title: Biomarkers of intermediate endpoints in environmental and occupational health.
abstract: The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal aberrations (CA), sister chromatid exchanges and micronuclei (MN). The validation of biomarkers includes measurements of sensitivity and specificity of biomarkers and round robin tests to ensure reproducible protocols within different laboratories. The predictive value of biomarkers with respect to adverse health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained cytogeneticists. Less time consuming, but robust biomarkers, sensitive to environmental exposures are suggested. From the selection of developed biomarkers, the comet assay is highly sensitive to lifestyle exposures, often confounding the output, while MN in lymphocytes seem promising with respect to laboratory and health effect (cancer) validity. Also, new biomarkers exploiting the new 'omics' technologies are being developed. A number of ethical issues arise from the use of biomarkers with a predictive value aiming at respecting the autonomy of the study person in participation (only upon written informed consent and with obligations of withdrawal at any time), access to personal information (right to know and right not to know the study result) and securing proper data management (data protection to avoid misuse in employment, insurance, loaning and learning opportunities).
authors.affiliation: Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark. l.knudsen@pubhealth.ku.dk
authors.forename: Lisbeth E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: Ase M
authors.initials: AM
authors.lastname: Hansen
mesh_terms: D000062:Accidents, Occupational; D000110:Acetylcholinesterase / Q000009:adverse effects; D020106:Acrylamide / Q000009:adverse effects; D000818:Animals; D015415:Biomarkers; D002869:Chromosome Aberrations / Q000139:chemically induced*; D018736:DNA Adducts; D004784:Environmental Monitoring; D005069:Evaluation Studies as Topic; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D009152:Mutagenicity Tests / Q000379:methods*; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D010575:Pesticides / Q000009:adverse effects; D011237:Predictive Value of Tests; D011506:Proteins / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D018736:DNA Adducts; D006454:Hemoglobins; D010575:Pesticides; D011506:Proteins; D020106:Acrylamide; D000110:Acetylcholinesterase; D006854:Hydrocortisone