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Cumulative risk assessment of phthalate exposure of Danish children and adolescents using the hazard index approach.

https://arctichealth.org/en/permalink/ahliterature127150
Source
Int J Androl. 2012 Jun;35(3):245-52
Publication Type
Article
Date
Jun-2012
Author
Søeborg T
Frederiksen H
Andersson AM
Author Affiliation
Department of Growth and Reproduction, Section 5064, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. tue.soeborg@rh.regionh.dk
Source
Int J Androl. 2012 Jun;35(3):245-52
Date
Jun-2012
Language
English
Publication Type
Article
Keywords
Adolescent
Androgen Antagonists - administration & dosage
Child
Denmark
Dibutyl Phthalate - administration & dosage
Diethylhexyl Phthalate - administration & dosage
Environmental Exposure - adverse effects
Humans
Phthalic Acids - urine
Risk Assessment - methods
Abstract
Human risk assessment of chemicals is traditionally presented as the ratio between the actual level of exposure and an acceptable level of exposure, with the acceptable level of exposure most often being estimated by appropriate authorities. This approach is generally sound when assessing the risk of individual chemicals. However, several chemicals may concurrently target the same receptor, work through the same mechanism or in other ways induce the same effect(s) in the body. In these cases, cumulative risk assessment should be applied. The present study uses biomonitoring data from 129 Danish children and adolescents and resulting estimated daily intakes of four different phthalates. These daily intake estimates are used for a cumulative risk assessment with anti-androgenic effects as the endpoint using Tolerable Daily Intake (TDI) values determined by the European Food Safety Authorities (EFSA) or Reference Doses for Anti-Androgenicity (RfD AA) determined by Kortenkamp and Faust [Int J Androl 33 (2010) 463] as acceptable levels of exposure. United States Environmental Protection Agency Reference Doses (US EPA RfD) could not be used as none of them identifies anti-androgenic effects as the most sensitive endpoint for the phthalates included in this article. Using the EFSA TDI values, 12 children exceeded the hazard quotient for the sum of di-n-butyl phthalate and di-iso-butyl phthalate (?DBP((i+n))) and one child exceeded the hazard quotient for di-(2-ethylhexyl)phthalate (DEHP). Nineteen children exceeded the cumulated hazard index for three phthalates. Using the RfD AA values, one child exceeded the hazard quotient for DEHP and the same child exceeded the cumulated hazard index for four phthalates. The EFSA TDI approach thus is more restrictive and identifies ?DBP((i+n)) as the compound(s) associated with the greatest risk, while DEHP is the compound associated with the greatest risk when using the RfD AA approach.
PubMed ID
22320716 View in PubMed
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Determination of 12 urinary phthalate metabolites in Norwegian pregnant women by core-shell high performance liquid chromatography with on-line solid-phase extraction, column switching and tandem mass spectrometry.

