An in vitro method of screening a candidate compound for inducing bile canalicular function disorders, said method comprising: exposing a cell culture to said candidate compound, wherein said cell culture comprises a cell culture medium, hepatocytes and a bile canalicular structure having a biliary space characterized by a lumen; detecting morphological alterations of the biliary space, exposing said cell culture and untreated cells as control to a marker compound which is a fluorescent compound, detecting and measuring movement of said marker compound inside and/or outside the lumen by calculating in treated cells and in control untreated cells Canalicular Clearance Efficiency (CCE) which is a percentage of accumulated marker compound cleared out of the canaliculi and canalicular lumen per time unit, quantifying Maximal Biliary Component Accumulation (MBCA) in the biliary space by exposing said culture and control untreated cells to an activated matrix metalloproteinase, added prior to, concomitantly with, or after the marker compound accumulation, for rapid release of accumulated biliary components into the medium for quantification; and calculating an amount of marker compound accumulated into the canalicular space during a defined period which is the expression of the MBCA which defines the maximal amount of small molecules having MW<500 Daltons or large molecules having MW>500 Daltons able to move either from the cell interior or from outside the cell to inside bile canaliculi and to accumulate into canaliculi and canalicular lumens comparing the CCE and the MBCA of said cell culture with that of control untreated cells, susceptibility of said candidate compound to cholestatic side-effects being characterized by reduced CCE levels associated with lower percentages of released marker compounds into the culture medium compared to control cells. exposing a cell culture to said candidate compound, wherein said cell culture comprises a cell culture medium, hepatocytes and a bile canalicular structure having a biliary space characterized by a lumen; detecting morphological alterations of the biliary space, exposing said cell culture and untreated cells as control to a marker compound which is a fluorescent compound, detecting and measuring movement of said marker compound inside and/or outside the lumen by calculating in treated cells and in control untreated cells Canalicular Clearance Efficiency (CCE) which is a percentage of accumulated marker compound cleared out of the canaliculi and canalicular lumen per time unit, quantifying Maximal Biliary Component Accumulation (MBCA) in the biliary space by exposing said culture and control untreated cells to an activated matrix metalloproteinase, added prior to, concomitantly with, or after the marker compound accumulation, for rapid release of accumulated biliary components into the medium for quantification; and calculating an amount of marker compound accumulated into the canalicular space during a defined period which is the expression of the MBCA which defines the maximal amount of small molecules having MW<500 Daltons or large molecules having MW>500 Daltons able to move either from the cell interior or from outside the cell to inside bile canaliculi and to accumulate into canaliculi and canalicular lumens comparing the CCE and the MBCA of said cell culture with that of control untreated cells, susceptibility of said candidate compound to cholestatic side-effects being characterized by reduced CCE levels associated with lower percentages of released marker compounds into the culture medium compared to control cells. <EOS>