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United States Department of Agriculture

Agricultural Research Service

Title: Halogenated 2,5 Pyrrolidinediones: Synthesis, Bacterial Mutagenicity in Ames Tester Strain Ta-100 and Semi-Empirical Molecular Orbital Calculations

Authors
item Freeman, Beverly -
item Wilson, Robert -
item Binder, Ronald
item Haddon, William

Submitted to: Mutation Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 31, 2000
Publication Date: February 20, 2001
Citation: Freeman, B., Wilson, R., Binder, R.G., Haddon, W.F. 2001. Halogenated 2,5-pyrrolidinediones: synthesis, bacterial mutagenicity in Ames tester strain TA-100 and semi-empirical molecular orbital calculations. 490(2):89-98.

Interpretive Summary: The Food Safety and Health Unit was asked by the Food Safety and Inspection Service to provide information on the chemical nature of biologically active by-products formed in poultry chiller water when premitted levels of chlorine were exceeded in poultry processing operations. The research led to the identification of a single chemical compound, a multiply-chlorinated imide. This compound accounted for most of the biological activity of simulated poultry chiller water, as measured in a widely accepted test method called the Ames bacterial mutagensis bioassay. The newly identified Ames-active compound is similar in molecular structure to a previously discovered disinfection by-product of drinking water chlorination called "MX". MX is a member of the chlorofuranone class of compounds. The present work links the toxicology risk assessment of these two classes of chemicals using a computer model based on calculated electronic properties. The newly discovered chloroimide and six synthetic analogs are compared with MX and nine additional chlorofuranones. This computer model will provide FSIS and the poultry industy with an improved understanding of the chemistry and toxicology of chlorinated poultry chiller water.

Technical Abstract: Computed energies of the lowest unoccupied molecular orbital, E(LUMO), and of the radical anion stability, deltaH(f,rad) - deltaH(rad), from MNDO-PM3 show a quantitative correlation with the Ames TA-100 bacterial mutagenicity assay for a novel set of chlorinated 2,5-pyrrolidinediones. One of these, chloroimides, is the principal mutagen produced by chlorination of simulated poultry chiller water. It is the second most potent mutagenic disinfection by product of chlorination ever reported. The molar mutagenicities (M) of these direct acting mutagenic imides having an exocyclic double bond fit the same linear correlations, 1n M vs. E. (LUMO) and 1n M vs. deltaH(f,rad) - deltaH(rad), as the chlorinated 2(5H)-furanone, a byproduct of water chlorination and paper bleaching with chlorine. Mutagencity data for related haloimides having endocyclic double bonds have significantly higher Ames mutagenicity compared to their structural analogs with exocyclic double bonds, but do not follow the same E(LUMO) or deltaH(f,rad)- deltaH(rad) correlation as the exocyclic chloroimides and the chlorinated 2(5H)-furanones.

Last Modified: 11/1/2014
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