TP14 Internal Exposure|
Tuesday, 15 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall
TP145 (LEE-1122-021478) Comparison and assessment of soil and soil-gas radon potential according to active and passive measurement methods.
Start time: 8:00 AM
Je, Hyun-Kuk1, Kang, Chigu2, Chun, Hae-Pyo3, Lee, Jin-Soo3, Chon, Hyo-Taek3, 1 Samdoo Co., Ltd., Gyunggi-do 462-120, Korea, South Korea2 Dept. of Environmental Eng., Ansan College of Technology, Kyungki-do, Korea, South Korea3 School of Civil, Urban and Geosystem Engineering, Seoul National University, Seoul 151-744, Korea, South Korea
The purposes of this study are to compare the soil and soil-gas radon concentrations according to active and passive techniques for radon measurement, and to determine the radon potential of ground where is under construction for houses and buildings. Six study areas were selected and classified according to their bedrock types. Soil-gas samples typically were collected by augering a hole and placing steel probe 50 to 70 cm below the soil surface of the study sites. Soil-gas sample of 160 ml was extracted into the RDA-200 radon detector and the radon concentrations were calculated by use of the Morse (1976) 3-minute method. In autumn season (Sep. to Nov., 2003), the mean concentrations of soil-gas radon for each area decreased in the order of Jikyeong (metamorphosed sandstone) > Homyoung (banded gneiss) > Gangcheon (biotite granite) > Choojung (phyllite) > Sanbook (banded gneiss) > Geumsung (limestone). To minimize daily variations of soil-gas radon concentrations and collect the monitoring data, integrating passive method with SSNTDs (Solid State Nuclear Track Detectors) was applied to the study areas. The plastic detector called TDR (Time integrated Detector for Radon) was placed inside a cylindrical tube (PVC material) of 50mm diameter and 500mm in length. Cylindrical tube with TDR was inserted to the ground at depth of 50-70cm and after exposure of 2-3 weeks, soil-gas radon concentration was analyzed by track etching method using NaOH solution. Results of statistical correlation analysis for 114 data sets between active (soil-gas extraction) and passive methods showed positive correlations in two methods with significance. For passive instrument (vessel test), the well-known "can technique" was used for the long-term measurements of radon emanation coefficient from soil sample from each study area. In this technique, a TDR was placed at 3cm height on the soil matrix, which sealed in the cylindrical vessel during 2 weeks. For active instrument (chamber test), soil samples were analyzed for Rn by radon monitor (RM-1024,), which placed in a chamber standardized to the temperature and humidity. The result of comparing the radon emanation coefficients between passive and active methods were as follows; Radon emanation coefficient (by vessel test) = 0.8 X Radon emanation coefficient (by chamber test) - 3.9 (R=0.95).
TP146 (SCH-1117-727718) Response spectrum of fluoranthene and pentachlorobenzene for the fathead minnow, Pimephales promelas.
Start time: 8:00 AM
Schuler, L1, Landrum, P2, Lydy, M1, 1 Southern Illinois University, Carbondale, Illinois, USA2 Great Lakes Environmental Research Laboratory, NOAA, Ann Arbor, Michigan, USA
The internal body residue has been recognized as a potential dose metric for toxicological assessments. This relationship between body residue and biological effects, including both lethal and sublethal effects, are critically important for determining environmental quality in hazard assessments. This study identified body residues for fluoranthene (FLU) and pentachlorobenzene (PCBz) associated with mortality, reduced growth, and decreased hatchability in the fathead minnow. The incipient lethal body residues corresponding to 50% mortality were 3.7 and 1.2 mol/gww for FLU and PCBz, respectively. As expected, residues associated with sublethal effects were determined to be 2 to 10 times lower than the lethal residues for PCBz and FLU, respectively. The information collected from this study will permit a greater understanding of residue-response relationships, which will be useful in hazard assessments.
TP147 (REI-1117-486921) Measuring the internal exposure of organic pollutants with equilibrium sampling devices.
Start time: 8:00 AM
Reichenberg, F.1, McLachlan, M.2, Mayer, P.1, 1 Department of environmental chemistry and microbiology, National Environmental Research Institute, Denmark2 Laboratory for Analytical Environmental Chemistry, Department of Applied Environmental Science, Stockholm University, Sweden
Fugacities and chemical activities of pollutants are very useful for environmental fate and exposure studies as they quantify the spontaneous tendency to distribute within the environment. In recent years, equilibrium sampling devices (ESDs) have found environmental application for the measurement of fugacities and chemical activities of organic pollutants in various exposure media such as air, water, soil and sediment. It is now a natural step to apply ESDs directly within biological samples for investigation of internal exposure. The application of polydimethylsiloxane (PDMS) based ESDs directly within animal tissue requires (1) an absorption of the pollutant into the PDMS, (2) that the sorptive property of the PDMS remains unaffected by the animal tissue and (3) that a thermodynamic equilibrium between sample and sampler can be obtained within a practical timespan. Applying fluoranthene as model substance, these requirements were tested with a few simple validation experiments. Our findings support that PDMS based ESDs can be applied directly to biological matrices, and the presentation will be concluded with actual measurements in animal tissue.
