Aluminum and Phthalates in Calcium Gluconate: Contribution From Glass and Plastic Packaging.
Aluminum contamination of parenteral nutrition solutions has been documented for 3 decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration in the past 3 decades has averaged approximately 4000 μg/L, compared with <200 μg/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity.



Aluminum was quantified in samples collected periodically for more than 2 years from 3 calcium gluconate sources used to prepare parenteral nutrition solutions; 2 packaged in glass (from France and the United States) and 1 in plastic (from Germany); in a recently released plastic-packaged solution (from the United States); and in the 2 glass containers. Phthalate concentration was determined in selected samples of each product and leachate of the plastic containers.



The initial aluminum concentration was approximately 5000 μg/L in the 2 glass-packaged products and approximately 20 μg/L in the plastic-packaged product, and increased approximately 30%, 50%, and 100% in 2 years, respectively. The aluminum concentration in a recently released Calcium Gluconate Injection USP was approximately 320 μg/L. Phthalates were not detected in any calcium gluconate solutions or leachates.



Plastic packaging greatly reduces the contribution of aluminum to parenteral nutrition solutions from calcium gluconate compared with the glass-packaged product.
*Pharmaceutical Sciences †Graduate Center for Toxicology ‡Plant and Soil Sciences, University of Kentucky, Lexington.
Robert A
RA
Yokel
Jason M
JM
Unrine
D000535:Aluminum / Q000009:adverse effects / Q000032:analysis*; D002125:Calcium Gluconate / Q000737:chemistry*; D004340:Drug Contamination; D004349:Drug Packaging / Q000379:methods*; D005602:France; D005858:Germany; D005898:Glass / Q000737:chemistry*; D006801:Humans; D010288:Parenteral Nutrition; D057947:Parenteral Nutrition Solutions / Q000737:chemistry*; D010795:Phthalic Acids / Q000032:analysis*; D010968:Plasticizers / Q000032:analysis; D010969:Plastics / Q000737:chemistry*; D014481:United States
D057947:Parenteral Nutrition Solutions; D010795:Phthalic Acids; D010968:Plasticizers; D010969:Plastics; D000535:Aluminum; D002125:Calcium Gluconate