https://arctichealth.org/en/permalink/ahliterature272929
Source
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Oct 1;1002:343-52
Publication Type
Article
Date
Oct-1-2015
Author
Azemira Sabaredzovic
Amrit Kaur Sakhi
Anne Lise Brantsæter
Cathrine Thomsen
Source
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Oct 1;1002:343-52
Date
Oct-1-2015
Language
English
Publication Type
Article
Keywords
Chromatography, High Pressure Liquid - methods
Female
Humans
Norway
Phthalic Acids - urine
Pregnancy
Solid Phase Extraction - methods
Tandem Mass Spectrometry - methods
Abstract
Phthalates (dialkyl or alkyl phenyl esters of phthalic acid, benzene-1.2-dicarboxylic acid) are a group of industrial chemicals that have been used for more than 50 years. Phthalates are ubiquitous and can potentially have adverse effects on humans. The present study presents an accurate, sensitive and automated analytical method for measuring 12 phthalate metabolites (free and conjugated) in human urine using on-line solid phase extraction coupled to high performance liquid chromatography - electrospray ionization - tandem mass spectrometry. A small volume of urine sample (300µL) is required. Glucoronidated phthalate metabolites are deconjugated by incubation with glucoronidase enzyme (Escherihia coli-K 12) and the reaction is stopped by adding formic acid. This is the only sample preparation needed prior to injection into the column switching system. Thus, the method involves minimal sample handling and minimizes possible contaminations from the surroundings. The method was validated by spiking synthetic urine at 5-8 levels in the range of 0.1-500ng phthalate metabolites/mL synthetic urine. The method is sensitive with limits of detection in the low nanogram range, and rapid with a total run time about 25min. The accuracy was between 90 and 120 % and the intermediate precision was given as relative standard deviation was below 20% for most of the compounds. The high sensitivity, high throughput and minimal manual handling make the method suitable for large-scale biomonitoring studies. The present method was applied for the determination of phthalate metabolites in urine samples from 116 pregnant women, a subproject within the Norwegian Mother and Child Cohort Study. Concentrations of all the twelve phthalate metabolites was >LOQ in 100% of the samples analysed. Mean urinary concentrations for different phthalate metabolites ranged from 1 to 100ng/mL, the highest concentrations were observed for di-2-ethylhexyl phthalate (DEHP) metabolites and lowest for di-iso-nonyl phthalate (DiNP) metabolites. The urinary concentrations for most of the phthalate metabolites in the present study were found to be in the same range as found in other studies of pregnant women.
PubMed ID
26355271 View in PubMed
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High urinary phthalate concentration associated with delayed pubarche in girls.

https://arctichealth.org/en/permalink/ahliterature126050
Source
Int J Androl. 2012 Jun;35(3):216-26
Publication Type
Article
Date
Jun-2012
Author
H. Frederiksen
K. Sørensen
A. Mouritsen
L. Aksglaede
C P Hagen
J H Petersen
N E Skakkebaek
A-M Andersson
A. Juul
Author Affiliation
Department of Growth and Reproduction, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. hanne.01.frederiksen@rh.regionh.dk
Source
Int J Androl. 2012 Jun;35(3):216-26
Date
Jun-2012
Language
English
Publication Type
Article
Keywords
Adolescent
Breast - drug effects - growth & development
Child
Child, Preschool
Denmark
Environmental Pollutants - pharmacology - urine
European Continental Ancestry Group
Female
Hair - growth & development
Humans
Phthalic Acids - urine
Puberty - drug effects
Puberty, Precocious - chemically induced - urine
Young Adult
Abstract
Phthalates are a group of chemicals present in numerous consumer products. They have anti-androgenic properties in experimental studies and are suspected to be involved in human male reproductive health problems. A few studies have shown associations between phthalate exposure and changes in pubertal timing among girls, although controversies exist. We determined the concentration of 12 phthalate metabolites in first morning urine samples from 725 healthy Danish girls (aged 5.6-19.1 years) in relation to age, pubertal development (breast and pubic hair stage) and reproductive hormone levels (luteinizing hormone, oestradiol and testosterone). Furthermore, urinary phthalates were determined in 25 girls with precocious puberty (PP). In general, the youngest girls with less advanced pubertal development had the highest first morning urinary concentration of the monobutyl phthalate isoforms (?MBP((i+n))), monobenzyl phthalate (MBzP), metabolites of di-(2-ethylhexyl) phthalate (?DEHPm) and of di-iso-nonyl phthalate (?DINPm). After stratification of the urinary phthalate excretion into quartiles, we found that the age at pubarche was increasing with increasing phthalate metabolite quartiles (except for MEP). This trend was statistically significant when all phthalate metabolites (except MEP) were summarized and expressed as quartiles. No association between phthalates and breast development was observed. In addition, there were no differences in urinary phthalate metabolite levels between girls with PP and controls. We demonstrated that delayed pubarche, but not thelarche, was associated with high phthalate excretion in urine samples from 725 healthy school girls, which may suggest anti-androgenic actions of phthalates in our study group of girls.
PubMed ID
22428786 View in PubMed
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Human urinary excretion of non-persistent environmental chemicals: an overview of Danish data collected between 2006 and 2012.

