Ingrid Nobels | University of Antwerp (original) (raw)

Papers by Ingrid Nobels

Universiteit Antwerpen/Universiteit van Amsterdam/VITO, Jun 1, 2009

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2012

Food Additives & Contaminants: Part A, 2011

In vitro risk assessment of dietary contaminants has become a priority in human food 22 safety. I... more In vitro risk assessment of dietary contaminants has become a priority in human food 22 safety. In the present paper, we propose an in vitro approach associating different 23 complementary tools in an original toolbox aiming at improving the assessment of the toxicological impact of dietary contaminants at realistic human exposure levels, with a 25 special focus on the intestinal compartment. The system is based on the use of four 26 complementary cellular tools, namely stress gene induction in transgenic strains of 27 Escherichia coli, modulation of the activity of key biotransformation enzymes 28 (cytochrome P-450 (CYP) 1A1 and 3A4) in a human intestinal cell line, and activation of 29 aryl hydrocarbon receptor (AhR) and estrogenic receptor (ER)-dependent genes in 30

Citation for published version (APA): D'Hollander, W., Roosens, L., Covaci, A., Cornelis, C.,... more Citation for published version (APA): D'Hollander, W., Roosens, L., Covaci, A., Cornelis, C., Smolders, R., Van den Heuvel, R., de Voogt, P., Nobels, I., Van Parys, C., De Coen, W., & Bervoets, L. (2009). Gebromeerde brandvertragers en perfluorverbindingen in Vlaanderen: onderzoek naar verspreiding, humane opname, gehaltes in humane weefsels en/of lichaamsvochten, en gezondheidseffecten als basis voor de selectie van geschikte milieuen gezondheidsindicatoren (BFRISK). Universiteit Antwerpen/Universiteit van Amsterdam/VITO. https://www.lne.be/gebromeerde-brandvertragers-en-perfluorverbindingen-in-vlaanderen

Fuel and Energy Abstracts, 2011

Abstracts / Toxicology Letters 205S (2011) S36-S59 S43 metabolomics. In this presentation, I will... more Abstracts / Toxicology Letters 205S (2011) S36-S59 S43 metabolomics. In this presentation, I will talk about the integration of genomics and metabolomics in addition to physiological experiments using yeast cells. Yeast Saccharomyces cerevisiae S288C was employed as the experimental organisms and cadmium for toxic substance. For genomics studies, we use commercially available yeast DNA microarray and CE/MS for metabolomics studies. Although genomics results suggested the induction of glutathione related metabolisms, the combined results among genomics and metabolomics discovered the conflicting results to accept the enhanced production of glutathione for this stress. The integrated results bring out the consequence that ␥-glutamylcyteine structures play the stars for cadmium stress response and oxidative stress responses. This was further confirmed with physiological and genetic experiments. In this meeting, we would like to show how we can integrate genomics and metabolomics using cadmium as model chemicals and yeast cells as model organisms.

Environmental toxicology and chemistry / SETAC, 2011

Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chloro... more Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chlorosubstitution, such as aniline, 4-chloroaniline, 3,5-dichloroaniline, and 2,3,4-trichloroaniline) are assumed to induce their toxic effects via the same predominant mode of action (MOA; membrane damage) at equitoxic exposure concentrations. In this study, a bacterial gene profiling assay consisting of 14 general stress genes was used to test this hypothesis for these four compounds. Although we found a consistent induction of membrane damage, the response cascade and the extent of the response differed among the different chemical treatments. The higher chlorosubstituted anilines also triggered significantly more genes involved in other general stress MOA classes (oxidative stress and protein perturbation). These findings illustrate that, along with the commonly used physicochemistry-based MOA categorization methods, alternative tests such as the bacterial gene profiling assay can yield valuable biological information on the MOA of a certain chemical or group of chemicals that is crucial in high-quality environmental risk assessment. In a second phase, the experimental gene profiling data sets of the chlorinated anilines were analyzed and weighed against existing data on other polar and non polar narcotic compounds to obtain a broader comparison in which the predefined chemical MOAs (narcosis and polar narcosis) were contrasted with the biological MOAs (gene expression profiles). Although additional optimization of the assay is needed, our results show that the bacterial gene profiling assay opens new perspectives for biology-based chemical grouping, thereby further enabling targeted MOA-based risk assessment.

