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R Brüggemann

Publications and source records attributed to R Brüggemann.

13 recordsLinked to original sources

Resources and uncertainties in evaluation of chemicals: basic methodological developments.

Conscious handling of uncertainty is critical in the assessment of chemicals, where the demand of knowledge is high compared to the available amount of resources. Consequently weighing between the use of resources and the acceptance of uncertainty has to be a transparent process and this sets up a challenge in relation to the application of mathematical methods. The maximum entropy principle is a useful paradigm for setting up prior information that is as non-informative as possible. It is shown how the use of partial ordering for deriving ranking results can be considered as a maximum entropy strategy in relation to the model structure uncertainty. In this way it seems possible to solve central parts of the problem of resource optimising risk assessment by combining the precautionary principle and screening before more detailed risk assessment is undertaken. The non-parametric approach of partial order technique further appears to be more transparent than most other ranking methodologies for complex systems. Because in the partial order techniques, no more or less known uncertainty will be hidden in the application of specific weighting factors and functional relationships among the criteria.

Environmental Exposure↗

QSAR's based on partial order ranking.

The development of Quantitative Structure Activity Relationships (QSAR's) often relies heavily on the application of statistical methods such as multi-linear regression (MLR) or principal component analysis/partial least square (PCA/PLS). Partial order ranking (POR), which from a mathematical point of view is based on elementary methods of Discrete Mathematics, appears as an attractive and operationally simple and more general alternative since the method does not require specific functional relationships between the single descriptors or the end-points. The POR method allows ranking of a series of compounds, based on selected descriptors characterizing their structural and/or electronic nature (model diagram). The ranking of the compounds based on their end-points (experimental ranking) can then be compared to the model diagram. If the model diagram resembles the experimental ranking of the end-points under investigation, other compounds, not being experimentally investigated, can be assigned a rank in the model and hereby obtain an identity based on the known compounds. The present study elucidates the applicability of POR as a simple tool for QSAR modeling. Based on illustrative examples the POR approach to QSAR modeling will be presented with special focus on the precision and the uncertainties of the method, which will be discussed in terms of the number of descriptors and compounds involved. The advantageous interplay between POR and PCA, the latter being applied in order to reduce a possible large number of descriptors into a limited number of latent descriptors will be discussed.

Endpoint Determination↗

The use of Hasse diagrams as a potential approach for inverse QSAR.

Quantitative structure-activity relationships are often based on standard multidimensional statistical analyses and sophisticated local and global molecular descriptors. Here, the aim is to develop a tool helpful to define a molecule or a class of molecules which fulfills pre-described properties, i.e., an Inverse QSAR approach. If highly sophisticated descriptors are used in QSAR, the structure and then the synthesis recipe may be hard to derive. Thus, descriptors, from which the synthesis recipe can be easily derived, seem appropriate to be included within this study. However, if descriptors simple enough to be useful for defining syntheses recipes of chemicals were used, the accuracy of a numeric expression may fail. This paper suggests a method, based on very simple elements of the theory of partially ordered sets, to find a qualitative basis for the relationship between such fairly simple descriptors on the one side and a series of ecotoxicological properties, on the other side. The partial order ranking method assumes neither linearity nor certain statistical distribution properties. Therefore the method may be more general compared to many standard statistical techniques. A series of chlorinated aliphatic compounds has been used as an illustrative example and a comparison with more sophisticated descriptors derived from quantum chemistry and graph theory is given. Among the results, it was disclosed that only for algae lethal concentration, as one of the four ecotoxicological properties, the synthesis specific predictors seem to be good estimators. For all other ecotoxicological properties quantum chemical descriptors appear as the more suitable estimators.

Ecosystem↗

An algebraic/graphical tool to compare ecosystems with respect to their pollution V: cluster analysis and Hasse diagrams.

In case of large data matrices comparative evaluations of objects/regions with the technique of Hasse diagrams may be troublesome due to a messy system of lines in the graphical representation. Here fuzzy clustering leads to useful simplifications because regions with slightly different pollution pattern are grouped together. However, fuzzy clustering implies to introduce a threshold value for the membership of an object to a cluster and to select the best number of clusters. Therefore many arbitrarities evolve. Within the systematic study presented here we found that some objects are very stable against variations of the threshold value and the number of cluster whereas other objects behaves different. According to their behaviour we investigated a classification of the objects. Formal Concept Analysis shows that in some cases specific pollution pattern imply the membership to one of these classes. For example objects which are characterized by high Pb-, Zn-concentration and moderate S-concentration imply a high stability against variants of the clustering process. Further implications are described in the paper.

Cadmium↗

Analysis of cholinesterase inactivation and reactivation by systematic structural modification and enantiomeric selectivity.

