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

Content Provider	Springer Nature Link
Author	Dawson, D. A. Mooneyham, T. Jeyaratnam, J. Schultz, T. W. Pöch, G.
Copyright Year	2011
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.
Starting Page	547
Ending Page	557
Page Count	11
File Format	PDF
ISSN	00904341
Journal	Archives of Environmental Contamination and Toxicology
Volume Number	61
Issue Number	4
e-ISSN	14320703
Language	English
Publisher	Springer-Verlag
Publisher Date	2011-03-31
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Environmental Monitoring/Analysis Environmental Health Ecotoxicology Pollution Soil Science & Conservation Environmental Chemistry
Content Type	Text
Resource Type	Article
Subject	Pollution Health, Toxicology and Mutagenesis Medicine Toxicology

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Mixture Toxicity of SN2-Reactive Soft Electrophiles: 3. Evaluation of Ethyl α-Halogenated Acetates with α-Halogenated Acetonitriles

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