Environmental contamination and human consumption of chickens could result in potential exposure to
Roxarsone (3-nitro-4-hydroxyphenylarsonic acid), an organic arsenical that has been used as a chicken feed additive in many countries. However, little is known about the metabolism of
Roxarsone in humans. The objective of this research was to investigate the metabolism of
Roxarsone in human liver cells and to identify new
arsenic metabolites of toxicological significance. Human primary hepatocytes and
hepatocellular carcinoma HepG2 cells were treated with 20 or 100 μM
Roxarsone.
Arsenic species were characterized using a strategy of complementary chromatography and mass spectrometry. The results showed that
Roxarsone was metabolized to more than 10
arsenic species in human hepatic cells. A new metabolite was identified as a thiolated
Roxarsone. The 24 h IC50 values of thiolated
Roxarsone for A549
lung cancer cells and T24
bladder cancer cells were 380 ± 80 and 42 ± 10 μM, respectively, more toxic than
Roxarsone, whose 24 h IC50 values for A549 and T24 were 9300 ± 1600 and 6800 ± 740 μM, respectively. The identification and toxicological studies of the new
arsenic metabolite are useful for understanding the fate of
arsenic species and assessing the potential impact of human exposure to
Roxarsone.