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Biomedical subjects

A Kettrup

Publications and source records attributed to A Kettrup.

At least 127 records · Page 7Linked to original sources
PubMed1995

Exposure analysis of the inhabitants living in the neighbourhood of a mercury-contaminated industrial site.

The inhabitants living in the neighbourhood of a deserted mercury-contaminated industrial site are subjected to an age-group differentiated mercury exposure assessment based on a scenario-linked calculation. Analytical input data for the calculation procedure are provided for from soil, air and plants in a large number. The most sensitive group are small children being mainly exposed by soil ingestion which makes up nearly 80% of the ADI, followed by inhalation of mercury contaminated indoor air. On the other hand, inhalation of indoor air has a predominant impact on youth and adults.

Adolescent↗
PubMed1994

Coupled-column high-performance liquid chromatographic method for the determination of four metabolites of polycyclic aromatic hydrocarbons, 1-, 4- and 9-hydroxyphenanthrene and 1-hydroxypyrene, in urine.

A coupled-column high-performance liquid chromatographic method applying system-integrated sample processing on a copper phthalocyanine modified solid-phase material, gradient elution and fluorescence detection for the quantification of 1-, 4- and 9-hydroxyphenanthrene as well as for 1-hydroxypyrene in urine is described. The automated chromatographic system tolerates direct and repeated injection of urine samples. Validation results presented indicate quantitative and matrix-independent recoveries, low imprecisions in within-series and between-series analysis in combination with broad linear working ranges (2-400 nmol/l) and low detection limits (< 0.1 nmol/l).

Chromatography, High Pressure Liquid↗
PubMed1994

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↗
PubMed1993

Herring gull eggs as bioindicators for chlorinated hydrocarbons (contribution to the German Federal Environmental Specimen Bank).

From its position in the marine food chain, the herring gull (Larus argentatus) is a suitable indicator for the level of contamination of its habitats with lipophilic chemicals, especially the chlorinated hydrocarbons. The gull's utility as an indicator is demonstrated by investigations performed at Trischen island in the Elbe estuary and Alte Mellum island situated in the Weser estuary, when judged by their ability to reflect variations in pollution levels. The use of the analysis technique developed and standardized for the German Environmental Specimen Bank gives comparable results for both temporal and spatial variations for contamination levels on the different islands in the Wadden Sea area (North Sea coast) of Germany.

Animals↗
PubMed1993

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↗
PubMed1993

The relevance of fat content in toxicity of lipophilic chemicals to terrestrial animals with special reference to dieldrin and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Lipophilic chemicals such as chlorinated hydrocarbon insecticides and other persistent chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are fat soluble chemicals and are readily bioconcentrated in animal fat depots. The modifying role of the body fat content in the toxicity of chlorinated cyclodiene insecticides to insects and in the toxicity of TCDD to different mammals was investigated. The single oral acute 30-day LD50 data of TCDD in different mammals are presented and correlated with their total body fat content. A two linear regression equation with log/log values was obtained. It is concluded that the storage of TCDD and other related lipophilic and persistent chemicals in lipids of organisms is, in a sense, a detoxication mechanism by which the compounds are removed from sites of action and/or receptors. Therefore, terrestrial organisms such as insects and mammals with higher total body fat content can accumulate and tolerate higher chlorinated hydrocarbon insecticide and TCDD doses than organisms with lower fat content. The different sensitivity of mammals of various species, strains, body weight, sex, age, etc. to acute toxicity of TCDD and related lipophilic persistent chemicals can mainly be explained by differences in total body fat content.

Adipose Tissue↗
PubMed1993

Indicator parameters for PCDD/F as a possible means to monitor emissions of toxicity equivalents from waste incinerators.

In the stack emissions from a hazardous waste incinerator we found highly significant correlations between 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents (I-TE) and pentachlorobenzene (CI5Bz) and between I-TE and heptachlorobiphenyl (CI7B). We therefore propose to utilize these substances as indicator parameters from which I-TE values can be estimated. Since they are easier to analyze than PCDD/F the use of indicator parameters such as CI5Bz and CI7B offers the chance to monitor I-TE emissions which are limited to 0.1 ng/m3 in many European countries.

Air Pollutants↗
PubMed1992

Coupled-column high-performance liquid chromatographic method for the determination of 1-hydroxypyrene in urine of subjects exposed to polycyclic aromatic hydrocarbons.

