{
  "fields": [{"id":"_id","type":"int"},{"id":"Chemical","type":"text"},{"id":"PMID","type":"numeric"},{"id":"Author,  year","type":"text"},{"id":"Study type","type":"text"},{"id":"Species","type":"text"},{"id":"Dose range","type":"text"},{"id":"Dosing/incubation timing","type":"text"},{"id":"Summary of findings","type":"text"}],
  "records": [
    [1,"2,3,7,8-Tetrachlorodibenzo-p-dioxin",19969063,"Zordoky, 2010","in vitro","H9c2","1, 5, 10, 20 nm","48h","No decrease in cell viability at 1 - 20 nM (98% compared to control). Significant induction of the hypertrophic marker ANP by 2.5-fold and BNP by 3-fold."],
    [2,"2,3,7,8-tetrachlorodibenzo-p-dioxin",15635151,"Antkiewicz, 2005","in vivo","Zebrafish","1 ppb","1h exposure, up to 96 hpf.","Pericardial effusion, altered looping, reduced blood flow at 72h. Ventricles became more compact, elongation of atria. Functional deficits in the developing hearts, including blood regurgitation and ventricular standstill at 120h. Sig. reduction in heart tissue volume, and in the total number of CMs."],
    [3,"3,3',4,4',5-pentachlorobiphenyl",18660518,"Grimes, 2008","in vivo","Zebrafish","7.5 μg/L","24h exposure, up to 72hpf","Reduced cell number and size in ventricular myocardium. Severely dysmorphic heart with a reduced bulbus arteriosus and abnormal atrioventricular and outflow valve formation in 90% of embryos. "],
    [4,"3,3',5,5'-tetrabromobisphenol A",24596333,"Yang, 2015","in vivo","Zebrafish","0.05, 0.1, 0.5, 1 mg/L","96h","Malformation, blood flow disorders, pericardial effusion, and spawn coagulation rates increased, survival decreased significantly after exposure to 0.5 and 1.0 mg. Induced ROS production dose-dependently. Cardiomyocyte apoptosis and induced expression of P53, Bax, and Caspase9. Bcl2 was down-regulated."],
    [5,"4-Fluoroamphetamine",31526813,"Zwartsen, 2019","in vitro","hiPSC-CMs","0.01, 0.1, 1, 10, 100, 300, 1000 μM","2-30 min, 24h","Decreased the spike amplitude at 100 μM. Decreased beat rate at 300 µM. Prolonged FPDc concentration-dependently. No sig. effect on cell viability."],
    [6,"5-fluorouracil",25034007,"Eskandari, 2014","in vitro","ARVMs","15 µM","1-3h","Reduced cell viability (65-75% of control), and 2-fold increase in ROS formation after 3h at 15 µM. Sig. reduced GSH/GSSG. Induced mitochondrial membrane potential (MMP) collapse. Sig. increase in caspase 3 activity."],
    [7,"5-fluorouracil",30634681,"Oliveira, 2019","in vitro","H9c2","0.13 - 5 µM","24h, 48h","Reduced cell viability at 48h: 5 µM (89.52 ± 5.38%), 2.5 µM (91.69 ± 5.43%), 1 µM (95.00 ± 6.51%) and 0.5 μM (93.89 ± 5.19%) compared to control (100%)."],
    [8,"5-fluorouracil",30862114,"Mendes, 2019","in vitro","H9c2","50 µM","48h","Reduced cell viability, both in MTT assay (93.7 ± 4.4%) and in NR uptake assay (86.6 ± 5.4%) compared to control (100%)."],
    [9,"5-fluorouracil",24704391,"Lamberti, 2014","in vitro","H9c2","400 µM","72h","Reduced cell viability to 50%. Increased Tbars and NO2- levels."],
    [10,"5-fluorouracil",25671635,"Focaccetti, 2015","in vitro","HCMs","10 nM to 1mM","96h","10 μM or higher concentrations exerted cytostatic effects, lower concentrations of 5-FU did not influence cell proliferation significantly. >1 μM significantly compromised cell membrane integrity. dose- and time-dependent generation of ROS in low doses (<10 µM). Dose dependent statistically significant increase in the percentage of senescent cells compared to control."],
    [11,"5-fluorouracil",1580574,"Millart, 1992","in and ex vivo","Rat perfused heart","1 mg/L for 80 minutes. 50 mg/kg.","80 mins (perf.) or 5 days","No differences in contractility. Consistent increase in oxygen consumption associated with a decrease in the fractional extraction of oxygen. Pretreatment of rats led to decrease in inotropism. Mean coronary flow was consistently increased, CK Leakage did not differ."],
    [12,"5-fluorouracil",35101590,"Li, 2022","in vivo","Mice","15, 30, 60 mg/kg","7 days","5-FU-induced cardiotoxicity was related with iron transport, oxidative stress and ferritinophagy in vivo: Impaired LV function with decrease of EF, FS, CO. LVID and LVAW was increased. Increased LDH and CK blood levels. MDA levels (lipid peroxidation) were 8-22 fold higher. Increased Fe2+ and decreased GSH. Lower GPX4 expression. Smaller, crumpled and broken mitochondria. Protein level of Nrf2, NQO1 and GPX4 was downregulated while the protein levels of p53 were upregulated. Decreased expression of LC3."],
    [13,"5-fluorouracil",35101590,"Li, 2022","in vitro","H9c2","2.5, 5, 10 µM","48h","Reduced cell viability under 50% at doses >5 µM. Increased Fe2+ levels. Increased ROS levels. Reduced mito activity. Protein expression levels of Nrf2, NQO1, LC3, GPX4 were inhibited, p53 and TfR were elevated."],
    [14,"Aconitine",30233701,"Zhang, 2018","in vitro","hiPSC-CMs","0.125, 0.25, 0.5, 1, 2, 4, 8 µM","2h, 6h, 24h","Reduced cell viability (% of control): 2h: ±90% at 8 µM. 6h: ±70% at 8 µM. 24h: ±70% at 0.25 µM, ±30% at 4 µM. Increased beating rate within 30 min: 3.7-fold at 0.25 µM, 7.3-fold at 3.0 µM. Increased caspase-3 and 9"],
    [15,"Aconitine",30410440,"Ma, 2018","in vitro","H9c2","0.01 - 50 μM","24h","Reduced cell viability dose dependent (IC50 32 µM). Sig. increase of the MDA level at 10 µM, increased ROS, LC3-II, Beclin-1-mRNA, cleaved caspase-3, and [Ca2+]i. Decreased ΔΨ causing membrane depolarization. Increased mRNA expression levels of DHPR, SCN5A and RyR2."],
    [16,"Aconitine",31657084,"Peng, 2020","in vitro","H9c2","0 - 100 µM","12, 24, 36, 48, 72, 96h","Reduced cell viability and increased ROS at 1 µM (24h). Increased TNFα, FADD, and cytochrome C and the cleavage of caspase-3 and -8. Decreased Bcl-2. Stimulation of RIPK and NLRP3, caspase 1 and IL-1B cleavage."],
    [17,"Aconitine",31975431,"Li, 2020","in vivo","Zebrafish","2, 8 µM","12, 24, 36, 48h","Sig. decreased heart rate at low dose, inhibition of contraction. Bioinformatics relates cardiotoxicity to regulation of Ca2+ signals and the p38 mitogen-activated protein kinase (MAPK) signalling pathway. 8 μm sig. increased the expression levels of cacna1c, RYR2, ATP2a2b, p38, caspase 3, Bax, and TnC at 12h, but decreased at 36 and 48h."],
    [18,"Aconitine",31975431,"Li, 2020","in vitro","H9c2","1.5, 4.5 mM","30m","[Ca2+]i oscillation. Decreased expression levels of TnT and Bcl-2, increased caspase 3 and Bax dose dependently."],
    [19,"Aconitine",34369901,"Zhao, 2021","in vitro","H9c2","0 - 100 µM","24h","Reduced cell viability (% of control): ± 90% at 5uM, ±80% at 10 µM, dose dependent decrease. Increased LDH release, CK-MB levels, and AST activity. Increased production of NO. Increased ROS and [Ca2+]i. Upregulated Bax and Cleaved-caspase-3 and downregulated expression of Bcl-2. SOD, Na+/K+-ATPase, and Ca2+-ATPase levels were significantly decreased (P < 0.01) and MDA production was markedly increased."],
    [20,"Aconitine",24840785,"Sun, 2014","in vivo","Rats","1,46 mg/kg/day for 10 days","3 or 6 days after last dose","Ventricular tc and premature beats. Severe myocardial damage. RyR and NCX protein levels increased. SERCA decreased. upregulated P53, BAX, caspase-9, and caspase-3, downregulated BCL-2. Ca2+ overload through activation of L-type Ca2+ channels, causing arrhythmia. Apoptotic development via activation of P38 MAPK."],
    [21,"Aconitine",24840785,"Sun, 2014","in vitro","ARVMs","1 µM","0 - 7 min","Normal rhythm and diastolic function of ARVMs were disrupted by aconitine in 7 min in a time-dependent manner. Increased resting Ca2 + ratio, amplitude of Ca2 + ratio and amplitude/resting calcium in 4 min after 1 μM"],
    [22,"Aconitine",24840785,"Sun, 2014","in vitro","NRVMs","0.01, 0.04, 0.16, and 0.64 μM","10h","Reduced cell viability (% of control): 4 ± 3.76%, 87 ± 2.21%, 79 ± 2.43%, and 71 ± 5.64% with 0.01, 0.04, 0.16, and 0.64 μM aconitine, respectively. LDH levels increased to 422.98 ± 31.76, 485.39 ± 52.60, 539.06 ± 27.27, and 624.93 ± 14.31 U/L with 0.01, 0.04, 0.16, and 0.64 μM aconitine, respectively. CK content 2-fold increase, AST 1.4 fold."],
    [23,"Aconitine",18779382,"Wang, 2008","in vitro","H9c2","1, 3, 10 µM","0-15 s","Dose dependent inhibition of IKur."],
    [24,"Aconitine",34520828,"Wang, 2022","in vitro","H9c2","3.125–400 μM","24h","Reduced cell viability, sig. => 50 µM (% of control): ±90% at 50 µM, ±50% at 400 µM. Dose dependent release of LDH. Autophagosome activation. increased ROS. Aconitine induces autophagy by activating AMPK/ULK1 signalling pathway."],
    [25,"Amitriptyline",32219715,"Aygun, 2020","in vivo","Rats","100 mg/kg","single dose","Sig. increased heartbeat, QRS Complex duration, T wave duration, QT interval duration, and elevated ST segment amplitude. 457% increase in cardiac damaged tissue, 303% plasma cTnT level compared to control"],
    [26,"Amitriptyline",18845675,"Chopra, 2009","in vitro","Mouse VCMs","0 - 300 µM","0 - 2h","AMT increased the rate of spontaneous Ca2+ releases and decreased the SR Ca2+ content.  Intracellular [AMT] were approximately 5-fold higher than extracellular [AMT]. Activation of RyR2 channels and increased SR Ca2+ leak may contribute to AMT's proarrhythmic and cardiotoxic effects"],
    [27,"Amitriptyline",29239964,"Tsujikawa, 2018","in vivo","Guinea pigs","15 mg/kg","15 min","Depression of mean arterial pressure (mean difference 19 mmHg) and prolongation of QRS duration (-12 ms)."],
    [28,"Amitriptyline",27994924,"Hocaoglu, 2016","ex vivo","Rat perfused heart","55 µM","1h","The amitriptyline infusion significantly decreased LVDP, dp/dtmax and heart rate (HR) and significantly prolonged QRS duration."],
    [29,"Amphetamine",31526813,"Zwartsen, 2019","in vitro","hiPSC-CMs","0.01, 0.1, 1, 10, 100, 300, 1000 μM","2-30 min, 24h","Decreased spike amplitude at 100 μM. Decreased beat rate at 300 µM. Prolonged FPDc concentration-dependently. No sig. effect on cell viability."],
    [30,"Amsacrine",3838387,"Kim, 1985","in vivo","Rats","3 - 12 mg/m2","Weekly, 13 weeks","Elevations of total serum creatine phosphokinase, creatine phosphokinase-MB fraction, aspartate aminotransferase, and lactate dehydrogenase levels at 12 mg/m2, suggesting myocardial damage; however, there was no associated pathologic evidence of cardiotoxicity."],
    [31,"Amsacrine",3839172,"Merkin, 1985","ex vivo","Rat perfused heart","1.5 - 2.5 µg/mL","Perfusion","Acute moderate negative inotropic effect. 90% effect (25% decrease in developed force compared to the control) was observed at drug concentration of 1.5 μg/ml. The refractory period (as measured by stimuli of twice diastolic threshold intensity) increased progressively as the drug concentration was increased (up to 2.5 μg/ml)."],
    [32,"Arsenic trioxide",23161055,"Vineetha, 2013","in vitro","H9c2","5, 7.5 and 10 μM","Analysis 48h after single dose","Reduction in cell viability: 10% at 5 µM, 23% at 7.5 µM, 35% at 10 µM reduction compared to controls."],
    [33,"Arsenic trioxide",34037972,"Vineetha, 2021","in vitro","H9c2","5 µM","Analysis 24h after single dose","ATO caused Ca2+ overload resulting in elevated expression of calcineurin and its downstream transcriptional effector NFATc causing the release of cytokines such as IL-2, IL-6, MCP-1, IFN-γ, and TNF-α"],
