title: IRAG working group 3. Cell function-based assays. Interagency Regulatory Alternatives Group.
abstract: Cell function-based tests measure responses of cells at sublytic concentrations of test agents. The fluorescein leakage assay measures effects of substances on the barrier function of epithelial monolayers or multilayers (MDCK or NHEK cells) as in vitro models of corneal epithelial function. Two IRAG data submissions suggest that the fluorescein leakage assay shows promise as a screening test for surfactants and alcohols. The test method requires further optimization, standardization and evaluation to fully determine its utility as an in vitro ocular irritancy test. The silicon microphysiometer test measures effects of test substances on the metabolic rate of cells; although a large number of cell types have been evaluated, L929 cells have been used for irritancy screening. Three IRAG data submissions on the silicon microphysiometer test showed strong in vivo/in vitro correlations for surfactants and surfactant-based personal care and household cleaning products in a range of mild to moderate ocular irritancy. This and published information support the reproducibility of the method and its use as an ocular irritancy screening test for aqueous-soluble liquid, surfactant-based formulations.
authors.affiliation: Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
authors.forename: P
authors.initials: P
authors.lastname: Botham
authors.forename: R
authors.initials: R
authors.lastname: Osborne
authors.forename: K
authors.initials: K
authors.lastname: Atkinson
authors.forename: G
authors.initials: G
authors.lastname: Carr
authors.forename: M
authors.initials: M
authors.lastname: Cottin
authors.forename: R G
authors.initials: RG
authors.lastname: van Buskirk
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004285:Dogs; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D015203:Reproducibility of Results; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D012879:Skin Physiological Phenomena; D018675:Toxicity Tests / Q000379:methods
chemical_list: D005452:Fluoresceins; D007509:Irritants