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.

Comparative studies of aerobic and anaerobic biodegradation of methylparaben and propylparaben in activated sludge

“…Benzoic acid is recognized as a nonspecific marker of parabens (Ye et al, 2006). In the present study, p-hydroxybenzoic acid, the reported common metabolite of all paraben esters Wang et al, 2015;Moos et al, 2015;Wang and Kannan, 2016), was not detected in the samples upon GC-MS analysis, while we did not detect the metabolite in the MP and PP controls as well. Therefore, it is possible that p-hydroxybenzoic acid was further oxidized to benzoic acid by mixed microbes during the rapid aerobic degradation process.…”

Parabens inhibit fatty acid amide hydrolase: A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation

“…This is due, in part, to their low metabolic stability and fast excretion with 81–85% excreted in the urine after the first 24 h and over half of that excreted as p -hydroxyhippuric acid, the primary metabolite (Moos et al, 2015). Despite the rapid metabolism, the high prevalence of these products may result in regular daily exposure, as evidenced by a high incidence of detection in urine (Ye et al, 2006; Tefre de Renzy-Martin et al, 2014).…”

Emerging exposures of developmental toxicants

“…Parabens are commonly detected in urine as the parent compound (largely conjugated). Newly identified specific oxidative metabolites may be more specific indicators of exposure than the parent compounds [9]. Triclosan and triclocarban have been banned recently for soaps, but still exist as biocides in many products [10].…”