Archives of Environmental Contamination and Toxicology

, Volume 61, Issue 4, pp 547–557

Mixture Toxicity of SN2-Reactive Soft Electrophiles: 2—Evaluation of Mixtures Containing Ethyl α-Halogenated Acetates

  • D. A. Dawson
  • T. Mooneyham
  • J. Jeyaratnam
  • T. W. Schultz
  • G. Pöch
Article

DOI: 10.1007/s00244-011-9663-1

Cite this article as:
Dawson, D.A., Mooneyham, T., Jeyaratnam, J. et al. Arch Environ Contam Toxicol (2011) 61: 547. doi:10.1007/s00244-011-9663-1

Abstract

Four ethyl α-halogenated acetates were tested in (1) sham and (2) nonsham combinations and (3) with a nonreactive nonpolar narcotic. Ethyl iodoacetate (EIAC), ethyl bromoacetate (EBAC), ethyl chloroacetate (ECAC), and ethyl fluoroacetate (EFAC), each considered to be an SN2-H-polar soft electrophile, were selected for testing based on their differences in electro(nucleo)philic reactivity and time-dependent toxicity (TDT). Agent reactivity was assessed using the model nucleophile glutathione, with EIAC and EBAC showing rapid reactivity, ECAC being less reactive, and EFAC lacking reactivity at ≤250 mM. The model nonpolar narcotic, 3-methyl-2-butanone (3M2B), was not reactive. Toxicity of the agents alone and in mixture was assessed using the Microtox acute toxicity test at three exposure durations: 15, 30 and 45 min. Two of the agents alone (EIAC and EBAC) had TDT values >100%. In contrast, ECAC (74 to 99%) and EFAC (9 to 12%) had partial TDT, whereas 3M2B completely lacked TDT (<0%). In mixture testing, sham combinations of each agent showed a combined effect consistent with predicted effects for dose-addition at each time point, as judged by EC50 dose-addition quotient values. Mixture toxicity results for nonsham ethyl acetate combinations were variable, with some mixtures being inconsistent with the predicted effects for dose-addition and/or independence. The ethyl acetate–3M2B combinations were somewhat more toxic than predicted for dose-addition, a finding differing from that observed previously for α-halogenated acetonitriles with 3M2B.

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • D. A. Dawson
    • 1
  • T. Mooneyham
    • 1
  • J. Jeyaratnam
    • 1
  • T. W. Schultz
    • 2
  • G. Pöch
    • 3
  1. 1.Department of Biology/ToxicologyAshland UniversityAshlandUSA
  2. 2.Department of Comparative Medicine, College of Veterinary MedicineThe University of TennesseeKnoxvilleUSA
  3. 3.Department of Pharmacology and ToxicologyUniversity of GrazGrazAustria