Applied Microbiology and Biotechnology, 2007

Because of increasing awareness and legislative demands, there is a demand for the development an... more Because of increasing awareness and legislative demands, there is a demand for the development and use of biological assays for the assessment of the toxicity of chemicals, environmental samples. Recently, a growing number of bacterial reporter assays have been developed and implemented. Nevertheless, little data is published on the performance of these assays in terms of analytical parameters. We present results on a battery of 14 transgenic Escherichia coli strains carrying different promoter::reporter fusions. Growth characteristics and basal expression levels were modeled and fitted, data show that growth curves should be taken into account during test development. Our study shows that the induction profiles reflect the mode of action, e.g., paraquat clearly induces the soxRS operon. The sensitivity of the assay compares well to that of whole organism tests, e.g., fish and Daphnia for polar organics. Metal toxicity is detected less efficiently, e.g., cadmium is detected near the LC50 of carp, considered a relatively insensitive species towards cadmium. The assay variability ranges from 10 to 40% depending on the strain, comparable to that of other bioassays. The variability was shown to be determined by the intrinsic traits of the promoter–strain combination, not by operating conditions.

Environmental Toxicology and Chemistry, 2011

Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chloro... more Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chlorosubstitution, such as aniline, 4-chloroaniline, 3,5-dichloroaniline, and 2,3,4-trichloroaniline) are assumed to induce their toxic effects via the same predominant mode of action (MOA; membrane damage) at equitoxic exposure concentrations. In this study, a bacterial gene profiling assay consisting of 14 general stress genes was used to test this hypothesis for these four compounds. Although we found a consistent induction of membrane damage, the response cascade and the extent of the response differed among the different chemical treatments. The higher chlorosubstituted anilines also triggered significantly more genes involved in other general stress MOA classes (oxidative stress and protein perturbation). These findings illustrate that, along with the commonly used physicochemistry-based MOA categorization methods, alternative tests such as the bacterial gene profiling assay can yield valuable biological information on the MOA of a certain chemical or group of chemicals that is crucial in high-quality environmental risk assessment. In a second phase, the experimental gene profiling data sets of the chlorinated anilines were analyzed and weighed against existing data on other polar and non polar narcotic compounds to obtain a broader comparison in which the predefined chemical MOAs (narcosis and polar narcosis) were contrasted with the biological MOAs (gene expression profiles). Although additional optimization of the assay is needed, our results show that the bacterial gene profiling assay opens new perspectives for biology-based chemical grouping, thereby further enabling targeted MOA-based risk assessment.

Atmospheric Environment, 2012

In this study we studied the effects of particulate matter samples (PM) through gene expression a... more In this study we studied the effects of particulate matter samples (PM) through gene expression analysis in a routine air quality monitoring campaign by the Flemish Environment Agency (VMM, Belgium). We selected a human hepatoma (HepG2) multiple endpoint reporter assay for targeted stress related endpoint screening. Organic extracts of air samples (total suspended particles, TSP) were collected during one year in an industrial, urban and background location in Flanders, Belgium. Simultaneously, meteorological conditions (temperature, wind speed and precipitation) and particulate matter size 10 mM (PM 10 ), organic (OC), elemental (EC) and total (TC) carbon were monitored and air samples were collected for chemical analysis (11 PAHs). Correlations between the induction of the different stress genes and the chemical pollutants were analysed.

