Human urinary excretion of non-persistent environmental chemicals: an overview of Danish data collected between 2006 and 2012.

Frederiksen H ，Jensen TK ，Jørgensen N ，Kyhl HB ，Husby S ，Skakkebæk NE ，Main KM ，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 ... -  《-》

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 ... -  《-》

Changes in urinary excretion of phthalates, phthalate substitutes, bisphenols and other polychlorinated and phenolic substances in young Danish men; 2009-2017.

During the past two decades human exposure to bisphenol A (BPA) and phthalates such as di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP) and di-(2-ethyl-hexyl) phthalate (DEHP) has received substantial interest due to widespread population exposures and potential endocrine disrupting effects. Therefore, these chemicals have gradually been restricted and phased out through legislation. However, humans are still exposed to a wide range of other less studied phthalates, phthalate substitutes and BPA analogues as well as other polychlorinated and phenolic substances. In this study, we investigated human exposure to these chemicals over the past decade. Three hundred urine samples collected in 2009, 2013 and 2017 (100 samples each year) from young Danish men of the general population, participating in a large on-going cross-sectional study, were selected for the present time trend study. The urinary concentration of metabolites of 15 phthalates, di-2-ethylhexyl terephthalate (DEHTP) and di-iso-nonyl-cyclohexane-1,2-dicarboxylate (DINCH), seven bisphenols including BPA, bisphenol S (BPS) and bisphenol F (BPF), as well as triclosan, triclocarban, benzophenone-3, three chlorophenols and two phenylphenols were analyzed by two new sensitive LC-MS/MS methods developed and validated for the present study. A significant decrease in urinary concentrations over time was observed for the majority of the chemicals. Median concentrations of BPA and the metabolites of DiBP, DnBP, BBzP and DEHP were more than halved from 2009 to 2017. Similar decreases were observed for triclosan and the chloro- and phenylphenols. In contrast, metabolites of the two phthalate substitutes DEHTP and DINCH increased more than 20 and 2 times, respectively. The potential BPA substitutes; BPS and BPF also increased, but only slightly. Despite these new exposure patterns, the exposure to the old well-known chemicals, such as DiBP, DnBP, BBzP, DEHP and BPA was still higher in 2017 compared to the exposure level of the new substitutes such as DEHTP, DINCH, BPS and BPF. A significant decrease in internal exposure to most of the common phthalates and BPA over the past decade was observed, reflecting market changes and regulatory measures implemented in EU. Despite increasing exposures to some of the known phthalate substitutes and BPA analogues, the total amount of each measured chemical group (original and substitute analytes combined) was lower in the more recently collected samples. This indicates only partial direct substitution or substitution by chemicals not covered in this approach, or a general decline in the exposure to these chemical/product groups over the last decade.

Frederiksen H ，Nielsen O ，Koch HM ，Skakkebaek NE ，Juul A ，Jørgensen N ，Andersson AM ... -  《-》

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 《-》