Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Soil hydrological modelling and sustainable agricultural crop production at multiple scales
Kroes, J.G. - \ 2018
Wageningen University. Promotor(en): Coen Ritsema, co-promotor(en): Jos van Dam; Iwan Supit; Jan Wesseling. - Wageningen : Wageningen University - ISBN 9789463433440 - 181
Effects of a soil surfactant on grass performance and soil wetting of a fairway prone to water repellency
Dekker, Louis W. ; Ritsema, Coen J. ; Oostindie, Klaas ; Wesseling, Jan G. ; Geissen, Violette - \ 2018
Geoderma (2018). - ISSN 0016-7061 - 12 p.
Actual soil water repellency - Critical soil water content - N mineralization - Surfactant - Time Domain Reflectometry - Water drop penetration time (WDPT) test

This study reports on the effects of applications of a soil surfactant on improvement of grass performance and wetting of a sandy golf course fairway, located near Arnhem, the Netherlands. In addition, the influence of the surfactant on soil water repellency and the nitrogen contents in grass leaves, roots and upper 18 cm of the soil profile was investigated. The sandy soil of the fairway exhibits a water repellent behaviour resulting in a lot of localized dry spots (LDS) and poor turf quality during dry periods in spring and summer. In 2012 an experimental site on fairway 10 was divided into eight plots of 2 m by 2 m. Four plots were used as control and on four plots the surfactant was applied 6 times. The effects of the surfactant were studied on the wetting of the soil by measuring the volumetric water content at depths of 0–5 cm with a hand-held Time Domain Reflectometry (TDR) device. The grass performance was estimated in 3 distinct classes with percentages of the existence of green grass. Actual water repellency was assessed by putting water drops at regular distances along soil cores which were taken to a depth of 25 cm with a small, 1.5 cm diameter, auger. Applications of the soil surfactant resulted in dramatically improved soil wetting and turfgrass performance. Surfactant applications also resulted in more homogeneous wetting of the soil, reduced development of water repellency and preferential flow paths, and higher N concentration in soil. Since microbial mediated N mineralization is affected by moisture content, the higher N concentrations in the soil are thought to be related to the higher and more homogeneous moisture levels in the treated versus untreated plots. In addition to improved moisture availability, the better turf performance is likely affected by the increased plant available N in the soil which resulted from the more desirable and uniform moisture levels.

A GIS-based approach for identifying potential sites for harvesting rainwater in the Western Desert of Iraq
Adham, Ammar ; Sayl, Khamis Naba ; Abed, Rasha ; Abdeladhim, Mohamed Arbi ; Wesseling, Jan G. ; Riksen, Michel ; Fleskens, Luuk ; Karim, Usama ; Ritsema, Coen J. - \ 2018
International Soil and Water Conservation Research 6 (2018)4. - ISSN 2095-6339 - p. 297 - 304.
GIS - Iraq's western desert - Rainwater harvesting - Suitability map

People living in arid and semi-arid areas with highly variable rainfall and unforeseeable periods of droughts or floods are severely affected by water shortages and often have insecure livelihoods. The construction of dams in wadies to harvest rainwater from small watersheds and to induce artificial groundwater recharge is one of the solutions available to overcome water shortages in the Western Desert of Iraq. The success of rainwater harvesting (RWH) systems depends heavily on their technical design and on the identification of suitable sites. Our main goal was to identify suitable sites for dams using a suitability model created with ModelBuilder in ArcGIS 10.2. The model combined various biophysical factors: slope, runoff depth, land use, soil texture, and stream order. The suitability map should be useful to hydrologists, decision-makers, and planners for quickly identifying areas with the highest potential for harvesting rainwater. The implementation of this method should also support any policy shifts towards the widespread adoption of RWH.