Fuel and Energy Abstracts, 2011

Ginkgo biloba is a widely consumed dietary supplement. Some dietary active compounds modulate the... more Ginkgo biloba is a widely consumed dietary supplement. Some dietary active compounds modulate the activity of biotransformation enzymes inside the enterocytes and more interestingly of cytochrome P-450 1A1 (CYP1A1). This enzyme is of a particular interest because of its implication in the metabolism of some exogenous pro-carcinogens or endogenous molecules. In the present work, we have used Caco-2 cells to study the effect of a standard reference material of a Ginkgo biloba extract (GBE) (10–400 μg/ml), as well as of its major individual active compounds (kaempferol, quercetin, isorhamnetin, ginkgolides and bilobalide), alone or in mixtures, at realistic intestinal concentrations, on the induction of CYP1A1 activity, in the presence or absence of benzo[a]pyrene (B[a]P) (0.1 μg/ml), a well-known CYP1A1 inducer. 3-O-rutinosides of kaempferol, quercetin and isorhamnetin were also tested. We have demonstrated a strong induction (p < 0.005) of CYP1A1 activity and a slight, but significant (p < 0.005), decrease of this activity in the presence of B[a]P by the GBE at the realistic exposure level of 100 μg/ml. The inductive effect was explained, in part, by quercetin and kaempferol after 24 h exposure while unknown compounds seem to be responsible for the strong CYP1A1 induction observed after 6 h exposure. The inhibitory potency of flavonols on CYP1A1 activity in presence of B[a]P was much stronger for the aglycones than for the 3-O-rutinosides, explaining the slight effect observed with the GBE, mainly composed of glycosylated flavonoids. These results indicate that GBEs may disturb intestinal CYP1A1 activity and, in turn, affect the metabolism of other compounds. The present paper thus highlights the necessity to take these side effects into account when administrating Ginkgo biloba herbal supplements.

Environmental Toxicology and Chemistry, 2007

As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxico... more As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxicological research has seen increasing interest in the assessment of mixture ecotoxicology. Often, mixtures are considered to follow one of two models, concentration addition (CA) or response addition (RA), both of which have been described in the literature. Nevertheless, mixtures that deviate from either or both models exist; they typically exhibit phenomena like synergism, ratio or concentration dependency, or inhibition. Moreover, both CA and RA have been challenged and evaluated mainly for acute responses at relatively high levels of biological organization (e.g., whole-organism mortality), and applicability to genetic responses has not received much attention. Genetic responses are considered to be the primary reaction in case of toxicant exposure and carry valuable mechanistic information. Effects at the gene-expression level are at the heart of the mode of action by toxicants and mixtures. The ability to predict mixture responses at this primary response level is an important asset in predicting and understanding mixture effects at different levels of biological organization. The present study evaluated the applicability of mixture models to stress gene inductions in Escherichia coli employing model toxicants with known modes of action in binary combinations. The results showed that even if the maximum of the dose-response curve is not known, making a classical ECx (concentration causing x% effect) approach impossible, mixture models can predict responses to the binary mixtures based on the single-toxicant response curves. In most cases, the mode of action of the toxicants does not determine the optimal choice of model (i.e., CA, RA, or a deviation thereof ).

Toxicology, Jan 10, 2010

Gene delivery has become an increasingly important strategy for treating a variety of human disea... more Gene delivery has become an increasingly important strategy for treating a variety of human diseases, including infections, genetic disorders and tumours. To avoid the difficulties of using viral carriers, more and more non-viral gene delivery nanoparticles are developed. Among these new approaches polyethylene imine (PEI) is currently considered as one of the most effective polymer based method solution and considered as the gold standard.

Environmental Toxicology and Chemistry - ENVIRON TOXICOL CHEM, 2008

As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxico... more As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxicological research has seen increasing interest in the assessment of mixture ecotoxicology. Often, mixtures are considered to follow one of two models, concentration addition (CA) or response addition (RA), both of which have been described in the literature. Nevertheless, mixtures that deviate from either or both models exist; they typically exhibit phenomena like synergism, ratio or concentration dependency, or inhibition. Moreover, both CA and RA have been challenged and evaluated mainly for acute responses at relatively high levels of biological organization (e.g., whole-organism mortality), and applicability to genetic responses has not received much attention. Genetic responses are considered to be the primary reaction in case of toxicant exposure and carry valuable mechanistic information. Effects at the gene-expression level are at the heart of the mode of action by toxicants and mixtures. The ability to predict mixture responses at this primary response level is an important asset in predicting and understanding mixture effects at different levels of biological organization. The present study evaluated the applicability of mixture models to stress gene inductions in Escherichia coli employing model toxicants with known modes of action in binary combinations. The results showed that even if the maximum of the dose-response curve is not known, making a classical ECx (concentration causing x% effect) approach impossible, mixture models can predict responses to the binary mixtures based on the single-toxicant response curves. In most cases, the mode of action of the toxicants does not determine the optimal choice of model (i.e., CA, RA, or a deviation thereof ).

