article
                ehp-118-182
                10.1289/ehp.0901234
                2831915
                20123617
                bce5951d-e762-415c-aac8-2eb39a88a030
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 29 June 2009
                : 5 October 2009
                Categories
                Review

                Public health
                manganese,cadmium,calcium,disease burden,iron,diet,environmental exposure,cancer,zinc
                Public health
                manganese, cadmium, calcium, disease burden, iron, diet, environmental exposure, cancer, zinc

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