    [34,"Arsenic trioxide",29867492,"Zhang, 2021","in vitro","H9c2","2.5, 5, 10 μM","24h","Mitochondrial dysfunction: mito structural damage, abnormal mPTP opening, increased ROS production, decreased ATP content."],
    [35,"Arsenic trioxide",26815588,"Khoei, 2016","in vitro","H9c2","0.5, 1, 2 µM","24h, 48h, 72h","Reduced cell viability compared to control (MTT-assay). 0.5uM: 80% at 24h, 70% at 48h, 60% at 72h. 1uM: 70% at 24h, 60% at 48h, 50% at 72h. 2uM: 50% at 24h, 45% at 48h, 40% at 72h. ROS generation increase up to 150% at 2uM. DNA synthesis reduced to 20% compared to control at 2uM. Caspase-3 150% at 2uM. Sig increase in apoptosis markers BAX and PUMA at 2uM. Sig decrease in NF-kB (70%) at 2 µM."],
    [36,"Arsenic trioxide",30717322,"Wang, 2019","in vitro","ARVMs","100 µM","20 minutes","Sig. increased sarcomere-shortening amplitude, ±dL/dt, TR90 and TPS, severely impaired cardiomyocyte contractile function, increase in resting Ca2+ ratio, Ca2+ transient amplitudes, ±d [Ca2+]/dtmax, the time to 50% peak [Ca2+]i, and the [Ca2+]i transient decay rate, reduced SERCA, SERCA2a and PLB activity compared to controls."],
    [37,"Arsenic trioxide",26886836,"Varghese, 2017","in vitro","H9c2","10 µM","24h","Reduced cell viability (MTT, 80% ), increased LDH release (160%), sig. increased lipid peroxidation and cellular Ca2+ levels. Sig. Alterations in ∆Ψm (JC-1 staining)."],
    [38,"Arsenic trioxide",28092839,"Yu, 2017","in vitro","H9c2","4 µM","24h","Reduced cell viability (MTT, 79%), cell injury deteriorated at ATO dosing >4 µM. At 4 µM, reduction in the activities of SOD, CAT, and GSH-Px, therefore induction of oxidative stress. Sig. increase in caspase 3, 8 and 9. Sig. reduction in the Bcl-2/Bax protein ratio. Sig. reduction in p-Akt/Akt ratio."],
    [39,"Arsenic trioxide",18346055,"Zhao, 2008","in vitro","H9c2","2 - 10 µM","24h","Reduced cell viability (MTT, 70% at 10 µM), increased LDH release (only sig. at 10 µM). 10 µM dosing induced necrosis, lower doses did not. Dose dependent increase in ROS levels and [Ca2+]i. "],
    [40,"Arsenic trioxide",30090381,"Zhang, 2016","in vitro","ARVMs","25, 50, 100 µM","0 - 20 min","Abnormal cardiomyocyte contraction in a dose-dependent and time-dependent manner. Increased amplitude of sarcomere shortening, -dL/dtmax and +dL/dtmax, TR90, and time-to-peak shortening. Intracellular imbalance of calcium homeostasis. Inhibition of SERCA2a, activation of ER stress."],
    [41,"Arsenic trioxide",29297235,"Vineetha, 2018","in vitro","H9c2","10 µM","48h","Sig. reduction in total antioxidant capacity, increased [Ca2+]i, reduction in MMP, increased ROS production. Decrease in Nrf2 and Bcl2 gene expression. "],
    [42,"Arsenic trioxide",32096187,"Chen, 2020","in vitro","H9c2","10 µM","24h, 48h, 72h","Sig. reduced cell viability in time dependent manner."],
    [43,"Arsenic trioxide",28391263,"Zhang, 2017","in vitro","H9c2","2.5, 5, 10, 20, and 40 µM","24h","Reduced cell viability to 70% at 2.5 µM, 57.92% ± 2.86% at 10 µM, 30% at 40 µM. Sig. increased LDH at 10 µM. Sig. decreased ΔΨm at 10 µM. Decreased SOD, CAT, and GSH-Px activities at 10 µM. Up-regulated caspase-3 and caspase-9 expression levels, decreased Bcl-2 protein expression and increased Bax protein expression. Cyt-c release. "],
    [44,"Arsenic trioxide",23201927,"Wang, 2013","in vitro","H9c2","2, 4, 6, 8, and 10 μM","24h","Reduced cell viability in concentration dependent manner to 38.92 ± 0.36% at 10 µM. Sig increased LDH, PI staining (necrosis), caspase-3 activity (200% at 10 µM), and ROS levels (250% at 10 µM compared to control levels). Downregulation of Bcl-2 and Bcl-xl, upregulation of Bax."],
    [45,"Arsenic trioxide",19203718,"Raghu, 2009","in vitro","Rat CMs (freshly isolated)","30, 60 and 90 µM","24h, 48h, 72h","ATO exposure caused alteration in mitochondrial integrity, generation of ROS, calcium overload and apoptosis in cardiac cells in dose- and duration-dependent manner."],
    [46,"Arsenic trioxide",28094846,"Kopljar, 2017","in vitro","hiPSC-CMs","1, 3, 10 µM","4h, 12h, 24h, 48h, 72h","Significantly decreased beat area, beat rate and contraction velocity (starting from 4 to 12 h) at a concentration of 10 μM. At 3 μM, there was a trend towards a decreased CV at 72h. Modest increase in FABP3 at 72 h, accompanied by a decrease in NT-proBNP"],
    [47,"Arsenic trioxide",16597375,"Saad, 2006","in vivo","Rats","5 mg/kg/day","10 days","Sig. increases in serum CK-MB, GPx, LDH and AST. Reduced GSH content, increased MDA and total NOx."],
    [48,"Atropine",29123207,"Perera, 2017","in vitro","Mouse VCMs","10 nm","0-1s","Positive inotropic and chronotropic effects. 10 nM potentiated the β-AR-induced cAMP response. Inhibition of cAMP-specific phosphodiesterase PDE4, leading to increased [cAMP]i, leading to elevated heart rate and increased contractility."],
    [49,"Azidothymidine",33161113,"Zhao, 2020","in vitro","NRVMs","50 µM","0, 6, 12, 24, 36h","Reduced cell viability (to 0.8 at 36h) and MMP in time dependent manner. Increased Cle-casp-3, cyt-c, apaf-1. Decreased p-bad, bcl-2."],
    [50,"Azidothymidine",21461578,"Gao, 2011","in vitro","HCMs","1, 3, 10, 30, 100 µM","48h","Cell apoptosis and necrosis in a dose-dependent manner. Elevation of caspase-3 and -7 activity, PARP activity. Sig. increased ROS."],
    [51,"Azidothymidine",9895221,"Szabados, 1999","in vivo","Rats","50 mg/kg/day, 2 weeks","3 days - 6 months","RR, PR and QT intervals prolonged sig. after 1 wk. Mitochondrial structure distortion. Increased ROS formation (235% - 328%) in heart muscle tissue, significant (2.56-fold) increase in TBA, increased carbonyl content. Activation of PARP, decrease in NAD+. Free ATP/ADP decreased 4-fold."],
    [52,"Azidothymidine",1715447,"Lewis, 1991","ex vivo","Rat perfused heart","0.2 to 1.0 mg/mL; 29 to 102 mg/kg/day","21, 35, or 49 days","Marked and widespread cardiac mitochondrial swelling with fractured and disrupted cristae after 35 days of 1 mg/ml. Mitochondrial cytochrome b mRNA expression was depressed."],
    [53,"Berberine",29233041,"Zhang, 2018","in vitro","NRCMs","0.03 - 10 µM","24h","Beating rate and amplitude were totally inhibited at 10 µM. Irregular beating occurred at 0.3, 1.0, and 3.0 μM (1.5h)."],
    [54,"Beta-naphtoflavone",19969063,"Zordoky, 2010","in vitro","H9c2","10, 20, 30, 50 µM","48h","No decrease in cell viability up to 10 µM. 20 - 50 µM decreased cell viability in dose dependent manner. Significant induction of the hypertrophic marker ANP by 2-fold and BNP by 4-fold. Sig. induction of CYP1A1, CYP1B1, CYP2E1 and CYP2J3"],
    [55,"Bisphenol A",32144343,"Reventun, 2020","in vivo","Mice","0-50 mg/kg per day","4, 8, 16 weeks","Increased BP, HR, sig. prolonged QT interval and PR segment suggesting first degree AV block. Sig. impairment of contractility (decreased EF and FS). IVSd increased, cardiac hypertrophy. Hearts sig. enlarged. Perivascular fibrosis sig. increased after 8 weeks. Sig. increased TNF-a, CCL-2, -7, -12. Cardiac interstitial edema with sig. disarranged myocardial fibers, increased vascular permeability and leakage. Increased RIP 3 (necroptosis). Increased CamKII phosphorylation."],
    [56,"Bisphenol A",32144343,"Reventun, 2020","in vitro","MAECs, H9c2","0 -100 µM","24, 48, 72h","No effect on H9c2 cells. Reduced cell viability in MAECs time and dose dependently, increased RIP 3, leading to necroptosis in aortic endothelial cells."],
    [57,"Bisphenol A",34419494,"Hyun, 2021","in vitro","hiPSC-CMs","0 - 100 µM","24h","No sig. effect on cell viability or LDH. Sig. decrease in amplitude and field potential duration (±70% of control) at 30 µM. Decreased APA, dV/dtmax, APD50, and APD90 in a dose-dependent manner, suggesting effects on Na, Ca and K channels. Dose-dependent reduction of calcium transient frequency, intracellular calcium peak, beating rate, and amplitude of cardiac contraction."],
    [58,"Bisphenol A",33986332,"Kofron, 2021","in vitro","3D cardiac microtissue","1, 10, 100, 1000 nM","20 minutes","Sig. increase in APD metrics at 1 nM, but shortened APD metrics at higher concentrations."],
    [59,"Bisphenol A",31830493,"Cheng, 2020","in vitro","hESC-CMs","1000, 200, 8 ng/mL","72h","No effect on cell viability. Proliferation of cells was sig. enhanced. At 8 ng: sig. increased relative mitochondria number and cell area, sig. decreased mitochondrial area and ATP production, sig. reduction in MMP. Increased mitochondrial length and cells with fragmented mitochondria. Increased [Ca2+]c. "],
    [60,"Bisphenol A",25572651,"Jiang, 2015","in vivo","Rats","50 µg/kg per day","24 and 48 weeks","Myocardial hypertrophy, cardiomyocyte enlargement, impairment of cardiac function at 48w. Sig. reduced ATP production, dissipated MMP, declined mitochondrial respiratory complex activity at 24w. Decreased mitochondrial function, followed by cardiomyopathy. Decreased expression and hypermethylation of PGC-1a in heart tissue."],
    [61,"Bisphenol A",24140712,"Gao, 2013","in vitro","ARVMs","1 nM","5 min","Increased spontaneous excitation after repeated pacing. Increased frequency of Ca2+ sparks, spontaneous release of Ca2+ from the SR through RyRs. Increased contractility. Functional analysis showed that PKA but not CAMKII activation contributed to sarcoplasmic reticulum Ca2+ leak."],
    [62,"Bisphenol A",31713131,"Amin, 2019","in vivo","Rats","30 mg/kg per day","4 weeks","Sig. increase in mean values of serum copeptin level, histopathological changes in the form of dilated congested blood vessels and extensive collagen fiber deposition in the myocardium. Sig. increased TLR2 immunoreactions and DNA damage."],
    [63,"Bisphenol A",31126002,"Lombo, 2019","in vivo","Zebrafish","2000 and 4000 μg/L","24h","30% of exposed embryo displayed cardiac malformations. Overexpression of hand2, a crucial factor for cardiomyocyte differentiation, increased the expression of oestrogen receptor (esr2b), promoted an overexpression of a histone acetyltransferase (kat6a) and also caused an increase in histone acetylation, both mechanisms being able to act in synergy."],
    [64,"Bisphenol AF",32408210,"Gu, 2020","in vitro","HCMs","0.02, 0.2, 2, 20, 100, 200 mg/L","24h","Sig. reduced cell viability at 20 mg and above. Sig. decrease in CAT and SOD activity accompanied by an increase in MDA levels. Sig. increased [ROS]i. Elevation in apoptosis rate. Sig. decreased MMP."],
    [65,"Bisphenol AF",31981723,"Yang, 2020","in vitro","hESC-CMs","0, 8, 200 and 1000 ng/mL","48h","Cardiomyocyte hypertrophy due to increased production of reactive nitrogen species (RNS) via increased endothelial NO synthase (eNOS). Upregulation of mRNA levels of MYH7, Gata4, Mef2c, PLCB1, IP3R, and CAM."],
    [66,"Bisphenol F",34023961,"Cheng, 2022","in vitro","hESC-CMs","7 (35 nM), 140, 700, 140, 2800, and 5600 ng/mL","48h","Increased [Ca2+]c, which was most noticeable at low dose (35 nM) rather than at higher doses. At 35 nM, altered morphological parameters of mitochondria and sig. decreases in ATP production, representing CM hypertrophy. Enhanced calcineurin (Cn) activity and induced abnormal mitochondrial fission via the CnAβ-DRP1 signalling pathway. Excessive Ca2+ influx by disrupted L-type Ca2+ channel."],
