title: Genotoxic and carcinogenic products arising from reductive transformations of the azo dye, Disperse Yellow 7.
abstract: Selected aromatic azo and benzidine based dyes are priority compounds under the Government of Canada's Chemical Management Plan (CMP) for environmental risk assessments. Organic compounds undergo chemical and biological transformations when they interact with environmental matrices and biotic species; identifying the transformation products is thus a critical component of the risk assessment process. Here, we used zero valent iron (ZVI) to initiate the reduction of the diazo compound dye Disperse Yellow 7 (DY 7). Using state-of-the-art accurate mass Liquid Chromatography-Quadrupole Time of Flight-Mass Spectroscopy (LC-QToF-MS), four transformation products were conclusively identified, while a fifth product was tentatively ascertained. The conclusively established transformation products included p-phenylenediamine (p-PDA, a known genotoxin), 4-aminoazobenzene (4-AAB, a category 2 carcinogen) and 4-aminobiphenyl (4-ABP, a category 1 human carcinogen). 4-ABP is thought to form via a benzidine rearrangement; this is the first report of DY 7 undergoing a benzidine rearrangement. Given the importance of reduction processes in the metabolism of organic contaminants by aquatic species, we used LC-MS/MS to analyze sediment samples that had been generated previously upon exposure of Western clawed frogs (Silurana tropicalis) to DY 7 (at exposure levels where cellular stress was observed in S. tropicalis). We found p-PDA, 4-AAB, and 4-ABP were present in all exposures, but not in any of the sediment controls, demonstrating that upon release of DY 7 to the aquatic environment, sediment dwelling organisms will metabolize DY 7 to generate known (and suspected) human carcinogens, including through a previously unreported in vivo benzidine rearrangement to produce 4-ABP.
authors.affiliation: Aquatic Contaminants Research Division, Water Science and Technology Directorate, Environment and Climate Change Canada, 867 Lakeshore Road, Burlington, ON, Canada. Electronic address: vimal.balakrishnan@canada.ca.
authors.forename: Vimal K
authors.initials: VK
authors.lastname: Balakrishnan
authors.affiliation: Aquatic Contaminants Research Division, Water Science and Technology Directorate, Environment and Climate Change Canada, 867 Lakeshore Road, Burlington, ON, Canada.
authors.forename: Salma
authors.initials: S
authors.lastname: Shirin
authors.affiliation: Ontario Institute for Cancer Research, 661 University Avenue, Suite 510 Toronto, ON, Canada.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Aman
authors.affiliation: Ecotoxicology and Wildlife Health Division, Wildlife and Landscape Science Directorate, Environment and Climate Change Canada, 867 Lakeshore Road, Burlington, ON, Canada.
authors.forename: Shane R
authors.initials: SR
authors.lastname: de Solla
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, P.O. Box 17 000 Stn Forces, Kingston, ON, Canada.
authors.forename: Justine
authors.initials: J
authors.lastname: Mathieu-Denoncourt
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, P.O. Box 17 000 Stn Forces, Kingston, ON, Canada.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Langlois
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D001711:Biotransformation; D002170:Canada; D002273:Carcinogens / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D004396:Coloring Agents / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D004784:Environmental Monitoring / Q000379:methods*; D019015:Geologic Sediments / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000737:chemistry; D009153:Mutagens / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D010084:Oxidation-Reduction; D053719:Tandem Mass Spectrometry; D014981:Xenopus / Q000378:metabolism
chemical_list: D001391:Azo Compounds; D002273:Carcinogens; D004396:Coloring Agents; C000611320:Disperse Yellow 7; D009153:Mutagens; D007501:Iron
keywords: Azo dye; Carcinogen; LC-QToF-MS; Reduction; Silurana tropicalis; Transformation products