title: Identification of phthalates in medications and dietary supplement formulations in the United States and Canada.
abstract: BACKGROUND
  In animal studies, some ortho-phthalates, including di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP), have been shown to be reproductive and developmental toxicants. Human studies show widespread population exposure to background levels of phthalates. Limited evidence suggests that particularly high exposure levels may result from orally ingested medicinal products containing phthalates as excipients (inactive ingredients).
  
  
  OBJECTIVE
  In this study we aimed to identify and describe the scope of prescription (RX) and nonprescription (over-the-counter; OTC) medicinal products and dietary supplements marketed in the United States and Canada since 1995 that include phthalates as excipients.
  
  
  METHODS
  We used lists of modified-release drug products to identify potential drug products. Inclusion of phthalates was verified using available electronic databases, print references, published package inserts, product packages, and direct communication from manufacturers. Additional products were identified using Internet searches utilizing keywords for phthalates.
  
  
  RESULTS
  Based on labeling information, 6 RX drug products included DBP as an excipient, and 45 specified the use of diethyl phthalate (DEP). Phthalate polymers with no known toxicity--hypromellose phthalate (HMP), cellulose acetate phthalate (CAP), and polyvinyl acetate phthalate (PVAP)--were included in 75 RX products. Three OTC drug and dietary supplement products listed DBP, 64 listed DEP, and > 90 indicated inclusion of polymers.
  
  
  CONCLUSIONS
  Numerous RX and OTC drug products and supplements from a wide range of therapeutic categories may use DBP or DEP as excipients in oral dosage forms. The potential effects of human exposure to these phthalates through medications are unknown and warrant further investigation.
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts 02215, USA. kekelley@bu.edu
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Kelley
authors.forename: Sonia
authors.initials: S
authors.lastname: Hernández-Díaz
authors.forename: Erica L
authors.initials: EL
authors.lastname: Chaplin
authors.forename: Russ
authors.initials: R
authors.lastname: Hauser
authors.forename: Allen A
authors.initials: AA
authors.lastname: Mitchell
mesh_terms: D002170:Canada; D003692:Delayed-Action Preparations / Q000032:analysis; D019587:Dietary Supplements / Q000032:analysis*; D004781:Environmental Exposure; D005079:Excipients / Q000032:analysis* / Q000145:classification; D004366:Nonprescription Drugs / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis; D010795:Phthalic Acids / Q000032:analysis* / Q000737:chemistry / Q000633:toxicity; D055553:Prescription Drugs / Q000032:analysis*; D014481:United States
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D004366:Nonprescription Drugs; D004364:Pharmaceutical Preparations; D010795:Phthalic Acids; D055553:Prescription Drugs