Natural occurrence of genotoxic and carcinogenic alkenylbenzenes in Indonesian jamu and evaluation of consumer risks
Suparmi, Suparmi ; Widiastuti, Diana ; Wesseling, Sebastiaan ; Rietjens, Ivonne M.C.M. - \ 2018
Food and Chemical Toxicology 118 (2018). - ISSN 0278-6915 - p. 53 - 67.
Alkenylbenzenes - Jamu - Margin of exposure (MOE) - Risk assessment
The consumer risks of jamu, Indonesian traditional herbal medicines, was assessed focussing on the presence of alkenylbenzene containing botanical ingredients. Twenty-three out of 25 samples contained alkenylbenzenes at levels ranging from 3.8 to 440 μg/kg, with methyleugenol being the most frequently encountered alkenylbenzene. The estimated daily intake (EDI) resulting from jamu consumption was estimated to amount to 0.2–171 μg/kg bw/day for individual alkenylbenzenes, to 0.9–203 μg/kg bw/day when adding up all alkenylbenzenes detected, and to 0.9–551 μg/kg bw/day when expressed in methyleugenol equivalents using interim relative potency (REP) factors. The margin of exposure (MOE) values obtained were generally <10,000 indicating a priority for risk management when assuming daily consumption during a lifetime. Using Haber's rule it was estimated that two weeks consumption of these jamu only once would not raise a concern (MOE >10,000). However, when considering use for two weeks every year during a lifetime, 5 samples still raise a concern. It is concluded that the consumption of alkenylbenzene containing jamu can be of concern especially when consumed on a daily basis for longer periods of time on a regular basis.
Use of physiologically based kinetic modelling-facilitated reverse dosimetry to convert in vitro cytotoxicity data to predicted in vivo liver toxicity of lasiocarpine and riddelliine in rat
Chen, Lu ; Ning, Jia ; Louisse, Jochem ; Wesseling, Sebas ; Rietjens, Ivonne M.C.M. - \ 2018
Food and Chemical Toxicology 116 (2018). - ISSN 0278-6915 - p. 216 - 226.
In vitro-in vivo extrapolation - Lasiocarpine - Liver toxicity - Physiologically based kinetic (PBK) model - Reverse dosimetry - Riddelliine
Lasiocarpine and riddelliine are pyrrolizidine alkaloids (PAs) present in food and able to cause liver toxicity. The aim of this study was to investigate whether physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry can adequately translate in vitro concentration-response curves for toxicity of lasiocarpine and riddelliine to in vivo liver toxicity data for the rat. To this purpose, PBK models were developed for lasiocarpine and riddelliine, and predicted blood concentrations were compared to available literature data to evaluate the models. Concentration-response curves obtained from in vitro cytotoxicity assays in primary rat hepatocytes were converted to in vivo dose-response curves from which points of departure (PODs) were derived and that were compared to available literature data on in vivo liver toxicity. The results showed that the predicted PODs fall well within the range of PODs derived from available in vivo toxicity data. To conclude, this study shows the proof-of-principle for a method to predict in vivo liver toxicity for PAs by an alternative testing strategy integrating in vitro cytotoxicity assays with in silico PBK modelling-facilitated reverse dosimetry. The approach may facilitate prediction of acute liver toxicity for the large number of PAs for which in vivo toxicity data are lacking.
Risk assessment of genotoxic and carcinogenic alkenylbenzenes in botanical containing products present on the Chinese market
Ning, Jia ; Cui, Xin Yue ; Kong, Xiang Nan ; Tang, Yi Fei ; Wulandari, Riana ; Chen, Lu ; Wesseling, Sebas ; Rietjens, Ivonne M.C.M. - \ 2018
Food and Chemical Toxicology 115 (2018). - ISSN 0278-6915 - p. 344 - 357.
Alkenylbenzenes - Chinese market - Herbal teas - Margin of Exposure (MOE) - Plant food supplement (PFS) - Traditional Chinese medicine (TCM)
In the present study, a risk assessment of plant food supplements (PFS), traditional Chinese medicines (TCM) and herbal teas containing alkenylbenzenes was performed using the Margin of Exposure (MOE) approach. The levels of alkenylbenzenes in botanical preparations collected on the Chinese market were quantified and the combined estimated daily intake (EDI) was determined using dose additivity. The combined EDI values obtained assuming equal potency of all alkenylbenzenes detected in the PFS, TCM and herbal teas were 0.3 to 14.3, 0.05 to 539.4 and 0.04 to 42.5 μg/kg bw/day, respectively. Calculating combined EDI values taking into account the toxic equivalency (TEQ) approach, the values for PFS, TCM and herbal teas were 0.3 to 7.7, 0.05 to 278.0 and 0.02 to 16.5 μg estragole equivalents/kg bw/day, respectively. The MOE values resulting from consumption of these PFS, TCM and one cup of herbal tea per day during life-time were generally lower than 10 000, suggesting a potential priority for risk management. For short-term exposure such as two weeks consumption, applying Haber's rule, only one TCM 6 (四神丸) still had an MOE value below 10 000. It is concluded that selected consumption of Chinese botanical preparations raise a concern because of exposure to alkenylbenzenes, especially when exposure is for longer periods of time.
Varkens en kippen lezen
Wesseling, M. ; Bolhuis, J.E. ; Rodenburg, T.B. - \ 2017
In: Hoe slaap je slim maakt en apen elkaar bedriegen Netherlands Society for Behavioural Biology (NVG) - p. 27 - 29.
Use of physiologically based kinetic modelling facilitated read-across in risk assessment of botanical food-borne alkenylbenzenes
Al-Malahmeh, Amer - \ 2017
University. Promotor(en): Ivonne Rietjens, co-promotor(en): Jacques Vervoort; Sebas Wesseling. - Wageningen : Wageningen University - ISBN 9789463434591 - 237

