title: In vitro toxicity screening of chemical mixtures using HepG2/C3A cells.
abstract: Traditional toxicological methods that utilize only single pure compounds may not accurately predict risks from substances with multiple chemical constituents. A complementary approach to conventional methodologies includes in vitro systems that assess toxicity of chemical mixtures and identify components that may adversely impact biological processes. Compared to animal models, in vitro assays are inexpensive, rapid, and reduce and refine related animal testing. We utilized HepG2/C3A cells as a hepatotoxicity screening model to evaluate the cytotoxic and metabolic effects of three commercially available oil dispersants, Corexit EC9500A and EC9527A and ZI-400. The surfactant DOSS, a primary active constituent of the Corexit dispersants, was also evaluated. Biologically relevant endpoints were measured including cell viability, oxidative stress, and mitochondrial activity. Significant increases in cytotoxicity were observed with Corexit dispersants (LC(50)∼250 ppm), whereas ZI-400 was moderately cytotoxic (LC(50) >>400 ppm). Each dispersant caused an accumulation of reactive oxygen species and altered mitochondrial activity and other cellular processes. Generally, DOSS made notable contributions to the effects of EC9500A and EC9527A, however, they were observed at concentrations higher than those used in most consumer products. Overall, this system may represent a valuable complementary tool for predicting the toxicity of complex mixtures.
authors.affiliation: Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708-2476, USA. omari.bandele@fda.hhs.gov
authors.forename: Omari J
authors.initials: OJ
authors.lastname: Bandele
authors.forename: Michael F
authors.initials: MF
authors.lastname: Santillo
authors.forename: Martine
authors.initials: M
authors.lastname: Ferguson
authors.forename: Paddy L
authors.initials: PL
authors.lastname: Wiesenfeld
mesh_terms: D002460:Cell Line; D045424:Complex Mixtures; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D008928:Mitochondria; D018384:Oxidative Stress; D018675:Toxicity Tests
chemical_list: D045424:Complex Mixtures; D019363:Cytochrome P-450 CYP1A1