Cadmium

The HBM4EU Scoping document on cadmium and chromium VI  Scoping document on cadmium and chromium VI provides background information on these substances, identifies relevant policy questions on the group of substances and outlines research activities under HBM4EU.

The lead authors of the scoping document were Milena Horvat of the Jožef Stefan Institute and Alessandro Alimonti of the Italian National Institute of Health. The document was produced in December 2017.

A short overview report was produced in 2017 to answer the main policy questions with the available data at the time.

This page was last updated on 4 May 2019.

Uses of cadmium

Cadmium levels in the environment vary widely and are a consequence of both natural (erosion of parent rocks, volcanic eruptions, forest fires; 10-50 %) and anthropogenic sources (used in : plastics as colour pigment and stabilizer, automobile radiators, alkaline batteries, mining activities, fertilizers, sewage sludge, inappropriate waste disposal; 50-90%). During the twentieth century the world consumption of Cd has increased continuously to a global supply of 22,000 metric tons (International Cadmium Association, 2002) and it has remained at this level since 2000. Cadmium is normally transported between the three main environmental compartments: air, water and soil. For more information on cadmium levels in these compartments please see the scoping document here.

Hazardous properties of cadmium

Cadmium is a potentially toxic metal that ranks 7th on the priority list of hazardous substances of US Agency for Toxic Substances and Disease Registry’s (ATSDR). International Agency for Research on Cancer (IARC) has classified cadmium and cadmium compounds as human carcinogens (Group 1).

Kidneys, as a major location of Cd accumulation, are primary organ of adverse metal effects that occur at general population after lifelong exposure resulting in urine concentrations of 4 μg Cd/g creatinine. The same level of exposure in more sensitive groups (pregnant and postmenopausal women, elderly) can also lead to bone effects such as osteoporosis and increased risk of fractures. The existence of Cd adverse effects at lower environmental exposures (<1 μg Cd/g creatinine) – related to bone diseases, effects on kidney functions, effects on endocrine system, reproduction and development ect. – has been recently seriously questioned (Åkesson et al., 2014; Nordberg et al., 2015; Apostoli and Catalani 2015; Bernard, 2016).

However, Cd co-exposure and effects in mixtures of chemicals has not been addressed sufficiently. Most experimental and human studies are dealing with exposure to a single element while real environmental exposure is generally characterised by many substances in unpredicted combinations or exposure conditions and by essential metal status (Apostoli and Catalani 2015, Nordberg 2015).

Human exposure to cadmium

Chronic occupational exposures (~45 years) to Cd in the air at concentrations of 5-10 μgCd/m3 could lead to renal tubular damage in some of exposed workers and exposure to higher levels of 100 μgCd/m3 may result in obstructive lung disease (Nordberg et al., 2015). Experimental studies showed that Cd can induce lung and prostate cancer in laboratory animals and some epidemiological studies have also found increased rates of cancer in the same and some other organs (Nordberg et al., 2015).

General population is exposed to Cd primarily through diet and drinking water (5-10 % of ingested Cd is absorbed), and tobacco smoke (10-50 % of inhaled Cd is absorbed). The mean exposure of adults in Europe and North America through food is 10-20 μg Cd/day, which results in average urinary excretion of 0.5-1.0 μg Cd/day and blood concentrations of 0.5-1.0 μgCd/L for non-smokers (twice as high in smokers) (Nordberg et al., 2015).

At the European level the biomarkers are collected in national HBM programs (German Environmental Survey, GerES; The Flemish Environment and Health Study, FLEHS; French Nutrition and Health Survey, ENNS; Czech Republic HBM, CZ-HBM; Slovenian National HBM; etc.) and international projects (Public health impact of long-term, low-level mixed element exposure in susceptible population strata, PHIME and DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale, COPHES/DEMOCOPHES).

Health-based reference values for cadmium in urine are 1 μg/L (μg/g creatinine; HBM I) and 4 μg/L (μg/g creatinine; HBM II) for adults, and 0.5 μg/L (μg/g creatinine; HBM I) and 2 μg/L (μg/g creatinine; HBM II) for children, as set by the German Human Biomonitoring Commission (Schulz et al., 2011). In blood, reference value is below 1 μg/L for adults (Wilhelm et al., 2004).

Technical challenges in biomonitoring cadmium in humans

Biomarkers related to low environmental cadmium exposure currently commonly used are (Nordberg et al., 2015, Bernard et al 2016):

▸ Cd in urine is usually accepted as a biomarker of body burden reflecting long term accumulation, but such definition is limited to occupational or really excessive exposures.

▸ In most laboratories, Cd in blood /plasma chemical analyses are not sensitive enough to permit the accurate measurement of plasma or serum. At low Cd levels blood represents recent and past exposure; they cannot be properly distinguished.

▸ Cd in placenta is used as an indicator of Cd exposure during pregnancy

▸ Cd in cord blood is indicating Cd transfer from maternal blood to cord blood

▸ Cd in faeces – at low doses comparable with urine excretion

▸ Cd in kidney, liver or bone tissues is reflecting Cd accumulation.

▸ Renal function biomarkers in urine such as: albumin (Alb) and Imunoglobulin G (IgG) indicating glomerular kidney damage, and N-acetyl-beta-D-glucosaminidase (NAG), α1-microglobulin (A1M), β2 microglobulin (B2M), retinol-binding protein (RBP), Kidney Injury Molecule-1 (KIM-1), metallothioneins (MTs) indicating tubular kidney damage (Nordberg et al., 2015) – at low levels they rather function as indicators of normal physiological processes, so they are unrepresentative for Cd risk assessment at low levels.

