Urinary Aromatic Amine Exposures in Pet Dogs With Urothelial Carcinoma and Unaffected Controls

Urothelial carcinoma (UC) in pet dogs resembles muscle-invasive UC in people. Human UC is strongly associated with aromatic amine exposures, either in tobacco smoke or through occupational exposures. However, the role of aromatic amines in canine UC is not understood. Urine from dogs diagnosed with UC (n = 37) and unaffected controls (n = 36), collected in a previous case-control study, were analysed for 12 aromatic amines. Eleven aromatic amines were (o-anisidine, p-toluidine, o-toluidine, 4-chloroaniline, 2,6-dimethylaniline, 3,5-dimethylaniline, aniline, 2-napthylamine, p-cresidine, 4,4'-methylenedianiline, and 4-ethoxyaniline) detected in most urine samples; 4-aminobiphenyl was detected in only three dogs. Urinary concentrations of o-toluidine were significantly higher in cases (median 0.16, range 0.03-2.00 ng/mg creat) versus controls (median 0.11, range 0.02-0.42 ng/mg/creat; p = 0.017), but differences were modest with substantial overlap between groups, and we did not control for multiple comparisons. Urinary o-toluidine was most strongly correlated with urinary aniline, which reached the highest median concentrations overall (1.65 ng/mg creat or 2.60 ng/mL). Total molar aromatic amine urinary exposures were not different between pet dogs living in metropolitan versus rural areas using USDA Rural-Urban Continuum codes in this small sample size. Follow-up studies are indicated to establish the genotoxic thresholds for o-toluidine and aniline in canine urothelial cells and determine whether some pet dogs are exposed to genotoxic urinary concentrations of these aromatic amines in vivo.