1. Principles and possibilities of human environmental biomonitoring (By: J. Angerer)

2. Status of Environmental Toxicology in Germany: Problems and Perspectives (By: Hermann M. Bolt)

3. Assessment of Risks of Endocrine Modelling Chemicals (By: Hermann M. Bolt)

4. The role of toxicokinetics in human environmental risk assessment (By: Johannes G. Filser)

5. New aspects on human health effects of polycyclic aromatic hydrocarbons (By: H. Foth)

6. The bioavailability of polycyclic aromatic hydrocarbons from polluted soils (By: Peter H. Roos)

7. Structure-Activity Relationships in Envionmental Toxicology (By: Gerrit Schürmann)

8. Mechanisms of Ionising Radiation and Chemicals in Carcinogenesis: Comparative Studies (By: Christian Streffer)

9. Environmental geology related to the risks of chemicals (By: Peter Wycisk)

10. Chemical Policy and standard setting by the Europian Union (By: K. Ziegler-Skylakakis)
     

Principles and possibilities of human environmental biomonitoring

J. Angerer
 

In our environment we are exposed to a multitude of chemical substances, anthropogenic ones as well as those which are provided by nature itself. The aim of environmental medicine is to beware human beings from chronic toxic effects exerted by these substances. This is done by measuring and reducing the amounts of chemicals in the environmental media like air, water, soil, diet etc. These measures of primary prevention however should be augmented by biological monitoring (BM). BM is the determination of these substances or their metabolites (exposure monitoring) or the reaction products of mutagenic substances which DNA or proteins in biological material, mostly in body fluids. This way it is possible to estimate internal exposure and health risk and to prevent individual person from adverse health effects (secondary prevention).

Suitable parameters for this purpose should indicate exposure specifically and sensitively. They moreover should be representative for the toxic effect. Reliable analytical methods are a prerequisite for BM as well as reference- and limit values for the interpretation of results.

These principles and prerequisites of BM will be discussed on hand of some actual problems in environmental medicine like pesticides, metals, phthalates, PAH etc. The state of the art and the possibilities of BM shall be outlined as well as the question of evaluation of limit and reference values for the general population.

In Germany within the so called “environmental survey” representative groups of the general population are investigated with respect to their exposure to chemical substances. This survey is the basis of evaluation of reference values as well as “human biomonitoring values” which are limit values preventing adverse effects to health. In the USA similar investigations are carried out by the centres of disease control (CDC) to estimate the exposure of the general population to chemical substances (NHANES).

 

Status of Environmental Toxicology in Germany:
Problems and Perspectives

Hermann M. Bolt
Institut für Arbeitsphysiologie an der Universität Dortmund
Leibniz Research Centre for Working Environment and Human Factors
Ardeystr. 67, D-44139 Dortmund, Germany

During the last three decades we have witnessed considerable progress in Germany related to both practical and theoretical aspects of environmental toxicology. A growing public awareness in the 1970ies, following chemical disasters, new regulations were introduced in the European Union and its member states at the end of the 1970ies and beginning of the 1980ies, marking a continuous trend towards European legislation on matters of chemical safety. Important issues, both on national and European levels were the reduction of automobile emissions, and in particular the ban of leaded gasoline that has led to significant decreases in the lead body burden within the population. In industrial areas, such as the Rhine-Ruhr area characterised by a long tradition of coal, steel, tar and metal industry, remediation of soil and groundwater of former industrial sites are quite important, with a particular focus on polycyclic aromatic hydrocarbons. Recent developments in molecular epidemiology and biomarkers have provided new tools for elucidating causalities and risk. The unification of Germany in 1990 has brought a number of new implications and problems in the field of environmental toxicology that will certainly persist in the following decades. In particular, these are connected with the former Soviet uranium mining activities (“SDAG Wismut”), with the chemical industry, and with former military training areas. Examples will be highlighted at this Workshop. Perspectives for further improvements in chemical and human environmental safety are presently being discussed at the level of the European Union, based on a “White Paper” on a new policy on chemicals that had been issued by the European Commission in 2001. The goals and implications of this policy will also be communicated.

Reference: Pesch B, Brüning T, Frentzel-Beyme R, Johnen G, Harth V, Hoffmann W, Ko Y, Ranft U, Traugott UG, Thier R, Taeger D, Bolt HM (2004) Challenges to environmental toxicology and epidemiology: where do we stand and which way do we go? Toxicol Lett. 151: 255-266.
 

Assessment of Risks of Endocrine Modelling Chemicals

Hermann M. Bolt

Institut für Arbeitsphysiologie an der Universität Dortmund
Leibniz Research Centre for Working Environment and Human Factors
Ardeystr. 67, D-44139 Dortmund, Germany

Controversy has arisen concerning the likelihood of adverse health effects due to exposure to hormonally active agents or endocrine modulators such as environmental estrogens. With the aim to improve the basis for their toxicological evaluation, several chemicals of anthropogenic (bisphenol A, octylphenol, o,p'-DDT) and of natural origin (daidzein, genistein) were investigated with regard to their mode of hormonal action and potency as well as toxicokinetics. Experimental toxicodynamic and toxicokinetic data illustrate important points in a comparative assessment of environmental estrogens. A novel concept, the Hygiene-Based Margin of Safety (HBMOS), has been suggested to characterise the relative impact of these potential endocrine modulators on human health: It integrates exposure scenarios (i.a. those generated within the European Existing Chemicals Programme) and in vivo rodent potency data for xenoestrogens and for dietary phyto-estrogens. On the basis of these information, HBMOS values calculated for the alkylphenol and bisphenol A appear sufficiently high to ensure the absence of a practical risk to human health under the present exposure conditions. For slowly accumulating compounds (e.g. DDT) with much longer half-lives than isoflavones, such comparison should be based on comparative blood levels rather than on scenarios of daily exposures.