Botanicals and botanical preparations have become widely available on the market in the form of food supplements and other food preparations. In Europe the safety of botanicals and derived food products placed on the market has to comply with the general requirements set out in regulation (EC) No 178/2002. In spite of this regulation, the risks of botanicals and botanical preparations are generally not assessed before they enter the market.

The present thesis aimed to perform a risk assessment of some selected botanicals and derived preparations focusing on samples containing the so-called alkenylbenzenes, including myristicin, apiol, safrole, methyleugenol, elemicin, and estragole. Samples containing alkenylbenzenes may be of concern because these compounds may be genotoxic and carcinogenic displaying similar characteristics regarding mode of action (MOA) and tumor formation. The aim of the present study was to develop a MOA based approach for read-across in risk assessment from safrole, for which in vivo toxicity studies are available to myristicin and apiol for which tumor data are not reported, thus contributing to alternatives in animal testing. This was done using physiologically based kinetic (PBK) modelling. Botanical preparations included in the risk assessments performed in the present thesis were basil-containing pesto and nutmeg-based plant food supplements (PFS). Given that several of the preparations analyzed contained several alkenylbenzenes a risk assessment of combined exposure to these alkenylbenzenes was included as well, to give a better understanding of when risk management actions would be needed for botanicals and derived preparations containing these ingredients.

The introduction chapter starts with a short background and definition of the aim of the thesis, followed by a description of the physicochemical properties, natural occurrence and estimated daily intake (EDI) of the alkenylbenzenes, as well as of their ADME (absorption, distribution, metabolism and excretion) characteristics, carcinogenicity and MOA, the relevant risk assessment approach, and finally PBK modelling.

Chapter 2 and 3 of the thesis describe the development of PBK models for myristicin and apiol in male rat and human, enabling the prediction of dose-dependent effects in bioactivation and detoxification of these alkenylbenzenes. This allows comparison of the PBK model-based prediction of bioactivation of myristicin or apiol to the PBK model-based predictions for bioactivation of the structurally related compound safrole, enabling estimation of a BMDL10 for myristicin and apiol from read-across to the BMDL10 available for safrole, thereby facilitating risk assessment of current dietary exposure to myristicin or apiol. The results from PBK analysis support that risk assessment of myristicin may be based on the BMDL10 derived for safrole, and that risk assessment of apiol may be performed using a BMDL10 value of 3 times the BMDL10 for safrole. These results enabled a preliminary risk assessment of current exposure to these alkenylbenzenes showing that the current exposure to myristicin results in MOE values indicating a priority for risk management (Chapter 2), while current exposure to apiol does not raise a concern (Chapter 3). The results obtained illustrate that PBK modeling can facilitate a read-across in risk assessment from a compound for which in vivo toxicity studies are available to a related compound for which tumor data are not reported, thus contributing to alternatives in animal testing.