    [67,"Bortezomib",20519734,"Nowis, 2010","in vivo","Rats","0.2mg/kg","3 times/week for 1 to 3 weeks","Left ventricular contractile dysfunction manifested by a significant drop in left ventricle ejection fraction"],
    [68,"Bortezomib",20519734,"Nowis, 2010","in vitro","H9c2","2.5, 5, 10, 20, 40 nM","24h","Reduced cell viability in a time- and dose-dependent manner observed at 5 - 10 nM concentrations."],
    [69,"Cadmium (Cd2+)",34255886,"Haverinen, 2021","in vitro","Rainbow trout CMs","10, 20, and 100 µM","5 min","Altered  ventricular APs in complex manner. Shortened ADP10, prolonged ADP50 and ADP90. Cd2+ reduced the density and slowed the kinetics of the Na+ current (INa) but left the inward rectifier K+ current (IK1) intact. Strong Cd2+-induced inhibition of the L-type calcium (Ca2+) current (ICaL)."],
    [70,"Cadmium chloride",29993192,"Shen, 2018","in vitro","hESC-CMs","0.1 - 100 µM","24h","Sig. reduced cell viability in dose dependent manner to ±50% at 100 µM. Sig. increased caspase-3 activity and ROS levels at 30 µM, increased apoptosis, cardiac sarcomeric disorganization, altered action potential profile and cardiac arrhythmias. Activated MAPK signalling pathway, suppression of P38 MAPK."],
    [71,"Cadmium chloride",33581611,"Zhao, 2021","in vivo","Swine","20 mg/kg diet","40 days","Myocardial conc. of CdCl2 was 0.147±0.011 mg/kg, 8.6-fold higher than control group. Apoptotic cells increased up to 4.1 fold. Activation of AHR, CAR and PXR, contributing to production of ROS. Restrained antioxidant capacity, causing oxidative stress. MAPK pathway including JNK, ERK and p38 was activated, triggering mitochondrial pathway apoptosis in myocardium."],
    [72,"Cadmium chloride",33626375,"Zhao, 2021","in vivo","Swine","20 mg/kg diet","40 days","Necrotic cell death and ion homeostasis imbalance in swine myocardium. Increased LXA4 content, inhibition of FPR2 expression, activated TGF-β pathway and suppressed Nrf2 pathway. Activation of the NF-κB pathway.  Increased expressions of necroptosis related-genes TNF-α, TNFR1, RIP1, RIP3 and MLKL."],
    [73,"Cadmium chloride",26182376,"Chen, 2015","in vitro","ARVMs","1 and 100 µM","4 or 12h","Increased mRNA levels of Grp78, Atf4 and Atf6 leading to dramatic endoplasmic reticulum (ER) stress and impaired energy homoeostasis. Inhibition of protein kinase B (AKT)/mTOR pathway."],
    [74,"Cadmium chloride",26462792,"Nazimabashir, 2015","in vivo","Rats","5 mg/kg per day","4 weeks","Sig. Increased cTnT & I, CK-MB, AST, ALT, ALP, and plasma TC, TG, PL and FFA. Increased oxidative stress, impaired mito function. TNF-α, NO, IL-6 and NF-κB subunit were increased sig. Expression of cytochrome C, caspase-3 were sig. Upregulated. Decreased Bcl-2 with increased Bax. Sig. decreased Nrf2. Degeneration and disruption of cardiac myofibers, wide cardiac fibrils spaces, cardiac inflammation and necrosis. Swelling of heart mitochondria with loss of cristae, irregular shape and sizes, vacuolization."],
    [75,"Cadmium chloride",9882592,"Limaye, 1999","in vitro","NRCMs","0.05 - 1 µM","0 - 60 min","Reduced cell viability sig. at 0.1 µM, beating stopped at 0.5 µM."],
    [76,"Carbachol",19159405,"Hussain, 2009","in vivo/ vitro","Rat cardiac muscle","10 µM","Unclear","Carbachol (10 µM) evoked a positive inotropic response only in muscles from rats with heart failure (not in healthy rat muscle)"],
    [77,"Carbachol",2790382,"Jakob, 1989","in vitro","human atrial heart muscle","10 µM","30 min","Carbachol evoked transient decreases of action potential duration and force of contraction in atrial heart tissue"],
    [78,"Chrysene",17112560,"Incardona, 2006","in vivo","Zebrafish","22 µM","Exp. between 6 and 72 hpf","Strong CYP1A induction (22-fold increase of mRNA), but no biological effects."],
    [79,"Cocaine",33668403,"Verma, 2021","in vitro","H9c2","0.1 - 10, 50, 100 µg/mL","72h","Reduced cell viability dose dependent. Increased ERK1-p44 and ERK2-p42 in first 24h. Dynamic remodelling of cytoskeleton, with changes in key cytoskeletal proteins (ERM,VASP) involved in mediating direct actin and plasma membrane/actin interactions."],
    [80,"Cocaine",18952886,"Fan, 2009","in vivo","Mice","15, 20, 25, 30 mg/kg, 3/day","14 days, 30 min after last injection","Sig. increased phosphorylated ERK1/2, p38 MAPK, and JNK (2.5-fold), increased p47phox (3.2-fold), Nox2 (2.34-fold). Sig. increased levels of ROS."],
    [81,"Cocaine",18952886,"Fan, 2009","in vitro","H9c2","0-100 µM","24h","Increased ROS production (5 µM 1.8-fold, 25uM 3-fold). Increased Nox2. Severe myocyte damage and cell death. Sig. increased ERK1/2 and p47phox."],
    [82,"Cocaine",12808488,"Henning, 2003","in vitro","ARVMs","0.1 - 10 µM","72h","1 µM increased myocyte protein content by 28±2%, caused a 45% increase in PKC ratio change."],
    [83,"Cocaine",16891908,"Henning, 2006","in vitro","ARVMs","0.1 - 10 µM","1, 10, 30, 60, 240, 480, or 1440 minutes","Translocation of CaMKII from cardiomyocyte soluble to particulate fractions (1 µM, 240 min). Increased total CM protein content by 29.2±3% at 5 µM, 20.5±3% at 1 µM. Increased B-MHC expression by 93% at 5 and 63% at 1 µM. Potentiation of peak calcium current. Increased [Ca2+]i 6-fold at highest dose."],
    [84,"Cocaine",16382175,"Lattanzio, 2005","in vitro","H9c2","0.1 - 10 mM","2-5 mins","Sig. Increased ROS production, MMP depolarization, [Ca2+]i increase."],
    [85,"Cocaine",16382175,"Lattanzio, 2005","in vivo","Rabbits","2mg/kg","30m","At 1 min after cocaine, the +MAX dP/dt had decreased, an indication of an impairment in the rate of contraction. At 5 min the MAX dP/dt had decreased, an indication of a reduction in the rate of relaxation."],
    [86,"Cocaine",8792843,"Yuan, 1996","in vitro","NRCMs","10^-5 - 10^-3 M","3 - 72h","Dose and time dependent increase in LDH leakage, decrease in ATP, reduced MMP."],
    [87,"Cocaine",8792843,"Yuan, 2000","in vitro","NRCMs","10^-5 - 10^-3 M","6, 12, 24h","Dose and time dependent increase in LDH leakage. Sig. decreased the mitochondrial respiratory control ratio at highest dose."],
    [88,"Cocaine",9455993,"Besse, 1997","in vivo","Rats","40 mg/kg per day","30m, 1, 2, 4h, 14-28 days","Left ventricular hypertrophy after 28d, 20% increase in the left to right ventricular weight ratio. T3 and T4 sig. decreased. Atrial natriuretic factor (ANF) increased, also in ventricular tissue."],
    [89,"Cocaine",1566279,"Welder, 1992","in vitro","ARCMs","10^-9 - 10^-3 M","1, 4, 24h","Morphological alterations included vacuolization, granulation and pseudopodia formation at 1h to highest doses. For all time points, the two highest doses sig. depressed contractility and induced LDH release. "],
    [90,"Cocaine",20702336,"Welder, 1988","in vitro","NRCMs","10^-7 - 10^-3 M","24h","Decrease in beating activity at 1h for highest doses 10^-5 -10^-3 M. Similar results were obtained at 24h. Morphological alterations at 10^-3 M. Vacuoles at 1h were replaced by dark granules within 24h. LDH release was sig. elevated at 10^-3 M for 24h."],
    [91,"Cocaine",8776273,"Bai, 1996","in vitro","Rat VCMs","50, 100, 150 µM","0 - 90 sec","Sig. decreased peak intracellular Ca2+ and cell-contraction rate in a dose-dependent manner. The K0.5 for the reduction of peak intracellular Ca2+ was 157.5 μM (calc.)."],
    [92,"Cocaine",31526813,"Zwartsen, 2019","in vitro","hiPSC-CMs","0.01, 0.1, 1, 10, 30, 100 μM","2-30 min, 24h","≥10 μM: beat rate and spike amplitude decreased by 44% and 51%, respectively, and the FPD(c) was prolonged ≥2-fold. ≥30 μM: quiescence, resulting in loss of signal from electrodes. No sig. effect on cell viability."],
    [93,"Cresyl diphenyl phosphate (CDP)",25661707,"Du, 2015","in vivo","Zebrafish","0.10, 0.50, 1.0 mg/L","72 hpf","Sig. Reduced heart rate at 0.1 mg. Pericardium edema and SV-BA distance extension, decreased number of cardiac muscle cells and thinner walls of ventricle and atrium at 0.1 mg. Disturbed expressions of transcriptional regulators, especially downregulation of BMP4, NKX2-5 and TBX5."],
    [94,"Daunorubicin",26279420,"Wu, 2015","in vitro","H9c2","1 µM","24h","Reduced cell viability (70.9 ± 2.6%) at 1 µM compared to control. Cell shrinkage, rounding, membrane blebbing. Degradation of cTnl and B-Tubulin. Increase in Annexin V from 3 to 21% vs control. Caspase-3 increase. Disturbance of MMP leading to cyt-c release and subsequent caspase-3 and 9 activation. Activation of ERKs (ratio of P-ERK to ERK was increased by 248%). Increases in phosphorylated ERK1/2, p53, and Bax protein content and  decreased Bcl-2."],
    [95,"Daunorubicin",21046361,"Vavrova, 2011","in vivo","Rabbits","3mg/kg","Weekly, 10 weeks","Heart failure evident from decreased left ventricular ejection fraction and release of cardiac troponins to circulation. GPx activity in cardiac tissue sig. increased."],
    [96,"Daunorubicin",21046361,"Vavrova, 2011","in vitro","H9c2","0.1 - 10 µM","24h","Significant dose dependent toxicity. TC50: 0.48 µM. Loss of MMP (ΔΨm, JC-1 staining) at 1 µM. Decrease in GSH (40%) at 1 µM."],
    [97,"Daunorubicin",17587482,"Adamcova, 2007","in vitro","NRVMs","0.1 - 3 µM","72h","Reduced cell viability (IC50 0.55 µM). Significant increase in LDH, cTnT and cTnI"],
    [98,"Daunorubicin",17587482,"Adamcova, 2007","in vivo","Rabbits","3mg/kg","Weekly, 10 weeks","Reduced left ventricular fractional shortening (FS). Sig. increase in cardiac troponin cTnT and cTnI"],
    [99,"Daunorubicin",16444662,"Mojzisova, 2006","in vitro","Rat CMs (freshly isolated)","40 µg/mL","24h, 48h","Reduced cell viability (38.6 ± 8.1% at 24h and 9.7 ± 4.1% at 48h). Increased LDH enzyme activity by 2-fold compared to control."],
    [100,"Daunorubicin",18803248,"Mojzisova, 2009","in vitro","H9c2","40 µg/mL","24h, 48h","Reduced cell viability (36.8 ± 7.3% at 24h and 19.8 ± 5.8% at 48h). Decreased Annexin V− (intact cell marker, 54.2 ± 7.4% compared to 98% in control cells). Increased Annexin V+ (early apoptosis marker, 45.4 ± 6.1% compared to 2.9 ± 0.5% in control cells)."],
    [101,"Daunorubicin",8808986,"Cusack, 1996","in vitro","Adult and old rat CMs (freshly isolated)","175 µM","210 min","Daunorubicin-induced decline in contractility (DS and dS/dt) was greater in old (24 - 28 months) compared to adult (6-9 months) myocardium (p < .02). Similarly, cardiac relaxation (90% relaxation time) was more impaired by daunorubicin in older preparations (p < 01). "],
    [102,"Daunorubicin",29039532,"Li, 2017","in vitro","H9c2","1 µM","24h","Reduced cell viability (MTT, ±50%). Sig. decrease in p-Akt/Akt ratio. Sig. increase in cleaved caspase-3/caspase-3 ratio. Sig. increase in [Ca2+]i."],
    [103,"Daunorubicin",35596909,"Cejas, 2022","in vitro","hiPSC-CMs","5 µM","14h","Reduced cell viability (down to 30.41 ± 19.73%)."],
    [104,"Decabrominated diphenyl ether",30802833,"Jing, 2019","in vivo","Rats","5, 50 and 500 mg/kg per day","28 days","congestion of intermuscular capillaries. At 500mg: severe fiber disruption with focal haemorrhagic areas between the muscle bundles, and nuclear condensation or dissolution and myocyte swelling. Sig. increased CK and LDH at 50 mg. Dose-dependent increase of ET-1 level. Increased TNF-a, IL-1B, IL-6, SOD, GSH-Px, MDA."],
