Revised and new reference values for environmental pollutants in urine or blood of children in Germany derived from the German environmental survey on children 2003-2006 (GerES IV).

Based on the representative data collection of the German Environmental Survey on Children 2003-2006 (GerES IV) the Human Biomonitoring Commission of the German Federal Environment Agency has updated the reference values for a comprehensive number of environmental pollutants in blood and urine of children in Germany. Reference values are statistically derived values that indicate the upper margin of background exposure to a given pollutant in a given population at a given time. They can be used as criteria to classify the measured values of individuals or population groups as being "elevated" or "not elevated". Since environmental conditions are changing, reference values are continuously checked and updated if new information becomes available. Therefore, the previously derived reference values for metabolites of pyrethroids (cis-, trans-Cl(2)Ca and 3-PBA: 1, 2, and 2microg/l), of PAH (1-hydroxypyrene: 0.5microg/l), for arsenic in urine (15microg/l), and for PCB 138, PCB 153, PCB 180 in whole blood (0.3, 0.4, 0.3microg/l) and for DDE (western Germany) in whole blood (0.7microg/l) were confirmed. The following reference values were lowered: lead in blood from 50 to 35microg/l, cadmium in urine from 0.5 to 0.2microg/l, mercury in whole blood from 1.0 to 0.8microg/l, mercury in urine from 0.7 to 0.4microg/l, beta-HCH in whole blood from 0.3 to 0.1microg/l, HCB in whole blood from 0.3 to 0.2microg/l, and DMP in urine from 135 to 75microg/l, and DMTP in urine from 160 to 100microg/l. Based on the extended data set of the GerES IV, the reference value for the sum of PCB 138+153+180 in whole blood of children aged 7 to 14 was raised from 0.9 to 1.0microg/l. The reference value for DEP in urine of children aged 3 to 14 was raised from 16 to 30microg/l. New reference values in urine of children aged 3 to 14 living in Germany were derived for antimony (0.3microg/l), nickel (4.5microg/l), thallium (0.6microg/l), uranium (0.04microg/l), metabolites of organophosphorous compounds (DMDTP, DETP: 10microg/l, 10microg/l) and metabolites of PAH (1-hydroxyphenanthrene: 0.6microg/l; 2/9-hydroxyphenanthrene: 0.4microg/l; 3-hydroxyphenanthrene: 0.5microg/l; 4-hydroxyphenanthrene: 0.2microg/l; Sigma hydroxyphenanthrene (1, 2/9, 3, 4): 1.5microg/l) in urine and for DDE in blood of children aged 7 to 14 years living in eastern Germany (1.4microg/l). If reliable and repeated measurements show a value above the reference value, an environmental hygiene-based search for the causes and sources of this exposure is recommended. After that, it should be checked whether the exposure can be decreased within reasonable bounds.

Human biomonitoring studies in North Rhine-Westphalia, Germany.

The areas along the rivers Rhine, Ruhr and Wupper in North Rhine-Westphalia (NRW), Germany, represent the largest urban and industrial agglomeration in Europe with about 10 million inhabitants. Human biomonitoring (HBM) studies have been conducted in these areas since more than 30 years, mainly designed to evaluate internal exposure to air pollutants. Recent studies were focussed on residents living near industrial sources. The contaminants studied comprise heavy metals, metabolites of polycyclic aromatic hydrocarbons (PAH), persistent organic pollutants (POPs), volatile organic compounds (VOC), and markers of DNA exposure. Study groups were mainly children and elderly subjects. Human milk, blood, urine, teeth, hair and nails were investigated. Time trend analyses demonstrate a significant decline of exposure to many contaminants such as POPs and heavy metals. More recent studies suggest that there still is an increased internal exposure to metals, PAH and DNA damaging agents in children and women living very close to industrial sources.

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.

Revised and new reference values for some trace elements in blood and urine for human biomonitoring in environmental medicine.

