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A Framework for Human Relevance Analysis of Information on Carcinogenic Modes of Action
TLDR
By providing a systematic approach to using MOA data, the HRF offers a new tool for the scientific community's overall effort to enhance the predictive power, reliability and transparency of cancer risk assessment.
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IPCS framework for analyzing the relevance of a cancer mode of action for humans.
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Methylated Arsenicals: The Implications of Metabolism and Carcinogenicity Studies in Rodents to Human Risk Assessment
TLDR
Using a margin-of-exposure approach for MMAV and DMAV risk assessment is appropriate and the evidence strongly supports a nonlinear dose-response relationship for the biologic processes involved in the carcinogenicity of arsenicals.
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Mode of action in relevance of rodent liver tumors to human cancer risk.
TLDR
It was concluded that the induction of rodent liver tumors by porphyrogenic compounds followed a cytotoxic MOA, and that liver tumors formed as a result of sustained cytotoxicity and regenerative proliferation are considered relevant for evaluating human cancer risk if appropriate metabolism occurs in the animal models and in humans.
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IPCS Framework for Analyzing the Relevance of a Cancer Mode of Action for Humans
TLDR
The IPCS human relevance framework for cancer provides an analytical tool to enable the transparent evaluation of the data, identification of key data gaps, and structured presentation of information that would be of value in the further risk assessment of the compound, even if relevancy cannot be excluded.
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Evaluation of Possible Carcinogenic Risk to Humans Based on Liver Tumors in Rodent Assays
TLDR
A short-term (thirteen-week) assay for screening for carcinogenic potential based on a mode of action analysis and on readily available, identifiable preneoplastic changes is proposed.
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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.
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Human carcinogenic risk evaluation: an alternative approach to the two-year rodent bioassay.
  • Samuel M. Cohen
  • Biology
    Toxicological sciences : an official journal of…
  • 1 August 2004
TLDR
An approach to the evaluation of carcinogenic risk resulting from exposure to a given chemical is presented in place of a reliance on two-year rodent bioassays, and an emphasis is placed on mechanistic understanding and evaluation of the dose response and relevance to humans.
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Possible role of dimethylarsinous acid in dimethylarsinic acid-induced urothelial toxicity and regeneration in the rat.
TLDR
It is hypothesized that formation of the reactive organic intermediate dimethylarsinous acid (DMA(III) is involved in the induction of the cytotoxicity and regenerative hyperplasia of the urothelium which was inhibited by co-administration with DMPS.
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Investigations of Rodent Urinary Bladder Carcinogens: Collection, Processing, and Evaluation of Urine and Bladders
TLDR
The urinary bladder must be handled gently and inflated with fixative in situ before the animal dies to avoid artifactual autolytic damage to the bladder epithelium that is visible by SEM and may be mistaken for treatment-related changes.
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