22/12/2009

Cadmium
Occurrence, exposure and dose
Cadmium occurs naturally in ores together with zinc, lead and copper.
Cadmium compounds are used as stabilizers in PVC products, colour
pigment, several alloys and, now most commonly, in re-chargeable nickel–
cadmium batteries. Metallic cadmium has mostly been used as an anticorrosion
agent (cadmiation). Cadmium is also present as a pollutant in
phosphate fertilizers. EU cadmium usage has decreased considerably
during the 1990s, mainly due to the gradual phase-out of cadmium products
other than Ni-Cd batteries and the implementation of more stringent EU
environmental legislation (Directive 91/338/ECC). Notwithstanding these
reductions in Europe, however, cadmium production, consumption and
emissions to the environment worldwide have increased dramatically
during the 20th century. Cadmium containing products are rarely re-cycled,
but frequently dumped together with household waste, thereby contaminating
the environment, especially if the waste is incinerated.
Natural as well as anthropogenic sources of cadmium, including
industrial emissions and the application of fertilizer and sewage sludge
to farm land, may lead to contamination of soils, and to increased cadmium
uptake by crops and vegetables, grown for human consumption. The
uptake process of soil cadmium by plants is enhanced at low pH4.
Cigarette smoking is a major source of cadmium exposure. Biological
monitoring of cadmium in the general population has shown that cigarette
smoking may cause significant increases in blood cadmium (B-Cd)
levels, the concentrations in smokers being on average 4–5 times higher
than those in non-smokers4. Despite evidence of exposure from environmental
tobacco smoke5, however, this is probably contributing little to
total cadmium body burden.
Food is the most important source of cadmium exposure in the general
non-smoking population in most countries6. Cadmium is present in most
foodstuffs, but concentrations vary greatly, and individual intake also varies
considerably due to differences in dietary habits4. Women usually have
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British Medical Bulletin 2003;68 171
lower daily cadmium intakes, because of lower energy consumption than
men. Gastrointestinal absorption of cadmium may be influenced by nutritional
factors, such as iron status7.
B-Cd generally reflects current exposure, but partly also lifetime body
burden8. The cadmium concentration in urine (U-Cd) is mainly influenced
by the body burden, U-Cd being proportional to the kidney concentration.
Smokers and people living in contaminated areas have higher urinary
cadmium concentrations, smokers having about twice as high concentrations
as non-smokers4.
Health effects
Inhalation of cadmium fumes or particles can be life threatening, and
although acute pulmonary effects and deaths are uncommon, sporadic
cases still occur9,10. Cadmium exposure may cause kidney damage. The
first sign of the renal lesion is usually a tubular dysfunction, evidenced
by an increased excretion of low molecular weight proteins [such as
â2-microglobulin and á1-microglobulin (protein HC)] or enzymes [such
as N-Acetyl-â-D-glucosaminidase (NAG)]4,6. It has been suggested that
the tubular damage is reversible11, but there is overwhelming evidence
that the cadmium induced tubular damage is indeed irreversible4.
WHO6 estimated that a urinary excretion of 10 nmol/mmol creatinine
(corresponding to circa 200 mg Cd/kg kidney cortex) would constitute a
‘critical limit’ below which kidney damage would not occur. However,
WHO calculated that circa 10% of individuals with this kidney concentration
would be affected by tubular damage. Several reports have since
shown that kidney damage and/or bone effects are likely to occur at lower
kidney cadmium levels. European studies have shown signs of cadmium
induced kidney damage in the general population at urinary cadmium
levels around 2–3 ìg Cd/g creatinine12,13.
The initial tubular damage may progress to more severe kidney damage,
and already in 1950 it was reported that some cadmium exposed workers
had developed decreased glomerular filtration rate (GFR)14. This has been
confirmed in later studies of occupationally exposed workers15,16. An excess
risk of kidney stones, possibly related to an increased excretion of calcium
in urine following the tubular damage, has been shown in several studies4.
Recently, an association between cadmium exposure and chronic renal
failure [end stage renal disease (ESRD)] was shown17. Using a registry of
patients, who had been treated for uraemia, the investigators found a
double risk of ESRD in persons living close to (<2 km) industrial cadmium
emitting plants as well as in occupationally exposed workers.
Long-term high cadmium exposure may cause skeletal damage, first
reported from Japan, where the itai-itai (ouch-ouch) disease (a combination
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172 British Medical Bulletin 2003;68
of osteomalacia and osteoporosis) was discovered in the 1950s. The
exposure was caused by cadmium-contaminated water used for irrigation of
local rice fields. A few studies outside Japan have reported similar findings4.
During recent years, new data have emerged suggesting that also relatively
low cadmium exposure may give rise to skeletal damage, evidenced by
low bone mineral density (osteoporosis) and fractures18–20.
Animal experiments have suggested that cadmium may be a risk factor
for cardiovascular disease, but studies of humans have not been able to
confirm this4. However, a Japanese study showed an excess risk of cardiovascular
mortality in cadmium-exposed persons with signs of tubular
kidney damage compared to individuals without kidney damage21.
Cancer
The IARC has classified cadmium as a human carcinogen (group I) on the
basis of sufficient evidence in both humans and experimental animals22.
IARC, however, noted that the assessment was based on few studies of
lung cancer in occupationally exposed populations, often with imperfect
exposure data, and without the capability to consider possible confounding
by smoking and other associated exposures (such as nickel and
arsenic). Cadmium has been associated with prostate cancer, but both
positive and negative studies have been published. Early data indicated
an association between cadmium exposure and kidney cancer23. Later
studies have not been able clearly to confirm this, but a large multi-centre
study showed a (borderline) significant over-all excess risk of renal-cell
cancer, although a negative dose–response relationship did not support
a causal relation24. Furthermore, a population-based multicentre-study of
renal cell carcinoma found an excess risk in occupationally exposed
persons25. In summary, the evidence for cadmium as a human carcinogen
is rather weak, in particular after oral exposure. Therefore, a classification
of cadmium as ‘probably carcinogenic to humans’ (IARC group 2A) would
be more appropriate. This conclusion also complies with the EC classification
of some cadmium compounds (Carcinogen Category 2; Annex 1
to the directive 67/548/EEC).