title: Population Exposure to Phthalate-containing Drugs.
abstract: Phthalates are known endocrine disruptors. Not commonly recognized, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of phthalate-containing drugs in Denmark from 2004 to 2015. National data on annual sale of medications (tablets only) were accessed from medstat.dk. Data from the Danish Medicines Agency on phthalate content per tablet were merged with data on total sale for each active substance and drug formulation. We used the 'defined daily dose' (DDD) as the unit of sale and calculated the total amount of phthalate (mg) dispensed per 1000 inhabitants. Specific tablet content was compared with the maximum daily exposure limits defined by regulatory agencies for diethyl phthalate (DEP) and dibutyl phthalate (DBP) of 4.0 and 0.01 mg/kg/day, respectively. Use of phthalate-containing drugs in Denmark was common. We found 154 drug products containing five different phthalates. Two low-molecular-weight phthalates and three high-molecular-weight phthalates were identified, with a total sale of 59.4 and 112 DDD per 1000 inhabitants per day during the study period, respectively. The highest amount of DBP was found in multi-enzymes (24.6-32.8 mg per DDD) and mesalazine (12.5-26.4 mg per DDD). Budesonide, lithium and bisacodyl also exceeded the DBP exposure limit of 0.01 mg/kg/day. Other drugs had high levels of DEP, although not exceeding the exposure limit. Sales of phthalate-containing drugs in Denmark from 2004 to 2015 were substantial, and phthalate exposure from several products exceeded the regulatory exposure limit introduced in 2014.
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Broe
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Zandra Nymand
authors.initials: ZN
authors.lastname: Ennis
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Anton
authors.initials: A
authors.lastname: Pottegård
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
authors.affiliation: Departments of Surgery and Biochemistry, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ahern
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Damkier
mesh_terms: D000328:Adult; D016208:Databases, Factual; D003718:Denmark; D003993:Dibutyl Phthalate / Q000737:chemistry / Q000633:toxicity; D004340:Drug Contamination / Q000331:legislation & jurisprudence / Q000517:prevention & control; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects*; D005079:Excipients / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007880:Legislation, Drug; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000191:economics / Q000592:standards; D010795:Phthalic Acids / Q000737:chemistry / Q000633:toxicity*; D010968:Plasticizers / Q000737:chemistry / Q000633:toxicity*; D013607:Tablets
chemical_list: D052244:Endocrine Disruptors; D005079:Excipients; D004364:Pharmaceutical Preparations; D010795:Phthalic Acids; D010968:Plasticizers; D013607:Tablets; D003993:Dibutyl Phthalate; C007379:diethyl phthalate