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AOP: 105
Title
Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
Short name
Graphical Representation
Point of Contact
Contributors
- Charles Wood
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
---|---|---|---|---|
1.29 |
This AOP was last modified on April 29, 2023 16:02
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) | September 16, 2017 10:16 |
Increase, Cytotoxicity (renal tubular cell) | March 03, 2022 15:14 |
Increase, Regenerative cell proliferation (tubular epithelial cells) | September 16, 2017 10:16 |
Increase, Adenomas/carcinomas (renal tubular) | September 16, 2017 10:16 |
Increase, Hyperplasia (renal tubular cells) | September 16, 2017 10:16 |
Increased, Binding of chemicals to 2u (serum) | September 16, 2017 10:16 |
Increased, Binding of chemicals to 2u (serum) leads to Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) | December 03, 2016 16:37 |
Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) leads to Increase, Cytotoxicity (renal tubular cell) | December 03, 2016 16:37 |
Increase, Cytotoxicity (renal tubular cell) leads to Increase, Regenerative cell proliferation (tubular epithelial cells) | December 03, 2016 16:37 |
Increase, Regenerative cell proliferation (tubular epithelial cells) leads to Increase, Hyperplasia (renal tubular cells) | December 03, 2016 16:38 |
Increase, Hyperplasia (renal tubular cells) leads to Increase, Adenomas/carcinomas (renal tubular) | December 03, 2016 16:38 |
Abstract
This putative adverse outcome pathway (AOP) outlines potential key events leading to a tumor outcome in standard carcinogenicity models. This information is based largely on modes of action described previously in cited literature sources and is intended as a resource template for AOP development and data organization. Presentation in this Wiki does not indicate EPA acceptance of a particular pathway for a given reference agent, only that the information has been proposed in some manner. In addition, this putative AOP relates to the model species indicated and does not directly address issues of human relevance.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 714 | Increased, Binding of chemicals to 2u (serum) | Increased, Binding of chemicals to 2u (serum) |
KE | 708 | Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) | Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) |
KE | 709 | Increase, Cytotoxicity (renal tubular cell) | Increase, Cytotoxicity (renal tubular cell) |
KE | 710 | Increase, Regenerative cell proliferation (tubular epithelial cells) | Increase, Regenerative cell proliferation (tubular epithelial cells) |
KE | 767 | Increase, Hyperplasia (renal tubular cells) | Increase, Hyperplasia (renal tubular cells) |
AO | 713 | Increase, Adenomas/carcinomas (renal tubular) | Increase, Adenomas/carcinomas (renal tubular) |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
Rattus norvegicus | Rattus norvegicus | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Male |
Overall Assessment of the AOP
Domain of Applicability
Life Stage Applicability, Taxonomic Applicability, Sex Applicability Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.
- Sex: This AOP applies to males only (Swenberg, 1993).
- Life stages: The relevant life stages for this AOP are reproductively mature adults. Alpha2u-microglobulin is found in the urine of female and sexually immature rats at concentrations that are less than 1/100 that found in young adult males (Vandoren et al 1983, Ekstrom et al 1984, as cited in Swenberg 1993). Hepatic synthesis accounts for most of the o2u in male rats, with synthesis beginning at the onset of sexual maturity and increasing to 20 weeks of age, after which it plateaus and then begins to decline with increasing age (Roy et al 1983, as cited in Swenberg 1993).
- Taxonomic: The taxonomic applicability domain of this AOP is rats, Rattus norvegicus (Swenberg, 1993).
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Quantitative Understanding
Considerations for Potential Applications of the AOP (optional)
References
Swenberg, J. A. (1993). Alpha 2u-globulin nephropathy: review of the cellular and molecular mechanisms involved and their implications for human risk assessment. Environ Health Perspect, 101 Suppl 6, 39-44.