A coupled-column high-performance liquid chromatographic system for integrated, on-line sample processing and the determination of free and conjugated 1-hydroxypyrene in urine has been developed. The method is based on a "tailor-made" copper phthalocyanine-modified porous-glass precolumn packing material, which allows a direct and repeated injection of urine samples and a selective enrichment of trace amounts of particular components. The fully automated method has a low detection limit (0.01 pmol), a quantitative and matrix-independent recovery and a highly reliability, as shown by an interlaboratory comparison of methods.

Chromatography, High Pressure Liquid↗
PubMed1992

Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part I: Acute toxicity and toxic equivalency factors (TEFs).

There is presently no scientifically proven method to assess the toxicity of environmental samples containing complex mixtures of chlorinated dibenzo-p-dioxins (CDDs) of known composition. Their risk assessment is currently based on the interim concept of toxicity equivalency factors (TEFs), with the unproven assumption that all interactions of CDDs are additive. To address this problem we conducted acute toxicity studies with four different CDDs, viz 2,3,7,8-tetrachlorodibenzo-p-dioxin (tetra-CDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (penta-CDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD), all containing chlorine substituents in the crucial 2,3,7,8-positions. The homologues, dissolved in corn oil/acetone, were administered to groups of five male Sprague Dawley rats at several doses (at least three) by gastric intubation. The obtained mortality data were employed to calculate the LD20,50 and 80 for each homologue. These data were subsequently used to prepare equipotent doses (expected mortality of 20, 50 and 80%) of a mixture containing all four homologues, each of them contributing one fourth of the toxicity, under the assumption of additive toxicity. The obtained LD50 value and (TEF) was for tetra-CDD 43 micrograms/kg (1), penta-CDD 206 micrograms/kg (0.2) hexa-CDD 887 micrograms/kg (0.05) and hepta-CDD 6325 micrograms/kg (0.007), respectively. The dose-response to the mixture confirmed the hypothesis of strict additivity in the acute toxicity of the four CDD homologues.

Animals↗
PubMed1992

Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part II: Structure-activity relationships with inhibition of hepatic phosphoenolpyruvate carboxykinase, pyruvate carboxylase, and gamma-glutamyl transpeptidase activities.

Male Sprague-Dawley rats were treated with an LD20, LD50 and LD80 respectively, of tetra-, penta-, hexa-, hepta-CDD and a mixture of the four CDDs, all carrying chlorine substituents in the biologically crucial 2, 3, 7, and 8 positions. Specific activities of two key enzymes of gluconeogenesis, viz, phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC), as well as the activity of the preneoplastic marker enzyme gamma-glutamyl transpeptidase (gamma-GT), were determined in livers of CDD-treated and ad libitum-fed control animals. PEPCK activity showed evidence for dose-related inhibition on the second day after dosing; PC activity was slightly reduced, whereas gamma-GT activity was dose-dependently inhibited. By 8 days after dosing PEPCK activities were dose-dependently decreased after administration of all four CDDs and their mixture. PC activities were significantly reduced, but no dose-response was evident. The activity of gamma-GT was dose-dependently inhibited, but only to a value of 25% below control activities. It is concluded that CDDs share a common mechanism of acute toxicity, viz, inhibition of glucocorticoid-dependent enzymes which results in a derailment of intermediary metabolism not compatible with survival of the animals.

Animals↗
PubMed1992

Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part III: Structure-activity relationship with increased plasma tryptophan levels, but no relationship to hepatic ethoxyresorufin o-deethylase activity.

Male Sprague-Dawley rats were treated with an LD20, an LD50, and an LD80 of 2,3,7,8-tetrachlorodibenzo-p-dioxin (tetra-CDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (penta-CDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD), 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD), respectively, and a mixture of the four homologues where each CDD was represented at one-fourth its previously established LD20, LD50, and LD80, respectively. Plasma tryptophan levels, liver ethoxyresorufin O-deethylase (EROD) activities, and liver weights were determined at 2 and 8 days after treatment. Plasma tryptophan levels were dose-dependently elevated, particularly at 8 days after treatment, by as much as 75% over control levels. EROD activity in CDD-treated animals was induced 27- to 28-fold, as compared with vehicle-treated controls, but did not show any dose-response. Liver weights were also significantly increased by the CDD treatments, but the increase was not dose related. There was no correlation between plasma tryptophan levels, a biomarker of acute toxicity of CDDs, and EROD activity, a biomarker of arylhydrocarbon (Ah) receptor-mediated enzyme induction. It is concluded that the acute toxicity of CDDs, which correlates and shows perfect structure-activity relationship with reduced activities of key enzymes of intermediary metabolism, and the induction of enzymes by much lower doses of CDDs in the liver, have different mechanisms of action.

