Individual and combined developmental toxicity assessment of bisphenol A and genistein using the embryonic stem cell test in vitro.
The potential developmental toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years. In this study, two typical environmental oestrogen, namely, bisphenol A (BPA) and genistein (GEN) were investigated for potential embryotoxicity using the embryonic stem cell test model. Afterwards, a 4×4 full factorial design and the estimated marginal means plot were performed to assess the combined effects of these two compounds. According to the linear discriminant functions and classification criteria, bisphenol A and genistein were classified as weakly embryotoxic and strongly embryotoxic respectively. As for combined effects, the overall interaction between BPA and GEN on embryonic stem cells (ESCs) differentiation was synergistic at low dosages, however, on ESCs and 3T3 cell proliferation, the predominate action was additive. Considering the actual daily intake of these chemicals, it is concluded that BPA alone might not have adverse reproductive or developmental effects on human being. However, given that BPA and GEN do have synergistic effect at low concentration, they may disturb normal embryo development together, which could result in birth defect and behavioral alterations later in life.
Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
Dan
D
Kong
Lina
L
Xing
Ran
R
Liu
Jianjun
J
Jiang
Wanyi
W
Wang
Lanqin
L
Shang
Xuetao
X
Wei
Weidong
W
Hao
D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D041702:BALB 3T3 Cells; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects; D019833:Genistein / Q000633:toxicity*; D016014:Linear Models; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D019833:Genistein; D010636:Phenols; D013723:Teratogens; C006780:bisphenol A; D000098826:Bisphenol A Compounds
5-FU; 5-Fluorouracil; Bisphenol A; Combined effect; EBs; ECETOC; ECVAM; EEDs; EEs; ER; ES; EST; Embronic stem cell test; Embryotoxicity; European Center for the Validation of Alternative Methods; European Centre for Ecotoxicology and Toxicology of Chemicals; GEN; Genistein; LB; LIF; LOAEL; MB; MM; NEAA; NOAEL; NTP; National Toxicology Program; PG; WEC; embryonic bodies; embryonic stem cell test; embryonic stem cells; environmental endocrine disruptors; environmental estrogens; estrogen receptors; genistein; leukaemia inhibitory factor; limb bud; lowest observed adverse-effect level; micromass culture; midbrain; no-observed adverse-effect level; none essential amino acid; penicillin G sodium; whole embryo culture