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Metal Impurities in Food and Drugs

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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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Correspondence to Anthony J. DeStefano.

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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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