Rapid determination of nine parabens and seven other environmental phenols in urine samples of German children and adults.

We developed a fast, selective and sensitive on-line LC/LC-MS/MS method for the simultaneous determination of nine parabens and seven environmental phenols in urine. Parabens are widely used as antimicrobial preservatives. Bisphenol A, triclosan, triclocarban, 2-phenylphenol, and benzophenones are used inter alia in disinfectants, sunscreens and in polymers. Some of these substances are suspected endocrine disruptors. Limits of quantification and analytical quality criteria fully met the needs for determining exposure levels occurring in the general population. We analyzed 157 spot urine samples from the general German population (59 females, 39 males and 59 children). For the parabens, we found methyl, ethyl and n-propyl paraben with high detection rates (77-98%), followed by n-butyl (36%), iso-butyl (17%), iso-propyl (3%) and benzyl paraben (3%). We detected no pentyl and heptyl paraben. Urinary concentrations were highest for methyl paraben (median 24.5 μg/L; 95th percentile 379 μg/L) followed by ethyl (1.4 μg/L; 35.2 μg/L) and n-propyl paraben (1.2 μg/L; 68.1 μg/L). Other environmental phenols with high detection rates were BPA (95%), triclosan (45%) and benzophenone 1 and 3 (26%). For most of the parabens/environmental phenols we found higher urinary levels in females than in males or children, probably due to differences in (personal care) product use. However, high levels (in the mg/L range) were also observed in children. Exposure to the above substances is occurring worldwide. Differences between countries do seem to exist and might be caused by different product compositions or different use habits. Human metabolism data is urgently needed to extrapolate from urinary biomarker levels to doses actually taken up.

Moos RK ，Angerer J ，Wittsiepe J ，Wilhelm M ，Brüning T ，Koch HM ... -  《-》

Widespread occurrence of bisphenol A diglycidyl ethers, p-hydroxybenzoic acid esters (parabens), benzophenone type-UV filters, triclosan, and triclocarban in human urine from Athens, Greece.

Biomonitoring of human exposure to bisphenol A diglycidyl ethers (BADGEs; resin coating for food cans), p-hydroxybenzoic acid esters (parabens; preservatives), benzophenone-type UV filters (BP-UV filters; sunscreen agents), triclosan (TCS; antimicrobials), and triclocarban (TCC; antimicrobials) has been investigated in western European countries and North America. Nevertheless, little is known about the exposure of Greek populations to these environmental chemicals. In this study, 100 urine samples collected from Athens, Greece, were analyzed by liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of total concentrations of five derivatives of BADGEs, six parabens and their metabolite (ethyl-protocatechuate), five derivatives of BP-UV filters, TCS, and TCC. Urinary concentrations of BADGEs, parabens, ethyl-protocatechuate, BP-UV filters, TCS and TCC (on a volume basis) ranged 0.3-20.9 (geometric mean: 0.9), 1.6-1010 (24.2), <2-71.0 (2.1), 0.5-1120 (4.4), <0.5-2580 (8.0) and <0.5-1.9 (0.6) ng/mL, respectively. All 19 target chemicals were found in urine, and the highest detection rates were observed for methyl paraben (100%), bisphenol A bis (2,3-dihydroxypropyl) ether (90%), ethyl paraben (87%), 2,4-dihydroxybenzophenone (78%), propyl paraben (72%), and TCS (71%). Estimated daily intakes (EDIurine), calculated on the basis of the measured urinary concentrations, ranged from 0.023 μg/kg bw/day for Σ5BADGEs to 31.4 μg/kg bw/day for Σ6Parabens.

Asimakopoulos AG ，Thomaidis NS ，Kannan K 《-》

Parabens in 24 h urine samples of the German Environmental Specimen Bank from 1995 to 2012.

Parabens are widely used as antimicrobial preservatives in personal care and consumer products, food and pharmaceuticals. Due to their ubiquity, humans are constantly exposed to these chemicals. We assessed exposure to nine parabens (methyl-, ethyl-, n- and iso-propyl-, n- and iso-butyl-, benzyl-, pentyl- and heptyl paraben) in the German population from 1995 to 2012 based on 660 24h urine samples from the German Environmental Specimen Bank (ESB) using on-line HPLC coupled to isotope dilution tandem mass spectrometry. The limit of quantification (LOQ) was 0.5 μg/L for all parabens. We detected methyl-, ethyl- and n-propyl paraben in 79-99% of samples, followed by n-butyl paraben in 40% of samples. We infrequently detected iso-butyl-, iso-propyl- and benzyl paraben in 24%, 4% and 1.4% of samples, respectively. Urinary concentrations were highest for methyl paraben (median 39.8 μg/L; 95th percentile 319 μg/L) followed by n-propyl paraben (4.8 μg/L; 95th percentile 74.0 μg/L) and ethyl paraben (2.1 μg/L; 95th percentile 39.1 μg/L). Women had significantly higher urinary levels for all parabens than men, except for benzyl paraben. Samples from the ESB revealed that over the investigation period of nearly 20 years urinary paraben levels remained surprisingly constant; only methyl paraben had a significant increase, for both men and women. We found strong correlations between methyl- and n-propyl paraben and between n- and iso-butyl paraben. These results indicate that parabens are used in combination and arise from common sources of exposure. Urinary excretion factors are needed to extrapolate from individual urinary concentrations to actual doses.

