Human biomonitoring: state of the art.
Human biomonitoring (HBM) of dose and biochemical effect nowadays has tremendous utility providing an efficient and cost effective means of measuring human exposure to chemical substances. HBM considers all routes of uptake and all sources which are relevant making it an ideal instrument for risk assessment and risk management. HBM can identify new chemical exposures, trends and changes in exposure, establish distribution of exposure among the general population, identify vulnerable groups and populations with higher exposures and identify environmental risks at specific contaminated sites with relatively low expenditure. The sensitivity of HBM methods moreover enables the elucidation of human metabolism and toxic mechanisms of the pollutants. So, HBM is a tool for scientists as well as for policy makers. Blood and urine are by far the most approved matrices. HBM can be done for most chemical substances which are in the focus of the worldwide discussion of environmental medicine. This especially applies for metals, PAH, phthalates, dioxins, pesticides, as well as for aromatic amines, perfluorinated chemicals, environmental tobacco smoke and volatile organic compounds. Protein adducts, especially Hb-adducts, as surrogates of DNA adducts measuring exposure as well as biochemical effect very specifically and sensitively are a still better means to estimate cancer risk than measuring genotoxic substances and their metabolites in human body fluids. Using very sophisticated but nevertheless routinely applicable analytical procedures Hb-adducts of alkylating agents, aromatic amines and nitro aromatic compounds are determined routinely today. To extend the spectrum of biochemical effect monitoring further methods should be elaborated which put up with cleavage and separation of the adducted protein molecules as a measure of sample preparation. This way all sites of adduction as well as further proteins, like serum albumin could be used for HBM. DNA-adducts indicate the mutagenicity of a chemical substance as well as an elevated cancer risk. DNA-adducts therefore would be ideal parameters for HBM. Though there are very sensitive techniques for DNA adduct monitoring like P32-postlabelling and immunological methods they lack specificity. For elucidating the mechanism of carcinogenesis and for a broad applicability and comparability in epidemiological studies analytical methods must be elaborated which are strictly specific for the chemical structure of the DNA-adduct. Current analytical possibilities however meet their borders. In HBM studies with exposure to genotoxic chemicals especially the measurement of DNA strand breaks in lymphocytes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in white blood cells has become very popular. However, there is still a lack of well-established dose-response relations between occupational or environmental exposures and the induction of 8-OHdG or formation of strand breaks which limits the applicability of these markers. Most of the biomarkers used in population studies are covered by standard operating procedures (SOPs) as well as by internal and external quality assessment schemes. Therefore, HBM results from the leading laboratories worldwide are analytically reliable and comparable. Newly upcoming substances of environmental relevance like perfluorinated compounds can rapidly be assessed in body fluids because there are very powerful laboratories which are able to elaborate the analytical prerequisites in due time. On the other hand, it is getting more and more difficult for the laboratories to keep up with a progress in instrumental analyses. In spite of this it will pay to reach the ultimate summit of HBM because it is the only way to identify and quantify human exposure and risk, elucidate the mechanism of toxic effects and to ultimately decide if measures have to be taken to reduce exposure. Risk assessment and risk management without HBM lead to wrong risk estimates and cause inadequate measures. In some countries like in USA and in Germany, thousands of inhabitants are regularly investigated with respect to their internal exposure to a broad range of environmentally occurring substances. For the evaluation of HBM results the German HBM Commission elaborates reference- and HBM-values.
Angerer
Jürgen
J
Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstrasse 25/29, 91054 Erlangen, Germany. angerer@asumed.med.uni-erlangen.de
Ewers
Ulrich
U
Wilhelm
Michael
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000652:urine; D020552:Comet Assay; D018736:DNA Adducts / Q000009:adverse effects / Q000032:analysis / Q000097:blood*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000009:adverse effects / Q000032:analysis; D006801:Humans; D008670:Metals / Q000009:adverse effects; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis; D009930:Organic Chemicals / Q000009:adverse effects; D012016:Reference Values
D015415:Biomarkers; D018736:DNA Adducts; D004785:Environmental Pollutants; D008670:Metals; D009930:Organic Chemicals; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine