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      Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

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          Abstract

          Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 μg/kg body weight/day or 70 μg/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge.

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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.
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            Cadmium carcinogenesis.

            Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis.
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              Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms.

              Recent findings have indicated that dietary calcium, vitamin D and folate can modulate and inhibit colon carcinogenesis. Supporting evidence has been obtained from a wide variety of preclinical experimental studies, epidemiological findings and a few human clinical trials. Important molecular events and cellular actions of these micronutrients that contribute to their tumour-modulating effects are discussed. They include a complex series of signalling events that affect the structural and functional organization of colon cells.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institue of Environmental Health Sciences
                0091-6765
                July 2004
                25 March 2004
                : 112
                : 10
                : 1099-1103
                Affiliations
                1National Research Centre for Environmental Toxicology, The University of Queensland, Brisbane, Queensland, Australia
                2Queensland Health Scientific Services, Brisbane, Queensland, Australia
                Author notes
                Address correspondence to S. Satarug, National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Rd., Coopers Plains, Brisbane, Queensland 4108, Australia. Telephone: 61-7-3274-9004. Fax: 61-7-3274-9003. E-mail: s.satarug@uq.edu.au

                We thank the Peanut Company of Australia for their support for cadmium research and for their total commitment to cadmium minimization through environmental management and agricultural practices.

                The National Research Centre for Environmental Toxicology is funded by The University of Queensland, Queensland Health, Queensland University of Technology, and Griffith University.

                The authors declare they have no competing financial interests.

                Article
                ehp0112-001099
                10.1289/ehp.6751
                1247384
                15238284
                c63820c3-188a-4a5c-9649-cfe14ad4e7eb
                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
                : 22 September 2003
                : 25 March 2004
                Categories
                Environmental Medicine
                Commentary

                Public health
                cadmium,proteinuria,dietary intake,estrogen,iron,zinc,nephrotoxicant,cancer,calcium,bone density,food legislation,maximum limit

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