TP148 (JAG-1117-748360) Relating internal concentrations to chronic endpoints in life-cycle studies.
Start time: 8:00 AM
Jager, T1, Alda Alvarez, O2, Kammenga, J2, Kooijman, SALM1, 1 Vrije Universiteit, Dept. Theoretical Biology, Amsterdam, The Netherlands2 Wageningen University, Dept. Nematology, Wageningen, The Netherlands
For mortality, internal concentrations can be directly related to toxicity because mortality is a quantal response (dead or alive). For continuous endpoints such as growth and reproduction, such a comparison is more difficult to make. At the EC50 for reproduction, it is not 50% of the animals that is responding; it is more likely that the response of all animals is approximately 50% of the control. Furthermore, the concentration-response curves (and thereby ECx estimates) will differ between endpoints (e.g. growth and reproduction) for the same chemical, and will change in time in curious ways. Clearly, the relationship between internal exposure and chronic effects requires more detailed ideas about resource allocation. It is still likely that the internal concentration causes the effects, but in a much more continuous fashion, and depending on the mode of action of the toxicants. We link internal concentrations to effects on growth and reproduction using the theory of Dynamic Energy Budgets (DEB). This theory aims to quantify individual growth, development and reproduction on the basis of a set of simple rules for metabolic organisation. The effects of toxicants can be understood as a change in energetic parameters, such as an increase in maintenance costs, or the costs for egg production, or a decrease of the assimilation of energy from food. This leads to (at least) five different energetics-based modes of action, that all have a very specific effect on the growth and reproduction patterns, and especially affect the extrapolation from individuals to populations. We demonstrate our approach using several life-cycle data sets for nematodes. This analysis shows that internal concentrations do dictate effects on growth and reproduction, not in a direct fashion, but indirectly by affecting resource allocation.
TP149 (REI-1117-552693) Effective chemical activity (EA50) used as a measure of exposure for baseline toxicity.
Start time: 8:00 AM
Reichenberg, F.1, Mayer, P.1, 1 Department of environmental chemistry and microbiology, National Environmental Research Institute, Roskilde, Denmark
The chemical activity of a pollutant is proposed as a good measure of exposure for baseline toxicity, since it applies to different exposure media such as air, water and sediment and since baseline toxicity is exerted at a relatively constant chemical activity of 0.01 to 0.1. The chemical activity needs not necessarily be determined internally to be valid internally, since chemical activity is equal in all equilibrated phases. It is sufficient to determine the chemical activity in a phase that is in equilibrium with the site of toxic action. The chemical activity can be calculated from measured concentrations or it can be measured with equilibrium sampling devices (ESDs). We exemplify this concept with historically reported toxicity data for three different organisms, 29 different chemicals, and two different exposure routes. Effective concentrations (EC50) span more than six orders of magnitude within and between the studies, and this variation is reduced to about one order of magnitude when expressing the same data as effective chemical activities (EA50). Main advantages of this procedure include: [i] The chemical activity of a single chemical can roughly be characterized as being below, at or above the level of baseline toxicity. [ii] The activities of individual substances contained in a complex mixture can be added. The sum of activities is an indicator of the baseline toxic potential of the mixture, since baseline toxicity of mixtures generally follows "concentration additivity". [iii] Single compound toxicity at an activity well below 0.01 would suggest a specific mode of toxic action.
TP151 (LEE-1117-828364) Development of a Multi-component Damage Assessment Model (MDAM) for time-dependent mixture toxicity with toxicokinetic interactions.