We show here with a congeneric series of Rp- and Sp-alkoxymethyl phosphonothiolates of known absolute stereochemistry that chiral selectivity in their reaction with acetylcholinesterase can be described in terms of discrete orientational and steric requirements. Stereoselectivity depends on acyl pocket dimensions, which govern leaving group orientation and a productive association of the phosphonyl oxygen in the oxyanion hole. Overall geometry is consistent with a pentavalent intermediate where the attacking serine and leaving group are at apical positions. Oxime reactivation of the phosphonylated enzyme occurs through a similar associative intermediate presumably forming an oxime phosphonate. The oximes of differing structure show distinct angles of attacking the phosphate where the attack angles and access to the phosphorus are constrained in the sterically impacted gorge. Hence, efficacy of oxime reactivation is dependent on both oxime and conjugated phosphonate structures.

Animals↗

Predicting bioconcentration factors (BCFs) of polychlorinated bornane (Toxaphene) congeners in fish and comparison with bioaccumulation factors (BAFs) in biota from the aquatic environment.

Polychlorinated bornanes, the main components of Toxaphene, are bioconcentrated in aquatic organisms to a high extent. However, up to this time no bioconcentration tests with individual chlorinated bornanes in aquatic organisms have been performed. Therefore, the bioconcentration factors (BCFs) of seven selected persistent chlorinated bornane congeners which are regularly found in aquatic organisms, were predicted from their n-octanol/water partition coefficients (log Kow). Furthermore, these BCF values were compared with the measured bioaccumulation factors (BAFs) in zooplankton and different fish species from the aquatic environment.

Animals↗

Soil Adsorption Coefficients of s-Triazines Estimated with a New Gradient HPLC Method.

A high-performance liquid chromatography (HPLC) method employing gradient elution was developed to predict soil adsorption coefficients (K(oc)) from HPLC capacity factors. The gradient method allows for the determination of K(oc) values over a range of 4.4 orders of magnitude in a single experiment without adjustment of the solvent composition, as is required in isocratic HPLC measurements. The range of K(oc) estimated can easily be extended by using reference compounds with lower or higher log K(oc) values. Therefore, gradient HPLC is an appropriate screening method for K(oc) and was used to investigate s-triazine herbicides and their degradation products. Log K(oc) ranged from 0.8 for cyromazine to a maximum of 2.6 for anilazine and aziprotryne. HPLC-derived K(oc) values of s-triazines containing an azido group were higher than and those of hydroxy-s-triazines were lower than K(oc) values estimated according to the fragment contribution method of Meylan et al. (1992). According to this method, the log K(oc) of the keto form of hydroxy-s-triazines was >1 log unit higher than that of the enol form.

Journal Article↗

Toxicology databases in the metadatabank of online databases.

Databases in science and technology dealing with toxicology subjects are of great and increasing interest to the scientific community. International hosts pay their tribute in creating toxicology clusters as a user-aid. Toxicology clusters of DataStar, DIALOG, DIMDI and STN are listed and compared. At the German National Research Centre for Environment and Health an 'Information System for Environmental Chemicals' has been developed. Within this research project approximately 400 online databases have been evaluated and the results are stored in the Metadatabank of Online Databases called DADB. A further step in this project is to assist the users of these metadatabases to choose the most appropriate database(s) for a special query. The retrieval of information out of a multitude of differently structured databases can be optimized using different evaluation criteria. We distinguished three groups of evaluation criteria: (1) general evaluation criteria, e.g. size of database, update frequency, cost of online search, etc., (2) evaluation criteria based on the characterization of environmental chemicals, and (3) evaluation criteria based on environmental-relevant data-types. We studied the influence of a number of different criteria in order to rank a set of objects, in this particular case toxicology databases. We used a six-number scoring system. The scoring is carried out using the scientific background of lattice theory and its graphical evaluation. The application of this scoring system for toxicologically-relevant databases, which is still in an early development stage, is useful in selecting the most appropriate database(s) in accordance with special items of interest. Applying our five chosen criteria, the databank CA (Chemical Abstracts) turns out to be the best, followed by four other databanks, which cannot be compared with each other.

Databases, Factual↗

The relevance of aquatic organisms' lipid content to the toxicity of lipophilic chemicals: toxicity of lindane to different fish species.

The acute toxicity (48-hr LC50) of lindane (gamma-HCH) to 16 fish species, belonging to eight families, ranges from 22 to 900 micrograms/liter (mean: 150 micrograms/liter). A significant positive linear relationship between the lipid content (% on a wet weight basis) of the fishes and their toxicity to gamma-HCH was found. If the toxicity is referred to 1% lipid, 48-hr LC50 values range between 13.2 and 32 micrograms/liter, and thus the coefficient of variation of the mean is reduced from 139 to 22%. It is concluded that the lipids of aquatic organisms serve as a protective reservoir against the toxic effects of lindane and other lipophilic, relatively persistent organic chemicals, because they are bioconcentrated mainly in the body lipids. Therefore, in organisms with high lipid content, only a relatively small fraction of the hydrophobic chemical can reach target organs (nerves, liver, etc.) and/or receptors. For comparing toxicity data of organic chemicals to aquatic organisms, the total lipid content of the organisms must be considered. The results of this investigation are important in comparative environmental toxicology for risk assessment of freshwater and marine organisms.

