D-03
Metabolism of a tattoo pigment, Pigment Yellow 74, using rat liver microsomal protein or xanthine oxidase
Y. Cui1, N. V. Gopee1, F. E. Evans2, L. H. Couch1, M. I. Churchwell1, D. R. Doerge1, P. C. Howard3, 1Div. Biochemical Toxicology, NCTR, FDA, Jefferson, AR, 2Div. Chemistry, NCTR, FDA, Jefferson, AR, 3NTP Center for Phototoxicology, NCTR, FDA, Jefferson, AR
Tattooing has increased in popularity in the past decade and now is considered a common form of personal artistic expression. Recent publications point out the increase in tattoo popularity has been accompanied by a change in the pigments used in tattoo inks from inorganic salts to organic-based pigments. Very little is known about the chemical compositions of these pigments or their biological availability, metabolism, or toxicity. In these initial studies, we examined the metabolism of Pigment Yellow 74 (PY74; CI 11741), a common monoazo pigment in yellow tattoo inks. Oxidative metabolism of PY74 was determined following aerobic incubation of PY74 with liver microsomes isolated from 3-methylcholanthrene-treated male F344 rats. PY74 solubility in the incubations was increased by inclusion of bovine serum albumin to 10 mg/mL. Consumption of PY74 and formation of metabolites was linear for up to 30 min at 0.5 mg/mL microsomal protein. The predominant metabolite was isolated by HPLC and identified as a ring hydroxylation product (4-hydroxylation on the 2-methoxyaniline ring) using NMR and MS methods. The identification of the second metabolite and determination of the CYP450 specificity of PY74 metabolism are in progress. PY74 contains a nitro group on the 2-methoxy-4-nitroaniline group that should be available for nitroreduction. PY74 was incubated with 0.2 U/mL xanthine oxidase under anaerobic conditions and the products extracted. The nitroreduction of PY74 to the amino-derivative of PY74(NH2-PY74) was detected by comigration on HPLC (UV-VIS and fluorescence detection) with authentic NH2-PY74, and additionally confirmed by MS analysis. These results demonstrate that PY74 can be metabolized by both aerobic oxidative and anaerobic nitroreductive pathways, and that these monoazo tattoo pigments should not be considered as inert chemicals.
2004 FDA Science Forum | FDA Chapter, Sigma Xi | CFSAN | FDA
Last updated on 2004-APR-02 by frf