title: Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats.
abstract: Occupational/accidental exposure data have showed hemorrhage as a result of transdermal exposure to warfarin, however, other effects are not known. In the present study, the impact of epicutaneous application of 10 μg or 100 μg of warfarin (three times, once a day) on peripheral blood polymorphonuclear (PMN) and mononuclear cells (PBMC) was examined in rats. Both doses resulted in prolongation of prothrombin time and changes in hematologic parameters. Increases in PMN intracellular myeloperoxidase (MPO) activity were seen at higher warfarin dose and both doses resulted in higher percentages of granular CD11b(+) cells. In contrast, a decrease in PMN TNF and IL-6 production (ELISA) and gene expression (RT-PCR) was observed. Epicutaneous application of warfarin resulted in decreased numbers of PBMC, higher numbers of mononuclear CD11b(+) cells, but without effect on PMBC cytokine production. The data obtained showed differential effects of transdermal exposure to warfarin depending on leukocyte type and activity.
authors.affiliation: Institute for Medical Biochemistry, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Subota
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mirkov
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Demenesku
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Popov Aleksandrov
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Ninkov
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors.forename: Dina
authors.initials: D
authors.lastname: Mileusnic
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia; Institute of Zoology, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Kataranovski
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia; Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia. Electronic address: milena@ibiss.bg.ac.rs.
authors.forename: Milena
authors.initials: M
authors.lastname: Kataranovski
mesh_terms: D000287:Administration, Topical; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects*; D016273:Occupational Exposure; D011517:Prothrombin Time; D051381:Rats; D012378:Rodenticides / Q000633:toxicity*; D014859:Warfarin / Q000633:toxicity*
chemical_list: D016207:Cytokines; D012378:Rodenticides; D014859:Warfarin
keywords: Peripheral blood leukocytes; Rats; Transdermal warfarin exposure