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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.

Preservatives continue to be in widespread use in ophthalmic medications due to the convenience they provide, regulatory requirements and the higher cost of alternatives. Benzalkonium chloride (BAK) remains the most commonly used preservative but there is a trend towards the use of preservative-free (PF) drops for glaucoma, although at a higher price. An extensive body of literature explores BAK toxicity on ocular structures in animal and laboratory studies (in vitro and in vivo). Non-randomised controlled studies have provided some supporting evidence of its toxicity in patients, especially in those with pre-existing ocular surface disease (OSD) or on multiple medications. However, there have been very few randomised controlled trials that compare the same medication with and without BAK preservative. Several of these trials have never been published in any peer reviewed journals. Notwithstanding, those that have been published, have not demonstrated any clear benefits of the BAK-free formulations. Short duration and exclusion of those with OSD are limitations of these studies. There is a lack of evidence of clinically significant harm from a small number of BAK preserved drops in patients without OSD. This means that generally more expensive PF glaucoma medications should only be recommended for those on poly pharmacy or those with OSD but are not necessarily required for all patients.

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother–child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation. Parabens are preservatives widely used in consumer products including cosmetics and food. Here the authors demonstrate that maternal paraben exposure may contribute to childhood overweight development by an altered neuronal appetite regulation.

Aim To compare 24 h intraocular pressure (IOP) control obtained with preservative free (PF) tafluprost 0.0015% versus branded preservative containing latanoprost 0.005% administered as first choice monotherapy in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Methods This prospective, observer-masked, crossover study included consecutive newly diagnosed patients with POAG or OHT, and baseline IOP between 24 and 33 mm Hg. Qualifying patients underwent baseline untreated 24 h IOP monitoring in habitual positions, with Goldmann tonometry at times 10:00, 14:00, 18:00 and 22:00, and Perkins supine tonometry at times 02:00 and 06:00. They were then randomised to either latanoprost or tafluprost, administered in the evening, for 3 months and then switched to the opposite therapy for another 3 months. 24 h monitoring was repeated at the end of each treatment period. Results 38 patients completed the study. Mean untreated 24 h IOP (24.9 mm Hg) was significantly reduced with both prostaglandins (p<0.001). Tafluprost demonstrated similar mean 24 h efficacy compared with latanoprost (17.8 vs 17.7 mm Hg; p=0.417). Latanoprost demonstrated significantly better 24 h trough IOP (15.9 vs 16.3 mm Hg; p=0.041) whereas tafluprost provided significantly lower 24 h IOP fluctuation (3.2 vs 3.8 mm Hg; p=0.008). No significant difference existed between the two prostaglandins for any adverse event. Conclusions PF tafluprost achieved similar 24 h IOP reduction to branded latanoprost. The current study highlights the importance of complete assessment of efficacy over 24 h. Clinical trials registration NCT01162603.

Betanin is the only betalain approved for use in food and pharmaceutical products as a natural red colorant. However, the antioxidant power and health-promoting properties of this pigment have been disregarded, perhaps due to the difficulty in obtaining a stable chemical compound, which impairs its absorption and metabolism evaluation. Herein, betanin was purified by semi-preparative HPLC-LC/MS and identified by LC-ESI(+)-MS/MS as the pseudomolecular ion m/z 551.16. Betanin showed significant stability up to −30 °C and mild stability at chilling temperature. The stability and antioxidant ability of this compound were assessed during a human digestion simulation and ex vivo colon fermentation. Half of the betanin amount was recovered in the small intestine digestive fluid and no traces were found after colon fermentation. Betanin high antioxidant ability was retained even after simulated small intestine digestion. Betanin, besides displaying an inherent colorant capacity, was equally effective as a natural antioxidant displaying peroxy-radical scavenger ability in pork meat. Betanin should be considered a multi-functional molecule able to confer an attractive color to frozen or refrigerated foods, but with the capacity to avoid lipid oxidation, thereby preserving food quality. Long-term supplementation by beetroot, a rich source of betanin, should be stimulated to protect organisms against oxidative stress.

Marine resources exist in vast numbers and show enormous diversity. As a result, there are likely many possible applications for marine molecules of interest in the cosmetic industry, whether as excipients or additives, but especially as active substances. It is possible to obtain extracts from active substances; for example, quite a few algae species can be used in moisturizing or anti-ageing products. In the field of topical photoprotection, mycosporine-like amino acids and gadusol are important lines of enquiry that should not be overlooked. In the field of additives, the demonstration that certain seaweed (algae) extracts have antimicrobial properties suggests that they could provide alternatives to currently authorized preservatives. These promising leads must be explored, but it should be kept in mind that it is a long process to bring ingredients to market that are both effective and safe to use.