Start time: 8:00 AM
Lee, J-H1, Landrum, P2, 1 Cooperative Institute for Limnology and Ecosystem Research (CILER), Ann Arbor, MI, USA2 Great Lakes Environmental Research Laboratory (GLERL), NOAA, Ann Arboro, MI, USA
A new mixture toxicity model was developed to predict the time-dependent toxicity of a mixture with toxicokinetic interactions that has specific application toward addressing biotransformation. The damage assessment model, a toxicokinetic-toxicodynamic model developed to describe and predict the time-dependent toxicity of a single compound, was extended to a Multi-component Damage Assessment Model (MDAM) for mixture toxicity. The model assumes that the cumulative damage from the parent compound, metabolites, and/or a biotransformation inhibitor are additive, and the sum of the cumulative damage determines mixture toxicity. Since incorporation of this Damage Addition hypothesis into the MDAM was found to be equivalent to the Independent Action model for mixture toxicity, it was applied to describe the combined effect of mixture components with dissimilar modes of action. From MDAM, a time-dependent toxic unit model was derived and applied to determine the toxic units of mixture components. This model suggests a series of experimental designs required to assess the role of biotransformation in the toxicity of metabolized organic compounds and the data analysis method to separately estimate toxicodynamic parameters for parent compound and metabolites. Finally, the toxicodynamic parameters, damage accrual rate coefficient and damage recovery rate constant for parent pyrene and fluorene, were first estimated to be 0.009 ∼ 0.020 mol-1 g h-1 and 0.003 ∼ 0.013 h-1, and the median lethal body residue (LBR50) values at infinite time were 0.237 ∼ 0.455 mol g-1, respectively. These values are similar to those of non-polar narcotics such as pentachlorobenzene (PCBz) and dichlorophenylchloroethylene (DDE). For fluorene metabolites, the values were 0.103 ± 0.034 mol-1 g h-1, 0.034 ± 0.021 h-1, and 0.325 ± 0.229 mol g-1, respectively. However, for pyrene metabolites, since toxicity of pyrene metabolites was negligible, the parameters could not be estimated.
TP152 (HON-1117-828504) Detoxifying enzymes and pyrene metabolites in salmon yolk-sac fry exposed to pyrene and humic substances.
Start time: 8:00 AM
Honkanen, J1, Wiegand, C2, 3, Kukkonen, J1, 1 Department of Biology, University of Joensuu, P.O. Box 111, FI-80101, Joensuu, Finland2 Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587, Berlin, Germany3 Humboldt University at Berlin, Unter den Linden 6, 10999, Berlin, Germany
Humic subtances may modify xenobiotic accumulation to aquatic animals. For example, humic substances may bind PAHs such as pyrene and decrease its bioavailability. In addition, humic substances may have direct effects on aquatic animals and thereafter modify indirectly accumulation and elimination of chemicals. The objective of this study was to characterize the effects of humic substances on pyrene accumulation, metabolite formation and detoxifying enzyme activities in landlocked salmon (Salmo salar m. sebago) yolk-sac fry. In a short-term (72 h) experiment yolk-sac fry were exposed to pyrene (4 g/l) in experimental waters, which were prepared in artificial freshwater, artificial freshwater with a reverse osmosis isolate of Lake Fuchskuhle (dissolved organic carbon concentration 5 and 25 mg/l) or water of Lake Oskajärvi (5 and 28 mg/l DOC). -naphthoflavone exposure was used as a positive control for ethoxyresorufin-o-deethylase (EROD, cytochrome P 450 1A1) activity measurements. Pyrene and its metabolites and detoxifying enzyme activities were analysed in whole yolk-sac fry extracts after 24 and 72 hours of exposure. Preliminary results of the experiment show that EROD activity was not induced after 24 hours of exposure, and after 72 h of exposure by -naphthoflavone only. However, 1-hydroxypyrene, the main metabolite of pyrene during phase I metabolism, was found in yolk-sac fry after 24 and 72 hours of exposure to pyrene. A water-soluble metabolite was observed after 24 and 72 h of exposure. Phase II metabolite 1-hydroxypyrene glucuronide-conjugate was not found in fry samples, but presence of other possible conjugates such as sulphate or glutathione will be assessed. Information about bioconcentration of pyrene in the presence of dissolved organic material, phase II enzyme activities (e.g. glutathione-S-transferase activity), and metabolite concentrations will be given during the presentation.
TP153 (SAC-1117-753868) Glucuronidation of polychlorobiphenylols by channel catfish (Ictalurus punctatus) liver and intestine.