https://arctichealth.org/en/permalink/ahliterature259730
Source
Reproduction. 2014;147(4):555-65
Publication Type
Article
Date
2014
Author
Hanne Frederiksen
Tina Kold Jensen
Niels Jørgensen
Henriette Boye Kyhl
Steffen Husby
Niels E Skakkebæk
Katharina M Main
Anders Juul
Anna-Maria Andersson
Source
Reproduction. 2014;147(4):555-65
Date
2014
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Benzhydryl Compounds - urine
Child
Child, Preschool
Denmark - epidemiology
Endocrine Disruptors - urine
Environmental Exposure - analysis - statistics & numerical data
Environmental Monitoring - statistics & numerical data
Environmental Pollutants - urine
Female
Health Surveys
Humans
Male
Parabens - analysis
Phenols - urine
Phthalic Acids - urine
Pregnancy
Triclosan - urine
Young Adult
Abstract
Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal studies and are suspected to be involved in human reproductive disorders. Among the non-persistent chemicals that have been discussed intensively during the past years are phthalates, bisphenol A (BPA), triclosan (TCS), and parabens because of their anti-androgenic and/or estrogenic effects. Phthalates are plasticizers used in numerous industrial products. Bisphenol A is the main component of polycarbonate plastics and epoxy resins. Parabens and TCS are antimicrobial preservatives and other phenols such as benzophenone-3 (BP-3) act as a UV-screener, while chlorophenols and phenyl phenols are used as pesticides and fungicides in agriculture. In spite of the widespread use of industrial chemicals, knowledge of exposure sources and human biomonitoring studies among different segments of the population is very limited. In Denmark, we have no survey programs for non-persistent environmental chemicals, unlike some countries such as the USA (NHANES) and Germany (GerES). However, we have analyzed the excretion of seven parabens, nine phenols, and the metabolites of eight different phthalates in urine samples collected over the past 6 years from four Danish cohorts. Here, we present biomonitoring data on more than 3600 Danish children, adolescents, young men, and pregnant women from the general population. Our study shows that nearly all Danes were exposed to the six most common phthalates, to BPA, TCS, and BP-3, and to at least two of the parabens. The exposure to other non-persistent chemicals was also widespread. Our data indicate decreasing excretion of two common phthalates (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate) over time.
PubMed ID
24395915 View in PubMed
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Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A in pooled urine specimens from pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa).

https://arctichealth.org/en/permalink/ahliterature95256
Source
Int J Hyg Environ Health. 2009 Sep;212(5):481-91
Publication Type
Article
Date
Sep-2009
Author
Ye Xibiao
Pierik Frank H
Angerer Jürgen
Meltzer Helle Margrete
Jaddoe Vincent W V
Tiemeier Henning
Hoppin Jane A
Longnecker Matthew P
Author Affiliation
Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), MD A3-05, PO Box 12233, Research Triangle Park, NC 27709, USA.
Source
Int J Hyg Environ Health. 2009 Sep;212(5):481-91
Date
Sep-2009
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Cohort Studies
Environmental Exposure - analysis
Female
Humans
Middle Aged
Norway
Pesticides - urine
Phenols - urine
Phosphoric Acid Esters - urine
Phthalic Acids - urine
Pregnancy
Abstract
Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples representing 110 pregnant women who participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004. Daily intakes were estimated from urinary data and compared with reference doses (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA concentration (4.50 microg/L) than the pregnant women in the Generation R Study (Generation R) in the Netherlands and the National Health and Nutrition Examination Survey (NHANES) in the United States. The mean concentration of total DAP metabolites (24.20 microg/L) in MoBa women was higher than that in NHANES women but lower than that in Generation R women. The diethyl phthalate metabolite mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three studies, with the mean concentrations of greater than 300 microg/L. The MoBa and Generation R women had higher mean concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated average daily intakes of BPA, chlorpyrifos/chlorpyrifos-methyl and phthalates in MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels of metabolites in the MoBa participants may have been from intake via pesticide residues in food (organophosphates), consumption of canned food, especially fish/seafood (BPA), and use of personal care products (selected phthalates).