Subsequently, in Chapter 4 the BMDL10 values obtained were used to perform a risk assessment for alkenylbenzenes in basil-based pesto sauce. To this end the levels of methyleugenol and other alkenylbenzenes in basil-containing sauce of pesto were quantified enabling an associated risk assessment based on the MOE approach, taking into consideration the possible combined exposure to different alkenylbenzenes and the BMDL10 values as defined in literature and in chapter 2 and 3 of the thesis. The MOE values obtained generally indicated a priority for risk management when assuming daily consumption of basil-based pesto sauce. It was concluded that consumption of pesto sauces would be of concern if consumed on a daily basis over longer periods of time.

Chapter 5 evaluates the risk of exposure to myristicin and related alkenylbenzenes through human exposure to nutmeg-based PFS based on the MOE approach. Chemical analysis of various PFS samples was performed and the amount of alkenylbenzenes that would be consumed through consumption of these nutmeg-based PFS where quantified. MOE values where calculated for the individual alkenylbenzenes as well as taking into account the presence of more than one alkenylbenzenes within selected PFS samples. It was concluded that the results reveal that daily nutmeg-based PFS consumption following recommendations for daily intake for especially longer periods of time would raise a concern.

Chapter 6 summarizes the results obtained in the thesis, compiles the overall discussion and presents the future perspectives that follow from the results obtained.

Mode of action based risk assessment of the botanical food-borne alkenylbenzenesapiol and myristicin
Alajlouni, Abdul - \ 2017
University. Promotor(en): Ivonne Rietjens, co-promotor(en): Jacques Vervoort; Sebas Wesseling. - Wageningen : Wageningen University - ISBN 9789463434584 - 212

Alkenylbenzenes including estragole, methyleugenol, safrole, elemicin, apiol, and myristicin are naturally occurring in many herbs such as parsley, dill, basil, tarragon, fennel and nutmeg (Kreydiyyeh and Usta, 2002, Smith et al., 2002, Semenov et al., 2007). Estragole, methyleugenol and safrole are genotoxic and carcinogenic in rodent bioassays inducing liver tumors (Boberg et al., 1986, Boberg et al., 1983, Drinkwater et al., 1976, Miller et al., 1983, Swanson et al., 1981, Wiseman et al., 1985, Wiseman et al., 1987, Wislocki et al., 1977). Because of that, the use of methyleugenol, safrole and estragole as pure substances in foodstuff has been prohibited in the EU from September 2008 onwards (European Commission (EC), 2008). For apiol and myristicin data for their risk assessment are limited and more research is needed to support the evaluation of the risk resulting from consumption of products containing these compounds (WHO, 2009). The aim of the current thesis was to perform a mode of action based risk assessment of exposure to low doses of apiol and myristicin by using physiologically based kinetic (PBK) modelling based read-across from other alkenylbenzenes and to use the results obtained for risk assessment of consumption of plant food supplements (PFS) and other botanical products containing parsley and dill.

Chapter 1 provides general background information to alkenylbenzenes especially apiol and myristicin, a description of the chemical, metabolic and toxicity characteristics of apiol and myristicin and other structurally related alkenylbenzenes, a brief outline of the method used for their risk assessment and a short introduction to PBK modelling. Besides that, Chapter 1 include the aim of the current thesis. In Chapter 2 and Chapter 3, PBK models for respectively apiol and myristicin in male rat and human were defined, enabling prediction of dose-dependent effects in bioactivation and detoxification of these alkenylbenzenes. The PBK model based predictions were subsequently compared to those for safrole enabling estimation of a BMDL10 for apiol and myristicin from read-across from the BMDL10 available for safrole, thereby enabling risk assessment of current dietary exposure to apiol. In Chapter 4 and 5, the risk assessment of exposure to apiol and related alkenylbenzenes through drinking of parsley and dill based herbal teas and consumption of parsley and dill containing PFS was performed using the BMDL10 values derived in Chapter 2 and 3. The results showed that consumption of parsley and dill based herbal teas and PFS would be a priority for risk management if consumed for longer periods of time. Chapter 6 includes a general discussion of the thesis results obtained and the future perspectives that describe the needs to further research, based on alternatives for animals testing, to improve the risk assessment approaches for different botanical preparations.

