Skip to main content
Log in

Predicting Long-Term Asbestos Prevalence in Human Lungs, Lymph Nodes, and Remote Organs from Short-Term Murine Experiments

  • Original Article
  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

Inhalation of asbestos fibers leads to a suite of fatal diseases that can manifest years, if not decades, after cessation of exposure. The first phase of disease progression occurs as fibers are transported from point of entry in the lungs throughout the entire body. A mathematical model is developed for the disposition of non-chrysotile asbestos in the body and, except for exposure levels, is parameterized by published data on short-term rat experiments. Asbestos exposure in individual humans is determined by matching published long-term lung data for nine patients. The resulting model predicts transport of fibers within the lymphatic system and prevalence of fibers in lymph nodes for these patients with reasonable accuracy. Model predictions for remote organs are compared against published observations. The model consists of a system of globally stable differential equations, and a sensitivity analysis was conducted. The model indicates that fiber density in lymph nodes is correlated with total exposure, level times duration, no matter whether there is a long-term, low-level exposure or short-term, high-level exposure. The model predicts that levels of sequestered asbestos reach steady state within five years of cessation of exposure, a timeline previously not known. The model suggests that the time to steady state is short compared to onset of disease, and that delayed onset of related disease may be a function of chemical and biological processes not in this model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Albertine KH, O’Morchoe CC (1979) Distribution and density of the canine renal cortical lymphatic system. Kidney Int 16(4):470–480

    Article  Google Scholar 

  • Auerbach O, Conston AS, Garfinkel L, Parks VR, Kaslow HD, Hammond EC (1980) Presence of asbestos bodies in organs other than the lung. Chest 77(2):133–137

    Article  Google Scholar 

  • Baumann F, Buck BJ, Metcalf RV, McLaurin BT, Merkler DJ, Carbone M (2015) The presence of asbestos in the natural environment is likely related to mesothelioma in young individuals and women from Southern Nevada. J Thorac Oncol 10(5):731–737

    Article  Google Scholar 

  • Bernstein DM, Rogers R, Sepulveda R, Kunzendorf P, Bellmann B, Ernst H, Phillips JI (2014) Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: interim results. Toxicol Appl Pharmacol 276(1):28–46

    Article  Google Scholar 

  • Camargo MC, Stayner LT, Straif K, Reina M, Al-Alem U, Demers PA, Landrigan PJ (2011) Occupational exposure to asbestos and ovarian cancer: a meta-analysis. Environ Health Perspect 119(9):1211–1217

    Article  Google Scholar 

  • Carlin DJ, Larson TC, Pfau JC, Gavett SH, Shukla A, Miller A, Hines R (2015) Current research and opportunities to address environmental asbestos exposures. Environ Health Perspect 123(8):A194–A197

    Article  Google Scholar 

  • Cook PM, Olson GF (1979) Ingested mineral fibers: elimination in human urine. Science 204(4389):195–198

    Article  Google Scholar 

  • DeStefano A, Martin CF, Wallace DI (2017) A dynamical model of the transport of asbestos fibres in the human body. J Biol Dyn 11(1):365–377

    Article  MathSciNet  MATH  Google Scholar 

  • De Vuyst P, Dumortier P, Swaen GM, Pairon JC, Brochard P (1995) Respiratory health effects of man-made vitreous (mineral) fibres. Eur Resp J 8(12):2149–2173

    Article  Google Scholar 

  • Dodson RF, Shepherd S, Levin J, Hammar SP (2007) Characteristics of asbestos concentration in lung as compared to asbestos concentration in various levels of lymph nodes that collect drainage from the lung. Ultrastruct Pathol 31(2):95–133

    Article  Google Scholar 

  • Freitas, RA (1999) Nanomedicine, Volume I: Basic Capabilities. Landes Biosciences, Georgetown, TX

  • Geiser M, Kreyling WG (2010) Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol 7(1):2

    Article  Google Scholar 

  • Graham J, Graham R (1967) Ovarian cancer and asbestos. Environ Res 1(2):115–128

