Since the 1960's, poultry and swine have been fed the benzenearsonic acids roxarsone (4-hydroxy-3-nitrobenzenearsonic acid) and arsanilic acid (p- amino-benzenearsonic acid) at ppm levels. These compounds exhibit antibacterial, antiparasitic, and growth promotion characteristics. Because about 90 percent of the benzenearsonate additive is excreted largely unchanged by the animal, the implication for any hazard to the human consumer has been considered negligible. Whole animal experiments in the old literature indicated the excretion of small amounts of n-acetylated arsanilate and of the reduced, N-acetylated roxarsone derivative. A related compound, p-nitrobenzoate, was shown in vitro to be reduced by the microsomal cytochrome P-450 system. In vitro systems to detect possible biotransformations of the benzenearsonic acids have not yet been reported. Considering the toxicity of arsenic and of nitro- and aminobenzene, the continuing seeming routine use of benzenearsonic acids as feed additives demands that more information on possible metabolites should be gathered. Biotransformation reactions can lead to less toxic intermediates, but amines, and nitro compounds after reduction to amino derivatives, can also be oxidized to more toxic products. These possibilities need to be reassessed with analytical tools of the 1990's . In this project assays will be developed to measure the expected detoxication reactions of reduction and acetylation catalyzed by the cytochrome P-450 microsomal and acetyltransferase supernatant enzyme systems, respectively. Additional possible reactions involving the functional groups of these compounds will be explored in vitro. Possible roles of these organoarsenicals as substrate or coenzyme inhibitors will be tested, as well. With such information, better conclusions can be drawn as to the potential hazard of chronic exposure to these additives.
| Bayse, Gladys S; Hammonds-Odie, Latanya P; Jackson, Kimberly M et al. (2013) Permeation of roxarsone and its metabolites increases caco-2 cell proliferation. Adv Biol Chem 3:389-396 |
