Application of the Adverse Outcome Pathway Framework to Risk Assessment for Predicting Carcinogenicity of Chemicals

Kang, Doo Seok; Yang, Jun; Kim, Hyun Soo; Koo, Bon Kon; Lee, Cheol Min; Ahn, Yeon-Soon; Jung, Jong-Hyeon; Seo, Young Rok

doi:10.15430/jcp.2018.23.3.126

Cited by 18 publications

(7 citation statements)

References 30 publications

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“…In studies of mouse skin carcinogenesis, a linear relationship has been observed between the dose of initiator and the quantity of tumors that can be produced ( Gills et al, 2006 ). Thus, the more exposure to the carcinogen, the higher the risk of developing tumors ( Kang et al, 2018 ). Cancer risk and slope factor are calculated in a linear dose-response ( Kang et al, 2018 ).…”

Section: Carcinogens and Inflammationmentioning

confidence: 99%

“…Thus, the more exposure to the carcinogen, the higher the risk of developing tumors ( Kang et al, 2018 ). Cancer risk and slope factor are calculated in a linear dose-response ( Kang et al, 2018 ). All known human carcinogens that have been studied for carcinogenesis in experimental animals have generated positive results in one or more animal species ( Tomatis, Aitio, Wilbourn, & Shuker, 1989 ; Wilbourn et al, 1986 ).…”

Section: Carcinogens and Inflammationmentioning

confidence: 99%

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Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

113

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Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

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Section: Carcinogens and Inflammationmentioning

confidence: 99%

Section: Carcinogens and Inflammationmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

113

View full text Add to dashboard Cite

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“…AOPs can also be used to identify mechanisms of toxicity associated with adverse outcomes found in toxicity tests, and thus help determine the relevance of the toxic effect to humans. In addition, information from AOP perturbations, such as from screenings, allows for incorporation of additional endpoints, such as induction of biotransformation enzymes, to explain liver effects (Kang et al 2018;Nepelska et al 2017). For example, when it is known that the tumorigenesis of a chemical in rodents is related to peroxisome proliferator-activated receptor alpha activation, using these data for risk assessment is questionable, since the pathway is not relevant in humans (Corton et al 2018).…”

Section: Outcome Of the Workhopmentioning

confidence: 99%

The use of adverse outcome pathways in the safety evaluation of food additives

et al. 2020

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In the last decade, adverse outcome pathways have been introduced in the fields of toxicology and risk assessment of chemicals as pragmatic tools with broad application potential. While their use in the pharmaceutical and cosmetics sectors has been well documented, their application in the food area remains largely unexplored. In this respect, an expert group of the International Life Sciences Institute Europe has recently explored the use of adverse outcome pathways in the safety evaluation of food additives. A key activity was the organization of a workshop, gathering delegates from the regulatory, industrial and academic areas, to discuss the potentials and challenges related to the application of adverse outcome pathways in the safety assessment of food additives. The present paper describes the outcome of this workshop followed by a number of critical considerations and perspectives defined by the International Life Sciences Institute Europe expert group.

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“…An AOP framework begins as a MIE, which leads to an AO through KEs at various biological levels, and these components are connected by KE relationships [19]. In the case of exposure to sulfuric acid mist, sulfate and/or hydrogen ions are dissociated in aqueous solvent or humidified environment because of its strong acidic characteristics [14].…”

Section: Current Evidence Related To Sulfuric Acid Mist-induced Toxicmentioning

confidence: 99%

A Putative Adverse Outcome Pathway Relevant to Carcinogenicity Induced by Sulfuric Acid in Strong Inorganic Acid Mists

et al. 2019

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Based on epidemiological studies, an International Agency for Research on Cancer Working Group determined that strong inorganic acid mists containing sulfuric acid are carcinogenic to human even though, sulfuric acid, per se, is not. Accumulative studies indicate that there is a link between chronic occupational exposure to sulfuric acid mists and an increased risk of laryngeal cancer. Unintended, acute exposure to sulfuric acid mists can cause corrosive damage to target tissues depending on the route of exposure. This review compares the toxicity and carcinogenicity of sulfuric acid mists compared to other strong inorganic acid mists. It also examines the routes and duration of exposure (short-term, prolonged, and long-term). In vivo evidence does not support or refute the carcinogenicity of sulfuric inorganic mists even though its co-carcinogenic or promoting potential has been considered. On the basis of existing evidence on sulfuric acid mist toxicity, we suggested a putative adverse outcome pathway (AOP) relevant to carcinogenicity caused by mists containing sulfuric acid. A possible key factor involved in sulfuric acid mist carcinogenesis is the genotoxic effects of low pH since it can increase instability in chromosomes and DNA. A putative AOP for sulfuric acid mist carcinogenicity would help generate better risk assessments and more accurate predictions regarding the risk of developing cancer due to prolonged exposure. Establishing an AOP would also be useful for future studies examining the carcinogenicity of other strong inorganic mists.

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Application of the Adverse Outcome Pathway Framework to Risk Assessment for Predicting Carcinogenicity of Chemicals

Cited by 18 publications

References 30 publications

Carcinogenesis: Failure of resolution of inflammation?

Carcinogenesis: Failure of resolution of inflammation?

The use of adverse outcome pathways in the safety evaluation of food additives

A Putative Adverse Outcome Pathway Relevant to Carcinogenicity Induced by Sulfuric Acid in Strong Inorganic Acid Mists

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