    Article  Google Scholar 

  • Grosso F, Randi L, Croce A, Mirabelli D, Libener R, Magnani C, Bellis D, Allegrina M, Bertolotti M, Degiovanni D, Rinaudo C (2015) Asbestos fibers in the gallbladder of patients affected by benign biliary tract diseases. Eur J Gastroenterol Hepatol 27(7):860–864

    Article  Google Scholar 

  • Gualtieri AF (2018) Towards a quantitative model to predict the toxicity/pathogenicity potential of mineral fibers. Toxicol Appl Pharmacol 361:89–98

    Article  Google Scholar 

  • Heintz NH, Janssen-Heininger YM, Mossman BT (2010) Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways. Am J Resp Cell Mol Biol 42(2):133–139

    Article  Google Scholar 

  • Hindel S, Söhner A, Maa M, Sauerwein W, Baba HA, Kramer M, Lüdemann L (2017) Validation of interstitial fractional volume quantification by using dynamic contrast-enhanced magnetic resonance imaging in porcine skeletal muscles. Invest Radiol 52(1):66–73

    Article  Google Scholar 

  • Huang J, Hisanaga N, Sakai K, Iwata M, Ono Y, Shibata E, Takeuchi Y (1988) Asbestos fibers in human pulmonary and extrapulmonary tissues. Am J Ind Med 14(3):331–339

    Article  Google Scholar 

  • Ilgren EB, Browne K (1991) Asbestos-related mesothelioma: evidence for a threshold in animals and humans. Regul Toxicol Pharmacol 13(2):116–132

    Article  Google Scholar 

  • Jargin SV (2015) Asbestos-related research: first objectivity then conclusions. J Environ Stud 1(1):6

    Google Scholar 

  • Kane AB (1996) Mechanisms of mineral fibre carcinogenesis. IARC Sci Publ 140:11–34

    Google Scholar 

  • Kanerva RL, Lefever FR, Alden CL (1983) Comparison of fresh and fixed organ weights of rats. Toxicol Pathol 11(2):129–131

    Article  Google Scholar 

  • Kazan-Allen L (2005) Asbestos and mesothelioma: worldwide trends. Lung Cancer 49:S3–S8

    Article  Google Scholar 

  • Kobayashi H, Ming ZW, Watanabe H, Ohnishi Y (1987) A quantitative study on the distribution of asbestos bodies in extrapulmonary organs. Pathol Int 37(3):375–383

    Article  Google Scholar 

  • Langer AM (1974) Inorganic particles in human tissues and their association with neoplastic disease. Environ Health Perspect 9:229–233

    Article  Google Scholar 

  • Lee KP, Barras CE, Griffith FD, Waritz RS (1981) Pulmonary response and transmigration of inorganic fibers by inhalation exposure. Am J Pathol 102(3):314

    Google Scholar 

  • MATLAB (2019) version 9.7.0.1434023 (R2019b). Natick, MA: The MathWorks Inc

  • Miserocchi G, Sancini G, Mantegazza F, Chiappino G (2008) Translocation pathways for inhaled asbestos fibers. Environ Health 7(1):1–8

    Article  Google Scholar 

  • Morgan A, Talbot RJ, Holmes A (1978) Significance of fibre length in the clearance of asbestos fibres from the lung. Occupat Environ Med 35(2):146–153

    Article  Google Scholar 

  • Mossman BT, Lippmann M, Hesterberg TW, Kelsey KT, Barchowsky A, Bonner JC (2011) Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos. J Toxicol Environ Health, Part B 14(1–4):76–121

    Article  Google Scholar 

  • Mowe G, Gylseth B, Hartveit F, Skaug V (1984) Occupational asbestos exposure, lung-fiber concentration and latency time in malignant mesothelioma. Scand J Work Environ Health 10(5):293–298

  • Noonan CW (2017) Environmental asbestos exposure and risk of mesothelioma. Ann Transl Med 5(11):234

