A novel equal frequency sampling of factor levels (EFSFL) method is applied to identify the dominant factor inducing the combined toxicities of 13 factors

Ting-Ting Ding; Shu-Shen Liu; Ze-Jun Wang; Peng Huang; Zhong-Wei Gu; Meng-Ting Tao

doi:10.1016/j.envint.2023.107940

A novel equal frequency sampling of factor levels (EFSFL) method is applied to identify the dominant factor inducing the combined toxicities of 13 factors

Environ Int. 2023 May:175:107940. doi: 10.1016/j.envint.2023.107940. Epub 2023 Apr 21.

Authors

Ting-Ting Ding¹, Shu-Shen Liu², Ze-Jun Wang³, Peng Huang⁴, Zhong-Wei Gu⁵, Meng-Ting Tao⁵

Affiliations

¹ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China.
² Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China. Electronic address: ssliuhl@263.net.
³ National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, PR China.
⁴ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China.
⁵ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China.

PMID: 37119652
DOI: 10.1016/j.envint.2023.107940

Abstract

The research framework combining global sensitivity analysis (GSA) with quantitative high-throughput screening (qHTS), called GSA-qHTS, provides a potentially feasible way to screen for important factors that induce toxicities of complex mixtures. Despite its value, the mixture samples designed using the GSA-qHTS technique still have a shortage of unequal factor levels, which leads to an asymmetry in the importance of elementary effects (EEs). In this study, we developed a novel method for mixture design that enables equal frequency sampling of factor levels (called EFSFL) by optimizing both the trajectory number and the design and expansion of the starting points for the trajectory. The EFSFL has been successfully employed to design 168 mixtures of 13 factors (12 chemicals and time) that each have three levels. By means of high-throughput microplate toxicity analysis, the toxicity change rules of the mixtures are revealed. Based on EE analysis, the important factors affecting the toxicities of the mixtures are screened. It was found that erythromycin is the dominant factor and time is an important non-chemical factor in mixture toxicities. The mixtures can be classified into types A, B, and C mixtures according to their toxicities at 12 h, and all the types B and C mixtures contain erythromycin at the maximum concentration. The toxicities of the type B mixtures increase firstly over time (0.25 ∼ 9 h) and then decrease (12 h), while those of the type C mixtures consistently increase over time. Some type A mixtures produce stimulation that increases with time. With the present new approach to mixture design, the frequency of factor levels in mixture samples is equal. Consequently, the accuracy of screening important factors is improved based on the EE method, providing a new method for the study of mixture toxicity.

Keywords: Antibiotics; Environmentally relevant concentrations; Mixture toxicity; Pesticides; Vibrio qinghaiensis sp.-Q67.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Complex Mixtures
Erythromycin / pharmacology
High-Throughput Screening Assays
Vibrio*

Substances

Erythromycin
Complex Mixtures