PLOS One, 2011

The omnipresent group of pesticide adjuvants are often referred to as ''inert'' ingredients, a ra... more The omnipresent group of pesticide adjuvants are often referred to as ''inert'' ingredients, a rather misleading term since consumers associate this term with ''safe''. The upcoming new EU regulation concerning the introduction of plant protection products on the market (EC1107/2009) includes for the first time the demand for information on the possible negative effects of not only the active ingredients but also the used adjuvants. This new regulation requires basic toxicological information that allows decisions on the use/ban or preference of use of available adjuvants. In this study we obtained toxicological relevant information through a multiple endpoint reporter assay for a broad selection of commonly used adjuvants including several solvents (e.g. isophorone) and non-ionic surfactants (e.g. ethoxylated alcohols). The used assay allows the toxicity screening in a mechanistic way, with direct measurement of specific toxicological responses (e.g. oxidative stress, DNA damage, membrane damage and general cell lesions). The results show that the selected solvents are less toxic than the surfactants, suggesting that solvents may have a preference of use, but further research on more compounds is needed to confirm this observation. The gene expression profiles of the selected surfactants reveal that a phenol (ethoxylated tristyrylphenol) and an organosilicone surfactant (ethoxylated trisiloxane) show little or no inductions at EC 20 concentrations, making them preferred surfactants for use in different applications. The organosilicone surfactant shows little or no toxicity and good adjuvant properties. However, this study also illustrates possible genotoxicity (induction of the bacterial SOS response) for several surfactants (POEA, AE, tri-EO, EO FA and EO NP) and one solvent (gammabutyrolactone). Although the number of compounds that were evaluated is rather limited (13), the results show that the used reporter assay is a promising tool to rank commonly used agricultural adjuvants based on toxicity and toxic mode of action data.

Toxicological Sciences - TOXICOL SCI, 2008

Universiteit Antwerpen/Universiteit van Amsterdam/VITO, Jun 1, 2009

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2012

Food Additives & Contaminants: Part A, 2011

In vitro risk assessment of dietary contaminants has become a priority in human food 22 safety. I... more In vitro risk assessment of dietary contaminants has become a priority in human food 22 safety. In the present paper, we propose an in vitro approach associating different 23 complementary tools in an original toolbox aiming at improving the assessment of the toxicological impact of dietary contaminants at realistic human exposure levels, with a 25 special focus on the intestinal compartment. The system is based on the use of four 26 complementary cellular tools, namely stress gene induction in transgenic strains of 27 Escherichia coli, modulation of the activity of key biotransformation enzymes 28 (cytochrome P-450 (CYP) 1A1 and 3A4) in a human intestinal cell line, and activation of 29 aryl hydrocarbon receptor (AhR) and estrogenic receptor (ER)-dependent genes in 30

Citation for published version (APA): D'Hollander, W., Roosens, L., Covaci, A., Cornelis, C.,... more Citation for published version (APA): D'Hollander, W., Roosens, L., Covaci, A., Cornelis, C., Smolders, R., Van den Heuvel, R., de Voogt, P., Nobels, I., Van Parys, C., De Coen, W., & Bervoets, L. (2009). Gebromeerde brandvertragers en perfluorverbindingen in Vlaanderen: onderzoek naar verspreiding, humane opname, gehaltes in humane weefsels en/of lichaamsvochten, en gezondheidseffecten als basis voor de selectie van geschikte milieuen gezondheidsindicatoren (BFRISK). Universiteit Antwerpen/Universiteit van Amsterdam/VITO. https://www.lne.be/gebromeerde-brandvertragers-en-perfluorverbindingen-in-vlaanderen

