Temporal variability in urinary excretion of bisphenol A and seven other phenols in spot, morning, and 24-h urine samples.

Human exposure to modern non-persistent chemicals is difficult to ascertain in epidemiological studies as exposure patterns and excretion rates may show temporal and diurnal variations. The aim of this study was to assess the temporal variability in repeated measurements of urinary excretion of bisphenol A (BPA) and seven other phenols. All analytes were determined using TurboFlow-LC-MS/MS. Two spot, three first morning and three 24-h urine samples were collected from 33 young Danish men over a three months period. Temporal variability was estimated by means of intraclass correlation coefficients (ICCs). More than 70% of the urine samples had detectable levels of BPA, triclosan (TCS), benzophenone-3 (BP-3) and sum of 2,4-dichlorophenol and 2,5-dichlorophenol (ΣDCP). We found low to moderate ICCs for BPA (0.10-0.42) and ΣDCP (0.39-0.72), whereas the ICCs for BP-3 (0.69-0.80) and TCS (0.55-0.90) were higher. The ICCs were highest for the two spot urine samples, which were collected approximately 4 days apart, compared with the 24-h urine samples and the first morning urine samples, which were collected approximately 40 days apart. A consequence of the considerable variability in urinary excretion of BPA may be misclassification of individual BPA exposure level in epidemiological studies, which may lead to attenuation of the association between BPA and outcomes. Our data do not support that collection of 24-h samples will improve individual exposure assessment for any of the analysed phenols.

Lassen TH ，Frederiksen H ，Jensen TK ，Petersen JH ，Main KM ，Skakkebæk NE ，Jørgensen N ，Kranich SK ，Andersson AM ... -  《-》

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 ... -  《-》

Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 2: personal care product ingredients.

An intensive study was conducted to provide data on intra- and inter-individual variation in urinary excretion of a series of ingredients in personal care products (parabens, triclosan, benzophenones) and bisphenol A (BPA, not expected to be an ingredient) in 8 volunteers over 6 days. Exposure diaries recorded use of personal care products with identified target analytes as ingredients. Participants' usual products were replaced with products without the target analytes for 2 of the 6 days. Urine void volumes and times were recorded. Methyl, ethyl, and n-propylparabens, triclosan, benzophenone-3, and BPA were frequently detected (≥70% of samples). Urinary concentrations of the parabens and triclosan were lower on product replacement days. First morning void concentrations correlated moderately to highly with 24-h composite concentrations for all analytes. Intraclass correlation coefficients (ICCs) for spot samples collected on days with usual product use were low for BPA (0.15), moderate for n-propylparaben and methylparaben (0.39 and 0.56, respectively), and high for ethylparaben, benzophenone-3, and triclosan (0.76, 0.81, and 0.934, respectively); ICCs were consistently higher on the basis of cr-adjusted concentrations. Hydration status adjustment methods were assessed by comparing unadjusted and adjusted concentrations to urinary excretion rates (ER, ng/kg-h) for all analytes and samples. Specific gravity-adjusted concentrations correlated slightly better with ER than creatinine-adjusted concentrations. Within-individual variation in biomarker concentrations was highest for methyl and ethylparabens (2 orders of magnitude variation in spot sample concentrations) and lower for the other analytes (1-1.5 orders of magnitude). This dataset provides insight into the design and interpretation of urinary biomonitoring studies for non-persistent chemicals.

Koch HM ，Aylward LL ，Hays SM ，Smolders R ，Moos RK ，Cocker J ，Jones K ，Warren N ，Levy L ，Bevan R ... -  《-》

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 《-》