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HERO ID
699818
Reference Type
Journal Article
Title
alpha 2u-globulin nephropathy and renal tumors in national toxicology program studies
Author(s)
Doi, A; Hill, G; Seely, J; Hailey, J; Kissling, G; Bucher, J
Year
2007
Is Peer Reviewed?
1
Journal
Toxicologic Pathology
ISSN:
0192-6233
EISSN:
1533-1601
Report Number
TOX/5001934
Volume
35
Issue
4
Page Numbers
533-540
Language
English
PMID
17562486
DOI
10.1080/01926230701338941
Web of Science Id
WOS:000248047700006
Abstract
Chemically induced renal neoplasms in male rats, developed coincident with alpha(2u)-globulin nephropathy, are not considered predictive of risk to humans by the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency. Criteria have been defined to establish the role of alpha(2u)-globulin nephropathy in renal carcinogenesis, based on a proposed mode of action involving sustained tubular cell proliferation resulting from alpha(2u)-induced nephropathy, with consequent development of neoplastic lesions. Recent NTP studies demonstrated inconsistencies with this proposed mechanism, including in some cases, far weaker kidney tumor responses than expected based on the extent of alpha(2u)-globulin nephropathy. NTP studies with decalin, propylene glycol mono-t-butyl ether and Stoddard solvent IIC included extended evaluations of alpha(2u)-related nephropathy, and were thus used in assessing the linkage between key events in 90-day studies with renal tumors in 2-year studies. This review revealed no or at best weak associations of tumor responses with renal alpha(2u)-globulin concentrations, indices of cell turnover, or microscopic evidence of alpha(2u)-associated nephropathy in prechronic studies. While tumor responses corresponded somewhat with a measure of cumulative alpha(2u)-associated nephropathy (linear mineralization of the papilla) at the end of the 2-year studies, the severity of chronic nephropathy was generally in best agreement with the pattern of tumor response. These results suggest that while alpha(2u)-globulin nephropathy may contribute to the renal tumor response, the critical component(s) of the nephropathy most closely associated with the development of tumors could not be clearly identified in this review.
Keywords
alpha 2u-globulin nephropathy; male rats; renal tubular cell tumors; pathogenesis
Tags
IRIS
•
tert-Butanol
Cited in Document
•
ETBE
•
Hexachloroethane (HCE) (Final, 2011)
•
Naphthalene
Previous HERO references
Database Searches
Toxline
Combined data set
Data set for title/abstract screening
Excluded - PECO criteria not met (TIAB)
•
Tetrachloroethylene (Perc) (Final, 2012)
Exposure
Hazard
Kidney
•
Trichloroethylene (TCE) (Final, 2011)
OPPT REs
•
OPPT_Perchloroethylene (Perc)_C. Engineering
Total – title/abstract screening
Off topic
•
OPPT_Perchloroethylene (Perc)_D. Exposure
Total – title/abstract screening
Off topic
•
OPPT_Perchloroethylene (Perc)_E. Fate
Total – title/abstract screening
Off topic
•
OPPT_Perchloroethylene (Perc)_F. Human Health
Total – title/abstract screening
Off topic
•
Naphthalene (2021 Evidence mapping publication)
Previous HERO references
Database Searches
Toxline
Combined data set
Data set for title/abstract screening
Excluded – PECO criteria not met
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