Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study

Anteneh Desalegn; Tessa Schillemans; Eleni Papadopoulou; Amrit K. Sakhi; Line S. Haug; Ida Henriette Caspersen; Andrea Rodriguez-Carrillo; Sylvie Remy; Greet Schoeters; Adrian Covaci; Michelle Laeremans; Mariana F. Fernández; Susana Pedraza-Diaz; Tina Kold Jensen; Hanne Frederiksen; Agneta Åkesson; Bianca Cox; Shereen Cynthia D’Cruz; Loïc Rambaud; Margaux Riou; Marike Kolossa-Gehring; Antje Gerofke; Aline Murawski; Nina Vogel; Catherine Gabriel; Spyros Karakitsios; Nafsika Papaioannou; Dimosthenis Sarigiannis; Fabio Barbone; Valentina Rosolen; Sanna Lignell; Anna Karin Lindroos; Janja Snoj Tratnik; Anja Stajnko; Tina Kosjek; Žiga Tkalec; Lucia Fabelova; Lubica Palkovicova Murinova; Branislav Kolena; Sona Wimmerova; Tamás Szigeti; Szilvia Középesy; Annick van den Brand; Jan Paul Zock; Beata Janasik; Wojciech Wasowicz; Annelies De Decker; Stefaan De Henauw; Eva Govarts; Nina Iszatt

doi:10.1016/j.envint.2024.108931

Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study

Anteneh Desalegn
, Tessa Schillemans
, Eleni Papadopoulou
, Amrit K. Sakhi
, Line S. Haug
, Ida Henriette Caspersen
, Andrea Rodriguez-Carrillo
, Sylvie Remy
, Greet Schoeters
, Adrian Covaci
, Michelle Laeremans
, Mariana F. Fernández
, Susana Pedraza-Diaz
, Tina Kold Jensen
, Hanne Frederiksen
, Agneta Åkesson
, Bianca Cox
, Shereen Cynthia D’Cruz
, Loïc Rambaud
, Margaux Riou

Marike Kolossa-Gehring, Antje Gerofke, Aline Murawski, Nina Vogel, Catherine Gabriel, Spyros Karakitsios, Nafsika Papaioannou, Dimosthenis Sarigiannis, Fabio Barbone, Valentina Rosolen, Sanna Lignell, Anna Karin Lindroos, Janja Snoj Tratnik, Anja Stajnko, Tina Kosjek, Žiga Tkalec, Lucia Fabelova, Lubica Palkovicova Murinova, Branislav Kolena, Sona Wimmerova, Tamás Szigeti, Szilvia Középesy, Annick van den Brand, Jan Paul Zock, Beata Janasik, Wojciech Wasowicz, Annelies De Decker, Stefaan De Henauw, Eva Govarts, Nina Iszatt^*

^*Corresponding author for this work

Norwegian Institute of Public Health
University of Oslo
Karolinska Institute
Flemish Institute of Technological Research
University of Antwerp
University of Granada
Biosanitary Institute of Granada (ibs.GRANADA)
CIBEREHD and CIBERESP, Madrid, Spain.
Instituto de Salud Carlos III
Rigshospitalet
University of Rennes
Santé Publique France
German Environment Agency (UBA)
Aristotle University of Thessaloniki
Balkan Center
Environmental Health Engineering, Institute of Advanced Study, Pavia
University of Trieste
Friuli Venezia Giulia Region
Swedish Food Agency (SFA)
University of Gothenburg
Jožef Stefan Institute
Slovak Medical University
Constantine the Philosopher University
National Public Health Center
Rijksinstituut voor Volksgezondheid en Milieu
Nofer Institute of Occupational Medicine
Provincial Institute of Hygiene
Ghent University

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear.

Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents.

Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6–12 years, 2014–2021) and 2499 adolescents (10 studies, 12–18 years, 2014–2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects.

Results: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 % CI: −0.19, −0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 % CI: −0.14, −0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 % CI: −0.25, 0.03, per joint exposure quantile). Conclusion: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.