Reference: Degen GH, Janning P, Wittsiepe J, Upmeier A, Bolt HM. (2002) Integration of mechanistic data in the toxicological evaluation of endocrine modulators. Toxicol Lett. 127: 225-237.
 

The role of toxicokinetics in human environmental risk assessment

Johannes G. Filser

GSF - National Research Center for Environment and Health, Institute of Toxicology, Neuherberg, Germany

The toxic or carcinogenic active species (AS) of a chemical taken up by an organism can be the chemical itself or a metabolite thereof. Given the exposure to a chemical it is most meaningful to relate the biological response to the AS. In an organism, the target dose of the AS is determined by its concentration and the time it remains at the site of action. Both parameters depend on the rates by which the chemical is absorbed, distributed in organs and tissues, biotransformed to active metabolites or to products of reduced effectiveness and on the rate of excretion from the body. Toxicokinetics describe these processes quantitatively.
Knowledge of the toxicokinetic behaviour of a chemical in animals and humans enables to predict the organ and tissue burden by the AS species-specifically for various conditions of exposure. This knowledge is indispensable for understanding dose-response relationships observed in animal studies. By extrapolating toxicokinetically dose-response relationships to the human exposure situation, the health risk of chemicals can be estimated based on animal experiments. Another way to estimate the risk of a chemical relies on the comparison of the body burden by the AS with that by an endogenous compound showing a comparable mechanism of action. Risk estimations based on toxicokinetic data are of utmost importance for regulating exposure limits.
After a short introduction to toxicokinetic procedures the relevance of toxicokinetics with regard to low-dose risk estimates will be demonstrated on the environmental chemicals ethylene and bisphenol A.
 

New aspects on human health effects of polycyclic aromatic hydrocarbons
H. Foth

Institute of Environmental Toxicology, Martin-Luther-University Halle, Germany

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds with fused aromatic rings. PAHs are formed by pyrolytic processes performed in industry (coke production, power generation), in traffic (motor vehicles, street construction) and in private homes (heating, cooking). Life long exposure towards PAHs is likely in almost all settings where people live and work. PAHs are present in ambient air in complex mixtures with a highly variable pattern of compounds. Thus it is an ongoing problem to specify the most relevant compounds or sources. It is still an open question whether complex mixtures are likely to have a unique toxicological activity which is not reflected by the sum of the compounds with highest concentration.
PAHs are well known toxicants because of their genotoxic potential leading to mutagenesis and tumor formation. PAHs are distributed as smoke, particles, are attached to or incorparted in food plants and are present in contaminated soils of industrial settings. New insights are emerging concerning the relevance of exposure towards PAHs by these non occupational routes such as ambient air, food, household practices and life style. The need to identify the most appropriate way to biomonitor human health effects is emerging in order identify unknown sources and to decide on priorities of action. It is also emerging to clarify whether specific risks exist for pregnancy and childhood which were adressed in epidemiological studies from heavy contaminated industrial settings.
Within the large group of PAHs those compounds with more than 5 aromatic rings are most relevant with respect to human health effects. The best known PAH is benzo(a)pyrene (BaP) which is used as an indicator compound for exposure and toxicity. Very high concentrations of BaP can occur at workplaces. Very high average BaP concentrations between 22 and 37 g/m3 were reported for the top side of older coke oven batteries. Other values for working places range between 1 and 10 g/m3 for coke plants, coal-gas works or aluminium-smelting industry. PAH concentrations in ambient air have decreased substantially in many western european countries and are now in the ng/m3 range. However, sometimes indoor air may be loaded with manyfold higher concentrations which approach high occupational values – cooking with biomass fuel in India is one important example.
BaP and / or metabolites are often used as biomarkers of exposure in order to indicate for PAHs present in the environment, in test organisms as well as in humans. However, a still ongoing problem comes from the side that excreted BaP metabolites mirror the exposure but not necessarily the formation rate of critical metabolites with regard to genotoxicity. Biomarkers of effect have been evaluated for enzyme induction profiles, mutagenicity in urine and feaces, chromosome aberrations and sister chromatid exchanges in peripheral lymphocytes, and DNA and protein adduct formation.
BaP as well as other PAHs have been shown to induce apoptosis perhaps via mitochondrial toxicity and are also active in antiapoptotic signals in a hepatoma cell line. It must be clarified whether cytochrome P450 1A1 is involved in this pathway and may have a decisive role. Taken together PAHs are likely to mediate toxic mechanisms which are beside the “classical” routes of adduct formation and genotoxic DNA damage. This may provide new insights in the understanding of cellular effects by BaP and PAHs in general.
Prof. Dr. Heidi Foth, Director of the Institute of Environmental Toxicology, Martin-Luther University Halle/Saale, email: heidi.foth@medizin.uni-halle.de
Member of the Advisory Council on the Environment, Germany