Altogether, the results obtained through different thesis chapters show that integration of different approaches provides the basis for a mode of action and PBK modelling based read-across from compounds for which tumor data are available to related compounds for which such data are lacking. This can contribute to the development of alternatives for animal testing and will facilitate the risk assessment of compounds for which in vivo toxicity studies on tumor formation data are unavailable.

Groesbeek-effect, wateroverlast, stroming door vingers en zandkuiltjes
Dekker, L.W. ; Oostindie, K. ; Ritsema, C.J. ; Wesseling, J.G. - \ 2017
Stromingen : vakblad voor hydrologen 28 (2017)2. - ISSN 1382-6069 - p. 7 - 16.
Risk assessment of combined exposure to alkenylbenzenes through consumption of plant food supplements containing parsley and dill
Alajlouni, Abdalmajeed M. ; Al-Malahmeh, Amer J. ; Wesseling, Sebastiaan ; Kalli, Marina ; Vervoort, Jacques ; Rietjens, Ivonne M.C.M. - \ 2017
Food Additives & Contaminants. Pt. A, Chemistry, Analysis, Control, Exposure & Risk Assessment 34 (2017)12. - ISSN 1944-0049 - p. 2201 - 2211.
alkenylbenzenes - estimated daily intake - margin of exposure - Parsley- and dill-based plant food supplements (PFS) - risk assessment - toxic equivalency approach
A risk assessment was performed of parsley- and dill-based plant food supplements (PFS) containing apiol and related alkenylbenzenes. First, the levels of the alkenylbenzenes in the PFS and the resulting estimated daily intake (EDI) resulting from use of the PFS were quantified. Since most PFS appeared to contain more than one alkenylbenzene, a combined risk assessment was performed based on equal potency or using a so-called toxic equivalency (TEQ) approach based on toxic equivalency factors (TEFs) for the different alkenylbenzenes. The EDIs resulting from daily PFS consumption amount to 0.74–125 µg kg–1 bw for the individual alkenylbenzenes, 0.74–160 µg kg–1 bw for the sum of the alkenylbenzenes, and 0.47–64 µg kg–1 bw for the sum of alkenylbenzenes when expressed in safrole equivalents. The margins of exposure (MOEs) obtained were generally below 10,000, indicating a priority for risk management if the PFS were to be consumed on a daily basis. Considering short-term use of the PFS, MOEs would increase above 10,000, indicating low priority for risk management. It is concluded that alkenylbenzene intake through consumption of parsley- and dill-based PFS is only of concern when these PFS are used for long periods of time.
Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in nutmeg-based plant food supplements
Al-Malahmeh, Amer J. ; Alajlouni, Abdul ; Ning, Jia ; Wesseling, Sebas ; Vervoort, Jacques ; Rietjens, Ivonne M.C.M. - \ 2017
Journal of Applied Toxicology 37 (2017)10. - ISSN 0260-437X - p. 1254 - 1264.
Alkenylbenzenes - Combined risk assessment - Margin of exposure (MOE) - Nutmeg-based PFS - Plant food supplement (PFS) - Toxic equivalency factors (TEFs)
A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312μg kg-1 body weight (bw) for individual alkenylbenzenes, to 1.5 to 631μg kg-1 bw when adding up the alkenylbenzene levels assuming equal potency, and to 0.4 to 295μg kg-1 bw when expressed in safrole equivalents using toxic equivalency factors (TEFs). The margin of exposure approach (MOE) was used to evaluate the potential risks. Independent of the method used for the intake estimate, the MOE values obtained were generally lower than 10000 indicating a priority for risk management. When taking into account that PFS may be used for shorter periods of time and using Haber's rule to correct for shorter than lifetime exposure it was shown that limiting exposure to only 1 or 2weeks would result in MOE values that would be, with the presently determined levels of alkenylbenzenes and proposed uses of the PFS, of low priority for risk management (MOE > 10000). It is concluded that the results of the present paper reveal that nutmeg-based PFS consumption following recommendations for daily intake especially for longer periods of time raise a concern.
Risk assessment for pyrrolizidine alkaloids detected in (herbal) teas and plant food supplements
Chen, Lu ; Mulder, Patrick P.J. ; Louisse, Jochem ; Peijnenburg, Ad ; Wesseling, Sebas ; Rietjens, Ivonne M.C.M. - \ 2017
Regulatory Toxicology and Pharmacology 86 (2017). - ISSN 0273-2300 - p. 292 - 302.
(Herbal) teas - BMDL - MOE - Plant food supplements - Pyrrolizidine alkaloids - REP - Risk assessment - T10 - T25