  • Odgerel CO, Takahashi K, Sorahan T, Driscoll T, Fitzmaurice C, Yoko-o M, van Zandwijk N (2017) Estimation of the global burden of mesothelioma deaths from incomplete national mortality data. Occup Environ Med 74(12):851–858

    Article  Google Scholar 

  • Pierce JS, McKinley MA, Paustenbach DJ, Finley BL (2008) An evaluation of reported no-effect chrysotile asbestos exposures for lung cancer and mesothelioma. Crit Rev Toxicol 38(3):191–214

    Article  Google Scholar 

  • Poland CA, Byrne F, Cho WS, Prina-Mello A, Murphy FA, Davies GL, Coey JMD, Gounko Y, Duffin R, Volkov Y, Donaldson K (2012) Length-dependent pathogenic effects of nickel nanowires in the lungs and the peritoneal cavity. Nanotoxicology 6(8):899–911

    Article  Google Scholar 

  • Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH, Seaton A, Stone V, Brown S, MacNee W, Donaldson K (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3 (7):423–428

  • Reid A, de Klerk N, Musk AWB (2011) Does exposure to asbestos cause ovarian cancer? A systematic literature review and meta-analysis. Cancer Epidemiol Prev Biomark 20(7):1287–1295

    Article  Google Scholar 

  • Schinwald A, Murphy FA, Prina-Mello A, Poland CA, Byrne F, Movia D, Glass JR, Dickerson JC, Schultz DA, Jeffree CE, MacNee W (2012) The threshold length for fiber-induced acute pleural inflammation: shedding light on the early events in asbestos-induced mesothelioma. Toxicol Sci 128(2):461–470

    Article  Google Scholar 

  • Seidman H, Selikoff IJ (1990) Decline in death rates among asbestos insulation workers 1967–1986 associated with diminution of work exposure to asbestos. Ann New York Acad Sci 609(1):300–318

    Article  Google Scholar 

  • Shukla A, Flanders T, Lounsbury KM, Mossman BT (2004) The-glutamylcysteine synthetase and glutathione regulate asbestos-induced expression of activator protein-1 family members and activity. Cancer Res 64(21):7780–7786

    Article  Google Scholar 

  • Stayner L, Welch LS, Lemen R (2013) The worldwide pandemic of asbestos-related diseases. Ann Rev Pub Health 34:205–216

    Article  Google Scholar 

  • Tucker P (2010) Agency for toxic substances and disease registry, case studies in environmental medicine: asbestos toxicity. U.S, Department of Health and Human Services, Atlanta

    Google Scholar 

  • Uibu T, Vanhala E, Sajantila A, Lunetta P, Mäkelä-Bengs P, Goebeler S, Jäntti M, Tossavainen A (2009) Asbestos fibers in para-aortic and mesenteric lymph nodes. Am J Ind Med 52(6):464–470

    Article  Google Scholar 

  • van Furth R, Cohn ZA (1968) The origin and kinetics of mononuclear phagocytes. J Exp Med 128(3):415–435

    Article  Google Scholar 

  • Weill D (2018) Proceedings of the monticello conference on elongate mineral particles (EMP). Toxicol Appl Pharmacol 361:1–186

    Article  Google Scholar 

  • Williams MG, Dodson RF, Dickson EW, Fraire AE (2001) An assessment of asbestos body formation in extrapulmonary sites: liver and spleen. Toxicol Ind health 17(1):1–6

    Article  Google Scholar 

  • Yang DC, Chen CH (2018) Cigarette smoking-mediated macrophage reprogramming: mechanistic insights and therapeutic implications. J Nat Sci 4(11):e539

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alisa DeStefano.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

DeStefano, A., Martin, C., Huang, A. et al. Predicting Long-Term Asbestos Prevalence in Human Lungs, Lymph Nodes, and Remote Organs from Short-Term Murine Experiments. Bull Math Biol 83, 54 (2021). https://doi.org/10.1007/s11538-021-00882-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11538-021-00882-8

Keywords

Navigation