Animals↗
PubMed1991

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↗
PubMed1990

Correlation between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and total body fat content in mammals.

Single oral 30-day LD50s of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were correlated with total body fat (TBF) content in various species and strains of laboratory mammals. LD50 values and TBF contents were either obtained from the literature or determined by experiments. A log (LD50) vs. log (TBF) plot yielded a highly significant linear regression equation (r2 = 0.834, P less than 0.001, n = 20). It is suggested that this correlation exists for at least two reasons: (1) increasing TBF content in organisms represents an enhanced capacity to remove TCDD from the systemic circulation and (2) different TBF content reflects a differential role and regulation of fat metabolism for various organisms. Extrapolation of this correlation to man suggests that adult humans are among the less sensitive species to the acute toxicity of TCDD.

Adipose Tissue↗
PubMed1988

Simultaneous thermal analysis/mass spectrometric detection of biological hazards.

A simultaneous working TA-MS instrument has been used to investigate the thermal behaviour and the decomposition of a series of toxic organic compounds such as flame protected polymers and chlorine-substituted aromatic products that are known to be injurious to health. The temperature-dependent TA-MS data given by the TG, DTG, DTA and MS results lead to a nearly complete description of the degradation properties of the materials. This includes the identification of the main decomposition components by means of in situ quadrupole MS ranging up to 511 a.m.u. The maximum working temperature of the coupling system with 1400 K has proved to be sufficient for the applications reported in this paper. From our investigations of hexa(penta)chlorobenzene and pentachlorophenol it can be concluded that there is a good correlation between the characteristic TA data and the course of the ion current intensities as a function of temperature. This can be shown for each detected mass fragment containing different numbers of chlorine atoms as well as for the molecular ions according to the relative abundance of their isotopes.

Differential Thermal Analysis↗
PubMedDate not supplied

Identification of surrogate compounds for the emission of PCdd/F (I-TEQ value) and evaluation of their on-line real-time detectability in flue gases of waste incineration plants by REMPI-TOFMS mass spectrometry.

Correlations between products of incomplete combustion (PIC), e.g., chloroaromatic compounds, can be used to characterise the emissions from combustion processes, like municipal or hazardous waste incineration. A possible application of such relationships may be the on-line real-time monitoring of a characteristic surrogate, e.g., with Resonance-Enhanced Multiphoton Ionization-Time-of-Flight Mass Spectrometry (REMPI-TOFMS). In this paper, we report the relationships of homologues and individual congeners of chlorinated benzenes (PCBz), dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF) and phenols (PCPh) to the International Toxicity Equivalent (I-TEQ) of the PCDD/F (I-TEQ value) in the flue gas and stack gas of a 22 MW hazardous waste incinerator (HWI). As the REMPI detection sensitivity is decreasing with the increase of the degree of chlorination, this study focuses on the lower chlorinated species of the compounds mentioned above. Lower chlorinated species, e.g., chlorobenzene (MCBz), 1,4-dichlorobenzene, 2,4,6-trichlorodibenzofuran or 2,4-dichlorophenol, were identified as I-TEQ surrogates in the flue gas. In contrast to the higher chlorinated phenols, the lower chlorinated phenols (degree of chlorination <4) were not reliable as surrogates in the stack gas. The identified surrogates are evaluated in terms of their detectability by REMPI-TOFMS laser mass spectrometry. The outcome is that MCBz is the best suited surrogate for (indirect) on-line measuring of the I-TEQ value in the flue gas by REMPI-TOFMS. The correlation coefficient r of the MCBz concentration to the I-TEQ in the flue gas was 0.85.

Journal Article↗
PubMedDate not supplied

Comparison of dioxin-like-response in vitro and chemical analysis of emissions and materials.

Samples from industrial and domestic emissions and materials were investigated by using in vitro assays for dioxin-like-response (DLR) and chemical analysis. The results show a small part of persistent bioaccumulative toxicants (PBT) to be responsive in vitro. Clean-up procedures directed to persistence decrease the amount of inducing toxicants substantially. The comparison of biological in vitro (B) and chemical (A) analysis show ratios between B and A below 10 for DLR of persistent inductors. The consideration of PAH improved the knowledge about unknown less persistent agonists.

Air Pollutants↗