| Autor: |
Hard GC; Private Consultant, 203 Paku Drive, Tairua 3508, New Zealand. gordonhard@msn.com, Banton MI, Bretzlaff RS, Dekant W, Fowles JR, Mallett AK, McGregor DB, Roberts KM, Sielken RL Jr, Valdez-Flores C, Cohen SM |
| Jazyk: |
angličtina |
| Zdroj: |
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2013 Apr; Vol. 132 (2), pp. 268-75. Date of Electronic Publication: 2012 Oct 26. |
| DOI: |
10.1093/toxsci/kfs305 |
| Abstrakt: |
Chronic progressive nephropathy (CPN) is a spontaneous renal disease of rats which can be a serious confounder in toxicology studies. It is a progressive disease with known physiological factors that modify disease progression, such as high dietary protein. The weight of evidence supports an absence of a renal counterpart in humans. There is extensive evidence that advanced CPN, particularly end-stage kidney, is a risk factor for development of a background incidence of atypical tubule hyperplasia and renal tubule tumors (RTT). The likely cause underlying this association with tubule neoplasia is the long-term increased tubule cell proliferation that occurs throughout CPN progression. As a variety of chemicals are able to exacerbate CPN, there is a potential for those exacerbating the severity up to and including end-stage kidney to cause a marginal increase in RTT and their precursor lesions. Extensive statistical analysis of National Toxicology Program studies shows a strong correlation between high-grade CPN, especially end-stage CPN, and renal tumor development. CPN as a mode of action (MOA) for rat RTT has received attention from regulatory authorities only recently. In the absence of toxic effects elsewhere, this does not constitute a carcinogenic effect of the chemical but can be addressed through a proposed MOA approach for regulatory purposes to reach a decision that RTT, developing as a result of CPN exacerbation in rats, have no relevance for human risk assessment. Guidelines are proposed for evaluation of exacerbation of CPN and RTT as a valid MOA for a given chemical. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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