Abstract
The major metals of potential health concern found in food, drugs (medicines), and dietary supplements are lead, cadmium, mercury, and arsenic. Other metals, such as chromium, copper, manganese, molybdenum, vanadium, nickel, osmium, rhodium, ruthenium, iridium, palladium, and platinum, may be used or introduced during manufacturing and may be controlled in the final article as impurities. Screening for metals in medicines and dietary supplements rarely indicates the presence of toxic metal impurities at levels of concern. The setting of heavy metal limits is appropriate for medicines and is appropriate for supplements when heavy metals are likely or certain to contaminate a given product. Setting reasonable health-based limits for some of these metals is challenging because of their ubiquity in the environment, limitations of current analytical procedures, and other factors. Taken together, compendial tests for metals in food and drugs present an array of issues that challenge compendial scientists.
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Abbreviations
- ATSDR:
-
Agency for Toxic Substances and Disease Registry
- CDC:
-
Centers for Disease Control and Prevention
- cGMP:
-
Current Good Manufacturing Practices
- EPA:
-
Environmental Protection Agency
- FDA:
-
Food and Drug Administration
- GFAAS:
-
Graphite Furnace Atomic Absorption Spectroscopy
- IARC:
-
International Agency for Research on Cancer
- ICP-OES:
-
Inductively Coupled Plasma–Optical Emission Spectroscopy
- ICP-MS:
-
Inductively Coupled Plasma–Mass Spectroscopy
- IPCS:
-
International Program on Chemical Safety
- IRIS:
-
Integrated Risk Information System
- JECFA:
-
Joint Expert Committee on Food Additives
- LOAEL:
-
Lowest Observed Adverse Effect Level
- MRL:
-
Minimal Risk Level
- NA:
-
Not Applicable
- ND:
-
Not Determined
- NOAEL:
-
No Observed Adverse Effect Level
- OEHHA:
-
Office of Environmental Health Hazard Assessment
- PDE:
-
Permissible Daily Exposure
- RfD:
-
Reference Dose
- USP:
-
US Pharmacopeial Convention
- WHO:
-
World Health Organization
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ACKNOWLEDGMENT
The authors thank Stefan Schuber, Ph.D., ELS, director of scientific reports at USP, for editorial assistance.
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*USP Metal Impurities Advisory Panel Members: Nancy Lewen (Chair), Timothy L. Shelbourn (Vice Chair), Charles Barton, Courtney M. Callis, Steven J. Dentali, Anna M Fan, Roland Frotschl, Assad Kazeminy, Richard Ko, Gregory C. Turk, Robert Wiens; Government Liaisons*: Renee Blosser, FDA, Mamata De, FDA, Bruce A. Fowler, CDC, John F. Kauffman, FDA
**The views expressed in this paper are those of the authors and do not represent official positions of the US Food and Drug Administration, the Centers for Disease Control and Prevention/ Agency for Toxic Substances and Disease Registry (CDC/ATSDR), or other US government bodies.
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Abernethy, D.R., DeStefano, A.J., Cecil, T.L. et al. Metal Impurities in Food and Drugs. Pharm Res 27, 750–755 (2010). https://doi.org/10.1007/s11095-010-0080-3
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DOI: https://doi.org/10.1007/s11095-010-0080-3