Fuel and Energy Abstracts, 2011

Abstracts / Toxicology Letters 205S (2011) S36-S59 S43 metabolomics. In this presentation, I will... more Abstracts / Toxicology Letters 205S (2011) S36-S59 S43 metabolomics. In this presentation, I will talk about the integration of genomics and metabolomics in addition to physiological experiments using yeast cells. Yeast Saccharomyces cerevisiae S288C was employed as the experimental organisms and cadmium for toxic substance. For genomics studies, we use commercially available yeast DNA microarray and CE/MS for metabolomics studies. Although genomics results suggested the induction of glutathione related metabolisms, the combined results among genomics and metabolomics discovered the conflicting results to accept the enhanced production of glutathione for this stress. The integrated results bring out the consequence that ␥-glutamylcyteine structures play the stars for cadmium stress response and oxidative stress responses. This was further confirmed with physiological and genetic experiments. In this meeting, we would like to show how we can integrate genomics and metabolomics using cadmium as model chemicals and yeast cells as model organisms.

Environmental toxicology and chemistry / SETAC, 2011

Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chloro... more Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chlorosubstitution, such as aniline, 4-chloroaniline, 3,5-dichloroaniline, and 2,3,4-trichloroaniline) are assumed to induce their toxic effects via the same predominant mode of action (MOA; membrane damage) at equitoxic exposure concentrations. In this study, a bacterial gene profiling assay consisting of 14 general stress genes was used to test this hypothesis for these four compounds. Although we found a consistent induction of membrane damage, the response cascade and the extent of the response differed among the different chemical treatments. The higher chlorosubstituted anilines also triggered significantly more genes involved in other general stress MOA classes (oxidative stress and protein perturbation). These findings illustrate that, along with the commonly used physicochemistry-based MOA categorization methods, alternative tests such as the bacterial gene profiling assay can yield valuable biological information on the MOA of a certain chemical or group of chemicals that is crucial in high-quality environmental risk assessment. In a second phase, the experimental gene profiling data sets of the chlorinated anilines were analyzed and weighed against existing data on other polar and non polar narcotic compounds to obtain a broader comparison in which the predefined chemical MOAs (narcosis and polar narcosis) were contrasted with the biological MOAs (gene expression profiles). Although additional optimization of the assay is needed, our results show that the bacterial gene profiling assay opens new perspectives for biology-based chemical grouping, thereby further enabling targeted MOA-based risk assessment.

Applied Microbiology and Biotechnology, 2007

Because of increasing awareness and legislative demands, there is a demand for the development an... more Because of increasing awareness and legislative demands, there is a demand for the development and use of biological assays for the assessment of the toxicity of chemicals, environmental samples. Recently, a growing number of bacterial reporter assays have been developed and implemented. Nevertheless, little data is published on the performance of these assays in terms of analytical parameters. We present results on a battery of 14 transgenic Escherichia coli strains carrying different promoter::reporter fusions. Growth characteristics and basal expression levels were modeled and fitted, data show that growth curves should be taken into account during test development. Our study shows that the induction profiles reflect the mode of action, e.g., paraquat clearly induces the soxRS operon. The sensitivity of the assay compares well to that of whole organism tests, e.g., fish and Daphnia for polar organics. Metal toxicity is detected less efficiently, e.g., cadmium is detected near the LC50 of carp, considered a relatively insensitive species towards cadmium. The assay variability ranges from 10 to 40% depending on the strain, comparable to that of other bioassays. The variability was shown to be determined by the intrinsic traits of the promoter–strain combination, not by operating conditions.

Environmental Toxicology and Chemistry, 2011

Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chloro... more Polar narcotic structural analogues (e.g., chlorinated anilines with a differing degree of chlorosubstitution, such as aniline, 4-chloroaniline, 3,5-dichloroaniline, and 2,3,4-trichloroaniline) are assumed to induce their toxic effects via the same predominant mode of action (MOA; membrane damage) at equitoxic exposure concentrations. In this study, a bacterial gene profiling assay consisting of 14 general stress genes was used to test this hypothesis for these four compounds. Although we found a consistent induction of membrane damage, the response cascade and the extent of the response differed among the different chemical treatments. The higher chlorosubstituted anilines also triggered significantly more genes involved in other general stress MOA classes (oxidative stress and protein perturbation). These findings illustrate that, along with the commonly used physicochemistry-based MOA categorization methods, alternative tests such as the bacterial gene profiling assay can yield valuable biological information on the MOA of a certain chemical or group of chemicals that is crucial in high-quality environmental risk assessment. In a second phase, the experimental gene profiling data sets of the chlorinated anilines were analyzed and weighed against existing data on other polar and non polar narcotic compounds to obtain a broader comparison in which the predefined chemical MOAs (narcosis and polar narcosis) were contrasted with the biological MOAs (gene expression profiles). Although additional optimization of the assay is needed, our results show that the bacterial gene profiling assay opens new perspectives for biology-based chemical grouping, thereby further enabling targeted MOA-based risk assessment.

