The Challenge of Predicting the Immunotoxic Potential of Chemicals

  • Hans-Werner Vohr


Well before the mechanisms were understood, pulmonary immune diseases had been associated with environmental chemicals, i.e., air contaminants. During the second half of the twentieth century, purpose and function of the different components of the immune system as well as their interactions with chemicals were extensively investigated and ultimately understood in more detail. In addition to a deeper understanding of immunological interactions and mechanisms, a series of accidents involving immunotoxic compounds pushed the development of immunotoxicological science in the last century.


Lymphoid Organ Applicability Domain Local Lymph Node Assay Immunotoxic Effect Cosmetic Directive 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Thanks go to my esteemed colleague Fred Aswad for his assistance and thoroughly reviewing the manuscript. I like to thank Anna Fischer-Berenbein for providing the basis for two modified figures included here.


  1. Angerer J, Ewers U, Wilhelm M (2007) Human biomonitoring: state of the art. Int J Hyg Environ Health 210:201–228CrossRefPubMedGoogle Scholar
  2. Annest JL, Pirkle JL, Makuc D, Neese JW, Bayse DD, Kovar MG (1983) Chronological trend in blood lead levels between 1976 and, 1980. N Engl J Med 308:1373–1377CrossRefPubMedGoogle Scholar
  3. Baker SR, Gibson BG (2014) Social oral epidemi(olog)2 y where next: one small step or one giant leap? Community Dent Oral Epidemiol. doi: 10.1111/cdoe.12118 [Epub ahead of print]
  4. Barnett J (2005) Developmental immunotoxicology. In: Vohr HW (ed) Immunotoxicology. Springer, Heidelberg, pp 201–203Google Scholar
  5. Boccia S, La Torre G, Persiani R, D’Ugo D, van Duijn CM, Ricciardi G (2007) A critical appraisal of epidemiological studies comes from basic knowledge: a reader’s guide to assess potential for biases. World J Emerg Surg 2:1–8CrossRefGoogle Scholar
  6. Boverhof DR, Ladics G, Luebke B, Botham J, Corsini E, Evans E, Germolec D, Holsapple M, Loveless SE, Lu H, van der Laan JW, White KL Jr, Yang Y (2014) Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: a workshop summary. Regul Toxicol Pharmacol 68:96–107CrossRefPubMedGoogle Scholar
  7. Chang ET, Boffetta P, Adami HO, Cole P, Mandel JS (2014) A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer. Eur J Epidemiol [Epub ahead of print]Google Scholar
  8. Dayan AD, Kuper F, Madsen C, Smialowicz RJ, Smith E, Van Loveren H, Vos JC, White KL (1998) Report of validation study of assessment of direct immunotoxicity in the rat. The ICICIS group investigators. International collaborative immunotoxicity study. Toxicology 125(2–3):183Google Scholar
  9. Descotes J (2005) Immunotoxicology: role in the safety assessment of drugs. Drug Saf 28(2):127–136CrossRefPubMedGoogle Scholar
  10. Dybing E, Schwarze PE, Løvik M, Magnus P (1996) [Air pollution and health]. Tidsskr Nor Laegeforen 116(18):2147–2148 (Norwegian)PubMedGoogle Scholar
  11. Fischer A, Koeper LM, Vohr HW (2011) Specific antibody responses of primary cells from different cell sources are able to predict immunotoxicity in vitro. Toxicol In Vitro 25:1966–1973CrossRefPubMedGoogle Scholar
  12. Geier J, Uter W, Krautheim A, Lessmann H, Schnuch A (2011) Die häufigsten Kontaktallergene der Jahre 2007–2009. Aktuelle Daten aus dem Informationsverbund Dermatologischer Kliniken (IVDK). Allergo J 20:93–101. GermanGoogle Scholar
  13. Germolec DR, Kashon M, Nyska A, Kuper CF, Portier C, Kommineni C, Johnson KA, Luster MI (2004) The accuracy of extended histopathology to detect immunotoxic chemicals. Toxicol Sci 82(2):504–514CrossRefPubMedGoogle Scholar
  14. Hermann-Kunz E (1999) Incidence of allergic diseases in East and West Germany. Gesundheitswesen 61:100–105. GermanGoogle Scholar
  15. Holladay SD, Smialowicz RJ (2000) Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure. Environ Health Perspect 108:463–473PubMedCentralCrossRefPubMedGoogle Scholar
  16. Hölzle E, Neumann N, Hausen B, Przybilla B, Schauder S, Hönigsmann H, Bircher A, Plewig G (1991) Photopatch testing: the 5-year experience of the German, Austrian, and Swiss Photopatch Test Group. J Am Acad Dermatol 25:59–68CrossRefPubMedGoogle Scholar
  17. Koeper LM, Vohr HW (2009) Functional assays are mandatory for a correct prediction of immunosuppressant properties of compounds in vitro. Food Chem Toxicol 47:110–118 [Epub 2008]CrossRefPubMedGoogle Scholar
  18. Lappin PB, Black LE (2003) Immune modulator studies in primates: the utility of flow cytometry and immunohistochemistry in the identification and characterization of immunotoxicity. Toxicol Pathol 31(Suppl):111–118PubMedGoogle Scholar
  19. Luster MI, Portier C, Pait DG et al (1992) Risk assessment in immunotoxicology. I. Sensitivity and predictability of immune tests. Fundam Appl Toxicol 18:200CrossRefPubMedGoogle Scholar
