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Journal articles
In vitro and in silico approach to study the hormonal activities of the alternative plasticizer tri-(2-ethylhexyl) trimellitate TEHTM and its metabolites
Abstract : Tri-(2-ethylhexyl) trimellitate (TEHTM) is a plasticizer for polyvinyl chloride (PVC) material used in medical devices. It is
an alternative to di-(2-ethylhexyl) phthalate (DEHP), a well-known reprotoxic and endocrine disruptor. As plasticizers are
known to easily migrate when in contact with fatty biological fluids, patient exposure to TEHTM is highly probable. However,
there is currently no data on the potential endocrine-disrupting effects of its human metabolites. To evaluate the effects of
TEHTM metabolites on endocrine activity, they were first synthesized and their effects on estrogen, androgen and thyroid
receptors, as well as steroid synthesis, were investigated by combining in vitro and in silico approaches. Among the primary
metabolites, only 4-MEHTM (4-mono-(2-ethylhexyl) trimellitate) showed agonist activities on ERs and TRs, while three
diesters were TR antagonists at non-cytotoxic concentrations. These results were completed by docking experiments which
specified the ER and TR isoforms involved. A mixture of 2/1-MEHTM significantly increased the estradiol level and reduced
the testosterone level in H295R cell culture supernatants. The oxidized secondary metabolites of TEHTM had no effect on
ER, AR, TR receptors or on steroid hormone synthesis. Among the fourteen metabolites, these data showed that two of them
(4-MEHTM and 2/1-MEHTM) induced effect on hormonal activities in vitro. However, by comparing the concentrations of
the primary metabolites found in human urine with the active concentrations determined in bioassays, it can be suggested that
the metabolites will not be active with regard to estrogen, androgen, thyroid receptors and steroidogenesis-mediated effects.
https://hal-agrosup-dijon.archives-ouvertes.fr/hal-03546832
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Submitted on : Friday, January 28, 2022 - 10:49:47 AM
Last modification on : Friday, May 20, 2022 - 9:06:21 AM
Contributor : Institut Agro Dijon Connect in order to contact the contributor
Submitted on : Friday, January 28, 2022 - 10:49:47 AM
Last modification on : Friday, May 20, 2022 - 9:06:21 AM