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Biomedical subjects

Matthias Grote

Publications and source records attributed to Matthias Grote.

6 recordsLinked to original sources

On the mode of action of N-phenyl-2-naphthylamine in plants.

N-phenyl-2-naphthylamine, a sediment contaminant previously identified as a major toxicant of site-specific importance was investigated for its mode of toxic action. From short-term bioassays with daphnids, fish eggs, bacteria, and algae it appears that this compound has specific phytotoxic properties at concentrations below 100 microg/L, which cannot be explained assuming an unspecific narcosis type of action in plants. Also, hydroxy-, nitro-, and methylderivatives show clear excess toxicity as compared to baseline toxic effects. Of several plant-specific growth and development processes investigated, only photosynthesis could be demonstrated to be affected at short exposure times and low concentrations. Disturbance of primary photosynthetic reactions such as oxygen evolution and fluorescence quenching, however, becomes only apparent after 2-3 h of exposure, which is in sharp contrast to known specific inhibitors targeting processes such as electron transport or ATP production. This, and concentration-time-effect modeling lead to the suggestion that N-phenyl-2-naphthylamine acts intracellular as a reactive compound in cell membranes producing irreversible, and thus cumulative, damage over time in algae. The effects may become first apparent in membrane-rich compartments such as the algal chloroplast.

2-Naphthylamine↗

Modeling photoinduced algal toxicity of polycyclic aromatic hydrocarbons.

The influence of light conditions on the toxicity of polycyclic aromatic hydrocarbons (PAHs) to different organisms has long been recognized. The aim of this study was to investigate whether previously proposed models can be used to qualitatively and quantitatively predict photoinduced toxicity to the green algae Scenedesmus vacuolatus. For this purpose 14 different PAH compounds were tested under three different light conditions for their effects on the algae reproduction. Illumination conditions comprised standard algae growth light, simulated sunlight aiming to mimic environmental light conditions, and UV-filtered light in order to minimize light influence on PAH toxicity. Models proposed for the prediction of photoinduced toxicity were modified in order to account for different exposure conditions and toxic endpoints used in the bioassay. The results of this study show that the gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) proposed as an indication for photoinduced toxicity to Daphnia magna can be used as a qualitative indication of a potential photoinduced toxicity to the green algae Scenedesmus vacuolatus. The impact of light conditions on PAH toxicity can be quantified by a linear model which allows the estimation of the ED50 of each compound from the amount of absorbed photons and an empirically determined relative phototoxic efficacy value of the compound.

Chlorophyta↗

Identification of toxicants from marine sediment using effect-directed analysis.

Effect-directed analysis (EDA) has been reported to be a powerful tool for the identification of the responsible toxicants in contaminated, hazardous environmental samples. The aim of this study was to investigate whether it also is possible to use currently available EDA methodology to identify potentially relevant toxicants in samples that do not pose obvious problems. For this purpose, compounds extracted from a marine sediment sample from the west coast of Sweden were separated into distinct fractions, using two preparative chromatographic techniques. One algal bioassay using Scenedesmus vacuolatus and two bacterial bioassays using Vibrio fischeri were applied as detectors of toxicity, representing acute and chronic end points. Chronic algal toxicity was a powerful tool for discriminating between toxic and nontoxic fractions, whereas acute and chronic bacterial toxicity failed to identify toxic fractions. Eight compounds were identified as potentially relevant toxicants by chemical analysis of toxic fractions: anthracene, fluoranthene, pyrene, benzo[a]anthracene, benzo[b]fluoranthene, benzo[a]pyrene, benzo[k]fluoranthene, and indeno[1,2,3-cd]pyrene.

Aliivibrio fischeri↗

Confirmation of cause-effect relationships using effect-directed analysis for complex environmental samples.

