In vitro and in silico hormonal activity ...
Document type :
Article dans une revue scientifique
DOI :
PMID :
30847963
Permalink :
Title :
In vitro and in silico hormonal activity studies of di-(2-ethylhexyl)terephthalate, a di-(2-ethylhexyl)phthalate substitute used in medical devices, and its metabolites.
Author(s) :
Kambia, Nicolas [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Severin, Isabelle [Auteur]
Farce, Amaury [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Moreau, Emmanuel [Auteur]
Dahbi, Laurence [Auteur]
Duval, Claire [Auteur]
dine, thierry [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Sautou, Valerie [Auteur]
Chagnon, Marie-Christine [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Severin, Isabelle [Auteur]
Farce, Amaury [Auteur]

Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Moreau, Emmanuel [Auteur]
Dahbi, Laurence [Auteur]
Duval, Claire [Auteur]
dine, thierry [Auteur]

Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Sautou, Valerie [Auteur]
Chagnon, Marie-Christine [Auteur]
Journal title :
Journal of applied toxicology . JAT
Abbreviated title :
J. Appl. Toxicol.
Publication date :
2019-03-08
ISSN :
1099-1263
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Plasticizers added to polyvinylchloride used in medical devices can be released into patients' biological fluids. The substitution of di-(2-ethylhexyl)phthalate (DEHP) by alternative plasticizers is essential but their ...
Show more >Plasticizers added to polyvinylchloride used in medical devices can be released into patients' biological fluids. The substitution of di-(2-ethylhexyl)phthalate (DEHP) by alternative plasticizers is essential but their safety must be demonstrated. DEHP, di-(2-ethylhexyl)terephthalate (DEHT) and their metabolites were investigated using level 2 Organization for Economic Co-operation and Development bioassays to screen for in vitro hormonal changes. Differences between the DEHP and DEHT metabolites were observed. Albeit weak, the hormonal activities of DEHT-derived metabolites, e.g., 5-OH metabolite of mono-(ethylhexyl)terephthalate (5-OH-MEHT), were detected and the results of docking experiments performed on estrogen receptor alpha and androgen receptor agreed with the biological results. A co-stimulation of human estrogen receptor alpha and human androgen receptor was also observed. With regard to steroidogenesis, a 16-fold increase in estrogen synthesis was measured with 5-OH-MEHT. Therefore, even if DEHT remains an interesting alternative to DEHP because of its low migration from medical devices, it seems important to verify that multi-exposed patients in neonatal intensive care units do not have urinary levels of oxidized metabolites, in particular 5-OH-MEHT, suggesting a potential endocrine-disrupting effect.Show less >
Show more >Plasticizers added to polyvinylchloride used in medical devices can be released into patients' biological fluids. The substitution of di-(2-ethylhexyl)phthalate (DEHP) by alternative plasticizers is essential but their safety must be demonstrated. DEHP, di-(2-ethylhexyl)terephthalate (DEHT) and their metabolites were investigated using level 2 Organization for Economic Co-operation and Development bioassays to screen for in vitro hormonal changes. Differences between the DEHP and DEHT metabolites were observed. Albeit weak, the hormonal activities of DEHT-derived metabolites, e.g., 5-OH metabolite of mono-(ethylhexyl)terephthalate (5-OH-MEHT), were detected and the results of docking experiments performed on estrogen receptor alpha and androgen receptor agreed with the biological results. A co-stimulation of human estrogen receptor alpha and human androgen receptor was also observed. With regard to steroidogenesis, a 16-fold increase in estrogen synthesis was measured with 5-OH-MEHT. Therefore, even if DEHT remains an interesting alternative to DEHP because of its low migration from medical devices, it seems important to verify that multi-exposed patients in neonatal intensive care units do not have urinary levels of oxidized metabolites, in particular 5-OH-MEHT, suggesting a potential endocrine-disrupting effect.Show less >
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Research team(s) :
Therapeutic innovation targetting inflammation
Submission date :
2019-05-17T13:14:48Z