Animals↗

A review of the relationship between acute toxicity (LC50) of gamma-hexachlorocyclohexane (gamma-HCH, Lindane) and total lipid content of different fish species.

This paper provides an explanation for a 40-fold difference in the acute toxicity (LC50) of gamma-hexachlorocyclohexane (gamma-HCH, Lindane) in 14 different fish species, based on well recognized principles of toxicokinetics and toxicodynamics in combination with a compilation of data from the literature and some original data. The 48-h median lethal concentration (48-h LC50) of gamma-HCH in 14 fish species, belonging to 6 families, range from 22 to 900 micrograms/l. A significant positive linear relationship was found between lipid content (% of wet weight) and the 48-h LC50 of gamma-HCH in these fish species, revealing that the toxicity of gamma-HCH in various fish species is decreasing with increasing total lipid content. If median lethal concentrations are normalized for 1% lipid content, then the range of 48-h LC50s is reduced to between 18 and 32 micrograms/l. It is concluded that lipids of aquatic organisms can serve (among other functions) as a protective storage site against the toxic effects of gamma-HCH and, possibly, of other lipophilic, persistent organic chemicals which are bioconcentrated in body lipids. Therefore, in organisms with higher lipid content, a smaller fraction of a lipophilic chemical will reach target organs (liver, lung, central and peripheral nerves, etc.) to cause adverse effects. Results suggest that this correlation can be used to extrapolate the acute toxicity (48-h LC50) of gamma-HCH to other fish species if their lipid content is known. Furthermore, the data generated by extrapolation of this correlation could be useful in the environmental risk assessment of freshwater and marine organisms.

Animals↗

QSAR for organic chemical bioconcentration in Daphnia, algae, and mussels.

Prediction of the bioconcentration of organic chemicals from water by aquatic organisms has important applications in the management of hazardous chemicals. This study gives a compilation of bioconcentration factors on a wet weight basis (BCFw) of 52 organic chemicals by Daphnia magna from aqueous solution. The bioconcentration factors for the chemicals in Daphnia were successfully correlated with their n-octanol/water partition coefficients (log Kow) using a linear regression analysis. In addition to the ordinary least-square regression technique, the geometric mean regression technique is also used because this takes into account deviations in Kow values. Both results show that the Kow value of a chemical is a good predictor of the BCF in Daphnia. The BCF-Kow relationships between Daphnia, algae (Chlorella), and mussels (Mytilus edulis) are compared with each other.

Animals↗

Estimation of releases into rivers with the steady-state surface water model EXWAT using dichloromethane.

The surface water model EXWAT is applied to monitoring studies of hazardous substances to estimate site-specific emissions from measured concentrations. The model includes the main processes which govern the fate of chemicals in rivers, namely, advection, volatility, degradation processes, sedimentation, resuspension, and protonic equilibria. The steady-state solution of the linear mass balance equations leads to proportionality between input and concentration of a chemical, which is used to assess input rates from measured concentrations. Subsequently, the model can be used for pollution control and identification of unknown releases. With measured concentrations in the Rhine near Koblenz (95 km downstream from the mouth of the river Main) the load of dichloromethane from the tributary Main was estimated. The comparison with measured concentrations in the tributary mouth has a good agreement in this case.

Environmental Monitoring↗

Applying the concept of partially ordered sets on the ranking of near-shore sediments by a battery of tests.

When a ranking of some objects (chemicals, geographical sites, river sections, etc.) by a multicriteria analysis is of concern, then it is often difficult to find a common scale among the criteria, and therefore even the simple sorting process is performed by applying additional constraints, just to get a ranking index. However such additional constraints, often arising from normative considerations, are controversially discussed. The theory of partially ordered sets and its graphical representation (Hasse diagrams) does not need such additional information just to sort the objects. Here, the approach of using partially ordered sets is described by applying it to a battery of tests, developed by Dutka et al. In our analysis we found the following: (1) The dimension analysis of partially ordered sets suggests that, at least in the case of the 55 analyzed samples and the evaluation by the scores, developed by Dutka et al., there is a considerable redundancy with respect to ranking. The visualization of the sediment sites can be performed within a two-dimensional grid. (2) Information, obtained from the structure of the Hasse diagram: For example six classes of sediment sites have high priority, and each class exhibits a different pattern of results. (3) Loss of information, when an aggregation of test results is used in order to guarantee complete comparability among all objects. A relation between information drawn from the graphic and the uncertainty of ranking after using an aggregation is given. (4) The sensitivity analysis identifies one test as most important, namely the test for Fecal Coliforms/Escherichia coli. This means that the ranking of samples is heavily influenced by the results of this specific test.

Ecosystem↗