Diphenyl Ether Herbicides and Related Compounds: Structure-Activity Relationships as Bacterial Mutagens

Abstract

Several 4-nitrodiphenyl ether herbicides and related compounds or their nitroso, hydroxyamino, or amino derivatives are mutagens or promutagens in the Salmonella typhimurium (strain TA100)/microsome (S9) assay. Six of eleven 4-nitrodiphenyl ethers examined with no 3-substituent are direct-acting mutagens (4-9 revertants/nmol) and ten of eleven of the analogous 4-aminodiphenyl ethers (including those of the herbicides fluorodifen, nitrofen, and CNP) are mutagens (1-30 revertants/nmol) but only on metabolic activation (+S9). Herbicides with a 3-substituent (i.e., acifluorfen, acifluorfen-methyl, bifenox, bifenox free acid, chlomethoxynil, and oxyfluorfen) and their amino derivatives are generally not detected as mutagens (±S9). However, nitroso- and (hydroxyamino)nitrofen, nitroso-CNP, nitrosooxyfluorfen, and nitrosoacifluorfen are direct-acting mutagens (2-7 revertants/nmol). Rats reduce orally administered nitrofen, CNP, oxyfluorfen, acifluorfen, acifluorfen-methyl, and bifenox, presumably via nitroso and hydroxyamino intermediates, to the amino compounds that are excreted in the feces. © 1983, American Chemical Society. All rights reserved.