    [105,"Decabromodiphenyl ethane",30802833,"Jing, 2019","in vivo","Rats","5, 50 and 500 mg/kg per day","28 days","No histological changes up to 50 mg. At 500 mg: congestion of intermuscular capillaries with mild disruption. No alteration of CK activity, sig. Increased LDH at 500 mg. Dose-dependent increase of ET-1 level. Increased TNF-a, IL-1B, IL-6, SOD, GSH-Px, MDA."],
    [106,"Di(2-ethylhexyl)phthalate ",22672789,"Posnack, 2012","in vitro","NRCMs","50-100 μg/mL","72h","Metabolic remodelling: upregulation of genes associated with fatty acid transport, esterification, mitochondrial import, and β-oxidation. Increased myocyte fatty acid-substrate utilization, oxygen consumption, mitochondrial mass, PPARα protein expression, and extracellular acidosis."],
    [107,"Di(2-ethylhexyl)phthalate ",29377175,"Tang, 2018","in vivo","Pregnant mice","250, 500, 1000 mg/kg per day","E6.5 to E14.5","Increased fetal cardiac development malformations (septal defects, ventricular myocardium noncompaction and cardiac hypoplasia) resulting from the inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARγ activation. "],
    [108,"Dieldrin",28385952,"Slade, 2017","in vivo","Zebrafish","0.03, 0.15 or 1.8 µg/g feed","21d","Activation of Akt/mTOR signalling and downregulation of lysosomal genes, participating in autophagy. Transcriptomics: fos and jun (cell proliferation regulators) were sig. dysregulated. Ace was increased 2-fold, oxytocin decreased 2-fold. Kcnj11l and kcnh2a increased. Increased IL-6, TNF-A. Decreased NF-kB, Ras. "],
    [109,"Doxorubicin",28300219,"Zhao, 2017","in vitro","hiPSC-CMs","1 nm - 100 µM","48h","Reduced cell viability (IC50 3.5 µM). Increased caspase-3 and DNA fragmentation. Release of cTnI. Dose-dependent increase in TNFR1, Fas, DR4, and DR5 at 450 nM. Increased caspase-3, 8 and FADD. TNF-related apoptosis inducing ligand (TRAIL) increase. Decrease in beating rate and amplitude."],
    [110,"Doxorubicin",26537877,"Chaudhari, 2016","in vitro","hiPSC-CMs","156 nm","48h, 144h","Reduced cell viability at 144h (±80%) but not at 48h indicating time dependent effect. Repeated doxorubicin exposure (144h) resulted in long-term arrhythmic beating in hiPSC-CMs. 84 genes related to cardiac functions, stress and apoptosis were deregulated sig."],
    [111,"Doxorubicin",21590773,"Budde, 2011","in vivo","Mice","20 mg/kg single dose i.p.","1, 3 and 5 days after injection","impaired cardiac function with decreased ejection fraction, diminished cardiac output, and decreased end-systolic pressure points. enhancement in P-gp protein expression levels of 180 ± 18% in doxorubicin-treated mice. significant upregulation of abcb1a (162 ± 15% of control) and abcb1b (418 ± 110% of control) mRNA transcripts after 3 days"],
    [112,"Doxorubicin",21590773,"Budde, 2011","in vitro","HL-1","10 - 1000 nM","24h, 48h","doxorubicin concentrations up to 333 nmol/L did not significantly alter the viability of adherent HL-1 cells."],
    [113,"Doxorubicin",34775319,"He, 2021","in vitro","NRCMs, H9c2","1 µM","48h","Reduced cell viability to 40% for NRCMs and H9c2. Sig. Increase in LDH (±10-fold compared to control). iron content of the Dox-treated group was significantly increased. PTGS2 expression was significantly increased, while GPX4 expression was decreased. mitochondria in Dox-treated NRCMs were severely distorted, with decreased cristae. expression of LC3/P62 slightly increased/decreased in NRCMs and H9C2 cells."],
    [114,"Doxorubicin",29133306,"Gupta, 2018","in vitro","hiPSC-CMs","0.1 µM","72h","Qki deletion in cardiomyocytes increased their sensitivity to doxorubicin, whereas overexpression inhibited doxorubicin-induced apoptosis. Mechanistically, Qki inhibits doxorubicin-mediated cardiotoxicity via regulating cardiac circular RNAs."],
    [115,"Doxorubicin",34525346,"Magdy, 2021","in vitro","hiPSC-CMs","0.01 - 100 µM","72h","SNP (rs2229774) in retinoic acid receptor-γ (RARG) is statistically associated with increased risk of anthracycline-induced cardiotoxicity. The hiPSC-CMs from patients with rs2229774 and who suffered doxorubicin-induced cardiotoxicity (DIC) are more sensitive to doxorubicin. The mechanism of this RARG variant effect is mediated via suppression of topoisomerase 2β (TOP2B) expression and activation of the cardioprotective extracellular regulated kinase (ERK) pathway."],
    [116,"Doxorubicin",34207549,"Adamczyk, 2021","in vitro","H9c2, hiPSC-CMs","5, 10 µM","90 min","Reduced cell viability (% of control): [H9c2: ±85% at 5uM, ±80% at 10 µM] [hiPSC-CMs: ±75% at 5 µM, ±65% at 10 µM]. Increased ROS production (±2-2.5 fold increase at 5-10 µM in H9c2, ±2-3 fold increase at 5-10 µM in hiPSC-CMs compared to controls). Significant increase in caspase 3/7 activity."],
    [117,"Doxorubicin",32487993,"Arai, 2020","in vitro","3D cardiac microtissue","10 µM","24h, 72h","Contractile force and beating rate of the cardiac constructs were evaluated by analysing changes in the movement of the needle tip and decreased dramatically 24h following DOX addition. Contraction of the cardiac construct completely ceased at 72h after DOX treatment"],
    [118,"Doxorubicin",28421296,"Chaudhari, 2017","in vitro","hiPSC-CMs","156 nM","48h, 144h","Impaired mitochondrial metabolism. Single exposure to DOX (48h) did not show alteration in the basal level of extracellular metabolites while repeated exposure to DOX (144h) caused reduction in the utilization of pyruvate and acetate, accumulation of formate, increased LDH release and reduced ATP levels compared to control culture medium. "],
    [119,"Doxorubicin",31231550,"McSweeney, 2019","in vitro","hiPSC-CMs","100, 500 nM. 1.5, 5 µM.","48h","Dose and time dependent decrease in cellular index: 0.75 at 500 nM, 0.55 at 1.5 µM, 0.45 at 5 µM (48h) compared to control (1.0 at 48h). No change at 100 nM. Further experiments were performed at 150 µM. Over a thousand genes were significantly dysregulated after 48h, mostly downregulation of genes pertained to cell cycle progression and cell division."],
    [120,"Doxorubicin",32075047,"Zhang, 2020","in vitro","hiPSC-CMs, AC16, H9c2","1 µM","24h","H9c2: dose dependent decrease in cell number, nuclear area, nuclear intensity, cell area, and an increase in calcium intensity and mitochondrial intensity (log curves available, EC50/IC50 all around 1 µM). 1 µM was selected for further experiments. Annexin V-was significantly increased at 1 μM Dox for 6h in AC16. Decreased rates of beating and amplitude, sig. upregulation of pro-BNP and IL6 in hiPSC-CMs, sig. downregulation of HDAC1, GATA4, and CTnI at 1uM Doxo."],
    [121,"Doxorubicin",31106979,"Cui, 2019","in vitro","hiPSC-CMs","2.5 µM","24h","Maturation decreased the cytotoxicity of DOX: day 30 hiPSC-CMs showed significantly reduced cell viability vs. day 60 group. DOX leads to more ROS in day 60 CMS due to increase in mitochondria. Higher concentration of topoisomerase IIa in day 30 CMs, which leads to more DNA damage."],
    [122,"Doxorubicin",26842497,"Chaudhari, 2016","in vitro","hiPSC-CMs","156 nM","48h, 144h","DOX in a range from 39 to 156 nM did not show a significant release of the cytotoxicity marker LDH compared to controls. DOX induced early deregulation of 14 miRNAs (10 up-regulated and 4 down-regulated) and persistent up-regulation of 5 miRNAs. Genes involved in cardiac contractile function. "],
    [123,"Doxorubicin",28456566,"Louisse, 2017","in vitro","hiPSC-CMs","150, 300 nM. 6, 12 µM.","Various","No effects on the beating rate and FPD at 6μm. Full stop of electrical act. and beating at 12μM, no effects on mitochondrial density and superoxide. Reduced cell survival and slightly altered mitochondrial membrane potential and mitochondrial calcium levels at 150 to 300 nM. Data available in sup."],
    [124,"Doxorubicin",32185414,"Karhu, 2020","in vitro","hiPSC-CMs","100, 300 nM. 1, 3 µM.","0 - 21 days","Reduced cell viability (<50%) at 1 and 3 µM, while 14-day treatment with 100 nM induced only 26% reduction in viability. Decreased DNA content. 4-day exposure to 100 nM induced a 3.1-fold increase (P < 0.001) in the percentage of cardiomyocytes positive for proBNP. 14 day exposure to 100 nM induced a 3.1-fold increase (P = 0.001) in the percentage of cells with active caspase-3/7."],
    [125,"Doxorubicin",28967302,"Takeda, 2017","in vitro","hiPSC-CMs","0.1, 1, 2, 5, 10 µM","24h","Sig. increase in LDH release: 5 μM (145% ± 48%) and 10 μM (228% ± 97%). Reduced viability: 2 μM (88.4% ± 13%), 5 μM (75.3% ± 9.0%), and 10 μM (58.3% ± 10%)"],
    [126,"Doxorubicin",28094846,"Kopljar, 2017","in vitro","hiPSC-CMs","1, 3, 10 µM","4h, 12h, 24h, 48h, 72h","Affected beat rate, beat area, and contraction velocity at 1 μM with higher concentrations eventually leading to beating arrest. Strong increase in FABP3 and cTnI levels at each time point. Down-regulation of TNNI3, GJA1 and GJC1"],
    [127,"Doxorubicin",34536182,"Atum, 2022","in vitro","hiPSC-CMs","2 µM","24h","Reduced cell viability (±40%). Reduced total NO level (±50%). Increased ROS production (H2O2, ±175%). Decreased expression of UCP2 mRNA and eNOS mRNA. Increased expression of miR-24."],
    [128,"Doxorubicin",34931757,"Berecz, 2022","in vitro","hiPSC-CMs","0, 1, 3, 10 µM","48h","Activation of caspase 3/7, mitochondrial depolarization, and nuclear fragmentation were increased in concentration-dependent manner. However, necrosis (TO-PRO-3) was only induced in up to 7% of hiPSC-CMs in response to 3 μM doxorubicin."],
    [129,"Doxorubicin",30634681,"Oliveira, 2019","in vitro","H9c2","0.13 - 5 µM","24h, 48h","Reduced cell viability at 48h (1 µM: 71.93 ± 10.49%, 2.5 µM: 68.10 ± 7.89% and 5 μM: 67.95 ± 8.01%) compared to control (100%). Significant impairment of lysosomal neutral red uptake. DOX 1 µM reduced mitochondrial membrane potential to 34.10 ± 10.48% at 48h."],
    [130,"Doxorubicin",30862114,"Mendes, 2019","in vitro","H9c2","1 µM","48h","Reduced cell viability, both in MTT assay (50.2 ± 3.8%) and in NR uptake assay (31.3 ± 9.3%) compared to control (100%). "],
    [131,"Doxorubicin",29913208,"Damiani, 2018","in vitro","H9c2","0.1, 1 µM","24h","Reduced cell viability (% of control): ±75% at 0.1 µM, ±50% at 1 µM. 1 µM induced sig. necrosis. Reduced ATP by half (1 µM). Decreased MMP. Increased ROS at 0.1 µM."],
    [132,"Doxorubicin",26660439,"Hasinoff, 2016","in vitro","NRVMs","0 - 100 µM","6h, 24h, 48h, 72h","After 6h, MMP was reduced sig. (90% of control) at 0.05 µM. 15% LDH increase over control at 0.8 µM (72h)"],
    [133,"Doxorubicin",32336319,"Ryu, 2020","in vivo/ vitro","Rats, NRCMs, hESC-CMs","2x 15 mg/kg, 5 µM","24h","Damaged myocytes with cell shrinkage, nuclear pyknosis, karyolysis, densed cyto-plasm, and vacuolation in rat hearts. Deterioration of α-actinin-2 arrangement. Increased apoptotic index by 10% in rats, 60-80% in NRCMs, 50-60% in hESC-CMs. Increase of oxidative stress indicators and gene levels of β-MHC, ANP, BNP, Spp1, IL-1β, IL-6, TLR2, TLR4, TNF-α, Bax/Bcl-2, and Casp9 and p53."],