PubMed ID
19394271 View in PubMed
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The Norwegian biomonitoring study from the EU project EuroMix: Levels of phenols and phthalates in 24-hour urine samples and exposure sources from food and personal care products.

https://arctichealth.org/en/permalink/ahliterature309209
Source
Environ Int. 2019 11; 132:105103
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Date
11-2019
Author
T Husøy
M Andreassen
H Hjertholm
M H Carlsen
N Norberg
C Sprong
E Papadopoulou
A K Sakhi
A Sabaredzovic
H A A M Dirven
Author Affiliation
Norwegian Institute of Public Health, Division of Infection Control and Environmental Health, 0403 Oslo, Norway. Electronic address: trine.husoy@fhi.no.
Source
Environ Int. 2019 11; 132:105103
Date
11-2019
Language
English
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Adult
Aged
Biological Monitoring
Cosmetics
Dietary Exposure
Environmental Pollutants - urine
Female
Food Contamination
Humans
Male
Middle Aged
Norway
Phenols - urine
Phthalic Acids - urine
Young Adult
Abstract
Exposure to multiple chemicals occurs daily through several routes; diet, inhalation and dermal contact. Real-life exposure assessment is needed to understand the risk. Therefore, a human biomonitoring (BM) study was performed to examine the plausibility of source-to-dose calculations for chemical mixtures in the Horizon 2020 EuroMix project.
To provide a detailed description of the design of the EuroMix BM study, and to present the initial results for urinary phenols and phthalates and to describe their exposure determinants from foods and personal care products (PCPs).
Adults (44 males and 100 females) kept detailed diaries on their food consumption, PCP use and handling of cash receipts. Urine samples were collected over the same 24-hour period. Urinary levels of four parabens, five bisphenols, oxybenzone/benzophenone-3 (OXBE), triclosan (TCS), triclocarban (TCC) and metabolites of eight phthalates and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were analysed by ultra-high-performance liquid chromatography and tandem mass spectrometry. Multivariable linear regressions were performed between PCPs/food categories and each dependent chemical variable separately, and were only sex-stratified when an interactions between sex and the independent variable was significant.
The detection rate for the metabolites of phthalates and DINCH, and bisphenol A (BPA) and TCS in urine was 88-100%, while bisphenol S (BPS) and bisphenol F (BPF) were only found in 29% and 4% of the urine samples, respectively. Bisphenol B (BPB), bisphenol AF (BPAF) and TCC were not detected. Food groups associated with phenol exposure were meat, bread, beverages and butter and oil. Food determinants for phthalate exposure were sweets, butter and oil, fruit and berries and other foods. The only positive association between the use of PCPs and phenols was found between BPA and lip gloss/balm. Phthalate exposure was associated with the use of shower gel, hand cream (females), toothpaste, anti-wrinkle cream (females) and shaving products (males).
The participants in the EuroMix BM study were exposed to a mixture of phenols and phthalates. A variety of food categories and PCPs were found to be possible sources of these chemicals. This indicates a complex pattern of exposure to numerous chemicals from multiple sources, depending on individual diet and PCP preferences.
PubMed ID
31470218 View in PubMed
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Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men.

https://arctichealth.org/en/permalink/ahliterature122284
Source
Environ Health Perspect. 2012 Oct;120(10):1397-403
Publication Type
Article
Date
Oct-2012
Author
Ulla Nordström Joensen
Hanne Frederiksen
Martin Blomberg Jensen
Mette Petri Lauritsen
Inge Ahlmann Olesen
Tina Harmer Lassen
Anna-Maria Andersson
Niels Jørgensen
Author Affiliation
Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark. ulla.nordstroem.joensen@rh.regionh.dk
Source
Environ Health Perspect. 2012 Oct;120(10):1397-403
Date
Oct-2012
Language
English
Publication Type
Article
Keywords
Adolescent
Chromatography, Liquid
Denmark
Environmental Exposure
Environmental monitoring
Gonadal Hormones - blood
Gonadotropins, Pituitary - blood
Humans
Immunoassay
Male
Phthalic Acids - urine
Semen Analysis
Sex Hormone-Binding Globulin - analysis
Tandem Mass Spectrometry
Young Adult
Abstract
In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function.
