German Environmental Specimen Bank: 24-hour urine samples from 1999 to 2017 reveal rapid increase in exposure to the para-phthalate plasticizer di(2-ethylhexyl) terephthalate (DEHTP)

Lessmann, Frederik; Kolossa-Gehring, Marike; Apel, Petra; Rüther, Maria; Pälmke, Claudia; Harth, Volker; Brüning, Thomas; Koch, Holger M.

doi:10.1016/j.envint.2019.105102

Cited by 47 publications

(28 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We similarly observed epigenetic associations in the analysis of two common phthalate alternatives. Methylation analyses with our more modest set of mother-infant pairs using sex-interaction models to account for the smaller sample sizes, found several associations with methylation at CpG sites that were related to increasingly common exposures to ΣDINCH, a complex mixture of 9-carbon molecules, rapidly replacing high-molecular weight phthalates ( Kasper-Sonnenberg et al, 2019 ), but not ΣDEHTP, a terephthalate commonly replacing DEHP ( Lessmann et al, 2019 ). While the sample sizes on this analysis were limited, the results underscore the need to closely examine the effects potential replacements before putting them into everyday use to avoid situations of regrettable substitution.…”

Section: Discussionmentioning

confidence: 98%

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

et al. 2022

View full text Add to dashboard Cite

Phthalates are a diverse group of chemicals used in consumer products. Because they are so widespread, exposure to these compounds is nearly unavoidable. Recently, growing scientific consensus has suggested that phthalates produce health effects in developing infants and children. These effects may be mediated through mechanisms related to the epigenome, the constellation of mitotically heritable chemical marks and small compounds that guide transcription and translation. The present study examined the relationship between prenatal, first-trimester exposure of seven phthalates and epigenetics in two pregnancy cohorts (n = 262) to investigate sex-specific alterations in infant blood DNA methylation at birth (cord blood or neonatal blood spots). Prenatal exposure to several phthalates was suggestive of association with altered DNA methylation at 4 loci in males (all related to ΣDEHP) and 4 loci in females (1 related to ΣDiNP; 2 related to BBzP; and 1 related to MCPP) at a cutoff of q < 0.2. Additionally, a subset of dyads (n = 79) was used to interrogate the relationships between two compounds increasingly used as substitutions for common phthalates (ΣDINCH and ΣDEHTP) and cord blood DNA methylation. ΣDINCH, but not ΣDEHTP, was suggestive of association with DNA methylation (q < 0.2). Together, these results demonstrate that prenatal exposure to both classically used phthalate metabolites and their newer alternatives is associated with sex-specific infant DNA methylation. Research and regulatory actions regarding this chemical class should consider the developmental health effects of these compounds and aim to avoid regrettable substitution scenarios in the present and future.

show abstract

Section: Discussionmentioning

confidence: 98%

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

et al. 2022

View full text Add to dashboard Cite

show abstract

“…2017 ; Zoeller et al. 2012 ), are being replaced with alternative phthalates, such as di(2-ethylhexyl) terephthalate (DEHTP) ( Eastman Chemical Company 2014 ), leading to changes in exposure profiles around the world ( Lessmann et al. 2019 ; Silva et al.…”

Section: Introductionmentioning

confidence: 99%

“…Phthalate exposure is ubiquitous in humans (Katsikantami et al 2016). Recently, certain phthalates, such as di(2-ethylhexyl) phthalate (DEHP), which is well characterized for its endocrine-disrupting effects (Benjamin et al 2017;Zoeller et al 2012), are being replaced with alternative phthalates, such as di(2-ethylhexyl) terephthalate (DEHTP) (Eastman Chemical Company 2014), leading to changes in exposure profiles around the world (Lessmann et al 2019;Silva et al 2017;Wu et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Maternal Phthalates Exposure and Blood Pressure during and after Pregnancy in the PROGRESS Study

