title: Intralaboratory and interlaboratory evaluation of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay.
abstract: A novel in vitro human reconstructed skin micronucleus (RSMN) assay has been developed using the EpiDerm 3D human skin model [R. D. Curren, G. C. Mun, D. P. Gibson, and M. J. Aardema, Development of a method for assessing micronucleus induction in a 3D human skin model EpiDerm, Mutat. Res. 607 (2006) 192-204]. The RSMN assay has potential use in genotoxicity assessments as a replacement for in vivo genotoxicity assays that will be banned starting in 2009 according to the EU 7th Amendment to the Cosmetics Directive. Utilizing EpiDerm tissues reconstructed with cells from four different donors, intralaboratory and interlaboratory reproducibility of the RSMN assay were examined. Seven chemicals were evaluated in three laboratories using a standard protocol. Each chemical was evaluated in at least two laboratories and in EpiDerm tissues from at least two different donors. Three model genotoxins, mitomycin C (MMC), vinblastine sulfate (VB) and methyl methanesulfonate (MMS) induced significant, dose-related increases in cytotoxicity and MN induction in EpiDerm tissues. Conversely, four dermal non-carcinogens, 4-nitrophenol (4-NP), trichloroethylene (TCE), 2-ethyl-1,3-hexanediol (EHD), and 1,2-epoxydodecane (EDD) were negative in the RSMN assay. Results between tissues reconstructed from different donors were comparable. These results indicate the RSMN assay using the EpiDerm 3D human skin model is a promising new in vitro genotoxicity assay that allows evaluation of chromosome damage following "in vivo-like" dermal exposures.
authors.affiliation: The Procter & Gamble Co., P.O. Box 538707, Cincinnati, OH 45253, United States.
authors.forename: Ting
authors.initials: T
authors.lastname: Hu
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kaluzhny
authors.forename: Greg C
authors.initials: GC
authors.lastname: Mun
authors.forename: Brenda
authors.initials: B
authors.lastname: Barnett
authors.forename: Viktor
authors.initials: V
authors.lastname: Karetsky
authors.forename: Nathan
authors.initials: N
authors.lastname: Wilt
authors.forename: Mitchell
authors.initials: M
authors.lastname: Klausner
authors.forename: Rodger D
authors.initials: RD
authors.lastname: Curren
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Aardema
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods / Q000592:standards; D004817:Epidermis / Q000187:drug effects / Q000502:physiology; D006018:Glycols / Q000633:toxicity; D006801:Humans; D007753:Laboratories / Q000592:standards; D008741:Methyl Methanesulfonate / Q000633:toxicity; D015162:Micronucleus Tests / Q000379:methods; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity; D009596:Nitrophenols / Q000633:toxicity; D015203:Reproducibility of Results; D012867:Skin / Q000166:cytology; D023422:Skin Irritancy Tests / Q000379:methods* / Q000592:standards; D023822:Tissue Engineering / Q000379:methods*; D014241:Trichloroethylene / Q000633:toxicity; D014747:Vinblastine / Q000633:toxicity
chemical_list: D006018:Glycols; D009153:Mutagens; D009596:Nitrophenols; D014241:Trichloroethylene; D016685:Mitomycin; D014747:Vinblastine; D008741:Methyl Methanesulfonate; C004917:ethohexadiol; C024836:4-nitrophenol