Lead in pharmaceutical products and dietary supplements John F. Kauffman a, * , Benjamin J. Westenberger a , J. David Robertson b,c , James Guthrie b , Abigail Jacobs d , Susan K. Cummins e a U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Sciences, Division of Pharmaceutical Analysis, 1114 Market St., St. Louis, MO 63101, USA b Research Reactor Center, University of Missouri, Columbia, MO, USA c Department of Chemistry, University of Missouri, Columbia, MO, USA d U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, USA e U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of the Center Director, Rockville, MD, USA Received 26 December 2006 Available online 27 March 2007 Abstract The objective of this study is to determine lead concentrations in a variety of widely used pharmaceutical products, and to assess the risk of lead exposure from using these products. Lead concentrations of 45 products were measured with inductively-coupled plasma mass spectrometry. Six products had lead concentrations greater than 100 parts per billion (ppb), and the highest measured concentra- tion was 500 ppb. The average mass of lead delivered to consumers by all products examined in this study when taken as directed was 0.22 micrograms per day, which is expected to increase the blood lead level of an adult by less than 1%. Five products were found to deliver more than 1 lg of lead per day when used as directed. Current tolerable lead limits in pharmaceutical substances vary widely, and in some cases exceed 10,000 ppb. The products examined in this study have lead concentrations far below these levels. However, in light of recent research demonstrating adverse effects in both children and adults from low level lead exposure, current lead limits for pharmaceutical substances are unacceptably high. Uniform lead limits that reflect current manufacturing capabilities are needed to insure the lowest achievable exposure to lead from these products. Ó 2007 Elsevier Inc. All rights reserved. Keywords: ICP-MS; Lead toxicity; Lead exposure; Pharmaceutical products; Calcium supplements; Vitamins; cGMP; USP lead limits 1. Introduction Lead is a toxic heavy metal with no known biologic function in humans (Royce et al., 2000). Recent National Health and Nutrition Survey data on lead exposure in the United States indicates that the average blood lead level (BLL) in the population is 1.6 lg/dL, and 1.9 lg/dL in chil- dren 1–5 years of age (Centers for Disease Control and Pre- vention, 2005)—a dramatic decline from the averages of 10–20 lg/dL measured in 1976–80 (Centers for Disease Control and Prevention, 2004). This decline is due to con- certed public health efforts to control common environ- mental sources of lead exposure. At the same time, blood lead levels in young children once thought harmless (those below 10 lg/dL) have been associated with adverse neuro- cognitive effects (Bellinger et al., 2003; Bowers and Beck, 2006; Canfield et al., 2003a,b, 2004, 2005; Kordas et al., 2006; Lanphear et al., 2005). These observations warrant continued vigilance to identify sources of lead exposure and to reduce them where possible. As the lead content in common environmental sources such as solder, house dust and soil declines, other sources of lead may measurably contribute to overall lead exposure in humans. Among pharmaceutical and nutritional prod- ucts, lead contamination of calcium supplements has been well documented (Bourgoin and Evans, 1993; Kim et al., 0273-2300/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yrtph.2007.03.001 * Corresponding author. Fax: +1 314 539 2113. E-mail address: John.Kauffman@fda.hhs.gov (J.F. Kauffman). www.elsevier.com/locate/yrtph Regulatory Toxicology and Pharmacology 48 (2007) 128–134