Arsenic(As), particularly inorganic arsenic is extremely toxic both acute and chronic, very thiophilic in nature and can cause partial paralysis and diabetes due to low-level exposures, while linked to bladder, lung, skin, kidney and colon cancer upon high level exposure. Humans can be exposed to arsenic mainly through inhalation as well as through ingestion. The most adverse effects cause due to exposure from drinking water, but food is the main source of exposure1.
Roxarsone (C6AsNH6O6, 3-nitro-4-hydroxyphenylarsonic acid, otherwise referred to as ROX) is an organic arsenical animal drug, which has been widely used as a feed additive in poultry production to increase weight gain, and to prevent parasitic infections (Coccidiosis, that infects the intestinal tracts) in swine and poultry2. However, under anaerobic conditions, within live chickens and on farm land, ROX can be converted into more toxic forms of inorganic arsenic. Chicken being the most consumed meat in North America people are particularly vulnerable to these metabolites if chicken livers are consumed. ROX is approved by the U.S. FDA and has been used for more than 60 years, but now banned in the European Union and North America due to concerns about exposure to cancer causing arsenic metabolites, although it is still used in some countries3.
In a recent study, three toxicologically relevant methylated phenyl-arsenical metabolites were identified in the chicken livers, in addition to eight previously reported metabolites of ROX, even five days after the supply of ROX was stopped4. The methylation follows the same pathway as inorganic arsenic does and aided by enzymatic methylated reactions which happens via trivalent ROXIII (substrate), As3MT (enzyme) and SAM (S-adenosyl methionine ;methyl donor). For the identification of these new phenyl-arsenical metabolites, for which standards do not exist, the use of HPLC-ICP-MS was complemented with ESI-MS measurements and several other analytical techniques. Moreover, it is found that after excretion, ROX itself and its metabolites occur in animal manure. The speciation of arsenic ROX to primary arsenate happens within 30 days, degradation biotic in nature suggested increased with increasing amount of water5. Rice is prone to accumulate arsenic and its metabolites than other staple food, thus, cancer causing metabolites can be incorporated to human food chain. In Vitro studies have demonstrated the inhibition of protein folding pathways from arsenic trioxides which also cause heart disease and various cancers6. Herein, the more problematic nature of these newly discovered arsenic poultry feed additive metabolites will be discussed in detail, along with their characterization and related aspects.

References
1. Bae, O.-N.; Lim, K.-M.; Chung, J.-H. Arsenic Toxicity 2015, 17–44. 2. Nachman, K. E.; Baron, P. A.; Raber, G.; Francesconi, K. A.; Navas-Acien, A.; Love, D. C. Environmental Health Perspectives2013, 121(7), 818–824. 3. Medicine, C. for V. Product Safety Information - Questions and Answers Regarding 3-Nitro (Roxarsone) https://www.fda.gov/animalveterinary/safetyhealth/productsafetyinformat… (accessed Sep 25, 2017). 4. Peng, H.; Hu, B.; Liu, Q.; Li, J.; Li, X.-F.; Zhang, H.; Le, X. C. Angewandte Chemie 2017, 129(24), 6779–6779. 5. Yao, L.; Li, G.; Dang, Z.; He, Z.; Zhou, C.; Yang, B. Plant and Soil2008, 316(1-2), 117–124. 6. Fisher, D. J.; Yonkos, L. T.; Staver, K. W. Environmental Science & Technology2015, 49(4), 1999–2012.