Atmospheric Environment, 2012

In this study we studied the effects of particulate matter samples (PM) through gene expression a... more In this study we studied the effects of particulate matter samples (PM) through gene expression analysis in a routine air quality monitoring campaign by the Flemish Environment Agency (VMM, Belgium). We selected a human hepatoma (HepG2) multiple endpoint reporter assay for targeted stress related endpoint screening. Organic extracts of air samples (total suspended particles, TSP) were collected during one year in an industrial, urban and background location in Flanders, Belgium. Simultaneously, meteorological conditions (temperature, wind speed and precipitation) and particulate matter size 10 mM (PM 10 ), organic (OC), elemental (EC) and total (TC) carbon were monitored and air samples were collected for chemical analysis (11 PAHs). Correlations between the induction of the different stress genes and the chemical pollutants were analysed.

Fuel and Energy Abstracts, 2011

Ginkgo biloba is a widely consumed dietary supplement. Some dietary active compounds modulate the... more Ginkgo biloba is a widely consumed dietary supplement. Some dietary active compounds modulate the activity of biotransformation enzymes inside the enterocytes and more interestingly of cytochrome P-450 1A1 (CYP1A1). This enzyme is of a particular interest because of its implication in the metabolism of some exogenous pro-carcinogens or endogenous molecules. In the present work, we have used Caco-2 cells to study the effect of a standard reference material of a Ginkgo biloba extract (GBE) (10–400 μg/ml), as well as of its major individual active compounds (kaempferol, quercetin, isorhamnetin, ginkgolides and bilobalide), alone or in mixtures, at realistic intestinal concentrations, on the induction of CYP1A1 activity, in the presence or absence of benzo[a]pyrene (B[a]P) (0.1 μg/ml), a well-known CYP1A1 inducer. 3-O-rutinosides of kaempferol, quercetin and isorhamnetin were also tested. We have demonstrated a strong induction (p < 0.005) of CYP1A1 activity and a slight, but significant (p < 0.005), decrease of this activity in the presence of B[a]P by the GBE at the realistic exposure level of 100 μg/ml. The inductive effect was explained, in part, by quercetin and kaempferol after 24 h exposure while unknown compounds seem to be responsible for the strong CYP1A1 induction observed after 6 h exposure. The inhibitory potency of flavonols on CYP1A1 activity in presence of B[a]P was much stronger for the aglycones than for the 3-O-rutinosides, explaining the slight effect observed with the GBE, mainly composed of glycosylated flavonoids. These results indicate that GBEs may disturb intestinal CYP1A1 activity and, in turn, affect the metabolism of other compounds. The present paper thus highlights the necessity to take these side effects into account when administrating Ginkgo biloba herbal supplements.

Environmental Toxicology and Chemistry, 2007

As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxico... more As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxicological research has seen increasing interest in the assessment of mixture ecotoxicology. Often, mixtures are considered to follow one of two models, concentration addition (CA) or response addition (RA), both of which have been described in the literature. Nevertheless, mixtures that deviate from either or both models exist; they typically exhibit phenomena like synergism, ratio or concentration dependency, or inhibition. Moreover, both CA and RA have been challenged and evaluated mainly for acute responses at relatively high levels of biological organization (e.g., whole-organism mortality), and applicability to genetic responses has not received much attention. Genetic responses are considered to be the primary reaction in case of toxicant exposure and carry valuable mechanistic information. Effects at the gene-expression level are at the heart of the mode of action by toxicants and mixtures. The ability to predict mixture responses at this primary response level is an important asset in predicting and understanding mixture effects at different levels of biological organization. The present study evaluated the applicability of mixture models to stress gene inductions in Escherichia coli employing model toxicants with known modes of action in binary combinations. The results showed that even if the maximum of the dose-response curve is not known, making a classical ECx (concentration causing x% effect) approach impossible, mixture models can predict responses to the binary mixtures based on the single-toxicant response curves. In most cases, the mode of action of the toxicants does not determine the optimal choice of model (i.e., CA, RA, or a deviation thereof ).