Background Dry eye is a condition related to long-term topical eye therapy. We wish to evaluate the effectiveness and tolerability of preservative free prostaglandin drops versus benzalkonium chloride containing prostaglandin drops in the treatment of glaucoma. Methods Patients undergoing prostaglandin monotherapy underwent a washout period of at least 1 month after which baseline measurements of dry eye severity were taken. Patients were randomised to receive either 0.0015% tafluprost drops or 0.005% latanoprost preserved with 0.02% benzalkonium chloride. Repeat measurements were taken after a 2-month interval. Results Thirty-five patients completed randomised treatment. No significant difference between groups was found in objective and subjective measurements of dry eye severity. No significant difference was found in measurement of treatment effectiveness. Conclusion Preservative-free and benzalkonium chloride–containing drops were found to be equally effective in lowering IOP with no significant difference in either subjective or objective measurements of dry eye severity.

2-Phenoxyethanol (PhE) is an amphiphilic organic compound frequently used as a broad-spectrum preservative in cosmetic products and other consumer goods. PhE is also used as a biocidal component in occupational settings. A previous volunteer study by our working group following oral exposure to PhE showed that PhE is almost completely taken up into the human body followed by an extensive metabolization and fast urinary elimination. However, with respect to the importance of transdermal uptake, we now conducted another volunteer study applying dermal PhE exposure: five volunteers were dermally exposed with 0.4 mg/kg body weight of PhE each on a specified 800 cm 2 skin area using non-occlusive conditions. Subsequently, blood and urine samples were collected up to 48 h post-exposure. The present study illustrates the fast transdermal uptake of PhE. Following systemic resorption, PhE was extensively metabolized and rapidly eliminated in urine mainly in form of the metabolites PhAA (phenoxyacetic acid) and 4-OH-PhAA (4-hydroxyphenoxyacetic acid) accounting together for over 99% of the renally excreted PhE dose. The absolute urinary recovery rate of PhE was observed to be significantly lower following dermal exposure compared to oral uptake indicating a dermal resorption rate of PhE of about 45% in humans. The present study provides for the first time detailed insights into human biotransformation and toxicokinetics of PhE after dermal exposure, thus establishing a reliable strategy for human biomonitoring of PhE. The here presented results may thus be useful for further toxicokinetic modeling and forward dosimetry.

Background: Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Objectives: We assessed exposure to methyl, ethyl, propyl, and butyl parabens in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005–2006 National Health and Nutrition Examination Survey. Methods: We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution—high-performance liquid chromatography/tandem mass spectrometry. Results: We detected methyl paraben (MP) and propyl paraben (PP) in 99.1% and 92.7% of the samples, respectively. We detected ethyl (42.4%) and butyl (47%) parabens less frequently and at median concentrations at least one order of magnitude lower than MP (63.5 μg/L) and PP (8.7 μg/L). Least-square geometric mean (LSGM) concentrations of MP were significantly higher (p ≤ 0.01) among non-Hispanic blacks than among non-Hispanic whites except at older ages (≥ 60 years). Adolescent and adult females had significantly higher (p < 0.01) LSGM concentrations of MP and PP than did adolescent and adult males. Females were more likely than males [adjusted odds ratios (ORs) and 95% confidence intervals (CIs): MP, 3.2 (2.99–5.27); PP, 4.19 (2.34–7.49)] and non-Hispanic blacks were more likely than non-Hispanic whites [MP, 4.99 (2.62–9.50); PP, 3.6 (1.86–7.05)] to have concentrations above the 95th percentile. Conclusions: The general U.S. population was exposed to several parabens during 2005–2006. Differences in the urinary concentration of MP and PP by sex and race/ethnicity likely reflect the use of personal care products containing these compounds.

Aim To compare the efficacy and safety of single-dose bimatoprost 0.03%/timolol 0.5% preservative-free (PF) ophthalmic solution with bimatoprost 0.03%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. Methods In this multicentre, randomised, parallel-group study, patients were randomised to bimatoprost/timolol PF or bimatoprost/timolol once daily in the morning for 12 weeks. Primary efficacy endpoints, reflecting differing regional regulatory requirements, included change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12, and the average eye IOP at weeks 2, 6 and 12 in the intent-to-treat population. Results 561 patients were randomised (278 to bimatoprost/timolol PF; 283 to bimatoprost/timolol); 96.3% completed the study. Both treatment groups showed statistically and clinically significant mean decreases from baseline in worse eye IOP and in average eye IOP at all follow-up time points (p<0.001). Bimatoprost/timolol PF met all pre-established criteria for non-inferiority and equivalence to bimatoprost/timolol. Ocular adverse events were similar between treatment groups, with conjunctival hyperaemia being the most frequent. Most were mild or moderate in severity. Conclusions Bimatoprost/timolol PF demonstrated non-inferiority and equivalence in IOP lowering compared with bimatoprost/timolol, with no significant differences in safety and tolerability. Trial registration number NCT01177098.