    [134,"Endosulfan",32344260,"Wei, 2020","in vitro","AC-16","0, 1.25, 2.5, 5, 10, 20, 40 μg/mL","24h","Reduced cell viability (±, % of control): 90% at 2.5, 80% at 5, 70% at 10, 60% at 20, 30% at 40 ug/ml. Sig. increased ROS levels at 5 ug., decreased ATP levels, suppression of COX IV. BCL-2 downregulated at 1.25 ug. Elevated cyt-c, caspase-3 at 1.25, caspase-9 at 5 ug. Decreased expression of PI3K, p-Akt and p-Foxo3a, increased Bim."],
    [135,"Endosulfan",32344260,"Wei, 2020","in vivo","Rats","1, 5 and 10 mg/kg","21 days","Myocardial cellular degeneration, sig. at 5 mg. Necrosis at 10 mg. cTnI were sig. higher at 5 and 10 mg groups, and the hFABP level elevated at 10 mg. Sig. elevated AST (but not ALT) at 10 mg. "],
    [136,"Endosulfan",15337585,"Kalender, 2004","in vivo","Rats","2 mg/kg per day","6 weeks","SOD, GPx, CAT activities and MDA level increased in the endosulfan-treated group heart tissue. Cytoplasmic edema and swelling and vacuolization of mitochondria. "],
    [137,"Endosulfan",23758152,"Ozmen, 2013","in vivo","Rabbits","1 mg/kg per day","6 weeks","Microscopic haemorrhages, single-cell necrosis, inflammatory reactions, and fibrotic changes in the myocardium. Sig. Caspase-3 immunoreactivity."],
    [138,"Endosulfan",19086562,"Jalili, 2007","in vivo","Rats","2 mg/kg per day","28 days","Myocardial haemorrhages with interstitial oedema. Diapedesis of leukocytes. Myocardium degeneration, granulation of myofibrils with pyknotic nuclei. Thickening of arterial walls."],
    [139,"Endosulfan",28273598,"Wei, 2017","in vivo","Rats","1, 5, 10 mg/kg per day","21 days","Injury of cardiac tissue with impaired mitochondria integrity and elevated 8-OHdG expression in myocardial cells. Increased expressions of Fas, FasL, Caspase-8, Cleaved Caspase-8, Caspase-3 and Cleaved Caspase-3 in cardiac tissue."],
    [140,"Endosulfan",28273598,"Wei, 2017","in vitro","HUVECs","1, 6, 12 μg/mL ","24h","DNA damage and activated DNA damage response signalling pathway (ATM/Chk2 and ATR/Chk1) and consequent cell cycle checkpoint. Apoptosis through death receptor pathway resulting from oxidative stress."],
    [141,"Endosulfan",1702244,"Anand, 1990","in vivo","Rabbits","2.5 and 5.0 mg/kg","2/week, 12 months","Rise in blood pressure and heart rate. Increases in PR, QT and RR intervals. Extensive myocardial damage with marked degeneration of muscle fibers vacuolization and leucocytic infiltration. Sig. increase of 11-hydroxycortisone at all time intervals."],
    [142,"Hexabromocyclododecane",26476318,"Wu, 2016","in vivo","Zebrafish","0, 2, 20, 200 nM","72h","cardiac hypertrophy. Sig. increased deposition of collagen (2-fold at 20 nM). Sig. increased ventricular wall thickness at 20 nM. Sig. Increased ANP and BNP at 200 nM. Decreased Ca2+ accumulation in cytoplasm. Increased SR uptake of Ca2+. Downregulation of miR-1 (regulator of cardiac hypertrophy)."],
    [143,"Hexabromocyclododecane",26476318,"Wu, 2016","in vitro","H9c2","200 nM","24h","Upregulation of Nkx2.5, downregulation of miRNA-1. Disordered Ca2+ handling. Imbalance of Ryr2, Serca2a and Ncx1 expression, inducing Ca2+ overload in the sarcoplasmic reticulum and high Ca2+-ATPase activities."],
    [144,"Idarubicin",34787021,"Zhang, 2021","in vitro","HL-1"," 1, 3, 5, 7, 9 µM","24h","Reduced cell viability (±90% at 1 µM, ±75% at 3 µM, ±60% at 5 µM, ±50% at 7 µM, ±30% at 9 µM) compared to control (100%). Increased ROS production. Increased level of intracellular MDA, LDH and NOS, but sig. reduced SOD, CAT, and GSH. Upregulated Bax–Bcl-2 ratio, caspase-3, caspase-7, and caspase-9 (all doses)."],
    [145,"Idarubicin",32629160,"Gossmann, 2020","in vitro","hiPSC-CMs","10, 100 nM. 1, 10 µM","1 to 5 days","Reduced beating amplitude (10 nM: ±60% at day 5. 100nM: ±60% at day 3. 1 µM: ±60% at day 1. 10 µM: 0% at day 1) compared and normalized to control (100%)."],
    [146,"Idarubicin",12426639,"Kalender, 2002","in vivo","Rats","5 mg kg weekly","8 weeks","Atrial contractility of heart tissue was significantly decreased in the idarubicin-treated group compared to control (P<0.01). QT duration significantly increased. SOD and GSHPx activity was decreased, CAT and MDA activity was significantly increased."],
    [147,"Imatinib",28964914,"Savi, 2018","in vivo","Rats","50, 100 mg/kg 3 times per week","3 weeks","dose-dependent LV dysfunction, dose-dependent increase in wall thickness-to-chamber radius ratio. structural composition of IM treated hearts was unaffected. dose-dependent reduction of both arteriolar and capillary density."],
    [148,"Imatinib",28964914,"Savi, 2018","in vitro","Cardiac progenitor cells","5 µM","6h, 24h","Small pro-apoptotic effect. Slight increase in DNA degradation that peaked at 24h after exposure, corresponding to nearly 70% increase in tail intensity. Significant damage at DNA level (yH2AX stain, 2-fold increase in DNA fragmentation)."],
    [149,"Imatinib",28315715,"Chambers, 2017","in vitro","H9c2","50 µM","24h","LD50: 26.2 μM ± 7.1 μM. At 50 µM: increased cyt-c, cleaved caspase 3, 7 and 9, 2.5-fold increase in ROS production, elevated lipid peroxidation, 3-fold incr. in protein carbonyls. At 12h: reduced respiration, decrease (15–20%) in ATP levels. Increased ΔΨm and ER stress."],
    [150,"Imatinib",34136360,"Kobara, 2021","in vitro","NRCMs","1, 5, 10 µM","6h","10 µM significantly increased the level of LC3-II expression by 2.5-fold. increased beclin 1, Cathepsin D. increased acridine orange-stained mature autolysosome expression. Increased ROS levels, caspase-3 activity at 10 µM."],
    [151,"Imatinib",34136360,"Kobara, 2021","in vivo","Mice","50, 200 mg/kg/day","5 weeks","200 mg: dilatation of the left ventricle (LV) and reduced LV fractional shortening. Apoptosis and LC3-II expression in cardiac tissue were increased."],
    [152,"Imatinib",30910525,"Burke, 2019","in vitro","Rat cardiact fibroblasts","3, 10 µM","24h, 48h","Reduced viability in a concentration-dependent manner. Significantly reduced CF proliferation from 35.5 ± 3.2% in control to 23.0 ± 5.5% for 3 μM and to 9.4 ± 2.5% for 10 μM.  Increased mRNA expression of TGFB1 7-fold, IL6 6-fold, and IL1B 7-fold and reduced PDGFD 15-fold at 10 µM."],
    [153,"Imatinib",24504921,"Maharsy, 2014","in vivo","Mice","200 mg/kg/day","5 weeks","Reduction in the mitral valve mean gradient due to impaired cardiac relaxation. Reduced LV posterior wall thickness (LVPW). 3-fold increase in TUNEL-positive nuclei. Myocyte-specific up-regulation of GATA4 or Bcl-2 protected against toxicity"],
    [154,"Imatinib",22641616,"Hu, 2012","in vitro","NRCMs","0 - 100 µM","24h","Cardiomyocyte dysfunction through disruption of autophagy and induction of ER stress, independent of c-Abl inhibition. "],
    [155,"Imatinib",16862153,"Kerkela, 2006","in vivo","Mice","50, 100, 200 mg/kg/d","3 or 6 weeks","200 mg for 5 weeks: enhanced Ca2+-induced opening of the MPTP. 30% increase in number of mitochondria. Deterioration in contractile function and moderate left ventricular dilation after 3–4 weeks of treatment"],
    [156,"Imatinib",16862153,"Kerkela, 2006","in vitro","NRVMs","2, 5, 10 µM","24h","Reduced Δψm, increased cyt-c release, reduced ATP and ATP/ADP ratio, increased caspase 3, 7 activity. Loss of sarcolemmal integrity (necrotic cell death). upregulation and cleavage of PKCδ. Increased phosphorylation of eIF2α"],
    [157,"Imatinib",22843568,"Rana, 2012","in vitro","hiPSC-CMs","0.01 - 100 µM","Unclear","Reduced cell viability and oxygen consumption rate to 5% at 100 µM."],
    [158,"Imatinib",25505575,"Herman, 2014","in vivo","Rats","50, 100, 200 mg/kg/day","28 days","Myofibrillar loss, cytoplasmic vacuolization, and necrosis at all doses. Severity of the alterations was dose-related with mean lesion scores (based on a scale of 0–3) of 1.2 (50 mg), 2.1 (100 mg) and 2.9 (200 mg). Increases in cTnI, cTnT, and FABP3 levels were noted primarily in 200 mg."],
    [159,"Imatinib",16597375,"Saad, 2006","in vivo","Rats","30 mg/kg/day","10 days","Sig. increases in serum CK-MB, GPx, LDH and AST. Sig. increase of cardiac GSH and MDA."],
    [160,"Imatinib",34973290,"Song, 2021","in vivo","Mice","25, 50, 100 mg/kg","14 days","High dose groups: sig. increased serum CK, LDH and AST. Dose-dependent decrease of GSH and increase of tissue iron and MDA. Sig. increased cardiac lipid accumulation (1.8-fold at 25, 2.4-fold at 50 and 5.6-fold at 100 mg). Sig. decreased GPX4 expression."],
    [161,"Imatinib",34973290,"Song, 2021","in vitro","H9c2","10, 20, 40 µM","24h","Reduced cell viability (81.9% at 10, 59.4% at 20 and 33.1% at 40 µM). Destroyed MMP in dose dependent manner. Increased cellular ROS and iron levels. Downregulation of Nrf2, NQO1, HO-1, GPX4 and FTH1, and upregulation of P53 and TfR expression. Ferroptosis."],
    [162,"Imatinib",35216404,"Bouitbir, 2022","in vitro","H9c2","1 to 100 µM","24h","Inhibited Complex I (CI)- and CIII- linked respiration. Mitochondrial superoxide accumulation and decreased cellular GSH. Caspase 3/7 activation increased. Impaired function of enzyme complexes of the ETS"],
    [163,"Imatinib",35710779,"Smith, 2022","in vitro","Cardiac progenitor cells","1, 5, 10, 100 µM","24h, 7 days","Reduced viability; 24h: 1uM 100%, 10 µM 90%, 100 µM 50%. 7 days: 1 µM 90%, 3 µM 70%, 5uM 60%. cells in S/G2/M phases reduced from 50.3 ± 5.1% in control cells to 29.3 ± 4.3% with 10 µM. Nkx2.5 expression was reduced 3 fold after 7 days."],
    [164,"Lead (Pb2+)",23391631,"Ansari, 2013","in vitro","H9c2","25, 50, and 100 μM","24h","Pb2+ was not cytotoxic, viability >90%. Increased β-MHC, α-MHC, and CYP1A1 mRNA. Resveratrol, an AhR antagonist, could sig. inhibit toxicity. Cardiotoxicity through AhR/CYP1A1-mediated mechanism."],
    [165,"Lead chloride",28836190,"Mattos, 2017","ex vivo","Guinea pig hearts","1-200 μM","5-10 min","Acute exposure had a negative inotropic effect and increased diastolic tension. Decreased amplitude of the contractile force."],
    [166,"Lead chloride",28836190,"Mattos, 2017","in vitro","Guinea pig CMs","1-200 μM","5-10 min","Extracellular lead blocked currents through Cav1.2 channels with IC50 of 18 µM, diminished their activation, and enhanced their fast inactivation, negatively affecting their gating currents."],
    [167,"Lead nitrate",23391631,"Ansari, 2013","in vivo","Rats","25, 50 and 100 mg/kg per day","3 days","Sig. cardiotoxicity and heart failure as evidenced by increase cardiac enzymes, LDH, AST, CK, and changes in histopathology at 100 mg. Decreased heart-BW ratio 35% at 100 mg. Induction of B-MHC and BNP while reduction of a-MHC mRNA and protein levels dose-dependently. "],
    [168,"Lindane",23458197,"Padma, 2013","in vivo","Rats","100 mg/kg per day","30 days, fu 1 year","Sig. elevated CK and LDH. Myocardial tissue had inflammatory cells and separated muscle fibers. Sig. increase in TBARS. Sig. decreased SOD, CAT, GPx, and GST. Sig. increase in Ca2+ATPase activity, sig. decrease in Na2+/K+ ATPase and Mg2+ ATPase activities. "],
    [169,"Lindane",1702244,"Anand, 1990","in vivo","Rabbits","2.5 and 5.0 mg/kg","2/week, 12 months","Rise in blood pressure and heart rate. Increases in PR, QT and RR intervals. Extensive myocardial damage with marked degeneration of muscle fibers vacuolization and leucocytic infiltration. Sig. increase of 11-hydroxycortisone at all time intervals."],