We aimed to provide estimates of the effects of phthalate exposure on reproductive hormone levels and semen quality in healthy men.
A total of 881 men gave urine, serum, and semen samples. Serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-B; semen quality; and urinary concentrations of 14 phthalate metabolites, including metabolites of di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP), were assessed. The proportions of DEHP and DiNP excreted as their respective primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-isononyl phthalate (MiNP)] were calculated and expressed as percentages (%MEHP and %MiNP, respectively).
The free androgen index was 15% lower [95% confidence interval (CI): -23, -8%] for men in the highest %MiNP quartile compared to the lowest quartile (p
Notes
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PubMed ID
22832070 View in PubMed
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Temporal trends of phthalate exposures during 2007-2010 in Swedish pregnant women.

https://arctichealth.org/en/permalink/ahliterature299368
Source
J Expo Sci Environ Epidemiol. 2018 09; 28(5):437-447
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Date
09-2018
Author
Huan Shu
Bo Ag Jönsson
Chris Gennings
Åke Svensson
Eewa Nånberg
Christian H Lindh
Malin Knutz
Tim K Takaro
Carl-Gustaf Bornehag
Author Affiliation
Department of Health Sciences, Karlstad University, Karlstad, Sweden.
Source
J Expo Sci Environ Epidemiol. 2018 09; 28(5):437-447
Date
09-2018
Language
English
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Adult
Biomarkers - urine
Cohort Studies
Endocrine Disruptors
Environmental Exposure - analysis
Environmental Monitoring - methods
Female
Humans
Phthalic Acids - urine
Pregnancy
Pregnancy Trimester, First
Pregnant Women
Regression Analysis
Surveys and Questionnaires
Sweden
Tandem Mass Spectrometry
Young Adult
Abstract
The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of "new generation compounds" coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH).
In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007-2010).
We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders.
All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period.
Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life.
PubMed ID
29472621 View in PubMed
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Urinary excretion of phthalate metabolites in 129 healthy Danish children and adolescents: estimation of daily phthalate intake.

https://arctichealth.org/en/permalink/ahliterature135948
Source
Environ Res. 2011 Jul;111(5):656-63
Publication Type
Article
Date
Jul-2011
Author
Hanne Frederiksen
Lise Aksglaede
Kaspar Sorensen
Niels E Skakkebaek
Anders Juul
Anna-Maria Andersson
Author Affiliation
Department of Growth and Reproduction, Section 5064, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. hanne.01.frederiksen@rh.regionh.dk
Source
Environ Res. 2011 Jul;111(5):656-63
Date
Jul-2011
Language
English
Publication Type
Article
Keywords
Adolescent
Child
Denmark
Dibutyl Phthalate - urine
Endocrine Disruptors - urine
Environmental Exposure - analysis - statistics & numerical data
Environmental Pollutants - urine
Environmental Pollution - statistics & numerical data
Female
Humans
Male
Phthalic Acids - urine
Young Adult
Abstract
Phthalates are a group of chemicals with widespread use in the industrial production of numerous consumer products. They are suspected to be involved in male reproductive health problems and have also been associated with several other health problems in children including obesity and asthma.
To study the urinary excretion of phthalate metabolites in Danish children recruited from the general population, and to estimate the daily intake of phthalates in this segment of the population.
One 24 h urine sample and to consecutive first morning urine samples were collected from 129 healthy Danish children and adolescents (range 6-21 yrs). The concentrations of 11 phthalate metabolites of 5 different phthalate diesters were analyzed by liquid chromatography-tandem mass spectrometry.
