PARENT SESSION
25 - State of the Art in Analytical Chemistry
8:30 AM to 12:20 PM, Tuesday, 14 May 2002
Session Chair: Spiteller, Michael ¹, Parlar, Harun ², ^{1 2} .
Stolz B

(25-05) Use of a novel short-term Chlorella vulgaris toxicity assay to develop QSARs .

Cronin, Mark^*,1, Edwards, Robert¹, Dearden, John¹, Aptula, Aynur², Worgan, Andrew¹, Netzeva, Tatiana¹, ¹ Liverpool John Moores University, Liverpool, England² UFZ Centre for Environmental Research, Leipzig, Germany

ABSTRACT- A novel short-term toxicity test has been developed to assess the effects of chemicals to the alga Chlorella vulgaris. The basis of the 15-minute C. vulgaris toxicity test is the inhibition of enzymatic activity within the cell. In this assay fluorescein diacetate (FDA) is added to the algal suspension and is assumed to be hydrolysed by esterase enzymes to fluorescein. The conversion can be measured spectrofluorimetrically, as fluorescein diacetate does not have a fluorophore whereas fluorescein does fluoresce. The results from the toxicity assay compare favourably to those from other algal assays. In this study, toxicity data from the C. vulgaris assay for more than 90 compounds have been utilised to develop QSARs. The compounds tested include those from a variety of mechanisms of action such as non-polar narcosis, polar narcosis, weak acid respiratory uncoupling, electrophiles and organophosphate pesticides. The compounds represent a very heterogeneous and diverse selection of chemicals. To develop QSARs a number of physico-chemical parameters were calculated. These included the logarithm of the octanol-water partition coefficient (log P) from the ClogP for Windows software, molecular orbital properties calculated utilising the AM1 Hamiltonian in the VAMP software available in the TSAR molecular spreadsheet, and other assorted topological and structural and fragment based descriptors from TSAR. Toxicity is strongly correlated to descriptors for hydrophobicity and electrophilicity (the energy of the lowest unoccupied molecular orbital, LUMO). This simplistic and mechanistically-based approach to toxicity prediction is demonstrated to have significant advantages over other techniques based on molecular connectivities and structural fragments. [This work was supported in part by the European Union IMAGETOX Research Training Network (HPRN-CT- 1999-00015)].

Key words: QSAR, Chlorella vulgaris, fluorescein diacetate