Human biomonitoring: State of the art

Abstract

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.

Introduction

The determination of chemical substances in human body fluids was first used in occupational medicine for health protection of exposed workers. The determination of lead (Kehoe et al., 1933) or benzene metabolites (Yant et al., 1936) in blood and urine are early examples of human biomonitoring (HBM) of workplace exposures. In the early 1960s, powerful analytical techniques that allowed to measure very low concentrations of chemical substances in blood and urine began to enter the laboratories. These techniques provided the possibility to determine much lower concentrations of chemical substances in human body fluids caused by environmental exposure. Using atomic absorption spectroscopy, e.g., it turned out that the general population of industrialized countries was exposed to lead in a degree that required immediate action. As a consequence, the lead content of gasoline was reduced and for the first time HBM was used in great population studies to determine the blood lead levels and to control the success of the measures taken. In 1977, the Commission of the European Communities (CEC) enacted the “council directive on biological screening of the general population for lead” (Council directive 77/312/EEC, 1977). This directive required that the member states of the European Union should take the necessary steps of applying a common procedure for biological screening in order to assess the exposure of the population to lead outside the work environment. Apart from a directive on the control of lead exposure at the workplace this was the only HBM activity of the Commission of the European Union for the next 30 years. However, in some countries national authorities started to apply the advantages of HBM in population surveys designed to monitor exposure to environmental pollutants of the general population. The German Environmental Surveys were started in 1985 (GerES I–IV, 1985–2003; Schulz et al., 2007a). The US National Health and Nutrition Examination Surveys (NHANES 1976–2004) regularly determine toxic substances in blood and urine of the general population (Needham et al., 2007). In 2004, the commission of the EU agreed to the European Environment and Health Action Plan where the member states confirmed their interest in “developing a coherent approach to biological monitoring” of the general population. It seems that within the 7th Framework Programme of the EU, HBM shall play a prominent role (Open Stakeholder Consultation, 2006). In the USA, an enthusiastic discussion about the advantages of biomonitoring took place in the last years that even entered public debate (Wanjek, 2004). The Health and Environmental Science Institute (HESI, 2004) of the International Life Science Institute (ILSI) created a Technical Committee on Biomonitoring with the goal to delineate the appropriate scientific use of HBM data and to define the criteria needed for the integration of HBM data into the risk assessment process (Angerer et al., 2006). The US National Research Council was asked by the US Congress to perform an independent study on the possibilities of biomonitoring (NRC, 2006). These activities clearly demonstrate, that HBM is a very actual issue in public health politics, in environmental medicine and in science.

It is the goal of this article to summarize the current state of the art of HBM mainly focussing on monitoring of exposure, and of biochemical effect. Additionally, the usefulness of DNA damage as measured by the comet assay in HBM studies will be discussed. The usefulness and limitations of other biological effect markers of genotoxicity such as sister chromatid exchanges, micronuclei and chromosome aberrations are described in another paper of this issue (Au, 2007).