title: Environmentally relevant organophosphate triesters in herring gulls: In vitro biotransformation and kinetics and diester metabolite formation using a hepatic microsomal assay.
abstract: The in vitro biotransformation and kinetics of six organophosphate triester (OPE) flame retardants were investigated in herring gulls (Larus argentatus) from the Great Lakes using a hepatic microsomal metabolism assay. Administration of each individual OPE (tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), triethyl phosphate (TEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP)) to the in vitro assay (concentration range 0.01 to 10μM) resulted in rapid depletion with the exception of TEP. Following the Michaelis-Menten enzyme kinetics model, a preliminary 2-minute incubation period was used to estimate the Vmax (±SE) values (i.e., the maximal rate of reaction for a saturated enzyme system), which ranged from 5.0±0.4 (TPHP) to 29±18pmol/min/mg protein (TBOEP), as well as the KM (±SE) values (i.e., the OPE concentration corresponding to one half of the Vmax), which ranged from 9.8±1 (TPHP) to 189±135nM (TBOEP). Biotransformation assays over a 100-minute incubation period revealed that TNBP was metabolized most rapidly (with a depletion rate of 73±4pmol/min/mg protein), followed by TBOEP (53±8pmol/min/mg), TCIPP (27±1pmol/min/mg), TPHP (22±2pmol/min/mg) and TDCIPP (8±1pmol/min/mg). In vitro biotransformation of OP triesters was clearly structure-dependent where non-halogenated alkyl OP triesters were metabolized more rapidly than halogenated alkyl triesters. Halogenated OP triesters were transformed to their respective diesters more efficiently relative to non-halogenated OP triesters. To our knowledge, this is the first study to investigate OP triester metabolism and OP diester formation in an avian or wildlife model system, which is important to understand the fate and biological activity of OPEs in an exposed organism.
authors: Wildlife and Landscape Directorate, Science and Technology Branch, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON K1A 0H3, Canada; Department of Chemistry, Carleton University, Ottawa, ON K1S 5B6, Canada.
authors: Alana K
authors: AK
authors: Greaves
authors: Wildlife and Landscape Directorate, Science and Technology Branch, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON K1A 0H3, Canada; Department of Chemistry, Carleton University, Ottawa, ON K1S 5B6, Canada. Electronic address: guanyong.su85@gmail.com.
authors: Guanyong
authors: G
authors: Su
authors: Wildlife and Landscape Directorate, Science and Technology Branch, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON K1A 0H3, Canada; Department of Chemistry, Carleton University, Ottawa, ON K1S 5B6, Canada. Electronic address: robert.letcher@canada.ca.
authors: Robert J
authors: RJ
authors: Letcher
mesh_terms: D000818:Animals; D055162:Biocatalysis; D001711:Biotransformation; D001717:Birds; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004785:Environmental Pollutants / Q000378:metabolism* / Q000493:pharmacokinetics; D004952:Esters; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010755:Organophosphates / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D004785:Environmental Pollutants; D004952:Esters; D010755:Organophosphates; D003577:Cytochrome P-450 Enzyme System
keywords: Herring gull; In vitro biotransformation; Liver microsomes; Metabolism; Organophosphate esters