Subchronic urinary bladder toxicity evaluation of N-Nitrosodiphenylamine in Fischer 344 rats
Article first published online: 14 AUG 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 5, pages 383–389, May 2013
How to Cite
Dodd, D. E., Pluta, L. J., Sochaski, M. A., Funk, K. A. and Thomas, R. S. (2013), Subchronic urinary bladder toxicity evaluation of N-Nitrosodiphenylamine in Fischer 344 rats. J. Appl. Toxicol., 33: 383–389. doi: 10.1002/jat.2798
- Issue published online: 23 MAR 2013
- Article first published online: 14 AUG 2012
- Manuscript Revised: 13 JUN 2012
- Manuscript Accepted: 13 JUN 2012
- Manuscript Received: 8 MAY 2012
- urinary bladder;
- F344 rats
Female Fischer 344 (F344) rats were exposed to N-nitrosodiphenylamine (NDPA) by dietary feed at concentrations of 0, 250, 1000, 2000, 3000 or 4000 ppm for 5 days, 2, 4 and 13 weeks duration. Endpoints evaluated included clinical observations, body weights, urinary bladder weights, blood NDPA, gross pathology and urinary bladder histopathology. There were no NDPA exposure-related clinical signs of toxicity. The mean body weight decreased 3% to 5% compared with the control in the 4000 ppm group during study weeks 2 through to 13. Statistically significant increases in urinary bladder weight were observed as early as after 5 days exposure and were concentration dependent at ≥ 3000 ppm. NDPA-related urinary bladder microscopic alterations consisted of mixed cell infiltrates, increased mitosis, increased necrosis of epithelial cells, diffuse and/or nodular transitional epithelial hyperplasia and squamous metaplasia of transitional epithelium. These changes affected only rats exposed to NDPA concentrations ≥ 2000 ppm. Blood NDPA concentrations were negligible in animals exposed to ≤ 1000 ppm and ranged from 0.12 to 0.19 µg ml–1 in rats of the ≥ 2000 ppm groups at the 5 days and 2 weeks time points. A no observable adverse effect level (NOAEL) of 1000 ppm NDPA (60 mg kg–1 day–1) was selected based on the absence of urinary bladder histopathology. Copyright © 2012 John Wiley & Sons, Ltd.