Article thumbnail

Combined Toxic Exposures and Human Health: Biomarkers of Exposure and Effect

By Ilona Silins and Johan Högberg


Procedures for risk assessment of chemical mixtures, combined and cumulative exposures are under development, but the scientific database needs considerable expansion. In particular, there is a lack of knowledge on how to monitor effects of complex exposures, and there are few reviews on biomonitoring complex exposures. In this review we summarize articles in which biomonitoring techniques have been developed and used. Most examples describe techniques for biomonitoring effects which may detect early changes induced by many chemical stressors and which have the potential to accelerate data gathering. Some emphasis is put on endocrine disrupters acting via epigenetic mechanisms and on carcinogens. Solid evidence shows that these groups of chemicals can interact and even produce synergistic effects. They may act during sensitive time windows and biomonitoring their effects in epidemiological studies is a challenging task

Topics: Review
Publisher: Molecular Diversity Preservation International (MDPI)
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2009). 30 years and a long way into p53 research. Lancet Oncol.
  2. (2009). A preliminary operational classification system for nonmutagenic modes of action for carcinogenesis.
  3. (2009). A Review of Human Carcinogens—Part F; International Agency for Research on Cancer
  4. (2005). Air pollution and cancer: biomarker studies in human populations. Carcinogenesis
  5. (2005). Altered gene expression patterns in MCF-7 cells induced by the urban dust particulate complex mixture standard reference material 1649a. Cancer Res.
  6. (2007). An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis
  7. (2007). Assessing cumulative health risks from exposure to environmental mixtures—three fundamental questions. Environ. Health Perspect.
  8. (2011). Assessment of Combined Exposures. Available online:
  9. (2009). Assessment of the total effective xenoestrogen burden in extracts of human placentas.
  10. (2009). Association between leukocyte telomere shortening and exposure to traffic pollution: A cross-sectional study on traffic officers and indoor office workers. Environ. Health
  11. (2010). Association between organophosphate pesticides exposure and thyroid hormones in floriculture workers.
  12. (2002). Biological monitoring of exposure to mixtures.
  13. (1996). Biomarker research in neurotoxicology: the role of mechanistic studies to bridge the gap between the laboratory and epidemiological investigations. Environ. Health Perspect.
  14. (2009). Biomarkers for Cumulative Risk Assessment. Available online: quick_finder/biomarkers.html (accessed on 11
  15. (2008). Biomarkers in toxicology and risk assessment: informing critical dose-response relationships.
  16. (2009). Biomarkers measured by cytokinesis-block micronucleus cytome assay for evaluating genetic damages induced by polycyclic aromatic hydrocarbons.
  17. (2007). Biomarkers of exposure to carcinogenic PAHs and their relationship with environmental factors.
  18. (2010). Biomarkers of exposure, effects and susceptibility in humans and their application in studies of interactions among metals in
  19. (2010). Biomonitoring for occupational health risk assessment
  20. (2005). Biomonitoring in occupational health: Scientific, socio-ethical, and regulatory issues.
  21. (2005). Biomonitoring of inhaled complex mixtures—ambient air, diesel exhaust and cigarette smoke.
  22. Bladder cancer risk in painters: a meta-analysis.
  23. (2007). Breath air analysis and its use as a biomarker in biological monitoring of occupational and environmental exposure to chemical agents.
  24. (2005). cigarette smoking, and telomere length in women. Lancet
  25. (2007). Clara cell protein as a biomarker for lung epithelial injury in asphalt workers.
  26. (2008). Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat.
  27. (2007). Committee on Toxicity Testing and Assessment of Environmental Agents. Toxicity Testing in the 21st Century: A Vision and a Strategy; National Research Council:
  28. (2005). Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis
  29. (2009). Council Conclusions on Combination Effects of Chemicals; Commission of the European
  30. (2009). Creating context for the use of DNA adduct data in cancer risk assessment: I. Data organization.
  31. (2005). Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ. Health Perspect.
  32. (2001). Determination of dichloroanilines in human urine by GC-MS, GC-MS-MS, and GC-ECD as markers of low-level pesticide exposure.
  33. (2006). Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res.
  34. (2005). Dose-dependent liver tissue repair after chloroform plus trichloroethylene binary mixture. Basic Clin.
  35. Dynamics of telomerase activity in response to acute psychological stress.
  36. (2009). Endocrine-disrupting chemicals: an Endocrine Society scientific statement.
  37. (2009). Environmental and biological monitoring of volatile organic compounds in the workplace. Chemosphere
  38. Environmental causes of cancer: endocrine disruptors as carcinogens.
  39. (2009). Environmental exposure measurement in cancer epidemiology. Mutagenesis
  40. (2009). Evaluation of a suitable DNA damage biomarker for human biomonitoring of exposed workers.
  41. (2002). Gene induction studies and toxicity of chemical mixtures. Environ. Health Perspect.
