Human biomonitoring assessment values: Approaches and data requirements

Human biomonitoring (HBM) data is a very useful metric for assessing human's exposures to chemicals in commerce. To assess the potential health risks associated with the presence of chemicals in blood, urine or other biological matrix requires HBM assessment values. While HBM assessment values based on human exposure–response data remain the most highly valuable and interpretable assessment values, enough data exists for such values for very few chemicals. As a consequence, efforts have been undertaken to derive HBM assessment values in which external dose based guidance values such as tolerable daily intakes have been translated into equivalent biomonitoring levels. The development of HBM values by the German HBM Commission and Biomonitoring Equivalents by Summit Toxicology has resulted in conceptually similar assessment values. The review of the development of these values provided here demonstrates examples and approaches that can be used to broaden the range of chemicals for which such assessment values can be derived. Efforts to date have resulted in the publication of HBM assessment values for more than 80 chemicals, and now provide tools that can be used for the evaluation of HBM data across chemicals and populations.     

Levels and predictors of urinary nickel concentrations of children in Germany: Results from the German Environmental Survey on children (GerES IV)

Human biomonitoring of nickel has gained interest in environmental medicine due to its wide distribution in the environment and its allergenic potential. There are indications that the prevalence of nickel sensitization in children is increased by nickel exposure and that oral uptake of nickel can exacerbate nickel dermatitis in nickel-sensitive individuals. Urinary nickel measurement is a good indicator of exposure. However, data on nickel levels in urine of children are rare. For the first time, the German Environmental Survey on children (GerES IV) 2003–2006 provided representative data to describe the internal nickel exposure of children aged 3–14 years in Germany. Nickel was measured after enrichment in the organic phase of urine by graphite furnace atomic absorption spectrometry with Zeeman background correction. Nickel levels (n = 1576) ranged from <0.5 to 15 μg/l. Geometric mean was 1.26 μg/l. Multivariate regression analysis showed that gender, age, socio-economic status, being overweighted, consumption of hazelnut spread, nuts, cereals, chocolate and urinary creatinine were significant predictors for urinary nickel excretion of children who do not smoke. 20.2% of the variance could be explained by these variables. With a contribution of 13.8% the urinary creatinine concentration was the most important predictor. No influence of nickel intake via drinking water and second hand smoke exposure was observed.     

Human biomonitoring pilot study DEMOCOPHES in Germany: Contribution to a harmonized European approach

Human biomonitoring (HBM) is an effective tool to assess human exposure to environmental pollutants, but comparable HBM data in Europe are lacking. In order to expedite harmonization of HBM studies on a European scale, the twin projects COPHES (Consortium to Perform Human Biomonitoring on a European Scale) and DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) were formed, comprising 35 partners from 27 European countries.In COPHES a research scheme and guidelines were developed to exemplarily measure in a pilot study mercury in hair, cadmium, cotinine and several phthalate metabolites in urine of 6–11 year old children and their mothers in an urban and a rural region. Seventeen European countries simultaneously conducted this cross-sectional DEMOCOPHES feasibility study.The German study population was taken in the city of Bochum and in the Higher Sauerland District, comprising 120 mother-child pairs. In the present paper features of the study implementation are presented. German exposure concentrations of the pollutants are reported and compared with European average concentrations from DEMOCOPHES and with those measured in the representative German Environmental Survey (GerES IV).German DEMOCOPHES concentrations for mercury and cotinine were lower than the European average. However, 47% of the children were still exposed to environmental tobacco smoke (ETS) outside their home, which gives further potential for enhancing protection of children from ETS.Compared with samples from the other European countries German participating children had lower concentrations of the phthalate metabolites MEP and of the sum of 3 DEHP-metabolites (MEHP, 5OH-MEHP and 5oxo-MEHP), about the same concentrations of the phthalate metabolites MBzP and MiBP and higher concentrations of the phthalate metabolite MnBP. 2.5% of the German children had concentrations of the sum of 4 DEHP-metabolites and 4.2% had concentrations of MnBP that exceeded health based guidance values, indicating reasons for concern.Continuous HBM is necessary to track changes of pollutant exposure over time. Therefore Germany will continue to cooperate on the harmonisation of European human biomonitoring to support the chemicals regulation with the best possible exposure data to protect Europe’s people against environmental health risks.     

The German Environmental Survey 1990/92 (GerES II): Primary Predictors of Blood Cadmium Levels in Adults

As part of the representative Environmental Survey in Germany in 1990–1992, investigators determined cadmium levels in blood provided by 3,965 subjects aged 25–69 yr. The investigators considered approximately 150 variables (i.e., demographics, household and occupational characteristics, environmental exposures, smoking habits, frequency of food consumption, and additional life-style features) as potential predictors in multivariate regression analysis. On the basis of the results of multivariate regression analysis, the authors derived 2 slightly different models for the prediction of blood cadmium levels in populations from West and East Germany. Both models included 3 primary predictors of blood cadmium levels. The 2 models explained 51.3% and 61.2% of the observed variance in blood cadmium levels in West and East Germany, respectively. The most important predictor was a specific indicator for smoking habits, which was determined from a separate mathematical model. In this model, the effect of smoking was considered, and the model accounted for the biological half-life of cadmium in blood.     

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.     

The distribution of blood concentrations of lead (Pb), cadmium (Cd), chromium (Cr) and manganese (Mn) in residents of the German Ruhr area and its potential association with occupational exposure in metal industry and/or other risk factors

Objective

This study investigated the metal distribution in blood samples from the general population and the risk of having high metal concentration for metal workers.