Toxicology, Jan 10, 2010

Gene delivery has become an increasingly important strategy for treating a variety of human disea... more Gene delivery has become an increasingly important strategy for treating a variety of human diseases, including infections, genetic disorders and tumours. To avoid the difficulties of using viral carriers, more and more non-viral gene delivery nanoparticles are developed. Among these new approaches polyethylene imine (PEI) is currently considered as one of the most effective polymer based method solution and considered as the gold standard.

Environmental Toxicology and Chemistry - ENVIRON TOXICOL CHEM, 2008

As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxico... more As a consequence of the nature of most real-life exposure scenarios, the last decade of ecotoxicological research has seen increasing interest in the assessment of mixture ecotoxicology. Often, mixtures are considered to follow one of two models, concentration addition (CA) or response addition (RA), both of which have been described in the literature. Nevertheless, mixtures that deviate from either or both models exist; they typically exhibit phenomena like synergism, ratio or concentration dependency, or inhibition. Moreover, both CA and RA have been challenged and evaluated mainly for acute responses at relatively high levels of biological organization (e.g., whole-organism mortality), and applicability to genetic responses has not received much attention. Genetic responses are considered to be the primary reaction in case of toxicant exposure and carry valuable mechanistic information. Effects at the gene-expression level are at the heart of the mode of action by toxicants and mixtures. The ability to predict mixture responses at this primary response level is an important asset in predicting and understanding mixture effects at different levels of biological organization. The present study evaluated the applicability of mixture models to stress gene inductions in Escherichia coli employing model toxicants with known modes of action in binary combinations. The results showed that even if the maximum of the dose-response curve is not known, making a classical ECx (concentration causing x% effect) approach impossible, mixture models can predict responses to the binary mixtures based on the single-toxicant response curves. In most cases, the mode of action of the toxicants does not determine the optimal choice of model (i.e., CA, RA, or a deviation thereof ).

PLOS One, 2011

The omnipresent group of pesticide adjuvants are often referred to as ''inert'' ingredients, a ra... more The omnipresent group of pesticide adjuvants are often referred to as ''inert'' ingredients, a rather misleading term since consumers associate this term with ''safe''. The upcoming new EU regulation concerning the introduction of plant protection products on the market (EC1107/2009) includes for the first time the demand for information on the possible negative effects of not only the active ingredients but also the used adjuvants. This new regulation requires basic toxicological information that allows decisions on the use/ban or preference of use of available adjuvants. In this study we obtained toxicological relevant information through a multiple endpoint reporter assay for a broad selection of commonly used adjuvants including several solvents (e.g. isophorone) and non-ionic surfactants (e.g. ethoxylated alcohols). The used assay allows the toxicity screening in a mechanistic way, with direct measurement of specific toxicological responses (e.g. oxidative stress, DNA damage, membrane damage and general cell lesions). The results show that the selected solvents are less toxic than the surfactants, suggesting that solvents may have a preference of use, but further research on more compounds is needed to confirm this observation. The gene expression profiles of the selected surfactants reveal that a phenol (ethoxylated tristyrylphenol) and an organosilicone surfactant (ethoxylated trisiloxane) show little or no inductions at EC 20 concentrations, making them preferred surfactants for use in different applications. The organosilicone surfactant shows little or no toxicity and good adjuvant properties. However, this study also illustrates possible genotoxicity (induction of the bacterial SOS response) for several surfactants (POEA, AE, tri-EO, EO FA and EO NP) and one solvent (gammabutyrolactone). Although the number of compounds that were evaluated is rather limited (13), the results show that the used reporter assay is a promising tool to rank commonly used agricultural adjuvants based on toxicity and toxic mode of action data.

Toxicological Sciences - TOXICOL SCI, 2008