Abstract
This is the first of four chapters that explain and apply the dynamic simulation approach to health risk assessment modeling introduced in Chap. 2. The exposition in this chapter is motivated by an observation made by toxicologist Julie Goodman of Gradient, who coauthored the article on which this chapter is based (Cox Jr et al. 2020): most of the key ideas of the dynamic simulation approach can be explained through relatively simple diagrams, without going through the underlying equations. This chapter undertakes such a high-level diagrammatic exposition. It returns to two of the diagrams used in Chap. 2 to introduce simulation modeling, and adds further discussion and diagrams to help understand and visualize the dynamic responses of internal doses to different time patterns of exposure. Chapters 4, 5, and 6 and their appendices then cover the same material in much greater depth, providing the underlying systems of equations used to model biological responses to exposures to inhaled respirable crystalline silica (Chap. 4) and asbestos (Chap. 5) and highlighting the importance of nonlinearities in these responses for risk assessment and risk management (Chap. 6).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aleksunes LM, Eaton DL. Principles of toxicology. In: Klaassen CD, editor. Casarett and Doull’s toxicology: the basic science of poisons. 9th ed. New York: McGraw-Hill Education; 2019. p. 25–64.
Allen TEH, Goodman JM, Gutsell S, Russell PJ. A history of the molecular initiating event. Chem Res Toxicol. 2016;29(12):2060–70. https://doi.org/10.1021/acs.chemrestox.6b00341.
Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrano JA, Tietge JE, Villeneuve DL. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 2010;29(3):730–41.
Becker RA, Patlewicz G, Simon TW, Rowlands JC, Budinsky RA. The adverse outcome pathway for rodent liver tumor promotion by sustained activation of the aryl hydrocarbon receptor. Regul Toxicol Pharmacol. 2015;73(1):172–90. https://doi.org/10.1016/j.yrtph.2015.06.015.
Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7(2):99–109. https://doi.org/10.1038/nrmicro2070.
Bogen K. Inflammation as a cancer co-initiator: new mechanistic model predicts low/negligible risk at noninflammatory carcinogen doses. Dose-Response. 2019;17(2):1–12. https://doi.org/10.1177/1559325819847834.
Cox LA (2018) Biological mechanisms of non-linear dose-response for respirable mineral fibers. Toxicol Appl Pharmacol. https://doi.org/10.1016/j.taap.2018.06.016
Cox LAT. Risk analysis implications of dose-response thresholds for NLRP3 inflammasome-mediated diseases: Respirable crystalline silica and lung cancer as an example. Dose-Response. 2019;17(2):1–21. https://doi.org/10.1177/1559325819836900.
Cox LA Jr, Goodman JE, Engel AM. Chronic inflammation, adverse outcome pathways, and risk assessment: a diagrammatic exposition. Regul Toxicol Pharmacol. 2020;114:104663. https://doi.org/10.1016/j.yrtph.2020.104663.
Jo EK, Kim JK, Shin DM, Sasakawa C. Molecular mechanisms regulating NLRP3 inflammasome activation. Cell Mol Immunol. 2016;13(2):148–59. https://doi.org/10.1038/cmi.2015.95.
Kaplan BLF, Sulentic CEW, Haggerty HG, Holsapple MP, Kaminski NE. Toxic responses of the immune system. In: Klaassen CD, editor. Casarett and Doull’s toxicology: the basic science of poisons. 9th ed. New York: McGraw-Hill Education; 2019. p. 633–717.
Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. 2019;20(13):3328. https://doi.org/10.3390/ijms20133328.
Meek ME, Boobis A, Cote I, Dellarco V, Fotakis G, Munn S, Seed J, Vickers C. New developments in the evolution and application of the WHO/IPCS framework on mode of action/species concordance analysis. J Appl Toxicol. 2014;34(1):1–18. https://doi.org/10.1002/jat.2949.
Page SE. The model thinker: what you need to know to make data work for you. New York: Basic Books; 2018.
Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 2019;10(2):128. https://doi.org/10.1038/s41419-019-1413-8.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Cox Jr., L.A. (2021). Simulating Exposure-Related Health Effects: Basic Ideas. In: Quantitative Risk Analysis of Air Pollution Health Effects. International Series in Operations Research & Management Science, vol 299. Springer, Cham. https://doi.org/10.1007/978-3-030-57358-4_3
Download citation
DOI: https://doi.org/10.1007/978-3-030-57358-4_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-57357-7
Online ISBN: 978-3-030-57358-4
eBook Packages: Business and ManagementBusiness and Management (R0)