Moos RK ，Koch HM ，Angerer J ，Apel P ，Schröter-Kermani C ，Brüning T ，Kolossa-Gehring M ... -  《-》

Bisphenol A and other phenols in urine from Danish children and adolescents analyzed by isotope diluted TurboFlow-LC-MS/MS.

Bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), dichoro- and phenyl phenols are industrial chemicals present in numerous consumer products such as polycarbonate plastics, preservatives in personal care products, sun screens, pesticides and fungicides, respectively, and they are all suspected endocrine disrupters. In this study the urinary excretion of eight phenols in Danish children recruited from the general population were investigated. One 24h urine and two consecutive first morning samples were collected from each of 129 healthy Danish children and adolescents (6-21 years). The concentrations of urinary phenols were analyzed by a new on-line TurboFlow-liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Most of the analyzed phenols were detectable in more than 80% of the 24h urine samples and the median concentration of BPA, TCS, BP-3, 2,4-dichorophenol and 2,5-dichorophenol (analyzed as ∑DCP), 2-phenylphenol and 4-phenylphenol were 1.37, 1.45, 1.41, 0.65, 0.36 and 0.53ng/mL, respectively. The ranges of the excreted TCS and BP-3 were wide; from below limit of detection to maximum levels of 955ng/mL and 162ng/mL, respectively, while the other phenols were excreted in a more narrow range with maximum levels below 25ng/mL. Concentrations in first morning urine were in general higher than in 24h urine and comprised 30-47% of the absolute amount excreted during 24h. The youngest children aged 6-10 years had a significantly higher urinary BPA concentration (ng/mL) and also a relatively higher daily BPA excretion (ng/kg bw/24h) than the older children and adolescents. The opposite pattern was observed for TCS, BP-3 and ∑DCP for which urinary levels increased significantly with age. No gender difference or associations to pubertal development were observed. In conclusion, our study showed that Danish children were exposed to multiple phenols simultaneously. Small children were relatively more exposed to BPA than older children, while higher exposures to TCS, BP-3 and ∑DCP were seen among adolescents.

Frederiksen H ，Aksglaede L ，Sorensen K ，Nielsen O ，Main KM ，Skakkebaek NE ，Juul A ，Andersson AM ... -  《-》

Urinary excretion of phthalate metabolites, phenols and parabens in rural and urban Danish mother-child pairs.

Some phthalates, parabens and phenols have shown adverse endocrine disrupting effects in animal studies and are also suspected to be involved in human reproductive problems. However, knowledge about exposure sources and biomonitoring data in different subsets of populations are still scarce. Thus, in this study first morning urine samples were collected from 6 to 11 years Danish children and their mothers. The content of seven parabens, nine phenols and metabolites of eight different phthalates were analysed by LC-MS/MS. Two parabens, six phenols and metabolites from six phthalate diesters were measurable in more than 50%, 75% and 90% of the participants, respectively. Thus the children and their mothers were generally exposed simultaneously to a range of phthalates, phenols and parabens. In general, the levels were low but for several of the compounds extreme creatinine adjusted concentrations 100-500-fold higher than the median level were seen in some participants. Children were significantly higher exposed to bisphenol A (BPA) and some of the phthalates (DiBP, DnBP, BBzP, DEHP and DiNP) than their mothers, whereas mothers were higher exposed to compounds related to cosmetics and personal care products such as parabens (MeP, EtP and n-PrP), benzophenone-3, triclosan and diethyl phthalate. However, a very high correlation between mothers and their children was observed for all chemicals. A high individual exposure to one chemical was often associated with a high exposure to other of the chemicals and the possibility of combination effects of multiple simultaneous exposures cannot be excluded.

Frederiksen H ，Nielsen JK ，Mørck TA ，Hansen PW ，Jensen JF ，Nielsen O ，Andersson AM ，Knudsen LE ... -  《-》