    [170,"Lindane",16127354,"Ananya, 2005","in vivo","Rats","1.5 and 7 mg/kg per day","21 days","Sig. increased myocardial TBARS, sig. decreased GSH. Increased SOD and catalase activities at 7 mg. Interstitial edema in the myocardium at 1.5 mg. Loss of integrity of the myofibrils, Z-band disruption, and mitochondrial damage."],
    [171,"Loperamide",30597669,"Olofinsan, 2019","in vivo","Rats","1.5, 3, 6 mg/kg/day","7 days","Dose-dependent increase in aspartate aminotransferase, LDH, creatine kinase-MB, and serum concentration of cardiac troponin I, total homocysteine, and nitric oxide. 50% decrease in antioxidant enzymes activity at 6 mg. Cardiotoxic through oxidative stress, lipid peroxidation, and DNA fragmentation."],
    [172,"Loperamide",33125619,"Wolfes, 2021","in vitro","Rabbit heart perfusion","0.2, 0.35, 0.5 µM","0-1s","Sig. increase in QT interval, APD90, and ventricular tachycardia (VT) episodes."],
    [173,"Lovastatin",14678744,"Rabkin, 2003","in vitro","Chicken embryo CMs","10, 50, 100 µM","24h","Concentration-dependent increase in apoptotic cell death and 100 μM lovastatin showed over a 4-fold increase in apoptosis through the mevalonate pathway. Caspase-2 and 3 were implicated. "],
    [174,"Lovastatin",17158337,"Hauck, 2006","in vivo/ vitro","Rats, NRVMs","20 mg/kg/day","14 days","Recruitment of forkhead box FoxO3a transcription factor to p21 promoter, mediating activation of the p21 gene. Stimulation of protein kinase B/Akt kinase activity, and Akt-dependent phosphorylation forces p21 in the cytoplasm, where it inhibits Rho-kinases contributing to the suppression of cardiomyocyte hypertrophy. "],
    [175,"MDMA",31526813,"Zwartsen, 2019","in vitro","hiPSC-CMs","0.01, 0.1, 1, 10, 100, 300, 1000 μM","2-30 min, 24h","Decreased the spike amplitude at 100 μM. Also, at 0.1 μM MDMA, yet not at higher concentrations, an increase in spike amplitude was seen. 10 µM increased the beat rate by 20%. Decreased beat rate at 300 µM. Prolonged FPDc concentration-dependently. Sig. decreased cell viability only at 1000 µM."],
    [176,"Mitomycin C",8763838,"Pritsos, 1996","in vivo","Mice","0, 5, 10, 20 mg/kg, 1 or 2 injections","48h after treatment","Decreased heart tissue ATP to 40% of control (single and double, all doses)."],
    [177,"Mitoxantrone",32894303,"Costa, 2020","in vitro","HL-1","0.1, 1, 10 µM","2, 4, 6, 12, 24, 48h","Decreased cell viability in conc./time dependent manner. Earliest effects at 6h (10 µM). At 24h: 10 µM (46.3 ± 8.7%), 1 µM (58.5 ± 10.4%), 0.1 µM (77.1 ± 12.6%). At 48h, viability was decreased dramatically. Increased GSH and caspase 9, 8, 3. Decreased proteasomal chymotrypsin-like activity in a conc./time dependent manner."],
    [178,"Mitoxantrone",29913208,"Damiani, 2018","in vitro","H9c2","0.1, 1 µM","24h","Reduced cell viability (% of control): ±75% at 0.1 µM, ±40% at 1 µM. 1 µM induced sig. necrosis. Reduced ATP by half (1 µM). Decrease MMP. Increased ROS at 0.1 µM."],
    [179,"Mitoxantrone",23545721,"Rossato, 2013","in vitro","H9c2","100 nM, 1 µM","24h","Reduced cell viability (% of control): 69 ± 5% (100nM), 63 ± 7 % (1 µM)"],
    [180,"Mitoxantrone",24046265,"Rossato, 2013","in vitro","H9c2","10, 100 nM, 1, 5, 10, 50, 100 μM","24, 48, 72, 96h","Reduced cell viability in conc./time dependent manner (% of control): 24h: ±80% at 10 µM, ±20% at 50 µM. 96h: ±80% at 1uM, ±30% at 5 µM. =>100 nM caused incr. in caspase-3 activity after 24h. ROS 96h (% of control): 137 ± 46.7% at 100 nM and 141 ± 56.9 % at 1 μM. At 96h, sig. decrease in GSH (100 nM). Change in MPP and sig. increase in [Ca2+]i."],
    [181,"Mitoxantrone",23261645,"Schweikart, 2013","in vitro","hiPSC-CMs","0.1, 1, 3, 10, 30 µM","1h, 12h, 24h, 72h","Decrease in beat rate at 30 μM at 1h, at both 10 μM at 6h, and at 0.1 µM at >24h. Beating stopped at >3 µM after 24h. Dose- and time-dependent decrease in beat amplitude. Mitochondrial staining was reduced but increased MMP."],
    [182,"Mitoxantrone",26660439,"Hasinoff, 2016","in vitro","NRVMs","0 - 100 µM","24h, 48h, 72h","15% LDH increase over control at 1 µM (72h), dose response plot available."],
    [183,"Mitoxantrone",24096626,"Rossato, 2014","in vivo","Rats","7.5 mg/kg","22 and 48 days","Treatment at day 20. Decrease of CK levels in  MTX22 group when compared to MTX48 group and control group. Only in MTX48 group: cardiac relative mass higher, ATP lower."],
    [184,"Mono(2-ethylhexyl)phthalate",33029813,"Wang, 2021","in vitro","AC-16","0 - 120 µM","24h","Reduced cell viability (sig. at 60 µM, 20% decrease, at 100 µM 50% decrease) and MMP, whereas it increased LDH leakage (sig. at 60 µM), production of ROS, and apoptosis."],
    [185,"Nifedipine",32336319,"Ryu, 2020","in vivo/ vitro","Rats, NRCMs, hESC-CMs","2x 100 mg/kg, 50 µM","24h","0-20% increase in apoptotic index in rats, NRCMs, hESC-CMs (not stat sig.). Increase of oxidative stress indicators and gene levels of β-MHC, ANP, BNP, Spp1, IL-1β, IL-6, TLR2, TLR4, TNF-α, Bax/Bcl-2, and Casp9 and p53."],
    [186,"Nifedipine",31526813,"Zwartsen, 2019","in vitro","hiPSC-CMs","3, 10, 30 nM","2-30 min, 24h","Sig. reduced FPDc (−11 ± 3.3%) at 30 nM, but no sig. effect on beat rate, spike amplitude or the number/percentage of active wells and electrodes. No sig. effect on cell viability."],
    [187,"Nifedipine",33109927,"Vinagre, 2021","in vitro","hiPSC-CMs","0.01, 0.03, 0.1, 0.3 µM","30 min exposure, 20s recording","Concentration-dependent decreased amplitude, contraction and relaxation time, APD (APD30 and APD90)"],
    [188,"Nifedipine",27184445,"Dempsey, 2016","in vitro","hiPSC-CMs","0 - 1 µM","Unclear","Decreased CT amplitude. 0.01 µM: 20% decrease in AP50 and AP90, 20% increase in AP rise time,  20% decrease in Ca2+ amplitude. 0.3 µM: Ca2+ flux stops. 1 µM: stopped beating. "],
    [189,"Nifedipine",31079550,"Lam, 2019","in vitro","hiPSC-CMs","433 nM (C ther.)","30 mins, 14 days","Reductions in beating rate and contraction velocities. Persistent blockade of L-type calcium current. Upregulation of gene S100A8."],
    [190,"Nifedipine",29274391,"Goineau, 2017","in vitro","hiPSC-CMs","0.01, 0.03, 0.1, 0.3 and 1 μM","5 min","Concentration-dependently shortened FPDcF, minimum effective concentration was 0.03 µM"],
    [191,"Nifedipine",20034863,"Braam, 2010","in vitro","hESC-CMs","1 nm - 100 µM","2 min","Dose-dependent shortening of the FPD, which was initiated at 10 nM and saturated at 1 μM"],
    [192,"Paclitaxel",17400210,"Pentassuglia, 2007","in vitro","ARVMs","0–15 μM","48h","Slightly decreased cell viability at concentrations ≤ 6 μM, higher doses resulted in a sig. increase of myofibrillar damage. No effect on mitochondrial respiration. No increase in LDH. Reduced basal phosphorylation of Erk1/2 (0.7 fold) and Akt (0.5 fold ). Mild oxidative stress."],
    [193,"Perfluorooctane sulfonamide (PFOSA)",35652794,"Chen, 2022","in vivo","Zebrafish","0.01, 0.1, 1, 10, and 100 μg/L","120 hpf","Abnormal cardiac morphology, disordered heartbeat signals, as well as reduced heart rate and cardiac output. Effects could be prevented by AHR antagonist and were alleviated by ahr2 knockdown, indicating sig. role for AhR activation pathway in PFOSA cardiotoxicity."],
    [194,"Perfluorooctane sulfonate (PFOS)",15737613,"Harada, 2005","in vitro","Guinea pig VMs","1, 10, 20, 100 µM","Unclear","Sig. decreased the rate of spike, action potential duration, and peak potential at doses over 10 µM. Increased the voltage-activated peak amplitude of I(CaL), and shifted the half-activation and inactivation voltages of I(CaL) to hyperpolarization."],
    [195,"Perfluorooctane sulfonate (PFOS)",32861759,"Liu, 2020","in vitro","mESC-CMs","40 µM","3 - 7 days","Induced swelling of mitochondria and autophagosome accumulation at 40 μM. Increased levels of LC3-II, p62, and ubiquitinated proteins. Induced an increase of LC3 and p62 localization into mitochondria, indicating that mitophagy degradation was impaired. Dysfunction of lysosomes. ATP depletion and reduced MMP. "],
    [196,"Perfluorooctane sulfonate (PFOS)",32088431,"Yang, 2020","in vitro","hESC-CMs","0.1, 1, 10, 30, and 60 μM","0 - 12 days","48h treatments did not lead to any obvious cell death at concentrations  60μM, only for doses  > 180 μM. Inhibited cardiac differentiation and promoted epicardial specification via upregulation of the WNT signalling pathway."],
    [197,"Perfluorooctane sulfonate (PFOS)",28288859,"Tang, 2017","in vitro","mESC-CMs","40 µM","3 - 7 days","Expression of L-type Ca2+ channel (LTCC) was decreased, interrupting [Ca 2+]c transient amplitude. Mitochondrial swelling. MMP was decreased and ATP production lowered. Increased EGFR phosphorylation, activated Rictor signalling, destroying the mitochondria-associated endoplasmic reticulum membrane (MAM) "],
    [198,"Perfluorooctane sulfonate (PFOS)",34815766,"Xu, 2022","in vivo","Rats","1 and 10 mg/kg  every other day","14 days","Sig. Increased heart to body weight ratio at 10 mg. Sig. Increased expression of myocardial injury markers, such as cTn-T, LDH, CK and CK-MB. Cardiac fibrosis and myocardial hypertrophy at 10 mg. Sig. upregulation of p53, Bax, IL-1B, TNF-a.  "],
    [199,"Perfluorooctanoic acid (PFOA)",31445018,"Lv, 2019","in vitro","Chicken embryo CMs","1, 10, 30 or 100 μg/mL","24, 48, 72h","Reduced cell viability at 24h, 15.6% at 30 ug and 17.0% at 100 μg/ml. 48h: 1, 10, 30 and 100 μg/ml, 19.2%, 30.7%, 51.7%, 53.0%, respectively. Silencing of PPARa alleviated cytotoxicity. Sig. higher [Ca2+]i levels."],
    [200,"Perfluorooctanoic acid (PFOA)",22273728,"Jiang, 2012","in vivo","Chicken embryo heart","0, 0.5, 1 and 2 mg/kg egg","D19, 2 days prior to hatch","Alteration of multiple cardiac structural and functional parameters. Reduced left ventricular wall thickness, altered left ventricular volume, heart rate, stroke volume, and ejection fraction."],
    [201,"Perfluorooctanoic acid (PFOA)",26098785,"Jiang, 2016","in vitro","Chicken embryo CMs","2 mg/kg of egg in ovo, 0 to 100 µg/mL in vitro","1 or 36h","Decreased viability at 1h of exposure to 100 and 36h of exposure to 75 and 100 µg/mL in vitro. Decreases in time to maximum departure velocity and cell length at peak contraction, reduction in the 50% relaxation time. Decreased cardiomyocytes axial length. Sig increased ROS generation."],
    [202,"Perfluorooctanoic acid (PFOA)",31037826,"Salimi, 2019","in vivo","Mice","1, 10, and 20 mg/kg per day","D5 - D9 of gestation.","Assessment on D15 of gestation. Thickening of endometrium (20% in group 20 mg/kg). Sig. increased mitochondrial swelling and ROS generation, sig. decreased MMP in heart mitochondria. "],
    [203,"Perfluorooctanoic acid (PFOA)",28934691,"Zhao, 2017","in vivo","Chicken","2 mg/kg egg in ovo","Unclear","Significant elevation of heart rate and thinning of right ventricular wall thickness. PPARa silencing sig. increased right ventricular wall thickness of PFOA treated animals."],
