title: Black pepper constituent piperine: genotoxicity studies in vitro and in vivo.
abstract: Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published. To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed. Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic.
authors: DSM Nutritional Products Ltd, Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address: anette.thiel@dsm.com.
authors: Anette
authors: A
authors: Thiel
authors: WIL Research Europe B.V., Hambakenwetering 7, 5231 DD 's-Hertogenbosch, The Netherlands.
authors: Carin
authors: C
authors: Buskens
authors: DSM Nutritional Products Ltd, Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
authors: Tina
authors: T
authors: Woehrle
authors: DSM Nutritional Products Ltd, Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
authors: Stéphane
authors: S
authors: Etheve
authors: WIL Research Europe B.V., Hambakenwetering 7, 5231 DD 's-Hertogenbosch, The Netherlands.
authors: Ankie
authors: A
authors: Schoenmakers
authors: DSM Nutritional Products Ltd, Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
authors: Markus
authors: M
authors: Fehr
authors: DSM Nutritional Products Ltd, Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
authors: Paul
authors: P
authors: Beilstein
mesh_terms: D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D052117:Benzodioxoles / Q000633:toxicity*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D029222:Piper nigrum / Q000737:chemistry*; D010880:Piperidines / Q000633:toxicity*; D053284:Polyunsaturated Alkamides / Q000633:toxicity*
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C008922:piperine
keywords: Black pepper; Genotoxicity; Micronucleus; Piperine