title: Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage.
abstract: Parabens are used as preservatives in personal care and consumer products, food and pharmaceuticals. Their use is controversial because of possible endocrine disrupting properties. In this study, we investigated metabolism and urinary excretion of methyl paraben (MeP), iso-butyl paraben (iso-BuP) and n-butyl paraben (n-BuP) after oral dosage of deuterium-labeled analogs (10 mg). Each volunteer received one dosage per investigated paraben separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h. In addition to the parent parabens (free and conjugated) which are already used as biomarkers of internal exposure and the known but non-specific metabolites, p-hydroxybenzoic acid (PHBA) and p-hydroxyhippuric acid (PHHA), we identified new, oxidized metabolites with hydroxy groups on the alkyl side chain (3OH-n-BuP and 2OH-iso-BuP) and species with oxidative modifications on the aromatic ring. MeP represented 17.4 % of the dose excreted in urine, while iso-BuP represented only 6.8 % and n-BuP 5.6 %. Additionally, for iso-BuP, about 16 % was excreted as 2OH-iso-BuP and for n-BuP about 6 % as 3OH-n-BuP. Less than 1 % was excreted as ring-hydroxylated metabolites. In all cases, PHHA was identified as the major but non-specific metabolite (57.2-63.8 %). PHBA represented 3.0-7.2 %. For all parabens, the majority of the oral dose captured by the above metabolites was excreted in the first 24 h (80.5-85.3 %). Complementary to the parent parabens excreted in urine, alkyl-chain-oxidized metabolites of the butyl parabens are introduced as valuable and contamination-free biomarkers of exposure.
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of Ruhr Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Moos
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of Ruhr Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Angerer
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of Ruhr Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Dierkes
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of Ruhr Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of Ruhr Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany. koch@ipa-dguv.de.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Koch
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D001711:Biotransformation; D003903:Deuterium; D052244:Endocrine Disruptors / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects*; D004784:Environmental Monitoring; D005520:Food Preservatives / Q000032:analysis / Q000378:metabolism / Q000633:toxicity; D005858:Germany; D006626:Hippurates / Q000378:metabolism / Q000652:urine; D006801:Humans; D006900:Hydroxylation; D010084:Oxidation-Reduction; D010226:Parabens / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D011310:Preservatives, Pharmaceutical / Q000032:analysis / Q000378:metabolism / Q000633:toxicity; D065667:Renal Elimination; D013237:Stereoisomerism; D066007:Toxicokinetics
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D005520:Food Preservatives; D006626:Hippurates; D010226:Parabens; D011310:Preservatives, Pharmaceutical; C471067:isobutylparaben; C038091:butylparaben; C056283:4-hydroxyhippuric acid; C015358:methylparaben; D003903:Deuterium; C038193:4-hydroxybenzoic acid
keywords: Human biomonitoring; Human metabolism; Parabens; Urinary metabolites