    [204,"Permethrin",34224971,"Feriani, 2021","in vivo","Rats","5 mg/kg/day","12 weeks","Decreased R amplitude, ST segment elevation, marked increase in heart rate with auricular flutter, indicating onset of myocardial infarction. Sig. higher plasma TC, TG, LDL-C, decrease in HDL-C. Sig. higher AST, CK-MB, LD, CRP and cTn-T. Sig. higher TNF-a and IL-6. Sig. lower CAT, SOD, GPx, GSH. Upregulation of Caspase-3, Bax, NF-KB. High cardiac TGF-B1 expression. Cardiac fibrosis."],
    [205,"Permethrin",23806482,"Vadhana, 2013","in vivo","Rats","34.05 mg/kg, per day, 21 days","500 days","1.62-fold increase in Nrf2 mRNA level. Decreased heart surface area (296.59 ± 8.09 vs control group (320.86 ± 4.93, mm2). Intracellular calcium influx increased 4.33-fold."],
    [206,"Permethrin",20574784,"Vadhana, 2010","in vitro","Rat CMs","5, 10, 20 µM","1h","5, 10, and 20μM reduced cell viability 1.02, 6.12 and 5.1%. Oxidative damage to purine bases. Sig. DNA damage."],
    [207,"Phenanthrene",31237719,"Vehniainen, 2019","in vitro","Rainbow trout CMs","0.3, 1.0, 10, and 30 µM","Unclear","Shortened APD0 at 30 µM. Increased +dV/dt at 1 µM and accelerated –dV/dt at 10 µM. Modulation of cardiac INa, ICaL, and IKr currents"],
    [208,"Phenanthrene",32738692,"Rigaud, 2020","in vivo","Rainbow trout","100 µg/L","1, 3, 7, 14 days","No detectable deformities or growth retardation. Sig. alteration of cacng7a (subunit of L-type Ca2+ channel). Altered key genes linked to the respiratory electron transport chain, as well as to oxygen and iron metabolism. "],
    [209,"Phenanthrene",33523501,"McGruer, 2021","in vivo","Zebrafish","12 or 15 µM","6 to 72 hpf","Pericardial edema and bradycardia. Sig. alteration of genes fdft1 and hmgcra (cholesterol biosynthetic pathway). 2-dimensional yolk area was sig. increased, suggesting that lipid transport from the yolk to the developing embryo was impaired."],
    [210,"Phenanthrene",32957295,"Zheng, 2020","in vivo","Medaka","0, 2, 10, 50, and 250 μg/L","28 days exposure","Exposure =>10 ug decreased survival rate. 2, 10, and 50 μg/L caused yolk sac edema and pericardial edema, accompanied by dysregulation of fgf8, bmp4, smyd1, ATPase and gata4 genes."],
    [211,"Phenanthrene",31499312,"Ainerua, 2020","in vitro","Brown trout VCMs","5, 15 or 25 μM","30 min","Prolongation of QT interval (±8.6%) and MAPD (±13.2%). Sig. reduced trabecular force generation by ±24% at 15 μM and above, suggesting reduced cellular Ca2+ cycling. Reduction (±39%) in the intracellular Ca2+ transient amplitude. Reduced repolarising delayed rectifier K+ current (±70%)."],
    [212,"Phenanthrene",28570901,"Cypher, 2017","in vivo","Zebrafish","0, 1, 100, and 1000 μg/L","Exposure between 24 and 72-96 hpf","Decrease in heart rate (58%), cardiac output (80%), and arterial red blood cell velocity (84%) compared to control (100%) at 1000 ug. Effects are exacerbated by simultaneous exposure to hypoxia."],
    [213,"Phenanthrene",26830171,"Huang, 2016","in vivo","Rats","0.5, 5, 50 μg/kg per day, 21 days","6 weeks","Increased heart weight and CM size dose-dependently, indicating cardiac hypertrophy. Increased deposition of collagen in the heart sections."],
    [214,"Phenanthrene",26830171,"Huang, 2016","in vitro","H9c2","0.05–50 nM","12, 24h","No inhibitory effect on cell viability. Sig. enlargement of cell size (2-fold) at 50 nM. Increased protein synthesis (2-fold). CM hypertrophy. Increased mRNA levels of ANP, BNP and c-Myc. Sig. reduced levels of miR-133a (regulator of CM hypertrophy). Increased CdC42, RhoA, DNMT1, DNMT3a and DNMT3b. Increased DNA methylation, leading to reduced miRNA-133a and hypertrophy phenotype."],
    [215,"Phenanthrene",23948075,"Zhang, 2013","in vivo","Zebrafish","0.05, 0.5, 5, 50 nM","72hpf","Sig. increased interbeat variation (arrhythmia) at 5 and 50 nM."],
    [216,"Phenanthrene",23948075,"Zhang, 2013","in vitro","H9c2","0.05, 0.5, 5, 50 nM","72h","Disordered Ca(2+) handling characterized by impaired SR Ca(2+) uptake, and obvious Ca(2+) accumulation in the cytoplasm. Sig. decreased mRNA level of the SERCA2a Ca(2+) pump. Both the mRNA and protein levels of TBX5, a direct regulator of SERCA2a, were sig. decreased"],
    [217,"Phenylephrine",29339422,"Sun, 2019","in vitro","NRVMs","50 µM","6, 12, 24h","Cardiomyocyte hypertrophy was induced. Level of ANGPTL4 was increased at 6 and 12 h after PE treatment and then gradually declined over the next 12 h"],
    [218,"Phenylephrine",29128355,"Romano, 2017","in vitro","NRCMs","100 µM","48h","Cardiomyocyte hypertrophy was induced. Sig. cell size increase over control."],
    [219,"Phenylephrine",32898528,"Li, 2020","in vitro","hESC-CMs","25, 50 µM","48h","Decreases of mitochondrial respiration, ATP, ATP synthetase and mitochondrial membrane potential. 50 µM increased the surface area of cardiomyocytes 2.7 fold. Downregulation of G6PD. Hypertrophic marker genes (ANP, BNP and β-MHC) were significantly elevated (50 µM)"],
    [220,"Phenylephrine",27940402,"Ji, 2017","in vitro","NRCMs","100 µM","48h","Increased size of cardiomyocytes: almost twice as large as control. Expression of ANP and BNP were enhanced. Sig. up-regulation of CaMKIIδ, STIM1. Peak amplitude of Ca2+ current in the SOCE was higher. Increased amplitude of Ca2+ release-activated currents"],
    [221,"Phenylephrine",34790705,"Fang, 2021","in vitro","NRVMs","50 µM","48h","Hypertrophy. Sig. reduced intracellular Zinc concentration, SLC39A2 is involved. Slc39a2 knockdown sig. potentiated  PE-induced cell size enlargement."],
    [222,"Phenylephrine",29862242,"Gao, 2018","in vitro","NRVMs","50 µM","48h","Hypertrophy. Reduced PPARγ and PGC1-α. Increased ANP and BNP, CM size."],
    [223,"Phenylephrine",27161004,"Zhang, 2016","in vitro","NRVMs","50 µM","48h","Hypertrophy. Obvious enlargement of cardiomyocytes as measured by cell surface labelled with α-actinin. ANP, BNP, and MYH7, were increased. Protein/DNA ratio was elevated. miR-199a-5p was upregulated."],
    [224,"Phenylephrine",34384564,"Sunagawa, 2021","in vitro","NRCMs","30 µM","48h","Increases in transcriptions of atrial naturistic factor (ANF) and brain naturistic peptide (BNP), markers of cardiomyocyte hypertrophy. PE induced acetylation of histone H3K9"],
    [225,"Phenylephrine",17287366,"Prasad, 2007","in vitro","NRCMs","20 µM","3-7 days","Hypertrophic enlargement. 69 ± 16% enhancement of overall protein expression. ANF was increased 2.97 ± 1.13- and 11.69 ± 1.95-fold after 3- or 7-day exposure to PE. SERCA2 transcription was reduced to 0.62 ± 0.24 and 0.44 ± 0.13 after 3- or 7-day."],
    [226,"Phenylephrine",27094368,"Shen, 2016","in vitro","NRCMs","100 µM","24h","PE increased the surface area of cardiomyocytes (±2.5-fold) and elevated the expression of hypertrophy marker genes (ANF ±2-fold, BNP ±2-fold, B-MHC 1.5-fold). Decreased protein expression of SIRT6, elevated p300"],
    [227,"Phenylephrine",34914791,"Peng, 2021","in vitro","Mouse VCMs","100 µM","48h","Enlargement of cells, increased ANP. Level of p-JNK was significantly increased, histone H3K9ac hyperacetylation. PCAF-HAT and MEF2A expression significantly increased. [Ca2+]i was clearly increased. LVAWT and LVPWT increased in vivo."],
    [228,"Phenylephrine",28194469,"Peng, 2017","in vivo","Mouse perfused heart","20 mg/kg/day","30 days, fu 1 year","Left ventricular hypertrophy, sig. increased heart to body weight ratio (1.5-fold). Increased HAT activity 1.6-fold, sig. increased p300, PCAF, SRC1, H3K9ac. mRNA-expression of MEF2A, Cx43, ANP, BNP, cTnT, and β-MHC were consistently higher. Sig. increase in left ventricular pressure and diastolic pressure. Survival rate 15%, HF incidence 90% after 1 year."],
    [229,"Phenylephrine",28497371,"Dong, 2017","in vitro","NRCMs","50 µM","48h","Expression of Sestrin 2 declined to 60% of control. Sig. increased ANP and cell surface area. MAPKs (including ERK1/2, JNK 1/2 and p38) and mTOR (including its downstream effector p70S6K) were significantly activated at 30 min"],
    [230,"Phenylephrine",25449040,"Dong, 2015","in vitro","NRVMs","10 µM","3 days","Sig. increase in cell surface area from 789±91 µm2 to 1201±140 µm2. Increased protein expression of ANP 2-fold. 2-fold and around 1.7-fold increases of RhoA and ROCK activity. Increased [ROS]i 3.14-fold. MDA 1.65-fold."],
    [231,"Phenylephrine",22818713,"Anestopoulos, 2013","in vitro","H9c2","100 µM","24h","Sig. increase in cell area, ANP, ERK1/2 activity and pAkt."],
    [232,"Phenylephrine",15452191,"Gan, 2005","in vitro","NRCMs","10 µM","24h","Increased cell size (35%) and ANP. Increased ERK phosphorylation. Rapid c-Fos induction during first 30 m. Expression of G-protein regulatory factors RGS2 and RGS4 were increased by nearly 3-fold and upregulation of Na/H exchange isoform 1 (NHE1) expression."],
    [233,"Phenylephrine",31163678,"Chaanine, 2019","in vitro","ARCMs","10 µM","2h","Mitochondrial fission, fragmentation, mitophagy, and vascular degeneration."],
    [234,"Phenylephrine",29110214,"Zhao, 2018","in vitro","NRCMs","50 µM","48h","Downregulation of miR-223, upregulation of STIM1."],
    [235,"Phenylephrine",29901150,"Liu, 2018","in vitro","NRCMs","10 µM","48h","Sig. reduced ATP concentration (4.9±0.5 vs 9.1±0.7 nmol/mg). MMP sig. decreased (50% of control). Sig. increase in ROS (162% of control). CPT-2, Acadm, ANP decreased."],
    [236,"Phenylephrine",16690042,"Kleiner, 2006","in vitro","NRCMs","10 µM","30m, 1, 3h","Transcript levels c-Jun and c-Fos were rapidly and markedly increased, JunD decreased. "],
    [237,"Phenylephrine",25770146,"Zhong, 2015","in vitro","NRVMs","10 µM","24h","Hypertrophic phenotype in NRVM characterized by increased cell-surface area and robust accumulation of ANP. Phosphorylation of ERK1/2 and GATA4 followed by nuclear translocation of the ANKRD1/ERK/GATA4 complex."],
    [238,"Phenylephrine",15276029,"Kemp, 2004","in vitro","NRVMs","100 µM","1h","Expression of three clones (C208, C53 (CTGF) and C64) was increased. Increased CTGF mRNA 2.25 ± 0.27-fold."],
    [239,"Phenylephrine",19966059,"Pang, 2009","in vitro","NRVMs","10 µM","6, 24h","Sig. hypertrophy (cell size and ANP). Sig. increased gene and protein expression of adenosine A1, A2a, and A3 receptors. Sig. increased production of adenosine, sig. upregulation in expression levels of equilibrative nucleoside transporter 1."],
    [240,"Phenylephrine",25636810,"Huang, 2015","in vitro","NRCMs","20 µM","24h","Increased cell surface area and free fatty acid content, increased ERK1/2 phosphorylation, decreased expression of PPARα, decreased expression and activity of SCAD and decreased levels of ATP."],
    [241,"Phenylephrine",35468773,"Qian, 2022","in vitro","NRCMs, AMCMs","50 µM","24h","Enhanced phosphorylation level of CaMKII, MEK, ERK1/2, PLN and RyR2. Increased Ca2+ spark frequency."],
    [242,"Pyrene",32738692,"Rigaud, 2020","in vivo","Rainbow trout","32 μg/L","1, 3, 7, 14 days","No detectable deformities or growth retardation. Sig. alteration of genes involved in the generation of the AP: cacna1i, kcna10a, kcnh8 and kcnj9. Altered key genes linked to the respiratory electron transport chain, as well as to oxygen and iron metabolism. "],