Start time: 8:00 AM
Sacco, J1, Zheng, R1, James, M1, 1 University of Florida, Gainesville, FL, USA
Polychlorobiphenylols (OH-PCBs), the hydroxylated metabolites of PCBs, have a variety of toxic effects. The objective of this study was to investigate the efficacy of detoxification, via glucuronidation, of a series of para-OH-PCBs by the channel catfish. Intestinal (proximal portion) and hepatic microsomes from untreated channel catfish were incubated in pH 7.6 buffer with varying concentrations of OH-PCBs and [14C]-UDPGA, 0.2 mM for intestine, 1.5 mM for liver. After 30 minutes, tetrabutylammonium sulfate was added, the glucuronides were extracted into ethyl acetate and quantitated by scintillation counting. The apparent Km and Vmax values ranged from 42-572 M and 163-784 pmol/min/mg for the glucuronidation of a series of 14 OH-PCBs by intestine. The estimated kinetic parameters for the glucuronidation of 6 OH-PCBs by liver ranged from 124-784 M and 681-2774 pmol/min/mg protein. In liver and intestine, the most efficiently glucuronidated compound was 4'-OH-CB69 (2,3′,4,5-tetrachlorobiphenyl-4′-ol). Analysis of the glucuronidation data for the 6 compounds tested with both tissues showed that the Vmax was significantly higher in liver than in intestine (p<0.05). For five of the six OH-PCBs tested in both tissues, estimated Km values for the intestine were lower than in liver. The presence of two chlorine substituents flanking the phenol significantly decreased the Vmax for the glucuronidation of OH-PCBs in proximal intestine (p<0.005) but not in liver. A weak positive correlation was found between intestinal Km and lipophilicity (R2=0.47, p=0.01) and the Connolly molecular surface area (R2=0.51, p<0.01). These relationships were not observed in liver. Chlorine substitution on both sides of the phenolic group affected the efficacy of intestinal, but not hepatic, glucuronidation as a detoxification pathway for OH-PCBs. These results suggest that different UGT isoforms and levels of UGT expression exist in liver and intestine. Supported in part by P42-ES-07375
TP154 (MAC-1124-477565) Paracelsus got it wrong: fugacity makes the poison.
Start time: 8:00 AM
Mackay, D1, Arnot, J1, 1 Trent University, Peterborough, Ontario, Canada
A perspective is offered on the relative merits of internal and external exposure as metrics of chemical toxicity. External exposure implies a two-stage process of toxicant delivery followed by disruption. Internal exposure focuses only on the disruption state. The delivery stage being essentially one of transport is more readily measured, correlated, and predicted. The disruption stage being biochemical in nature is more difficult to quantify, but it is the true metric of inherent toxicity or potency. It is suggested that viewing these processes through the lense of fugacity clarifies their roles. The delivery stage involves the conversion of an external concentration to a fugacity then estimation of an internal / external fugacity ration using bioaccumulation, biomagnification, metabolic or pharmacokinetic information. The disruption stage involves estimation of a critical internal tissue, fluid or body fugacity from biochemcial mode-of-action information. Internal exposure assessment is simply a comparison of internal and critical fugacities whereas external exposure involves the external and critical fugacities. Both are useful, but for different purposes. Examples are presented illustrating the calculation of the fugacities and the time-dependence of the internal:external fugacity ration. It is clear that "poisoning" arises because the magnitude and duration of the external chemical fugacity causes the internal fugacity to reach the critical fugacity, thus it is fugacity, not dose that makes the poison.
TP155 (VOE-1117-844992) Accumulation, subcellular distribution and toxicity of metals in the zebra mussel 'Dreissena polymorpha' under field conditions.
Start time: 8:00 AM
Voets, J1, Bervoets, L1, Blust, R1, 1 University of Antwerp; Laboratorium for Ecophysiology, Biochemistry and Toxicology, Antwerp, Belgium
In the aquatic environment, metal concentrations accumulated in organisms are a better indicator for metal toxicity than environmental metal concentrations. However, in many cases, and especially under field conditions, there is no clear relation between accumulated metals and biomarker responses. Physiological factors, like the condition and detoxification capacity of the organisms, have and important effect on subcellular distribution of the metals and as a result will influence metal toxicity. In this study we investigated the relation between physiological condition and accumulation, internal distribution and toxicity of metals in the zebra mussel, Dreissena polymorpha, under field conditions. In a biomonitoring experiment, biomarker responses were related to accumulated metals, taking into account the subcellular metal distribution (determined by differential centrifugation and measurements of metallothionein like proteins). An additional experiment was conducted whereby the influence of physiological condition on accumulation, subcellular distribution and toxicity of metals was assessed. Zebra mussels were subjected to natural (different food levels) or chemical stress in order to manipulate their physiological condition. Subsequently, the mussels from the different treatments were exposed in a metal pollution gradient (mainly Cd and Zn) and physiological condition, metal accumulation, subcellular partitioning and toxicity was assessed. The toxicity was determined using biomarker responses at different levels of biological organisation, considering biochemical, physiological and organismal responses. Special attention was given to biomarkers related to the energy metabolism (energy uptake and cellular energy allocation).