Advanced

Risk assessment of effects of cadmium on human health (IUPAC Technical Report)

Nordberg, Gunnar F.; Bernard, Alfred; Diamond, Gary L.; Duffus, John H.; Illing, Paul; Nordberg, Monica; Bergdahl, Ingvar A. LU ; Jin, Taiyi and Skerfving, Staffan LU (2018) In Pure and Applied Chemistry
Abstract

Chemistry and Human Health, Division VII of the International Union on Pure and Applied Chemistry (IUPAC), provides guidance on risk assessment methodology and, as appropriate, assessment of risks to human health from chemicals of exceptional toxicity. The aim of this document is to describe dose-response relationships for the health effects of low-level exposure to cadmium, in particular, with an emphasis on causation. The term "cadmium" in this document includes all chemical species of cadmium, as well as those in cadmium compounds. Diet is the main source of cadmium exposure in the general population. Smokers and workers in cadmium industries have additional exposure. Adverse effects have been shown in populations with high... (More)

Chemistry and Human Health, Division VII of the International Union on Pure and Applied Chemistry (IUPAC), provides guidance on risk assessment methodology and, as appropriate, assessment of risks to human health from chemicals of exceptional toxicity. The aim of this document is to describe dose-response relationships for the health effects of low-level exposure to cadmium, in particular, with an emphasis on causation. The term "cadmium" in this document includes all chemical species of cadmium, as well as those in cadmium compounds. Diet is the main source of cadmium exposure in the general population. Smokers and workers in cadmium industries have additional exposure. Adverse effects have been shown in populations with high industrial or environmental exposures. Epidemiological studies in general populations have also reported statistically significant associations with a number of adverse health effects at low exposures. Cadmium is recognized as a human carcinogen, a classification mainly based on occupational studies of lung cancer. Other cancers have been reported, but dose-response relationships cannot be defined. Cardiovascular disease has been associated with cadmium exposure in recent epidemiological studies, but more evidence is needed in order to establish causality. Adequate evidence of dose-response relationships is available for kidney effects. There is a relationship between cadmium exposure and kidney effects in terms of low molecular mass (LMM) proteinuria. Long-term cadmium exposures with urine cadmium of 2 nmol mmol-1 creatinine cause such effects in a susceptible part of the population. Higher exposures result in increases in the size of these effects. This assessment is supported by toxicokinetic and toxicodynamic (TKTD) modelling. Associations between urine cadmium lower than 2 nmol mmol-1 creatinine and LMM proteinuria are influenced by confounding by co-excretion of cadmium with protein. A number of epidemiological studies, including some on low exposures, have reported statistically significant associations between cadmium exposure and bone demineralization and fracture risk. Exposures leading to urine cadmium of 5 nmol mmol-1 creatinine and more increase the risk of bone effects. Similar associations at much lower urine cadmium levels have been reported. However, complexities in the cause and effect relationship mean that a no-effect level cannot be defined. LMM proteinuria was selected as the critical effect for cadmium, thus identifying the kidney cortex as the critical organ, although bone effects may occur at exposure levels similar to those giving rise to kidney effects. To avoid these effects, population exposures should not exceed that resulting in cadmium values in urine of more than 2 nmol mmol-1 creatinine. As cadmium is carcinogenic, a 'safe' exposure level cannot be defined. We therefore recommend that cadmium exposures be kept as low as possible. Because the safety margin for toxic effects in kidney and bone is small, or non-existent, in many populations around the world, there is a need to reduce cadmium pollution globally.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
biomarkers, cadmium, cancer, exposure, hazard assessment, kidney, risk assessment, skeleton, toxicokinetics, urine
in
Pure and Applied Chemistry
publisher
IUPAC
external identifiers
  • scopus:85041018133
ISSN
0033-4545
DOI
10.1515/pac-2016-0910
language
English
LU publication?
yes
id
e0bbbc75-1559-4f73-a5a3-4ea126f1ec97
date added to LUP
2018-02-06 08:55:16
date last changed
2018-02-06 08:55:16
@article{e0bbbc75-1559-4f73-a5a3-4ea126f1ec97,
  abstract     = {<p>Chemistry and Human Health, Division VII of the International Union on Pure and Applied Chemistry (IUPAC), provides guidance on risk assessment methodology and, as appropriate, assessment of risks to human health from chemicals of exceptional toxicity. The aim of this document is to describe dose-response relationships for the health effects of low-level exposure to cadmium, in particular, with an emphasis on causation. The term "cadmium" in this document includes all chemical species of cadmium, as well as those in cadmium compounds. Diet is the main source of cadmium exposure in the general population. Smokers and workers in cadmium industries have additional exposure. Adverse effects have been shown in populations with high industrial or environmental exposures. Epidemiological studies in general populations have also reported statistically significant associations with a number of adverse health effects at low exposures. Cadmium is recognized as a human carcinogen, a classification mainly based on occupational studies of lung cancer. Other cancers have been reported, but dose-response relationships cannot be defined. Cardiovascular disease has been associated with cadmium exposure in recent epidemiological studies, but more evidence is needed in order to establish causality. Adequate evidence of dose-response relationships is available for kidney effects. There is a relationship between cadmium exposure and kidney effects in terms of low molecular mass (LMM) proteinuria. Long-term cadmium exposures with urine cadmium of 2 nmol mmol<sup>-1</sup> creatinine cause such effects in a susceptible part of the population. Higher exposures result in increases in the size of these effects. This assessment is supported by toxicokinetic and toxicodynamic (TKTD) modelling. Associations between urine cadmium lower than 2 nmol mmol<sup>-1</sup> creatinine and LMM proteinuria are influenced by confounding by co-excretion of cadmium with protein. A number of epidemiological studies, including some on low exposures, have reported statistically significant associations between cadmium exposure and bone demineralization and fracture risk. Exposures leading to urine cadmium of 5 nmol mmol<sup>-1</sup> creatinine and more increase the risk of bone effects. Similar associations at much lower urine cadmium levels have been reported. However, complexities in the cause and effect relationship mean that a no-effect level cannot be defined. LMM proteinuria was selected as the critical effect for cadmium, thus identifying the kidney cortex as the critical organ, although bone effects may occur at exposure levels similar to those giving rise to kidney effects. To avoid these effects, population exposures should not exceed that resulting in cadmium values in urine of more than 2 nmol mmol<sup>-1</sup> creatinine. As cadmium is carcinogenic, a 'safe' exposure level cannot be defined. We therefore recommend that cadmium exposures be kept as low as possible. Because the safety margin for toxic effects in kidney and bone is small, or non-existent, in many populations around the world, there is a need to reduce cadmium pollution globally.</p>},
  articleno    = {20160910},
  author       = {Nordberg, Gunnar F. and Bernard, Alfred and Diamond, Gary L. and Duffus, John H. and Illing, Paul and Nordberg, Monica and Bergdahl, Ingvar A. and Jin, Taiyi and Skerfving, Staffan},
  issn         = {0033-4545},
  keyword      = {biomarkers,cadmium,cancer,exposure,hazard assessment,kidney,risk assessment,skeleton,toxicokinetics,urine},
  language     = {eng},
  month        = {01},
  publisher    = {IUPAC},
  series       = {Pure and Applied Chemistry},
  title        = {Risk assessment of effects of cadmium on human health (IUPAC Technical Report)},
  url          = {http://dx.doi.org/10.1515/pac-2016-0910},
  year         = {2018},
}