Kupsco

Just

et al. 2021

Environ Health Perspect

View full text Add to dashboard Cite

Background: Phthalate exposure is ubiquitous and may affect biological pathways related to regulators of blood pressure. Given the profound changes in vasculature during pregnancy, pregnant women may be particularly susceptible to the potential effects of phthalates on blood pressure. Objectives: We examined associations of phthalate exposure during pregnancy with maternal blood pressure trajectories from mid-pregnancy through 72 months postpartum. Methods: Women with singleton pregnancies delivering a live birth in Mexico City were enrolled during the second trimester ( ). Spot urine samples from the second and third trimesters were analyzed for 15 phthalate metabolites. Blood pressure and covariate data were collected over nine visits through 72 months postpartum. We used linear, logistic, and linear mixed models; latent class growth models (LCGMs); and Bayesian kernel machine regression to estimate the relationship of urinary phthalate biomarkers with maternal blood pressure. Results: As a joint mixture, phthalate biomarker concentrations during pregnancy were associated with higher blood pressure rise during mid-to-late gestation. With respect to individual biomarkers, second trimester concentrations of monobenzyl phthalate (MBzP) and di(2-ethylhexyl) phthalate biomarkers ( ) were associated with higher third trimester blood pressure. Two trajectory classes were identified by LCGM, characterized by increasing blood pressure through 72 months postpartum (“increase–increase”) or decreased blood pressure through 18 months postpartum with a gradual increase thereafter (“decrease–increase”). Increasing exposure to phthalate mixtures during pregnancy was associated with higher odds of being in the increase–increase class. Similar associations were observed for mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and dibutyl phthalate ( ) biomarkers. When specific time periods were examined, we observed specific temporal relationships were observed for , MECPTP, MBzP, and . Discussion: In our cohort of pregnant women from Mexico City, exposure to phthalates and phthalate biomarkers was associated with higher blood pressure during late pregnancy, as well as with long-term changes in blood pressure trajectories. https://doi.org/10.1289/EHP8562

show abstract

“…Urinary excretion fractions ( F UE ) allow the robust back-calculation of the external NP dose [i.e., daily intakes (DIs)] from urinary metabolite levels and thus enable a long needed cumulative exposure and risk assessment based on human biomonitoring (HBM) data. This way, HBM can complement specific source external exposure assessments and modeled exposures. − Measuring oxidized NP metabolites in HBM circumvents contamination issues that hampered parent NP analyses. − …”

Section: Introductionmentioning

confidence: 99%

Human Metabolism and Urinary Excretion Kinetics of Nonylphenol in Three Volunteers after a Single Oral Dose

Ringbeck

Belov

Schmidtkunz³

et al. 2021

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Nonylphenol (NP) is an endocrine-disrupting anthropogenic chemical that is ubiquitous in the environment. Human biomonitoring data and knowledge on internal NP exposure are still sparse, and its human metabolism is largely unknown. Therefore, in this study, we investigated human metabolism and urinary excretion of NP. Three male volunteers received a single oral dose of 1 mg 13 C 6 -labeled NP (10.6−11.7 μg/kg body weight). Consecutive full urine voids were collected for 48 h. A metabolite screening identified nine ring-and/or side chain-oxidized metabolites. We chose the most promising hits, the alkyl chainoxidized metabolites hydroxy-NP (OH-NP) and oxo-NP, for quantitative investigation next to the parent NP. For this purpose, we newly synthesized specific n − 1-oxidized monoisomeric analytical standards. Quantification of the polyisomeric metabolites was performed via online-solid phase extraction-LC-MS/MS with stable isotope dilution using a previously published consensus method. Alkyl chain hydroxylation (OH-NP) constituted the major metabolism pathway representing 43.7 or 62.2% (depending on the mass transition used for quantification) of the NP dose excreted in urine. The urinary excretion fraction (F UE ) for oxo-NP was 6.0 or 9.3%. The parent NP, quantified via an analogous isomeric 13 C 6 -NP standard, represented 6.6%. All target analytes were excreted predominately as glucuronic acid conjugates. Excretion was rather quick, with concentration maxima in urine 2.3−3.4 h after dosing and biphasic elimination kinetics (elimination half-times first phase: 1.0−1.5 h and second phase: 5.2−6.8 h). Due to its high F UE and insusceptibility to external contamination (contrary to parent NP), OH-NP represents a robust and sensitive novel exposure biomarker for NP. The novel F UE s enable to robustly back-calculate the overall NP intakes from urinary metabolite levels in population samples for a well-informed cumulative exposure and risk assessment.

show abstract

German Environmental Specimen Bank: 24-hour urine samples from 1999 to 2017 reveal rapid increase in exposure to the para-phthalate plasticizer di(2-ethylhexyl) terephthalate (DEHTP)

Cited by 47 publications

References 43 publications

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

Maternal Phthalates Exposure and Blood Pressure during and after Pregnancy in the PROGRESS Study

Human Metabolism and Urinary Excretion Kinetics of Nonylphenol in Three Volunteers after a Single Oral Dose

Contact Info

Product

Resources

About