The establishment of causal links between chemical contamination and observed ecotoxic effects of environmental samples is a major challenge in ecotoxicology. Effect-directed analysis is an approach combining fractionation with toxicity testing before chemical nontarget analysis to separate and subsequently identify toxic compounds in environmental samples. A final confirmation step in this procedure evaluates how much of the observed toxicity in the environmental sample can be attributed to the mixture of identified toxicants. The aim of the present study is to advance the methodology for the confirmation of mixtures in effect-directed analysis by using tools for the assessment of mixture toxicity accounting for unknown modes of action and heterogeneity of concentration-response curves. For this purpose, toxicants were identified in sediment extracts from two different sites. All identified compounds were tested both individually as pure compounds and in mixtures at ratios equal to those found in the sediment extracts. The observed extract toxicity was then compared with the expected combined effects calculated according to the models of concentration addition and independent action as well as with the observed toxicity of the synthetic mixture. Drawbacks of the established approach using toxic unit summation are demonstrated, and the Index of Confirmation Quality, an easy-to-read representation that allows a quantitative measure of confirmation over a range of different effect levels, is introduced.

Chemical Fractionation↗

Light as a confounding factor for toxicity assessment of complex contaminated sediments.

Polycyclic aromatic hydrocarbons (PAHs) are contaminants often found in sediments. Their relevant contribution to toxic effects induced by environmental samples has been demonstrated using effect-directed analysis (EDA). Toxicity of PAHs previously has been reported to depend on light conditions. The aim of this study was to analyze the influence of simulated sunlight, in comparison to standard algal growth light, on the toxicity of samples, in which PAHs were identified as major toxicants using EDA. Additionally, toxicity of identified toxicants and mixtures of these compounds were assessed. It can be shown that the samples, the PAH compounds, and the created mixtures exhibit photoenhanced toxicity. The combined effects of the mixtures can be predicted using the model of concentration addition. This is surprising because different modes of action have been reported to contribute to phototoxicity of the identified toxicants. For the confirmation step in EDA, the toxicity assessment under simulated sunlight reveals that less of the samples' toxicity can be explained by the identified compounds, compared to the assessment conducted under standard growth light. Finally, the relevance of light conditions in the toxicity assessment is demonstrated for eight out of 13 transect samples of sediment extracts from river Elbe, Germany.

Confounding Factors, Epidemiologic↗

What contributes to the combined effect of a complex mixture?

The effect of a mixture of 10 compounds, which have previously been identified in an effect-directed analysis as potentially relevant for a specific contaminated riverine sediment (Brack et al. Arch. Environ. Contam. Toxicol. 1999, 37, 164), were investigated for the underlying joint effect. Components identified in an organic sediment extract included several PAHs (benzo[ghi]fluoranthene, benz[a]anthracene, fluoranthene, pyrene, 2-phenylnaphthalene, anthracene, and phenanthrene) plus prometryn, N-phenyl-2-naphthylamine, and parathion-methyl. Experiments were performed using a one-generation algal bioassay with the unicellular green algae Scenedesmus vacuolatus as well as chlorophyll fluorescence quenching analysis to describe the effects of the components and mixtures thereof. Analysis of the mixture effects based on concentration-response modeling of the effect data reveals that indeed effect contributions of several components can be expected although the mixture ratio is not equitoxic and the individual components vary greatly with respect to biological effect. Comparing predicted and observed mixture effects, the combined effect may not be attributed to a joint narcotic effect of the mixture components. Evidently, some of the components act specifically and dissimilar and may therefore be best described in their combined effect by response addition while for others a similar mode of action seems plausible. Chlorophyll fluorescence quenching analysis supports to discriminate between prometryn, N-phenyl-2-naphthylamine, and PAHs. A joint model for calculating the combined effect using concentration addition for the suspected unspecifically acting components in algae (PAHs and parathion-methyl) and subsequently response addition for this group and the other components clearly improves the description of the observed combined effect. Allocation of effect contributions to specific components using toxic units or effect contributions lead to different judgments. The observed combined effect of a 3-compound mixture of prometryn, N-phenyl-2-naphthylamine, and benzo[ghi]fluoranthene is indistinguishable from the effects of the original 10-compound mixture, demonstrating the need in site-specific assessment of complex contamination to account for the mode of action of contaminants. Implications forthe confirmation step in effect-directed analysis of substances causing effects in complex contaminated samples are discussed.

2-Naphthylamine↗