Environmental surveys, specimen bank and health related environmental monitoring in Germany

Production of chemicals, use of products and consumer goods, contamination of food as well as today's living conditions are related to a substantial exposure of humans to chemicals. Safety of human beings and the environment has to be safeguarded by producers and government. Human biomonitoring (HBM) has proven to be a useful and powerful tool to control human exposure and facilitate risk assessment. Therefore, the German Federal Environment Agency (Umweltbundesamt, UBA) employs two major HBM tools, the German Environmental Survey (GerES) and the German Environmental Specimen Bank (ESB). GerES is a nationwide population representative study on HBM and external human exposure, which has, inter alia, been used to identify lead in tap water, lead dustfall, time spent in traffic, and age of dwelling as exposure sources for lead and, thus, to derive risk reduction measures. The ESB is a permanent monitoring instrument and an archive for human specimens. Retrospective monitoring of phthalates and bisphenol A provides a continuous historical record of human exposure in Germany, over the last decades. Additionally it revealed that estimations of human exposure based on production and consumption data may supply misleading information on human exposure. HBM data demonstrated that (a) the use if the restricted isomer di-n-butylphthalat decreased while di-i-butylphthalate levels remained constant and (b) human bisphenol A exposure might be overestimated without monitoring data. The decrease of polycyclic aromatic hydrocarbon-exposure proves the success of German environmental policy after German re-unification. In addition to GerES and ESB UBA is involved in different co-operation networks, the two most prominent of which are (1) the harmonization of HBM in Europe (ESBIO; Expert Team to Support Biomonitoring in Europe, COPHES/DEMOCOPHES; Consortium to Perform Human Biomonitoring on a European Scale/Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) and (2) the co-operation between BMU and the German Chemical Industry Association (VCI). In the latter project emphasis will be placed on substances with a potential relevance for health and on substances to which the general population might potentially be exposed to a considerable extent and for which HBM methods are not available up to now.     

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.     

GerES IV pilot study: assessment of the exposure of German children to organophosphorus and pyrethroid pesticides

Organophosphorus pesticides and pyrethroids are widely used in German agriculture and residential settings. Their occurrence in human biological samples can be used as an indicator for the exposure of children to these compounds. Using multivariate evaluation the routes of exposure can be identified. In the pilot study of GerES IV, metabolites of pyrethroids and organophosporus pesticides were analysed in urine of children aged 2-17 years (n = 396 and 363). The 95th percentiles for the metabolites of the pyrethroids in urine were: cis-DCCA 0.74 microg/l, trans-DCCA 1.7 microg/l, DBCA 0.52 microg/l, F-PBA < 0.1 microg/l, and 3-PBA 2.4 microg/l. 3-PBA was detected in 90% of the samples. The 95th percentiles for the organophosphorus metabolites in urine were: DMP 118 microg/l, DEP 20 microg/l, DMTP 124 microg/l, DETP 11 microg/l, DMDTP 11 microg/l, DEDTP < 1.0microg/l. DMTP was the metabolite most frequently detected in the samples (90%). Based on the metabolites analysed in urine the exposure to organophosphorus pesticides is mainly influenced by age, consumption of fresh fruits and fruit juice, living in an urban area, and season. A rough estimation revealed that the ADI values for organophosphorus pesticides might be exceeded. However, these results require further exploration. The exposure to pyrethroids is influenced by age, sampling location, consumption of boiled vegetables, and the use of biocides indoors at home. In addition, a significant correlation between permethrin in house dust and the metabolite concentrations in urine could be observed. Thus it seems likely that ingestion of house dust contributes to children's exposure.     

German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population

The German Environmental Survey was conducted for the third time in 1998 (GerES III). The probability sample of about 4800 subjects was selected to be representative for the German population with regard to region (East-/West-Germany), community size, age (18 to 69 years) and gender. Blood samples were taken from each study participant and questionnaires were used to get exposure-related information. Cadmium, lead, mercury, hexachlorobenzene (HCB), hexachlorocyclohexane (alpha-HCH, beta-HCH, gamma-HCH), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p, p'-DDE) and polychlorinated biphenyls (PCB-138, PCB-153, PCB-180) were analysed in whole blood to document the extent, distribution, and determinants of exposure of the general population to these substances. The geometric means of Cd, Pb, and Hg in blood amounted to 0.44, 31, and 0.58 microgram/l, respectively. Smokers showed a Cadmium level of 1.1 micrograms/l and non-smokers a level of 0.28 microgram/l. The geometric mean of lead was higher in the blood of males than of females (36 micrograms/l vs. 26 micrograms/l). The concentration of mercury in blood depends on fish consumption and the number of teeth with amalgam fillings. The mean concentrations of HCB and p, p'-DDE in blood were 0.44 microgram/l and 1.6 micrograms/l, respectively. In East-Germany (the former GDR) the DDE concentration in blood was more than twice as high as in West-Germany. Geometric means for PCB were 0.42, 0.68 and 0.44 microgram/l for PCB-138, PCB-153, and PCB-180, respectively. A marked increase of HCB, DDE and PCB levels with age could be observed. alpha-HCH and gamma-HCH could be detected in 1.7% and 5.2% of the samples only. beta-HCH was quantified in 34% of the samples with a 95th percentile of 0.5 microgram/l.