Title
QSAR models for predicting in vivo aquatic toxicity of chlorinated alkanes to fish
Author
Zvinavashe, E.
van den Berg, H.
Soffers, A.E.M.F.
Vervoort, J.
Freidig, A.
Murk, A.J.
Rietjens, I.M.C.M.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
Quantitative structure-activity relationship (QSAR) models are expected to play a crucial role in reducing the number of animals to be used for toxicity testing resulting from the adoption of the new European Union chemical control system called Registration, Evaluation, and Authorization of Chemicals (REACH). The objective of the present study was to generate in vitro acute toxicity data that could be used to develop a QSAR model to describe acute in vivo toxicity of chlorinated alkanes. Cytotoxicity of a series of chlorinated alkanes to Chinese hamster ovary (CHO) cells was observed at concentrations similar to those that have been shown previously to be toxic to fish. Strong correlations exist between the acute in vitro toxicity of the chlorinated alkanes and (i) hydrophobicity [modeled by the calculated log Kow (octanol-water partition coefficient); r2 = 0.883 and rint2 = 0.854] and (ii) in vivo acute toxicity to fish (r2 = 0.758). A QSAR model has been developed to predict in vivo acute toxicity to fish, based on the in vitro data and even on in silico log Kow data only. The developed QSAR model is applicable to chlorinated alkanes with up to 10 carbon atoms, up to eight chlorine atoms, and log Kow values lying within the range from 1.71 to 5.70. Out of the 100204 compounds on the European Inventory of Existing Chemicals (EINECS), our QSAR model covers 77 (0.1%) of them. Our findings demonstrate that in vitro experiments and even in silico calculations can replace animal experiments in the prediction of the acute toxicity of chlorinated alkanes. © 2008 American Chemical Society.
Subject
Physiological Sciences
1 chloro 2 methylbutane
1 chloro 2,2 dimethylpropane
1 chlorodecane
1 chlorododecane
1 chloroheptane
1 chlorohexane
1 chlorononane
1 chlorooctane
1 chloropentane
1,1 dichloro 3,3 dimethylbutane
1,1,2 trichloroethane
1,10 dichlorodecane
1,2 dichlorobutane
1,2 dichloropropane
1,3 dichloropropane
1,6 dichlorohexane
1,8 dichlorooctane
1,9 dichlorononane
alkane derivative
carbon
carbon tetrachloride
chlorine
tetrachloroethane
animal cell
animal experiment
aquatic environment
article
cell viability
chlorination
CHO cell
controlled study
cytotoxicity
fish
hydrophobicity
nonhuman
quantitative structure activity relation
Algorithms
Animals
Artificial Intelligence
Cell Survival
Chemistry, Physical
CHO Cells
Cricetinae
Cricetulus
Fishes
Hydrocarbons, Chlorinated
Predictive Value of Tests
Quantitative Structure-Activity Relationship
Tetrazolium Salts
Thiazoles
Animalia
Cricetulus griseus
To reference this document use:
http://resolver.tudelft.nl/uuid:8bfd4732-8d7e-4e5c-965e-5d12193ee0e1
DOI
https://doi.org/10.1021/tx700367c
TNO identifier
240666
ISSN
0893-228X
Source
Chemical Research in Toxicology, 21 (3), 739-745
Document type
article