title: Interpreting aquatic toxicity QSARs: the significance of toxicant body residues at the pharmacologic endpoint.
abstract: Aquatic QSAR investigations employ bioassay data where a biological response is associated with a toxicant concentration in the exposure water. Although convenient this ignores the fundamental principle that the response is more closely related to an amount present in the organism. This problem has been examined using acute toxicity and bioconcentration QSARs employing log Kow as the molecular descriptor. Combining these QSAR relationships enables estimates of the amount of toxicant in organisms to be made. For acute narcosis (50% mortality) the toxicant level in the hydrophobic (lipid) phase of an exposed organism is, as a first approximation, constant at approximately 50 mmol l-1 of lipid. For the acute toxicity of a variety of hydrophobic narcotic organics examined by US EPA-Duluth in tests with fathead minnows, this corresponds to a whole-body residue of about 4 mmol kg-1. Although the level in the hydrophobic phase remains constant, for hydrophilic chemicals (log Kow less than 1.5) the contribution of the hydrophilic (water) phase of the organism dominates and total body residues should be similar to the respective threshold LC50s. This has important implications in simple pharmacokinetic modelling and in interpreting residue levels in organisms collected in environmental monitoring studies.
authors.affiliation: CanTox Inc., Mississauga, Ontario, Canada.
authors.forename: L S
authors.initials: LS
authors.lastname: McCarty
authors.forename: D
authors.initials: D
authors.lastname: Mackay
authors.forename: A D
authors.initials: AD
authors.lastname: Smith
authors.forename: G W
authors.initials: GW
authors.lastname: Ozburn
authors.forename: D G
authors.initials: DG
authors.lastname: Dixon
mesh_terms: D000818:Animals; D001822:Body Burden; D003530:Cyprinidae; D007700:Kinetics; D008962:Models, Theoretical; D013329:Structure-Activity Relationship; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D015262:Xenobiotics