title: Toxicity assessment of mono-substituted benzenes and phenols using a Pseudomonas initial oxygen uptake assay.
abstract: A methodology is presented for assessing the toxicity of chemical substances through their inhibitory action toward the Pseudomonas initial oxygen uptake (PIOU) rate. The current studies reveal that the PIOU assay is rapid, cost-efficient, and easy to perform. The oxygen uptake rate was found to be associated with a putative benzoate transporter and highly dependent on benzoate concentration. The putative benzoate transporter has been shown to follow Michaelis-Menten kinetics. Most phenols were found to be noncompetitive inhibitors of the benzoate transporter. The inhibition constant (Ki) of these noncompetitive inhibitors can be related to the concentration causing 50% oxygen uptake inhibition in Pseudomonas putida. Modeling these data by using the response-surface approach leads to the development of a quantitative structure-activity relationship (QSAR) for the toxicity of phenols ((1/Ki) = -0.435 (+/-0.038) lowest-unoccupied-molecular orbital + 0.517 (+/-0.027)log K(OW) - 2.340 (+/-0.068), n = 49, r2 = 0.930, s = 0.107, r2adj = 0.926, F = 303.1). A comparison of QSAR models derived from the Ki data of the PIOU method and the toxicity data of 40-h Tetrahymena pyrifomis growth inhibition assay (Tetratox) indicated that there was a high correlation between the two approaches (r2 = 0.925).
authors.affiliation: Department of Chemistry, National Cheng Kung University, Tainan, Taiwan 701. dedshih@mail.ncku.edu.tw
authors.forename: Ded-Shih
authors.initials: DS
authors.lastname: Huang
authors.forename: Thou-Jen
authors.initials: TJ
authors.lastname: Whang
authors.forename: Fei-Chen
authors.initials: FC
authors.lastname: Cheng
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wu
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Wang
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Luo
authors.forename: Yane-Shih
authors.initials: YS
authors.lastname: Wang
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D001565:Benzoates / Q000633:toxicity; D064420:Drug-Related Side Effects and Adverse Reactions; D007700:Kinetics; D010100:Oxygen / Q000378:metabolism*; D010636:Phenols / Q000633:toxicity*; D016958:Pseudomonas putida / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D001555:Benzene Derivatives; D001565:Benzoates; D010636:Phenols; D014874:Water Pollutants, Chemical; D010100:Oxygen