pyrethroids cytotoxicity and induction of cyp isoforms in human hepatocytes deltamethrin salphacyano3phenoxybenzylcis1 r3r322dibromovinyl22dimethylcyclopropanecarboxylate and permethrin 3phenoxybenzyl1rscistrans322dichlorovinyl22dimethylcyclopropanecarboxylate are pyrethroid insecticides used in agriculture public health and military deployments pyrethroids are known to be capable of inducing cytochrome p450 cyp 2b12b2 cyp1a1 and overall cyp content in rat liver the objectives of this study were to evaluate the potential of deltamethrin and permethrin to cause cytotoxicity and to induce cyp isoforms in human hepatocytes permethrin and deltamethrin showed dosedependent effects on adenylate kinase activity in hepg2 cells in which 50 and 100 microm doses respectively induced a 35 fold increase in activity and also induced adenylate kinase activity in primary human hepatocytes an approximately 3fold induction was noted at 200 microm deltamethrin and a 4fold induction at 100 microm permethrin cytotoxicity was noted in hepg2 cells following 4872 h exposure to 100 or 200 microm deltamethrin and permethrin respectively dosedependent induction of caspase37 was initiated by 125 microm deltamethrin or by 3125 microm permethrin actinomycin d a positive control for induction of caspase 37 induced caspase37 an effect completely abrogated by the specific inhibitor zdevdfmk at 100 microm deltamethrin 23 fold induction of cyp1a1 and cyp2b6 mrna was observed while at the same time an approximately 25fold induction of cyp3a4 was noted permethrinmediated cyp induction was much less potent 4fold or less for cyp1a1 cyp3a4 cyp3a5 cyp2b6 and cyp2a6 it has also been shown that these pyrethroids are ligands for the pregnane x receptor pxr