The urinary metabolites of DINCH® have an impact on the activities of the human nuclear receptors ERα, ERß, AR, PPARα and PPARγ.
Toxicol Lett
; 287: 83-91, 2018 May 01.
Article
em En
| MEDLINE
| ID: mdl-29421333
ABSTRACT
DINCH® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH®, there are almost no toxicological data available regarding its primary and secondary metabolites. The present study aimed at the characterization of potential endocrine properties of DINCH® and five DINCH® metabolites by using reporter gene assays to monitor the activity of the human nuclear receptors ERα, ERß, AR, PPARα and PPARγ in vitro. DINCH® itself did not have any effect on the activity of these receptors whereas DINCH® metabolites were shown to activate all these receptors. In the case of AR, DINCH® metabolites predominantly enhanced dihydrotestosterone-stimulated AR activity. In the H295R steroidogenesis assay, neither DINCH® nor any of its metabolites affected estradiol or testosterone synthesis. In conclusion, primary and secondary DINCH® metabolites exert different effects at the molecular level compared to DINCH® itself. All these in vitro effects of DINCH® metabolites, however, were only observed at high concentrations such as 10⯵M or above which is about three orders of magnitude above reported DINCH® metabolite concentrations in human urine. Thus, the in vitro data do not support the notion that DINCH® or any of the investigated metabolites may exert considerable endocrine effects in vivo at relevant human exposure levels.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plastificantes
/
Receptores Androgênicos
/
Ácidos Cicloexanocarboxílicos
/
PPAR alfa
/
PPAR gama
/
Receptor alfa de Estrogênio
/
Receptor beta de Estrogênio
/
Ácidos Dicarboxílicos
/
Estrogênios
/
Disruptores Endócrinos
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article