Modeling non-monotonic dose-response relationships: model evaluation and hormetic quantities exploration. 2013

Xiang-Wei Zhu, and Shu-Shen Liu, and Li-Tang Qin, and Fu Chen, and Hai-Ling Liu
Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China.

Non-monotonic (biphasic) dose-response relationships, known as hormetic relationships, have been observed across multiple experimental systems. Several models were proposed to describe non-monotonic relationships. However, few studies provided comprehensive description of hermetic quantities and their potential application. In this study, five biphasic models were used to fit five hormetic datasets from three different experimental systems of our lab. The bisection algorithm based on individual monotone functions was proposed to calculate arbitrary hormetic quantities instead of traditional methods (e.g., model reparameterization) which need complex mathematical manipulation. Results showed that all the five biphasic models could describe those datasets fairly well with coefficient of determination ( R(2) adj) greater than 0.95 and root mean square error (RMSE) smaller than 0.10. The best-fit model could be selected based on EC(R10), RMSE, and a supplemental criterion of Akaike information criterion (AIC). Hormetic quantities that trigger 10% stimulation at the left (EC(L10)) and right (EC(R10)) side of stimulatory peak were calculated and emphasized for their implication in hormesis exploration for the first time. Furthermore, the EC(L10), proposed as an alarm threshold for hormesis, was expected to be useful in risk assessment of environmental chemicals. This study lays a foundation in the quantitative description of the low dose hormetic effect and the investigation of hormesis in environmental risk assessment.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D059165 Hormesis Biphasic dose responses of cells or organisms (including microorganisms) to an exogenous or intrinsic factor, in which the factor induces stimulatory or beneficial effects at low doses and inhibitory or adverse effects at high doses. Hormetic Dose-Response,Dose-Response, Hormetic,Dose-Responses, Hormetic,Hormeses,Hormetic Dose Response,Hormetic Dose-Responses
D018570 Risk Assessment The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988) Assessment, Risk,Benefit-Risk Assessment,Risk Analysis,Risk-Benefit Assessment,Health Risk Assessment,Risks and Benefits,Analysis, Risk,Assessment, Benefit-Risk,Assessment, Health Risk,Assessment, Risk-Benefit,Benefit Risk Assessment,Benefit-Risk Assessments,Benefits and Risks,Health Risk Assessments,Risk Analyses,Risk Assessment, Health,Risk Assessments,Risk Benefit Assessment,Risk-Benefit Assessments

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