    [243,"Pyrene",17112560,"Incardona, 2006","in vivo","Zebrafish","25 µM","Exp. between 6 and 72 hpf","Strong CYP1A induction (12-fold increase of mRNA). Reduced peripheral circulation, anaemia, pericardial edema that evolves into yolk sac edema"],
    [244,"Retene",31237719,"Vehniainen, 2019","in vitro","Rainbow trout CMs","0.1, 1.0, and 10 µM","Unclear","Shortened APD50 and APD0 at 1 µM. Augmented AP amplitude at 10 µM and increased overshoot at 1 µM. Modulation of cardiac INa, ICaL, and IKr currents."],
    [245,"Retene",32738692,"Rigaud, 2020","in vivo","Rainbow trout","32 μg/L","1, 3, 7, 14 days","No detectable deformities or growth retardation. Dysregulation of genes related to cardiac ion channels, calcium homeostasis and muscle contraction: sig. alteration of genes related to actin filaments (fscn2b and actn3b), myosin filaments (myha, myhc4, myhz1.1, myhz1.2 and myhz2) and the troponin complex (tnni1c, tnni2a.4, tnnt1 and tpma)."],
    [246,"Retene",26667672,"Vehniainen, 2016","in vivo","Rainbow trout","32 μg/L","1, 3, 7, 14 days","Retene up- or down-regulated 122 genes. The largest Gene Ontology groups were signal transduction, transcription, apoptosis, cell growth, cytoskeleton, cell adhesion/mobility, cardiovascular development, xenobiotic metabolism, protein metabolism, lipid metabolism and transport, and amino acid metabolism."],
    [247,"Retene",21040984,"Scott, 2011","in vivo","Zebrafish","12.5 μg/mL","24, 36, 48 and 72 hpf","At 36h: pericardial edema and reduced blood flow, reduced layer of cardiac jelly in the atrium and reduced diastolic filling. Mechanism of retene toxicity is AhR2-mediated and CYP1A-independent."],
    [248,"Rofecoxib",32111102,"Brenner, 2020","in vivo","Rats","5.12 mg/kg/day","28 days","Rofecoxib treatment increased the mortality rate in the ischemia/reperfusion (I/R) group in vivo (OR = 7.8) due to its proarrhythmic effect via increased APD during I/R. Reduced infarct size. Increased viability of CMs in normoxia and in simulated ischemia/reperfusion injury."],
    [249,"Rosiglitazone",24449420,"He, 2014","ex vivo","Mouse perfused heart","1, 3, 10, 30 µM","2h","Myocardial energy deficiency and mitochondrial dysfunction. 10-30μM decreased [PCr], [ATP], ΔGATP, oxidation rates of glucose and palmitate, mitochondrial respiration rate and complex 1 and 4. Increased ROS and cardiac contractile dysfunction independent of PPARy."],
    [250,"Rosiglitazone",24249632,"Mishra, 2014","in vitro","H9c2","50, 60 µM","24h","Dose dependent reduction in cell viability. Sig. ROS increase. Increase in the expression of NOX-2 (4-fold), MMP-2 (6-fold), MMP-9 (64-fold), p40phox (4.8-fold), p47phox (6.6-fold), xanthine oxidase (162-fold). Increased iNOS (70-250 fold), nNOS (100-250 fold). Increased SOD, catalase, GR, GST and GPx. Cardiotoxicity mediated through HO1-nrf2-PKCδ Pathway."],
    [251,"Rosiglitazone",24249632,"Mishra, 2014","in vivo","Mice","10 mg/kg/day","10 days","Increased serum CK-MB, tissue cTnT, and iNOS expression. Increased SOD (2-fold), catalase (6-fold), GR (2-fold), GST (5-fold), GPX (7-fold). Global gene expression studies also showed the perturbation of oxidative phosphorylation, fat cell differentiation, and electron transport chain upon treatment in vivo."],
    [252,"Rosiglitazone",28822817,"Pharaon, 2017","in vitro","NRCMs","0.5, 1, 2, 5, 10, 50 and 100 μM","12, 24, 48 and 72h","10 μM 48h sig. increased BNP (1.6 fold), 50 μM (1.5 fold) and 100 μM (1.6 fold). After 72h, 10 μM and 100 μM sig. increased BNP (1.4 and 1.8 fold). At 72h, 100 µM: increased surface area (1.6-fold), increased ANP (2.2 fold), increased phosphorylation of p38-MAPK (1.4 fold) and histone H3 (1.9 fold)."],
    [253,"Sibutramine",33389602,"Alyu, 2021","in vitro","ARVMs","10 µM","3h","Sig. prolongation of APD25, APD50, reduction of amplitude, inhibition of RMP values. Inhibition of K+ current in a dose dependent manner. The mRNA levels of fast (Kv4.2 and Kv4.3) and slow (Kv1.4 and Kv2.1) components of K+-channels were decreased sig. Decreased resting basal Ca2+. ROS levels markedly increased."],
    [254,"Tebuconazole",32980069,"Othmene, 2020","in vivo","Rats","0.9, 9, 27 and 45 mg/kg","28 days","MDA, PC, AOPP, GPx, GR and GSSG levels increased, while GSH and GSH/GSSG ratio decreased. SOD and CAT initially increased at 0.9, 9 and 27 mg and then decreased at 45 mg. Increased SOD1, CAT and HSP70 protein levels. Myocardial tissue damage: leucocytic infiltration, haemorrhage congestion of cardiac blood vessels and cytoplasmic vacuolization. "],
    [255,"Tebuconazole",32006631,"Othmene, 2020","in vivo","Rats","0.9, 9, 27 mg/kg","28 days","Increased relative weight at 9 and 27 mg (14.73% and 26.09%). Inhibition of cardiac AChE activity at 0.9, 9, 27 mg (12.52%, 28.18% and 42.93%). Sig. elevated activity of CPK and LDH, T-CHOL, TG, and LDL-C and decreased significantly HDL-C levels. Sig. increase in p53, upregulation of Bax, downregulation of Bcl-2, overexpression of cyt-c, caspase-9 and -3. Increased DNA damage and PCEMN. Increased myocardial fibrotic content at 9 and 27 mg (12 and 15%)."],
    [256,"Tebuconazole",32798748,"Othmene, 2020","in vitro","H9c2","20-120 µM, 60 µM","24h","Dose-dependent cell death: 95% at 120, 80% at 100, 70% at 80, 50% at 60, 35% at 40, 20% at 20 µM. DNA damage: 2.48 and 4.65 fold at 30 and 60 µM. Sig. upregulation of p53, p21, Bax. Downregulation of Bcl2. Increased active forms of caspase-9 and -3. Cleavage of PARP. Increased ROS and MDA."],
    [257,"Tebuconazole",35202779,"Miranda, 2022","ex vivo","Mouse perfused heart","0.3, 3, 30, and 300 μM","Unclear","ECG abnormalities: increased QT and QTc interval, reduced intrinsic frequency. Changes in P duration, PR interval, decreased heart rate. Atrioventricular block. Elimination of electric activity at 300 µM. "],
    [258,"Tebuconazole",35202779,"Miranda, 2022","in vitro","Mouse VCMs","30 µM","Unclear","Prolongation of APR. No effect on AP potential amplitude and resting membrane potential. Reduced the peak amplitude of ICa,L in a concentration-dependent manner. Increased total Ca2+ load, sarcomere shortening and calcium transient."],
    [259,"Telmisartan",23073892,"Kim, 2012","ex vivo","Rat perfused heart","3, 10, 30, and 100 μM","3h","Dose dependent MI: infarct size was 10% (10 μM), 20% (30 μM), and 65% (100 μM) of the total heart area. 30 μM sig. altered cardiac performance, hypercontractile LV with bradycardia and cardiac arrhythmia. Reduced heart rate (48% of control), average coronary flow rate (50%), higher LV developed pressure (169.4 ± 8.8%). LV internal dimension at end systole was sig. decreased.  Increased cytosolic Ca2+ and Na+, no effect on Ca2+ currents but delayed inactivation of voltage-gated Na+ currents. Prolonged APD."],
    [260,"Tetrabromobisphenol A",25846749,"Wu, 2016","in vivo","Zebrafish","0.1, 0.4, 0.7, 1 mg/L","8 days","Dose-response alteration of hatching rate, survival rate, malformation rate, growth rate. Heart impairment. Decreased activities of Cu/Zn-SOD, CAT, GPx at 0.4 mg. Apoptotic cells mainly accumulated in the brain, heart, and tail, indicating possible TBBPA-induced brain, cardiac, and blood circulation system impairment."],
    [261,"Tetrabromobisphenol A",24596333,"Yang, 2015","in vivo","Zebrafish","0.5, 1 mg/L","24 - 96h","Malformation, blood flow disorders, pericardial edema, and spawn coagulation rates increased, whereas survival decreased significantly. Dose-dependent increase of ROS production. CM apoptosis. Increased P53, Bax, and Caspase9. Downregulation of Bcl-2. Alteration of cardiac genes: Tbx1, Raldh2, and Bmp2b."],
    [262,"Tributyltin",30690233,"Pereira, 2019","ex vivo","Mouse perfused heart","1 nM to 10 mM","5 min","Depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. Increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential."],
    [263,"Tributyltin",30690233,"Pereira, 2019","in vitro","Mouse VCMs","100 nM","5 min","Depressed Ca2+ transient peaks and the rates of twitch [Ca2+]i decline. Higher concentrations led to cell death. Sig. reduced SR Ca2+ content via RyR leak. Increased cytosolic ROS production after 5 min. Decreased MMP."],
    [264,"Tributyltin",22852845,"Santos, 2012","ex vivo","Rat perfused heart","100 ng/kg per day","15 days","Sig. increased the baseline coronary perfusion pressure and impaired vasodilation. Sig. decreased serum 17β-oestradiol levels accompanied by a significant rise in serum progesterone levels. Elevated collagen in heart.  Increased coronary perfusion pressure and incidence of cardiac hypertrophy."],
    [265,"Triphenyl phosphate (TPhP)",25661707,"Du, 2015","in vivo","Zebrafish","0.10, 0.50, 1.0 mg/L","72 hpf","Sig. Reduced heart rate at 0.5 mg. Pericardium edema and SV-BA distance extension, decreased number of cardiac muscle cells and thinner walls of ventricle and atrium at 0.5 mg. Disturbed expressions of transcriptional regulators, especially downregulation of BMP4, NKX2-5 and TBX5."],
    [266,"Tris (2-butoxyethyl) phosphate (TBOEP)",33069947,"Xiong, 2021","in vivo","Zebrafish","20, 200, 1000 and 2000 µg/L","Exp. Between 2 - 120 hpf","No effect <20 ug. Sig. apoptosis in heart region. Increased oxidative stress. Heart rate declined at 1000 ug. Expression of dvl3, axin1 and axin2 was increased while the transcriptional abundance of β-catenin, pkc, wnt11, fzd, nkx2.5 and sox9b was downregulated."],
    [267,"Tris-(1,3-dichloro-2-propyl) phosphate (TDCPP)",30685670,"Zhong, 2019","in vivo","Zebrafish","300 and 500 μg/L","72hpf","Impeded growth of  micro- and macrovessels. Decreased HR. mRNA levels of Vegfa, Vegfr1, Vegfr2 and Vegfa inducer Hifa dose-dependently decreased. mRNA levels of the Nrf2 and its target genes Sod1, Sod2, Gclm and Txn were reduced."],
    [268,"Tris-(1,3-dichloro-2-propyl) phosphate (TDCPP)",30685670,"Zhong, 2019","in vitro","HUVECs","10 - 200 µM","24h","Increased cell proliferation induced by VEGF was suppressed by TDCPP exposure in a dose-dependent manner. repression of Nrf2 expression and activity. Application of a potent Nrf2 activator enhanced VEGF and protected against defective vascular development in zebrafish."],
    [269,"Verapamil",24840785,"Sun, 2014","in vitro","ARVMs","10 µM","0 - 7 min","Sarcomeric contractile function decreased continually. decreased the resting Ca2 + ratio, amplitude of Ca2 + ratio and amplitude/resting calcium"],
    [270,"Verapamil",27184445,"Dempsey, 2016","in vitro","hiPSC-CMs","0 - 1 µM","Unclear","Decreased CT amplitude. 0.1 µM: 20% decrease in AP50 and AP90, 20% increase in AP rise time, 20% decrease in Ca2+ amplitude. 1 µM: stopped beating, Ca2+ flux stops."],
    [271,"Verapamil",31079550,"Lam, 2019","in vitro","hiPSC-CMs","813 nM (C ther.)","30 mins, 14 days","Reductions in beating rate and contraction velocities. Set of cardiac contraction-related genes were significantly downregulated (myofibril and sarcomeric structure–related pathways)."],
    [272,"Verapamil",29274391,"Goineau, 2017","in vitro","hiPSC-CMs","3, 10, 30, 100 and 300 nM","5 min","Concentration-dependently shortened FPDcF, minimum effective concentration was 30 nM"],
    [273,"Verapamil",11581079,"Hill, 2001","ex vivo","Rat left ventricular muscle","31 to 1020 nM","15m","510 nM produced consistent reduction in developed tension of 52.9±3.2%. "]
]}