  42. Genital anomalies in boys and the environment.
  43. (2008). Genotoxic effects of fumes from asphalt modified with waste plastic and tall oil pitch.
  44. (2004). Guidance Manual for the Assessment of Joint Toxic Action of Chemical Mixtures; U.S. Department of Health and Human Services Public Health Service, Agency for Toxic Substances and Disease Registry, Division of Toxicology:
  45. (1986). Guidelines for the Health Risk Assessment of Chemical Mixtures; U.S. Environmental Protection Agency:
  46. (2007). Human biomonitoring: state of the art.
  47. (2009). Human body burdens of chemicals used in plastic manufacture.
  48. (2007). Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: A nested case-control study. Environ. Health Perspect.
  49. Human population studies with the exfoliated buccal micronucleus assay: Statistical and epidemiological issues.
  50. (2007). Identification and determination of highly carcinogenic dibenzopyrene isomers in air particulate samples from a street canyon, a rooftop, and a subway station in
  51. (2004). Immunological biomarkers in salt miners exposed to salt dust, diesel exhaust and nitrogen oxides.
  52. (2009). In vitro recapitulating of TP53 mutagenesis in hepatocellular carcinoma associated with dietary aflatoxin B1 exposure. Gastroenterology
  53. (2005). Increased serum bile acids as a possible biomarker of hepatotoxicity in Brazilian workers exposed to solvents in car repainting shops. Biomarkers
  54. (2005). Mechanistic data and cancer risk assessment: the need for quantitative molecular endpoints.
  55. (1992). Molecular and genetic damage in humans from environmental pollution in Poland. Nature
  56. (2010). Molecular markers for early detection.
  57. (2008). New biomarkers of occupational exposure to polycyclic aromatic hydrocarbons.
  58. (2009). Non-invasive matrices in human biomonitoring: A review.
  59. (2009). Occupational airborne contamination in south Brazil: 1. Oxidative stress detected in the blood of coal miners. Ecotoxicology
  60. (2009). Oral exposure to bisphenol a increases dimethylbenzanthracene-induced mammary cancer in rats. Environ. Health Perspect.
  61. (2008). Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ. Health Perspect.
  62. (2009). Phthalate risks, phthalate regulation, and public health: A review.
  63. (2009). Population analysis of myelosuppression profiles using routine clinical data after the ICE (ifosfamide/carboplatin/etoposide) regimen for malignant gliomas.
  64. (2009). Profiling chemicals based on chronic toxicity results from the U.S. EPA ToxRef Database. Environ. Health Perspect.
  65. (2009). Prospects for epigenetic epidemiology.
  66. (2004). Results of common laboratory tests in solvent-exposed workers.
  67. (2004). Role of biomarkers in monitoring exposures to chemicals: Present position, future prospects. Biomarkers
  68. (2008). Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium and arsenic.
  69. (2009). Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.
  70. (2010). Shorter telomere length in peripheral blood lymphocytes of workers exposed to polycyclic aromatic hydrocarbons. Carcinogenesis
  71. (1995). Significance of dermal and respiratory uptake in creosote workers: exposure to polycyclic aromatic hydrocarbons and urinary excretion of 1-hydroxypyrene.
  72. (2011). Societal and ethical issues in human biomonitoring—A view from science studies.
  73. (2009). State of the Art Report on Mixture Toxicity; The School of Pharmacy,
  74. (2000). Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures; U.S. Environmental Protection Agency:
  75. (2009). Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ. Health Perspect.
  76. (2010). Systems toxicology approaches for understanding the joint effects of environmental chemical mixtures. Sci. Total Environ.
  77. (2008). Telomere length assessment: Biomarker of chronic oxidative stress? Free Radic.
  78. (2006). Telomere shortening in smokers with and without
  79. (2008). Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects.
  80. (2006). The influence of environmental exposure to complex mixtures including PAHs and lead on genotoxic effects in children living in Upper Silesia, Poland. Mutagenesis
  81. (2009). The synergistic toxicity of pesticide mixtures: implications for risk assessment and the conservation of endangered Pacific salmon. Environ. Health Perspect.
  82. (2008). The total effective xenoestrogen burden, a biomarker of exposure to xenoestrogen mixtures, is predicted by the (anti)estrogenicity of its components.
  83. (1989). The use of biological markers in toxicology.
  84. (2007). Toxicity assessment of unintentional exposure to multiple chemicals.
  85. (1998). Toxicological evaluation and risk assessment of chemical mixtures.
  86. (2001). Toxicology of simple and complex mixtures. Trends Pharmacol. Sci.
  87. (2007). TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene
  88. (2004). Urinary 1-hydroxypyrene and polycyclic aromatic hydrocarbon exposure among asphalt paving workers.
  89. (2008). Urinary excretion of an oxidative stress marker, 8-hydroxyguanine (8-OH-Gua), among nickel-cadmium battery workers.
  90. (2008). Urinary mutagenicity in chemical laboratory workers exposed to solvents.
  91. (2003). US-EPA Framework for Cumulative Risk Assessment; U.S. Environmental Protection Agency:
  92. (2007). Using biomarkers to inform cumulative risk assessment. Environ. Health Perspect.