Original language	English
Article number	108931
Journal	Environment International
Volume	190
Number of pages	13
ISSN	0160-4120
DOIs	https://doi.org/10.1016/j.envint.2024.108931
Publication status	Published - Aug 2024

Keywords

Adolescent
Biological Monitoring
Body Mass Index
Child
Cross-Sectional Studies
Environmental Exposure/analysis
Environmental Pollutants/urine
Europe
Female
Humans
Male
Phthalic Acids/urine

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Desalegn, A., Schillemans, T., Papadopoulou, E., Sakhi, A. K., Haug, L. S., Caspersen, I. H., Rodriguez-Carrillo, A., Remy, S., Schoeters, G., Covaci, A., Laeremans, M., Fernández, M. F., Pedraza-Diaz, S., Jensen, T. K., Frederiksen, H., Åkesson, A., Cox, B., D’Cruz, S. C., Rambaud, L., ... Iszatt, N. (2024). Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study. Environment International, 190, Article 108931. https://doi.org/10.1016/j.envint.2024.108931

@article{75389a22cc0a448fb3c232bcf42efd77,

title = "Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study",

abstract = "Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6{\textendash}12 years, 2014{\textendash}2021) and 2499 adolescents (10 studies, 12{\textendash}18 years, 2014{\textendash}2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. Results: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 \% CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 \% CI: −0.19, −0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 \% CI: −0.14, −0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 \% CI: −0.25, 0.03, per joint exposure quantile). Conclusion: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.",

keywords = "Adolescent, Biological Monitoring, Body Mass Index, Child, Cross-Sectional Studies, Environmental Exposure/analysis, Environmental Pollutants/urine, Europe, Female, Humans, Male, Phthalic Acids/urine",

author = "Anteneh Desalegn and Tessa Schillemans and Eleni Papadopoulou and Sakhi, \{Amrit K.\} and Haug, \{Line S.\} and Caspersen, \{Ida Henriette\} and Andrea Rodriguez-Carrillo and Sylvie Remy and Greet Schoeters and Adrian Covaci and Michelle Laeremans and Fern{\'a}ndez, \{Mariana F.\} and Susana Pedraza-Diaz and Jensen, \{Tina Kold\} and Hanne Frederiksen and Agneta {\AA}kesson and Bianca Cox and D{\textquoteright}Cruz, \{Shereen Cynthia\} and Lo{\"i}c Rambaud and Margaux Riou and Marike Kolossa-Gehring and Antje Gerofke and Aline Murawski and Nina Vogel and Catherine Gabriel and Spyros Karakitsios and Nafsika Papaioannou and Dimosthenis Sarigiannis and Fabio Barbone and Valentina Rosolen and Sanna Lignell and Lindroos, \{Anna Karin\} and Tratnik, \{Janja Snoj\} and Anja Stajnko and Tina Kosjek and {\v Z}iga Tkalec and Lucia Fabelova and Murinova, \{Lubica Palkovicova\} and Branislav Kolena and Sona Wimmerova and Tam{\'a}s Szigeti and Szilvia K{\"o}z{\'e}pesy and \{van den Brand\}, Annick and Zock, \{Jan Paul\} and Beata Janasik and Wojciech Wasowicz and \{De Decker\}, Annelies and \{De Henauw\}, Stefaan and Eva Govarts and Nina Iszatt",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = aug,