The most common methods for Cd determination in human matrices are inductively coupled plasma mass spectrometry (ICP-MS), atomic absorption spectrophotometry (AAS) and atomic fluorescence spectrophotometry (AFS). For the in vivo determination of Cd in tissues, X-ray fluorescence is used. For the determination of renal function biomarkers in urine the standard nephelometric immunochemical method is used, which is less accurate than the measurement of Cd levels in urine or blood. Therefore, determination of renal function biomarkers in relation to Cd exposure and health risk assessment is more reliable at high Cd exposures (> 4 μgCd/ml).

Legislative status in the European Union

Since cadmium is listed in Regulation (EC) No 1272/2008 as human carcinogen, (Carc. 1B) and due to its increasing evidence of toxicity, both national and international agencies have sought to regulate its exposure. The WHO (2004) guidelines for drinking water quality has been revised from 5 to 3 μgCd/L and WHO (2000) guidelines for ambient air 5 ngCd/L. The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2012) has recommended a maximum intake from food of 25 μg/kg bw/month (Nordberg et al., 2015). The main rational for action/inaction lies in Regulation (EC) No. 1881/2006 of 19 December 2006 that sets maximum levels for certain contaminants in foodstuffs and contains the most recent maximum levels for Cd in foodstuffs. Furthermore, use of Cd is restricted in certain products (Annex XVII of REACH), among them recycled PVC, the existing allowed limit of which is currently in review. There is also ongoing discussion as regards allowable maximum levels in phosphate fertilizers with a link to acceptable maximum levels in food. Overall, the levels in food, recycled PVC and fertilizers continue to be reviewed by the Commission. An updated scientific basis is therefore of great importance.          

Policy questions on cadmium

Throughout the duration of this project, the following policy questions will be addressed:

  1. Is there a link between high soil contamination with Cd and human exposure via dietary sources?
  2. Are environmental quality standards for Cd in water sufficiently restrictive to protect human health from exposure to Cd via the environment and via dietary sources?
  3. What is the maximum acceptable level for Cd in food stuffs?
  4. Can input be given to the decision as to whether the exemption for Cd in quantum dots under the RoHS Directive can be scrapped?

Stakeholders comments on the scoping document

In the interest of transparency and accountability, HBM4EU invites interested stakeholders to submit comments on the scoping document.

All submitted comments will be made available for download on this webpage and will be taken into consideration by the HBM4EU consortium, where possible.

Please click here to submit your comments.

References

Åkesson, A., Barregard, L., Bergdahl, I. a, Nordberg, G.F., Nordberg, M., Skerfving, S., 2014. Non-renal effects and the risk assessment of environmental cadmium exposure. Environ. Health Perspect. doi:10.1289/ehp.1307110 https://ehp.niehs.nih.gov/doi/pdf/10.1289/ehp.1307110

Apostoli, P., Catalani, S., 2015. Effects of Metallic Elements on Reproduction and Development, in: Nordberg, G.F., Fowler, B.A., Nordberg, M. (Eds.), Handbook on the Toxicology of Metals. Elsevier, Academic Press, USA, pp. 399 – 423. https://www.elsevier.com/books/handbook-on-the-toxicology-of-metals/nordberg/978-0-444-59453-2

Bernard, A., 2016. Confusion about cadmium risks: The unrecognized limitations of an extrapolated paradigm. Environ. Health Perspect. 124, 1–5. doi:10.1289/ehp.1509691 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710609/pdf/ehp.1509691.pdf

Nordberg, G.F., Nogawa, K., Nordberg, M., 2015. Cadmium, in: Nordberg, G.F., Fowler, B.A., Nordberg, M. (Eds.), Handbook on the Toxicology of Metals. Elsevier, Academic Press, USA, pp. 667–716. https://www.elsevier.com/books/handbook-on-the-toxicology-of-metals/nordberg/978-0-444-59453-2

Schulz, C., Wilhelm, M., Heudorf, U., Kolossa-Gehring, M., 2011. Update of the reference and HBM values derived by the German Human Biomonitoring Commission. Int. J. Hyg. Environ. Health 215, 26–35. doi:10.1016/j.ijheh.2011.06.007 https://www.sciencedirect.com/science/article/pii/S1438463911000794

WHO (World Health Organisation). 2000. Air Quality Guidelines, second edition. Chapter 6.4 ―Chromium‖. Regional Office for Europe, World Health Organization (Copenhagen). Available at: http://www.euro.who.int/__data/assets/pdf_file/0005/74732/E71922.pdf

JECFA (2011) Evaluation of certain food additives and contaminants: seventy-third report of the Joint

FAO/WHO Geneva, World Health Organization, Joint FAO/WHO Expert Committee on Food Additives (76th meeting). http://www.fao.org/3/a-at871e.pdf

Wilhelm, M., Ewers, U., Schulz, C., 2004. Revised and new reference values for some trace elements in blood and urine for human biomonitoring in environmental medicine. Int. J. Hyg. Environ. Health 207, 69–73. doi:10.1078/1438-4639-00260 https://www.sciencedirect.com/science/article/pii/S1438463904702655