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PPARα Agonist-Induced Rodent Tumors: Modes of Action and Human Relevance
TLDR
An in-depth analysis of the state of the science on several topics critical to evaluating the relationship between the MOA for PPARα agonists and the human relevance of related animal tumors produces a range of outcomes, depending partly on the quality and quantity of MOA data available from laboratory animals and related information from human data sources.
PPARalpha agonist-induced rodent tumors: modes of action and human relevance.
TLDR
An in-depth analysis of the state of the science on several topics critical to evaluating the relationship between the MOA for PPARalpha agonists and the human relevance of related animal tumors is provided.
Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats.
TLDR
It is suggested that estradiol may play a role in enhancement of Leydig cell tumors in the rat, and that peroxisome proliferators may induce tumors via a non-LH type mechanism.
A Theoretical Model for Utilizing Mammalian Pharmacology and Safety Data to Prioritize Potential Impacts of Human Pharmaceuticals to Fish
TLDR
A model has been developed to utilize the information from mammalian pharmacology and toxicology studies to evaluate the potential for chronic receptor mediated responses in fish and to strengthen the applicability of this approach as a viable tool for prioritizing research initiatives that examine the potential impact of pharmaceuticals on fish.
Rodent Leydig cell tumorigenesis: a review of the physiology, pathology, mechanisms, and relevance to humans.
TLDR
This review attempts to fill deficiencies in the literature on Leydig cell tumors by comparing the cytology and ontogeny of the LC, as well as the endocrine and paracrine regulation of both normal and tumorigenic LCs, and the pathology of LCTs in rodents and humans is compared.
Effects of ammonium perfluorooctanoate on Leydig cell function: in vitro, in vivo, and ex vivo studies.
TLDR
The hypothesis that C8 produces an increase in estradiol by inducing cytochrome P450 XIX (aromatase), which converts testosterone to Estradiol, and that the elevated estradio levels ultimately produce Leydig cell hyperplasia and adenoma formation is investigated.
Hemangiosarcoma in rodents: mode-of-action evaluation and human relevance.
TLDR
This review proposes a working MOA for HS induced by nongenotoxic compounds that can guide future research in this area, and explores knowledge gaps and uncertainties related to the mode of action for the induction of HS in rodents.
Uncertainties for endocrine disrupters: our view on progress.
TLDR
What started out as a hypothesis has become one of the biggest testing programs conceived in the history of toxicology and the only one that has ever been based on mechanism of action as its premise.
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