title: Cytotoxicity of alkylphenols and alkylated non-phenolics in a primary culture of rainbow trout (Onchorhynchus mykiss) hepatocytes.
abstract: Alkylphenols are common aquatic pollutants originating from industrial use of the compounds themselves or as biodegradation products of alkylphenol polyethoxylates. The cytotoxicity of a range of alkylphenols and alkylated non-phenolics were assessed in a primary culture of rainbow trout (Onchorhynchus mykiss) hepatocytes to construct a structure-toxicity relationship for this group of ubiquitous aquatic pollutants. Metabolic inhibition and loss of membrane integrity were used as cytotoxic endpoints through use of the cellular markers Alamar blue and 5-carboxyfluorescein diacetate acetoxymethyl ester, respectively. The results show that cytotoxicity increased with the hydrophobicity of the alkylphenols for compounds with logK(OW)<4.9. Normal chained alkylphenols, branched alkylphenols and multi-substituted alkylphenols with logK(OW)4.9 deviated clearly from this relationship. The alkylphenols displayed greater cytotoxicity than alkylated non-phenolics and it is proposed that most alkylated non-phenolic caused non-polar narcosis (baseline toxicity) whereas the alkylphenols caused polar narcosis. Observations that metabolic inhibition occurred at lower concentrations than loss of membrane integrity for most chemicals indicated that interference with cellular metabolic functions was the main cause of cytotoxicity. Metabolic inhibition corresponded better than loss of membrane integrity to reported acute toxicity to fish, although the in vivo acute toxicity of hydrophobic compounds (logK(OW)>2-3) was clearly underestimated by both endpoints.
authors.affiliation: Norwegian Institute for Water Research (NIVA), Gaustadallèen 21, N-0349 Oslo, Norway. knut.erik.tollefsen@niva.no <knut.erik.tollefsen@niva.no>
authors.forename: K-E
authors.initials: KE
authors.lastname: Tollefsen
authors.forename: Camilla
authors.initials: C
authors.lastname: Blikstad
authors.forename: Sissel
authors.initials: S
authors.lastname: Eikvar
authors.forename: Eivind
authors.initials: E
authors.lastname: Farmen Finne
authors.forename: Inger
authors.initials: I
authors.lastname: Katharina Gregersen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects*; D006838:Hydrocarbons / Q000737:chemistry / Q000633:toxicity*; D015394:Molecular Structure; D017686:Oncorhynchus mykiss; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D006838:Hydrocarbons; D010636:Phenols; D014874:Water Pollutants, Chemical