Toxicology in vitro : an international journal published in association with BIBRA
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The aim of this study was to determine the steroidogenic endocrine disrupting effect of three widely used serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol, using two in vitro models, the H295R assay and a recombinant CYP17 enzyme assay. Steroid hormones were quantified using LC-MS/MS. Duloxetine showed endocrine disrupting effects at 5-20μM with CYP17 being the main target. ⋯ Overall, results from the recombinant CYP17 assay confirmed the results from the H295R cell assay. Using testosterone as end point, the margin of safety (defined as NOAEL/Cmax) for duloxetine was 1.6 indicating that duloxetine may have endocrine disrupting effects. In contrast, venlafaxine and tramadol showed higher margins of safety (venlafaxine: 24; tramadol: 157) indicating a lower potential to disrupt the human steroidogenesis.