Comparative toxicity, oxidative stress and endocrine disruption potential of plasticizers in JEG-3 human placental cells. (February 2017)

• Record Type: Journal Article
• Authors: Pérez-Albaladejo, Elisabet; Fernandes, Denise; Lacorte, Silvia; Porte, Cinta
• Is Part Of: Toxicology in vitro. Volume 38(2017)
• Page Start: 41
• Page End: 48
• Publication Date: 2017-02
• Subjects: P450 aromatase -- ROS generation -- JEG-3 cells -- Bioavailability -- Plasticizers; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.11.003
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Plasticizers are suspected to be toxic and/or to modulate or disrupt the endocrine system of humans and to cross the placental barrier, being embryonic and fetal development a particularly vulnerable period. This work investigates the comparative toxicity and ability to interfere with the synthesis of steroids and to generate reactive oxygen species (ROS) of a selected number of plasticizers, including bisphenol A (BPA), nonyl- (NP) and octylphenol (OP), benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), di(2-ethylhexyl)phthalate (DEHP) and dimethyl phthalate (DMP), in the human placenta JEG-3 cells. Moreover, the bioavailability of chemicals in culture medium has been investigated. After 24 h exposure, OP and NP showed the highest cytotoxicity (EC50 : 36–40 μM) followed by BPA (138–219 μM), whereas no significant toxicity was observed for phthalates. Notwithstanding, BBP and DBP significantly decreased P450 aromatase activity (experimental IC50 : 14–15 μM), while NP and OP (20 μM) increased the activity. Overall, this study evidences the differential toxicity and ability to modulate placental aromatase activity of some of the compounds nowadays used as plasticizers, and highlights the need of an accurate determination of the bioavailability of chemicals to improve the sensitivity of in-vitro tests. Highlights: Alkylphenols increased P450 aromatase activity in human placental cells JEG-3. The low bioavailability masked the endocrine disrupting potential of BBP and DBP. NP, OP and BPA generated reactive oxygen species in JEG-3 cells.