Chronic progressive nephropathy

Chronic inhalation exposure to 0, 75, 250 or 750 ppm [0, 0.32, 1.1 or 3.3 g/m ] ethylbenzene for 6 h per day on five days per week for 104 weeks caused an increased incidence of renal tubule h erplasia in male Fischer 344/N rats and increased severity of spontaneous, age-related chronic progressive nephropathy in males and females. Male B6C3Fi mice developed an increased incidence of alveolar epithelial metaplasia, syncytial alterations of hepatocytes, hepatocellular hypertrophy, hepatocyte necrosis and thyroid gland follicular-cell h erplasia. Exposure to ethylbenzene also caused an... 

Hard, G.C., Whysner, J., English, J.C., Zang, E. Williams, GM. (1997) Relationship of hydro-quinone-associated rat renal tumors with spontaneous chronic progressive nephropathy. Toxicol. Pathol., 25, 132-143... 

Figure 3 The PCA showing the metabolic differences in urinary metabolite profiles between young (3 months) and old (15 months) male and female Sprague-Dawley rats. Older rats develop chronic progressive nephropathy that affects renal histopa-thology and function, and these biochemical differences have been captured by metabonomic analyses.

In another study, a single subcutaneous injection of MeCCNU (20-140 mg kg resulted in rapid decrease in renal function leading to a chronic progressive nephropathy in male Fischer 344 rats. 

Whole body exposure of rats to <100 ppm NMP vapor for 6hday, 5 days week for a lifetime resulted in only a slight decrement in male body weight at 100 ppm. In another study, rats receiving a lifetime dietary exposure to NMP exhibited decrements in body weight and an increase in the severity of chronic progressive nephropathy (males only) at the highest doses tested, 678 mg kg (males) and 939 mg kg... 

ALPHA2U-GL0BULIN NEPHROPATHY AND CHRONIC PROGRESSIVE NEPHROPATHY AS MODES OF ACTION FOR RENAL TUBULE TUMOR INDUCTION IN RATS, AND THEIR POSSIBLE INTERACTION... 

Male rats—and, to a lesser extent, female rats—are also predisposed to developing chronic progressive nephropathy (CPN), and this age-related, spontaneous disease entity appears to convey a slightly increased risk for development of atypical tubule hyperplasia, a preneoplastic lesion, and RTT later in life (Hard 1998, 2002 Seely et al. 2002 Lock and Hard 2004 Hard and Khan 2004). 

CHEMICALS INCREASING THE INCIDENCE OF RENAL TUMORS THROUGH EXACERBATION OF SPONTANEOUS CHRONIC PROGRESSIVE NEPHROPATHY (CPN)... 

Barthold, S. W. (1979). Chronic progressive nephropathy in aging rats. Toxicol Pathol 7, 1-6. 

Hard, G. C., Johnson, K. J., and Cohen, S. M. (2009). Acomparison of rat chronic progressive nephropathy with human renal disease—Implications for human risk assessment Crit Rev Toxicol 39,... 

Hard, G. C., and Khan, K. N. (2004). A contemporary overview of chronic progressive nephropathy in the laboratory rat, and its significance for human risk assessment Toxicol Pathol 32, 171-180. 

Seely, J. C., Haseman, J. K., Nyska, A., Wolf, D. C., Everitt, J. I., and Hailey, J. R. (2002). The effect of chronic progressive nephropathy on the incidence of renal tubule cell neoplasms in control male F344 rats. Toxicol Pathol 30, 681-686. 

Fig. 3 Involvement of chronic progressive nephropathy in rat renal tubule cell neoplasia...

Study reduced the incidence of these tumours so it was barely significant. The available data strongly support the hypothesis that the mode action is dependent on a2u- globulin nephropathy and exacerbation of chronic progressive nephropathy, both of which are considered of no human relevance. 

Several chronic toxicity studies of the compound hydroquinone in rats have shown nephropathy after long-term dietary or other oral exposure, with male rats being significantly more affected than female rats (Hoffman-Bohm and Simon 1992 Kari et al. 1992 Shibata et al. 1991). Reviews of the toxicology of hydroquinone note that chronic progressive nephropathy is characteristic of aged male rats (DeCaprio 1999 McGregor 2007). 

Lock, E.A. and Hard, G.C. (2010) Alpha2u-globulin nephropathy and chronic progressive nephropathy as modes of action for renal tubule tumor induction in rats, and their possible interaction. In Cancer Risk Assessment—Chemical Carcinogenesis, Hazard Evaluation, and Risk Quantification, (Hsu, C.H. and Stedeford, T. Eds.), pp. 248-255, John Wiley Sons, Ltd., Oxford, England. 

Travlos, G.S., Betz, L., and Hard, G.C. 2007) Influence of diet or route of exposure on chronic progressive nephropathy, kidney weight, blood urea nitrogen and creatinine concentrations in 13-week toxicity studies for control F344/N male rats [abstract]. Toxicol. Pathol. 35,190-191. 

Chronic progressive nephropathy and increased mortality in male rats (Chun et al., 1992)... 

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