doi = "10.1016/j.envint.2024.108931",

language = "English",

volume = "190",

journal = "Environment International",

issn = "0160-4120",

publisher = "Elsevier",

}

Desalegn, A, Schillemans, T, Papadopoulou, E, Sakhi, AK, Haug, LS, Caspersen, IH, Rodriguez-Carrillo, A, Remy, S, Schoeters, G, Covaci, A, Laeremans, M, Fernández, MF, Pedraza-Diaz, S, Jensen, TK, Frederiksen, H, Åkesson, A, Cox, B, D’Cruz, SC, Rambaud, L, Riou, M, Kolossa-Gehring, M, Gerofke, A, Murawski, A, Vogel, N, Gabriel, C, Karakitsios, S, Papaioannou, N, Sarigiannis, D, Barbone, F, Rosolen, V, Lignell, S, Lindroos, AK, Tratnik, JS, Stajnko, A, Kosjek, T, Tkalec, Ž, Fabelova, L, Murinova, LP, Kolena, B, Wimmerova, S, Szigeti, T, Középesy, S, van den Brand, A, Zock, JP, Janasik, B, Wasowicz, W, De Decker, A, De Henauw, S, Govarts, E & Iszatt, N 2024, 'Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study', Environment International, vol. 190, 108931. https://doi.org/10.1016/j.envint.2024.108931

Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study. / Desalegn, Anteneh; Schillemans, Tessa; Papadopoulou, Eleni et al.
In: Environment International, Vol. 190, 108931, 08.2024.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies

T2 - A cross-sectional multi-country study

AU - Desalegn, Anteneh

AU - Schillemans, Tessa

AU - Papadopoulou, Eleni

AU - Sakhi, Amrit K.

AU - Haug, Line S.

AU - Caspersen, Ida Henriette

AU - Rodriguez-Carrillo, Andrea

AU - Remy, Sylvie

AU - Schoeters, Greet

AU - Covaci, Adrian

AU - Laeremans, Michelle

AU - Fernández, Mariana F.

AU - Pedraza-Diaz, Susana

AU - Jensen, Tina Kold

AU - Frederiksen, Hanne

AU - Åkesson, Agneta

AU - Cox, Bianca

AU - D’Cruz, Shereen Cynthia

AU - Rambaud, Loïc

AU - Riou, Margaux

AU - Kolossa-Gehring, Marike

AU - Gerofke, Antje

AU - Murawski, Aline

AU - Vogel, Nina

AU - Gabriel, Catherine

AU - Karakitsios, Spyros

AU - Papaioannou, Nafsika

AU - Sarigiannis, Dimosthenis

AU - Barbone, Fabio

AU - Rosolen, Valentina

AU - Lignell, Sanna

AU - Lindroos, Anna Karin

AU - Tratnik, Janja Snoj

AU - Stajnko, Anja

AU - Kosjek, Tina

AU - Tkalec, Žiga

AU - Fabelova, Lucia

AU - Murinova, Lubica Palkovicova

AU - Kolena, Branislav

AU - Wimmerova, Sona

AU - Szigeti, Tamás

AU - Középesy, Szilvia

AU - van den Brand, Annick

AU - Zock, Jan Paul

AU - Janasik, Beata

AU - Wasowicz, Wojciech

AU - De Decker, Annelies

AU - De Henauw, Stefaan

AU - Govarts, Eva

AU - Iszatt, Nina

PY - 2024/8

Y1 - 2024/8

N2 - Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6–12 years, 2014–2021) and 2499 adolescents (10 studies, 12–18 years, 2014–2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. Results: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 % CI: −0.19, −0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 % CI: −0.14, −0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 % CI: −0.25, 0.03, per joint exposure quantile). Conclusion: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.

AB - Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6–12 years, 2014–2021) and 2499 adolescents (10 studies, 12–18 years, 2014–2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. Results: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 % CI: −0.19, −0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 % CI: −0.14, −0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 % CI: −0.25, 0.03, per joint exposure quantile). Conclusion: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.

KW - Adolescent

KW - Biological Monitoring

KW - Body Mass Index

KW - Child

KW - Cross-Sectional Studies

KW - Environmental Exposure/analysis

KW - Environmental Pollutants/urine

KW - Europe

KW - Female

KW - Humans

KW - Male

KW - Phthalic Acids/urine

U2 - 10.1016/j.envint.2024.108931

DO - 10.1016/j.envint.2024.108931

M3 - Journal article

C2 - 39142134

AN - SCOPUS:85201115432

SN - 0160-4120

VL - 190

JO - Environment International

JF - Environment International

M1 - 108931

ER -

Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study

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