Structure-toxicity relationships for selected halogenated aliphatic chemicals

Kevin S. Akers, Glendon D. Sinks, T. Wayne Schultz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Toxicity to the ciliate Tetrahymena pyriformis (log(IGC50-1)) for 39 halogen-substituted alkanes, alkanols, and alkanitriles were obtained experimentally. Log(IGC50-1) along with the hydrophobic term, logK(ow) (1-octanol/water partition coefficient) and the electrophilic parameter, E(lumo) (the energy of the lowest unoccupied molecular orbital) were used to develop quantitative structure-activity relationships (QSARs). Two strong hydrophobic dependent relationships were obtained: one for the haloalkanes and a second for the haloalcohols. The relationship for the haloalkanes [log(IGC50-1)=0.92 (logK(ow))-2.58; n=4, r2=0.993, s=0.063, f=276, Pr>f=0.0036] was not different from baseline toxicity. With the rejection of 1,3-dibromo-2-propanol as a statistical outlier, the relationship [log(IGC50-1)=0.63(logK(ow))-1.18; n=19, r2=0.860, s=0.274, f=104, Pr>f=0.0001] was observed for the haloalcohols. No hydrophobicity-dependent model (r2=0.165) was observed for the halonitriles. However, an electrophilicity-dependent model [log(IGC50-1)=-1.245(E(lumo))+0.73; n=15, r2=0.588, s=0.764, F=18.6, Pr>f=0.0009] was developed for the halonitriles. Additional analysis designed to examine surface-response modeling of all three chemical classes met with some success. Following rejection of statistical outliers, the plane [log(IGC50-1)=0.60(logK(ow))-0.747(E(lumo))-0.37; n=34, r2=0.915, s=0.297, F=162, Pr>F=0.0001] was developed. The halogenated alcohols and nitriles tested all had observed toxicity in excess of non-reactive baseline toxicity (non-polar narcosis). This observation along with the complexity of the structure-toxicity relationships developed in this study suggests that the toxicity of haloalcohols and halonitriles is by multiple and/or mixed mechanisms of action which are electro(nucleo)philic in character. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)33-39
Number of pages7
JournalEnvironmental Toxicology and Pharmacology
Issue number1
StatePublished - Mar 1999
Externally publishedYes


  • Reactive toxicity
  • Structure-activity
  • Tetrahymena pyriformis


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