Toxicity assessment of mono-substituted benzenes and phenols using a Pseudomonas initial oxygen uptake assay.
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).
Huang
Ded-Shih
DS
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan 701. dedshih@mail.ncku.edu.tw
Whang
Thou-Jen
TJ
Cheng
Fei-Chen
FC
Wu
Ya-Ping
YP
Wang
Yi-Ting
YT
Luo
Wen-I
WI
Wang
Yane-Shih
YS
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*
D001555:Benzene Derivatives; D001565:Benzoates; D010636:Phenols; D014874:Water Pollutants, Chemical; D010100:Oxygen