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http://www.sciencedirect.com/science/issue/7159-2009-997619996-1283057
Gunnar F. Nordberga,
a
Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå
University, SE-90187 Umeå, Sweden
Abstract
The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and
gastrointestinal symptoms occurred among persons using Cd-containing polishing
agent. The first experimental toxicological studies are from 1919. Bone effects and
proteinuria in humans were reported in the 1940's. After World War II, a bone disease
with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal
osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and
toxicodynamics of Cd were described including its binding to the protein
metallothionein. International warnings of health risks from Cd-pollution were issued in
the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a
quantitative assessment of these effects in humans is still subject to considerable
uncertainty. The World Health Organization in its International Program on Chemical
Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134,
IPCS. WHO, Geneva, 1–280.) identified renal dysfunction as the critical effect and a
crude quantitative evaluation was presented. In the 1990's and 2000 several
epidemiological studies have reported adverse health effects, sometimes at low
environmental exposures to Cd, in population groups in Japan, China, Europe and USA
(reviewed in other contributions to the present volume). The early identification of an
important role of metallothionein in cadmium toxicology formed the basis for recent
studies using biomarkers of susceptibility to development of Cd-related renal
dysfunction such as gene expression of metallothionein in peripheral lymphocytes and
autoantibodies against metallothionein in blood plasma. Findings in these studies
indicate that very low exposure levels to cadmium may give rise to renal dysfunction
among sensitive subgroups of human populations such as persons with diabetes.
Lars Järupa, b, ,
and Agneta Åkessonb
a
Department of Epidemiology and Public Health, Imperial College London, UK
b
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Abstract
Bruce A. Fowlera,
a
Division of Toxicology and Environmental Medicine, Agency for Toxic Substances
and Disease Registry, Atlanta, GA 30333, USA
Abstract
Exposure of human populations to cadmium (Cd) from air, food and water may produce
effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and
reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers
for early detection of susceptibility to cancer are of an importance to public health. The
ability to document Cd exposure and uptake of this element through biological
monitoring is a first step towards understanding its health effects. Interpretation and
application of biological monitoring data for predicting human health outcomes require
correlation with biological measures of organ system responses to the documented
exposure. Essential to this understanding is the detection and linkage of early biological
responses toxic effects in target cell populations. Fortunately, advances in cell biology
have resulted in the development of pre-clinical biological markers (biomarkers) that
demonstrate measurable and characteristic molecular changes in organ systems
following chemical exposures that occur prior to the onset of overt clinical disease or
development of cancer. Technical advances have rendered a number of these
biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be
increasingly important in relation to monitoring effects from the exposure to new Cd-
based high technology materials. For example, cadmium-selenium (CdSe), nano-
materials made from combinations of these elements have greatly altered cellular uptake
characteristics due to particle size. These differences may greatly alter effects at the
target cell level and hence risks for organ toxicities from such exposures. The value of
validated biomarkers for early detection of systemic Cd-induced effects in humans
cannot be underestimated due to the rapid expansion of nano-material technologies.
This review will attempt to briefly summarize the applications, to date, of biomarker
endpoints for assessing target organ system effects in humans and experimental systems
from Cd exposure. Further, it will attempt to provide a prospective look at the possible
future of biomarkers. The emphasis will be on the detection of early toxic effects from
exposure to Cd in new products such as nano-materials and identification of populations
at special risk for Cd toxicity.
a
Center for Biomedical Research, Population Council, 1230 York Avenue, New York,
NY 10065, USA
b
Section of Experimental Endocrinology, Department of Pharmacology, Universidade
Federal de Sao Paulo, Escola Paulista de Medicina, Rua Tres de maio 100, INFAR, Vila
Clementino, Sao Paulo, SP04044-020, Brazil
Abstract
Abstract