  20. Luster MI, Portier C, Pait DG et al (1993) Risk assessment in immunotoxicology. II. Relationship between immune and host resistance tests. Fundam Appl Toxicol 21:71–82CrossRefPubMedGoogle Scholar
  21. Luster MI, Dean JH, Germolec DR (2003) Consensus workshop on methods to evaluate developmental immunotoxicity. Environ Health Perspect 111:579–583PubMedCentralCrossRefPubMedGoogle Scholar
  22. OECD, Organisation for Economic Cooperation and Development (1981) OECD guidelines for testing of chemicals no. 407 (Repeated Dose 28-day Oral Toxicity Study in Rodents), adopted 1992Google Scholar
  23. Paustenbach D, Galbraith D (2006a) Biomonitoring: is body burden relevant to public health? Regul Toxicol Pharmacol 44:249–261CrossRefPubMedGoogle Scholar
  24. Paustenbach D, Galbraith D (2006b) Biomonitoring and biomarkers: exposure assessment will never be the same. Environ Health Perspect 114:1143–1149PubMedCentralCrossRefPubMedGoogle Scholar
  25. Richter-Reichhelm H-B, Dasenbrock C, Descotes G, Emmendörfer A, Heinrich UE, Harlemann JH, Hilde¬brand B, Küttler K, Rühl-Fehlert CI, Schilling K, Schulte AE, Vohr H-W (1995) Validation of a modified 28-Day rat study to evidence effects of test compounds on the immune system. Regul Toxicol Pharmakol 22:54–56CrossRefGoogle Scholar
  26. Schnuch A, Uter W, Geier J, Lessmann H, Frosch PJ (2004) Contact allergy to farnesol in 2021 consecutively patch tested patients. Results of the IVDK. Contact Dermatitis 50:117–121CrossRefPubMedGoogle Scholar
  27. Schulz C, Angerer J, Ewers U, Kolossa-Gehring M (2007a) The German human biomonitoring commission. Int J Hyg Environ Health 210:373–382CrossRefPubMedGoogle Scholar
  28. Schulz C, Conrad A, Becker K, Kolossa-Gehring M, Seiwert M, Seifert B (2007b) Twenty years of the German Environmental Survey (GerES): human biomonitoring – Temporal and spatial (West Germany/East Germany) differences in population exposure. Int J Hyg Environ Health 210:271–297CrossRefPubMedGoogle Scholar
  29. Stokstad E (2004) Pollution gets personal. Science 304:1892–1894CrossRefPubMedGoogle Scholar
  30. Thyssen JP, Giménez-Arnau E, Lepoittevin J-P, Menné T, Boman A, Schnuch A (2012a) The critical review of methodologies and approaches to assess the inherent skin sensitization potential (skin allergies) of chemicals. Part I. Contact Dermatitis 66(Suppl 1):11–24CrossRefPubMedGoogle Scholar
  31. Thyssen JP, Giménez-Arnau E, Lepoittevin J-P, Menné T, Boman A, Schnuch A (2012b) The critical review of methodologies and approaches to assess the inherent skin sensitization potential (skin allergies) of chemicals. Part II. Contact Dermatitis 66(Suppl 1):25–52CrossRefPubMedGoogle Scholar
  32. Thyssen JP, Giménez-Arnau E, Lepoittevin J-P, Menné T, Boman A, Schnuch A (2012c) The critical review of methodologies and approaches to assess the inherent skin sensitization potential (skin allergies) of chemicals. Part III. Contact Dermatitis 66(Suppl 1):53–70CrossRefPubMedGoogle Scholar
  33. US-EPA, United States Environmental Protection Agency (1998) Health effects test guidelines: OPPTS 870.7800. ImmunotoxicityGoogle Scholar
  34. Uter W, Geier J, Schnuch A, Frosch PJ (2007) Patch test results with patients’ own perfumes, deodorants and shaving lotions: results of the IVDK 1998–2002. J Eur Acade Dermatol Venereol 21:374–379CrossRefGoogle Scholar
  35. Uter W, Hegewald J, Pfahlberg A, Lessmann H, Schnuch A, Gefeller O (2010) Contact allergy to thiurams: multifactorial analysis of clinical surveillance data collected by the IVDK network. Int Arch Occup Environ Health 83:675–681PubMedCentralCrossRefPubMedGoogle Scholar
  36. Van der Veen JW, Soeteman-Hernández LG, Ezendam J, Stierum R, Kuper FC, van Loveren H (2014) Anchoring molecular mechanisms to the adverse outcome pathway for skin sensitization: Analysis of existing data. Crit Rev Toxikol 44(7):590–599CrossRefGoogle Scholar
  37. Van Loveren H, Germolec D, Koren HS, Luster MI, Nolan C, Repetto R, Smith E, Vos JG, Vogt RF (1999) Report of the Bilthoven Symposium: Advancement of epidemiological studies in assessing the human health effects of immunotoxic agents in the environment and the workplace. Biomarkers 4:135–157CrossRefGoogle Scholar
  38. Vohr H-W (1995) Experiences with an advanced screening procedure for the identification of chemicals with an immunotoxic potential in routine toxicology. Toxicology 104:149–158CrossRefPubMedGoogle Scholar
  39. Vohr H-W, Rühl-Fehlert C (2001) Industry experience in the identification of the immunotoxic potential of agrochemicals. Sci Total Environ 270:123–134CrossRefPubMedGoogle Scholar
  40. Vos JG, van Loveren H (1995) Markers for immunotoxic effects in rodents and man. Toxicol Lett 82–83:385–394CrossRefPubMedGoogle Scholar
  41. Vos JG, Van Logten MJ, Kreeftenberg JG, Steerenberg PA, Kruizinga W (1979) Effect of hexachlorobenzene on the immune system of rats following combined pre- and post-natal exposure. Drug Chem Toxicol 2:61CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Heinrich-Heine-UniversityDüsseldorfGermany

Personalised recommendations