Reference values for environmental pollutants related to the German population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency. The reference values for arsenic, cadmium, lead, mercury and platinum in blood or urine were derived from the German Environmental Survey 1998 (adults aged 18-69 years). The reference value for lead in blood was lowered for females from 90 to 70 micrograms/l and for males from 120 to 90 micrograms/l, while the values for cadmium of 1.0 and for mercury of 2.0 micrograms/l in blood remained unchanged. For cadmium in urine the reference value was lowered from 1.5 to 0.8 micrograms/l and for mercury in urine from 1.4 to 1.0 micrograms/l. New reference values were derived for arsenic (15 micrograms/l) and platinum in urine (0.01 microgram/l). Additionally, for nickel in urine a new reference value of 3.0 micrograms/l based on data from the literature was established. Reference values for estimation of the selenium status were summarized from the literature. For aluminium in blood or urine no reference values were derived and the use of human biomonitoring to estimate aluminium exposure in environmental medicine is not recommended.

Revised and new reference values for some persistent organic pollutants (POPs) in blood for human biomonitoring in environmental medicine.

Reference values for environmental pollutants related to the German population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency. The revised and new reference values for organochlorine compounds in whole blood are derived from the German Environmental Survey 1998 (adults aged 18-69 years) and from a survey performed with children (age 9-11 years) in south-west Germany 1998/99. The levels of organochlorine compounds in blood of adults increased with increasing age. Therefore the reference values are revised for different age groups (age groups: 18-19, 20-29, 30-39, 40-49, 50-59, 60-69). The reference values for PCB 138 in whole blood range from 0.4 to 2.2 micrograms/l, for PCB 153 from 0.6 to 3.3 micrograms/l, for PCB 180 from 0.3 to 2.4 micrograms/l, for beta-HCH from 0.3 to 0.9 microgram/l and for HCB from 0.4 to 5.8 micrograms/l. The reference values for DDE among adults in East Germany are higher compared to those in West Germany. The reference values of DDE in blood for adults in West Germany increase from 1.5 micrograms/l to 11 micrograms/l for the different age groups. The corresponding results for East Germany are 3 and 31 micrograms/l. The following reference values in blood of children (age 9-11 years) are recommended: 0.3 microgram/l for PCB 138, 0.4 microgram/l for PCB 153, 0.3 microgram/l for PCB 180, 0.9 microgram/l for sum of PCB (138 + 153 + 180), 0.3 microgram/l for beta-HCH, 0.3 microgram/l for HCB and 0.7 microgram/l for DDE. In comparison with the former evaluation the revised reference values for PCB, beta-HCH and HCB levels in blood were reduced especially for younger adults.

Prevalence of respiratory symptoms in school children and salivary IgA--an epidemiological study in a rural area of Northrhine-Westphalia, Germany.

An elevated frequency of wheezing was found in school children in a rural area of Northrhine-Westphalia, Germany (Duhme and Keil, Institut für Epidemiologie und Sozialmedizin, Universität Münster, Münster, Germany 1997). In this study the prevalence of wheezing was reinvestigated by including main influencing factors. A cross-sectional survey was performed in all school children visiting school classes 1, 2 and 7, 8 (n = 1161). Two corresponding questionnaires were used: a parental questionnaire and a questionnaire for self-completion by the children aged 12-15. The latter included the ISAAC video questionnaire. The levels of immunoglobulins A, G and M were determined in 995 saliva samples. Testing of lung function (whole body plethysmography before and after physical exercise) was performed in children with and without parent-reported wheezing in the last 12 months (n = 377). Response rate (questionnaire: 93%) and participation rates (saliva samples: 86%, lung function tests: 93%) were high. Our study confirmed higher prevalence of asthmatic symptoms in children aged 6-8 in Ochtrup (13.2%) compared to children of the same age in Muenster (8.5% (Duhme et al., Eur. Respir. J. 11, 840-847, 1998)). However, in the age group 12-15 years the prevalence was significantly lower in Ochtrup (9.8%), when compared to the former investigation and in comparison to Muenster (former survey: 17.9%; Muenster: 13.1%). Prevalence of wheezing was consistently higher in families with atopic disease. Additionally, history of respiratory disease, premature birth and presence of pets during 1st year of life showed a positive association with prevalence of wheezing. Mean salivary IgA levels were 61.4 (SD (standard deviation) 35.1, median: 53.7) mg/l in children aged 6-8 years and 83.4 (SD 39.0, median: 76.3) mg/l in children aged 12-15 years. No significant association between salivary immunoglobulins and wheezing was detected.