Table 1. Mechanistic classification, cytotoxicity to HepG2 cells and selected concentrations of the compounds included in the metabolomic study.

Compound	Abbreviation	Therapeutic class	Mechanisma	IC10(μM)b	IC50 (μM)b	Cmaxc (μM)	Concentrationd (μM)
Citrate	Cit	Urinary alkalinizer	C	>1000		NA	500, 1000
Ketotifen	Ket	Antihistaminic	C	130 ± 50	400 ± 200	0.0014	50, 100
Cumene hydroperoxide	Cum		OS	480 ± 90	800 ± 200	NA	50, 100, 250
tert-Butyl hydroperoxide	Tert		OS	280 ± 40	590 ± 180	NA	50, 100, 250
Amiodarone	Am	Antiarrhythmic	P	26 ± 4	78 ± 13	2.2	5, 10, 20
Clozapine	Clo	Antipsychotic	P	41 ± 12	60 ± 10	1.09	10, 20
Fluoxetine	Fluo	Antidepressant	P	12 ± 2	43 ± 5	0.93	20
Tilorone	Til	Antiviral	P	14 ± 3	65 ± 7	-	5, 20
Tamoxifen	Tam	Antiestrogen	P	32 ± 2	57 ± 5	0.27	15
Doxycycline	Dox	Antibiotic	S	600 ± 200	2200 ± 500	8.77	250, 500
Tetracycline	Tet	Antibiotic	S	640 ± 180	1350 ± 150	14.2	50, 100, 200, 400
Valproate	Val	Anticonvulsant	S	8870 ± 1500	17800 ± 3000	481	2000, 4000, 8000

NA: not applicable.

^aMajor mechanism involved in hepatotoxicity induced by the compound: S, steatosis; P, phospholipidosis; OS, oxidative stress; C, non-hepatotoxic (control)²⁸,⁵⁰.

^bIC10 and IC50: the compound concentration that leads to a reduction of 10% and 50%, respectively, in viability (MTT assay) of HepG2 cells after 24 h of treatment¹⁴,²⁰,⁵⁰.

^cC_max: Therapeutically active average plasma maximum concentration values upon single-dose administration at commonly recommended therapeutic doses¹¹,³⁵,⁵⁰.

^dConcentrations used in the metabolomic study.