title: Kinetics of the phthalate metabolites mono-2-ethylhexyl phthalate (MEHP) and mono-n-butyl phthalate (MnBP) in male subjects after a single oral dose.
abstract: Humans have been exposed to dialkyl ortho-phthalates for decades. Due to degradation the phthalate monoesters, responsible for the toxic effects, are additionally found in environmental media as well as food samples. Nevertheless, the toxicokinetic properties of the monoesters are not known. Therefore, metabolism of the phthalate monoesters mono-2-ethylhexyl phthalate (MEHP) and mono-n-butyl phthalate (MnBP) was studied in four male volunteers (23-58 years of age) after ingestion of a single dose of 50μg/kg bw D4-MEHP or 10μg/kg bw D4-MnBP. The main metabolites in urine were determined up to 46h after administration. In the MEHP-study, more than 90% of each metabolite appeared in the urine within the first 22h, and the average excreted amount of D4-MEHP and its four secondary metabolites was 62% of the administered dose. The highest value of 15% was observed for mono-2-ethyl-5-carboxy-pentyl phthalate (D4-5cx-MEPP). The mean elimination half-life of D4-MEHP was estimated to be 3.5±1.4h. In the MnBP-study, the total recovered values of D4-MnBP and its secondary metabolites ranged from 52% to 130%. The monoester itself, with a half-life of 1.9±0.5h, accounted for the majority of the ingested dose (92%), while the secondary metabolites D4-mono-3-hydroxy-n-butyl phthalate (D4-3OH-MnBP) and D4-3-carboxy-mono-propyl phthalate (D4-3cx-MPP) represented only 7.1% and 1.0% of the ingested dose, respectively. Overall, this study determined that the kinetics of the phthalate monoesters MEHP and MnBP after oral dosage are comparable to the properties of their diesters.
authors.affiliation: Bavarian Health and Food Safety Authority, Department of Chemical Safety and Toxicology, Pfarrstrasse 3, 80538 Munich, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Mittermeier
authors.affiliation: Bavarian Health and Food Safety Authority, Department of Chemical Safety and Toxicology, Pfarrstrasse 3, 80538 Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Völkel
authors.affiliation: Bavarian Health and Food Safety Authority, Department of Chemical Safety and Toxicology, Pfarrstrasse 3, 80538 Munich, Germany; Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University Munich, Ziemssenstrasse 1, 80336, Munich Germany, Germany. Electronic address: hermann.fromme@lgl.bayern.de.
authors.forename: Hermann
authors.initials: H
authors.lastname: Fromme
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000652:urine; D011897:Random Allocation; D012737:Sex Factors; D016482:Urinalysis; D055815:Young Adult
chemical_list: D010795:Phthalic Acids; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; C028577:monobutyl phthalate
keywords: Exposure; Kinetic; MEHP; MnBP; Monoesters; Phthalates