Comparative toxicity, oxidative stress and endocrine disruption potential of plasticizers in JEG-3 human placental cells.
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 24h exposure, OP and NP showed the highest cytotoxicity (EC50: 36-40μM) followed by BPA (138-219μM), whereas no significant toxicity was observed for phthalates. Notwithstanding, BBP and DBP significantly decreased P450 aromatase activity (experimental IC50: 14-15μM), while NP and OP (20μM) 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.
Environmental Chemistry Department, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona, Spain. Electronic address: ealqam@cid.csic.es.
Elisabet
E
Pérez-Albaladejo
Environmental Chemistry Department, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona, Spain.
Denise
D
Fernandes
Environmental Chemistry Department, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona, Spain.
Silvia
S
Lacorte
Environmental Chemistry Department, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona, Spain. Electronic address: cinta.porte@cid.csic.es.
Cinta
C
Porte
D001141:Aromatase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D010795:Phthalic Acids / Q000633:toxicity*; D010920:Placenta / Q000166:cytology; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism
D052244:Endocrine Disruptors; D010636:Phenols; D010795:Phthalic Acids; D010968:Plasticizers; D017382:Reactive Oxygen Species; D001141:Aromatase
Bioavailability; JEG-3 cells; P450 aromatase; Plasticizers; ROS generation