A method of screening a compound for its potential to causing systemic and/or hepatic toxicity, the method comprising the steps of: (a) providing a compound to be screened; (b) establishing a hepatic cell system comprising a capacity for bile acid synthesis, bile acid transport and/or bile acid regulation; (c) exposing the HCS to a range of concentrations of a bile acid to determine a toxicity profile of the bile acid, wherein the bile acid toxicity profile comprises a toxicity potency; (d) exposing the HCS to a range of concentrations of a bile acid in the presence of the compound to be screened and determining a toxicity profile of the bile acid, wherein the bile acid toxicity profile comprises a toxicity potency; and (e) comparing the toxicity potency of the bile acid between steps (c) and (d) to determine the potential of the compound to cause systemic and/or hepatic toxicity, wherein an increase in the toxicity potency in the step (d) as compared to step (c) indicates a potential to cause cholestatic hepatotoxicity, wherein a decrease in the toxicity potency in step (d) as compared to step (c) indicates a potential to cause cholestasis resulting in systemic toxicity, and wherein determining the potential of the compound to cause systemic and/or hepatic toxicity comprises characterizing a compound as having a potential to cause cholestatic hepatic toxicity if the compound causes an increase in the bile acid toxicity potency; and determining whether the compound is a bile acid efflux inhibitor, a farnesoid X receptor antagonist, or a combination thereof. (a) providing a compound to be screened; (b) establishing a hepatic cell system comprising a capacity for bile acid synthesis, bile acid transport and/or bile acid regulation; (c) exposing the HCS to a range of concentrations of a bile acid to determine a toxicity profile of the bile acid, wherein the bile acid toxicity profile comprises a toxicity potency; (d) exposing the HCS to a range of concentrations of a bile acid in the presence of the compound to be screened and determining a toxicity profile of the bile acid, wherein the bile acid toxicity profile comprises a toxicity potency; and (e) comparing the toxicity potency of the bile acid between steps (c) and (d) to determine the potential of the compound to cause systemic and/or hepatic toxicity, wherein an increase in the toxicity potency in the step (d) as compared to step (c) indicates a potential to cause cholestatic hepatotoxicity, wherein a decrease in the toxicity potency in step (d) as compared to step (c) indicates a potential to cause cholestasis resulting in systemic toxicity, and wherein determining the potential of the compound to cause systemic and/or hepatic toxicity comprises characterizing a compound as having a potential to cause cholestatic hepatic toxicity if the compound causes an increase in the bile acid toxicity potency; and determining whether the compound is a bile acid efflux inhibitor, a farnesoid X receptor antagonist, or a combination thereof. wherein an increase in the toxicity potency in the step (d) as compared to step (c) indicates a potential to cause cholestatic hepatotoxicity, wherein a decrease in the toxicity potency in step (d) as compared to step (c) indicates a potential to cause cholestasis resulting in systemic toxicity, and wherein determining the potential of the compound to cause systemic and/or hepatic toxicity comprises characterizing a compound as having a potential to cause cholestatic hepatic toxicity if the compound causes an increase in the bile acid toxicity potency; and determining whether the compound is a bile acid efflux inhibitor, a farnesoid X receptor antagonist, or a combination thereof.