TOXSCI ADVANCE ACCESS ORIGINALLY PUBLISHED ONLINE ON NOVEMBER 28, 2007 Toxicological Sciences 2008 102(1):129-137; doi:10.This Article All Versions of this Article: 102/1/129 _most recent_ Services Google Scholar PubMed EFFECTS AND INTERACTIONS IN AN ENVIRONMENTALLY RELEVANT MIXTURE OF PHARMACEUTICALS FRANCESCO POMATI,1, CHIARA ORLANDI, MOIRA CLERICI, FABIO LUCIANI AND ETTORE ZUCCATO _School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney 2052, Australia_ Department of Clinical and Biological Sciences, University of Insubria, Varese 21100, Italy Department of Biomedical, Experimental and Clinical Sciences, University of Insubria, Varese 21100, Italy Department of Environmental Health Sciences, "Mario Negri" Institute for Pharmacological Research, Milan 20157, Italy 1 To whom correspondence should be addressed.+612 9385 1591.Edu.Received October 9, 2007; accepted November 26, 2007 ABSTRACT With the goal of assessing the environmental risk of pharmaceuticals, we have previously observed that a mixture of 13 different drugs at environmentally relevant concentrations had adverse consequences on human and zebra fish cells _in vitro_.We aimed to identify both main and interaction effects within the same environmentally relevant mixture of pharmaceuticals.Studied _in vitro_ cytotoxicity in _Escherichia coli_, human embryonic HEK293, and estrogen-responsive OVCAR3 tumor cells using fractional-factorial experimental design.Approach identified a subset ofpounds of primary environmental concern, namely atenolol, bezafibrate, ciprofloxacin, and liycin, that had statistically significant effects on prokaryotic and eukaryotic cells at environmentally relevant exposure levels (ng/l).Could interact and behave as chemosensitizers, with joint effects representing a statistically significant element of mixture toxicity.And interactions were concentration dependent, confirming the difficulty of dose extrapolation in mixture toxicity data.Study suggests that a thorough investigation of mixture effects can direct environmental concerns toward a handful of pharmaceuticals, which may represent an actual risk at environmental concentrations.Indicate that risk identification may strongly depend on the use of environmentally relevant exposure scenarios.Interactions and dose dependency of effects may hamper the modeling and prediction of mixture toxicity with pharmaceuticals.Identification for micropollutants depends heavily on appropriate study designs, and we indicate the use of _in vitro_ cytotoxicity threshold and statistical design of experiments (DOEs) as a valid approach._Key Words:_ _E.HEK293; interaction; mixtures; OVCAR3; pharmaceuticals.Read more The use of tamsulozin as adjunctive treatment after eswl in patients with distal ureteral stone: do we really need it?
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