The analyzed metabolites were detectable in almost all 24h urine samples. The median concentrations of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP) and the sums of the two monobutyl phthalate isoforms (?MBP(i+n)), metabolites of di-(2-ethylhexyl) phthalate (?DEHPm) and of di-iso-nonyl phthalate (?DiNPm) were 29, 17, 111, 107 and 31 ng/mL, respectively. The youngest children were generally more exposed to phthalates than older children and adolescents (except diethyl phthalate (DEP)). Boys were more exposed than girls. The median estimated daily intake of phthalate diesters was: 4.29 (dibutyl phthalate isoforms (DBP(i+n))), 4.04 (DEHP), 1.70 (DiNP), 1.09 (DEP) and 0.62 (butylbenzyl phthalate (BBzP)), all calculated as µg/kg body weight/24h. Between 40% and 48% of the absolute amount of phthalate metabolites excreted over 24h were excreted in first morning urine voids.
Danish children are exposed simultaneously to multiple phthalates. The highest exposure levels were found for DBP(i+n) and DEHP, which in animal models are the known most potent anti-androgenic phthalates. The combined exposure to the two isoforms of DBP, which have similar endocrine-disrupting potencies in animal models, exceeded the TDI for di-n-butyl phthalate (DnBP) in several of the younger children.
PubMed ID
21429484 View in PubMed
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Urinary phthalates from 168 girls and boys measured twice a year during a 5-year period: associations with adrenal androgen levels and puberty.

https://arctichealth.org/en/permalink/ahliterature112499
Source
J Clin Endocrinol Metab. 2013 Sep;98(9):3755-64
Publication Type
Article
Date
Sep-2013
Author
A. Mouritsen
H. Frederiksen
K. Sørensen
L. Aksglaede
C. Hagen
N E Skakkebaek
K M Main
A M Andersson
A. Juul
Author Affiliation
Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. annette.mouritsen@rh.regionh.dk
Source
J Clin Endocrinol Metab. 2013 Sep;98(9):3755-64
Date
Sep-2013
Language
English
Publication Type
Article
Keywords
Adolescent
Androstenedione - blood
Child
Child, Preschool
Dehydroepiandrosterone Sulfate - blood
Denmark
Environmental Exposure
Environmental Pollutants - urine
Female
Humans
Longitudinal Studies
Male
Phthalic Acids - urine
Puberty - blood - urine
Testosterone - blood
Abstract
Little is known about the possible deleterious effects of phthalate exposure on endogenous sex steroid levels in children.
Our objective was to investigate whether urinary phthalate metabolite levels are associated with circulating adrenal androgen levels and age at puberty.
This was a longitudinal study of 168 healthy children (84 girls) examined every 6 months for 5 years. Serum levels of dehydroepiandrostenedione sulfate (DHEAS), ?4-androstenedione, testosterone, and urinary morning excretion of 14 phthalate metabolites, corresponding to 7 different phthalate diesters were determined. A variation in urinary excretion of phthalates was evident in each child, which made a mean of repetitive samples more representative for long-term excretion than a single determination.
We found that girls with excretion of monobutyl phthalate isomers (MBP) and di(2-ethylhexyl) phthalate metabolites above the geometric group mean (795 and 730 ng/kg, respectively) had lower levels of DHEAS and ?4-androstenedione, although statistically significant only at 13 years of age. In boys, we found that excretion of monobenzyl phthalate above the geometric group mean (346 ng/kg) was associated with lower levels of DHEAS at 11 years of age but higher levels of testosterone at 13 years of age. The same trend was observed for MBP excretion, albeit not statistically significant. A lower age at pubarche was observed in boys with excretion of MBP above the geometric group mean (11.0 vs 12.3 years, P = 0.005).
Our data indicate that exposure to dibutyl phthalate isomers (DBP) (in girls) and butylbenzyl phthalate (in boys) are negatively associated with adrenal androgen levels and in boys positively associated with testosterone level at 13 years of age. High exposure to DBP was associated with earlier age at pubarche in boys. In girls, no associations between phthalate exposure and age at pubertal milestones were observed.
PubMed ID
23824423 View in PubMed
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