Cadmium

Cadmium metal is used as an antirust coating on ferrous metals, and as a component of welding and brazing alloys. Cadmium compounds are used as pigments in paints and plastics, and as electrode components in rechargeable batteries. Acute toxicity may arise from the ingestion of cadmium salts or from the inhalation of fumes from the heating of cadmium-coated metal, for example, when structures are being dismantled by oxy-acetylene torch, or from brazing with cadmium-containing materials in badly ventilated spaces.

Toxicity
Acute ingestion of cadmium salts causes nausea, vomiting and diarrhoea, whereas inhalation of cadmium fumes gives rise to acute pulmonary oedema and to pneumonitis. Chronic exposure to lower concentrations of cadmium vapour results in respiratory impairment with increasing breathlessness on exertion. Attribution of the condition to cadmium may be difficult due to the common occurrence of chronic bronchitis and emphysema secondary to cigarette smoking. Cadmium entering the body is bound to a low molecular weight protein metallothionein, which contains a high proportion of cysteine residues. Initial concentration is in the liver, followed by translocation to the kidney, and long term absorption of cadmium causes renal tubular damage with a marked increase of cadmium excretion in the urine and a low molecular weight proteinuria. The latter has usually been assessed by measurement of the urinary excretion of ß-2 microglobulin; however this protein is rapidly degraded at low urinary pH, and an alternative measurement such as retinol binding protein (RBP) is now preferred. A variety of other tubular disorders may occur, such as aminoaciduria, glycosuria and impaired hydrogen ion excretion.
Long term absorption of cadmium has significant effects on calcium metabolism, which may result from renal damage, although the mechanism remains unclear. The effects were seen most clearly in the exposure of a Japanese population to oral ingestion of cadmium salts from contaminated crops and water, giving rise to the condition known as ‘Itai-itai’ disease. The subjects showed the renal damage mentioned above but in addition extreme bone pain, easily-caused fractures, and osteomalacia. The disease was most manifest in women who had had multiple pregnancies or who were post menopausal, and may have been exacerbated by dietary inadequacies of calcium and/or vitamin D. However, instances of cadmium toxicity elsewhere have also shown derangements of calcium metabolism, in particular, osteomalacia, hypercalciuria and nephrocalcinosis.

Laboratory Indices of Cadmium Status
Circulating cadmium is largely bound to the erythrocytes, so that measurement of blood cadmium is the determination of choice, especially for chronic exposure. It is less reliable, however, in assessing acute toxicity in previously exposed individuals as such exposure may give rise to a continuing elevation of the blood cadmium long after the exposure has ceased. It should be noted that cadmium is one of the most persistent poisons known, its biological half-life in the liver and kidney being of the order of seven and thirty years respectively. Urine cadmium concentration may remain low during significant cadmium exposure until a critical renal concentration is reached. When renal damage occurs, output then increases markedly. The degree of renal damage may be assessed by measurement of the proteinuria which is, however, frequently small in amount. A qualitative assessment by electrophoresis to distinguish the characteristic tubular pattern is useful, but quantitative estimation of retinol binding protein is more satisfactory. Creatinine clearance, glycosuria and aminoaciduria can also be assessed, although the changes are frequently mild.

Cadmium Reference Ranges

 

 

 

Reference

Serum/plasma

nmol/L

<0.4

1,2

Blood

nmol/L

<17

<7 (non-smokers)

<30 (smokers)

1,2,3

4,5

4,5

Urine

nmol/L

<9

6-9

nmol/24 h

<29

10

 

nmol/mmol creatinine

<0.9

7-9

Occupational Guidance

Biological exposure index (ACGIH): blood 45 nmol/L, urine 5.0 nmol/mmol creatinine (11)

OSHA threshold limit: blood 89 nmol/L, urine 7.0 nmol/mmol creatinine (11)

References (ref range)

1. Goullé J-P, Mahieu L, Castermant J et al. Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values. Forensic Sci Int 2005: 153; 39-44

2. Cesbron A, Saussereau E, Mahieu L, Couland I, Guerbet M, Goulle. J-P Metallic profile of whole blood and plasma in a series of 106 healthy volunteers.  J. Anal Tox 2013; 37: 401-405

3. Heitland P, Köster HD.  Biomonitoring of 37 trace elements in blood samples from inhabitants of northern Germany by ICP-MS. J Trace Elem Med Biol.2006;20(4):253-62

4. Wilhelm M, Ewers U, Schulz C.  Revised and new reference values for some trace elements in blood and urine for human biomonitoring in environmental medicine.  Int J. Environ Health 2004; 207; 69-73

5. Batariova A, Spevackova V, Bohuslav B, Cejchanova M, Smid J, Cerna M.  Blood and urine levels of Pb, Cd and HG in the general population of the Czech Republic and proposed reference values.  Int J Hyg Environ Health 2006; 209: 359-366

6. Heitland P, Köster H.  Fast, simple and reliable routine determination of 23 elements in urine by ICP-MS.  J. Anal. At .Spectrom. 2004, 19, 1552–1558

7. Hoet P, Jacquerye C, Deumer G, Lison D, Haufroid V.  Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium, Clin Chem Lab Med, 2013; 51: 839-849.

8. Morton J, Leese E, Tan E, Cocker J. Determination of 61 elements in urine samples collected from a non-occupationally exposed UK adult population, Toxicol. Letters (2014), http://dx.doi.org/10.1016/j.toxlet.2014.08.019

9. Fréry N, Saoudi A, Garnier R, Zeghnoun A, Falq G., Exposition de la population français aux substances chimiques de l’environement, Saint-Maurice: Instsitute de Veille Sanitaire, 2011

10. Sieniawska CE, Jung LC, Olufadi R, Walker V, Twenty-four hour urinary trace element excretion: reference intervals and interpretive issues.  Ann Clin Biochem 2012; 49: 341-51

11. www.lhsc.on.ca/lab/metals/element/48cd.htm, accessed 070816

References:
Stokinger HE Chapter 29 – Metals, in Patty’s Industrial Hygiene and Toxicology, 3rd Revised Edition, Volume 2A. Eds Clayton GD and Clayton FE. Wiley Interscience, 1981.
UNEP/ILO/WHO. International Programme on Chemical Safety, Environmental Health Criteria 134 Cadmium. WHO, Geneva, 1992
Jung K, Pergande M, Graubaum H-J, Fels LM, Endl U, Stolte H. Urinary proteins and enzymes as early indicators of renal dysfunction in chronic exposure to cadmium. Clin Chem 1993; 39: 757-65

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