Pyrrolizidine alkaloids (PAs) are plant metabolites present in some botanical preparations, with especially 1,2-unsaturated PAs being of concern because they are genotoxic carcinogens. This study presents an overview of tumour data on PAs and points of departure (PODs) derived from them, corroborating that the BMDL10 for lasiocarpine represents a conservative POD for risk assessment. A risk assessment using this BMDL10 and mean levels of PAs reported in literature for (herbal) teas, indicates that consumption of one cup of tea a day would result in MOE values lower than 10 000 for several types of (herbal) teas, indicating a priority for risk management for these products A refined risk assessment using interim relative potency (REP) factors showed that based on the mean PA levels, 7(54%) of 13 types of (herbal) teas and 1 (14%) of 7 types of plant food supplements (PFS) resulted in MOE values lower than 10 000, indicating a priority for risk management also for these products in particular. This includes both preparations containing PA-producing and non-PA-producing plants. Our study provides insight in the current state-of-the art and limitations in the risk assessment of PA-containing food products, especially (herbal) teas and PFS, indicating that PAs in food presents a field of interest for current and future risk management.

Study on inter-ethnic human differences in bioactivation and detoxification of estragole using physiologically based kinetic modeling
Ning, Jia ; Louisse, Jochem ; Spenkelink, Bert ; Wesseling, Sebas ; Rietjens, Ivonne M.C.M. - \ 2017
Archives of Toxicology 91 (2017)9. - ISSN 0340-5761 - p. 3093 - 3108.
Caucasian - Chinese - Estragole - Inter-ethnic difference - Physiologically based kinetic modeling
Considering the rapid developments in food safety in the past decade in China, it is of importance to obtain insight into what extent safety and risk assessments of chemicals performed for the Caucasian population apply to the Chinese population. The aim of the present study was to determine physiologically based kinetic (PBK) modeling-based predictions for differences between Chinese and Caucasians in terms of metabolic bioactivation and detoxification of the food-borne genotoxic carcinogen estragole. The PBK models were defined based on kinetic constants for hepatic metabolism derived from in vitro incubations using liver fractions of the two ethnic groups, and used to evaluate the inter-ethnic differences in metabolic activation and detoxification of estragole. The models predicted that at realistic dietary intake levels, only 0.02% of the dose was converted to the ultimate carcinogenic metabolite 1′-sulfooxyestragole in Chinese subjects, whereas this amounted to 0.09% of the dose in Caucasian subjects. Detoxification of 1′-hydroxyestragole, mainly via conversion to 1′-oxoestragole, was similar within the two ethnic groups. The 4.5-fold variation in formation of the ultimate carcinogenic metabolite of estragole accompanied by similar rates of detoxification may indicate a lower risk of estragole for the Chinese population at similar levels of exposure. The study provides a proof of principle for how PBK modeling can identify differences in ethnic sensitivity and provide a more refined risk assessment for a specific ethnic group for a compound of concern.
Integrated strategy for the assessment of kidney toxicity : the case of aristolochic acids
Abdullah, Rozaini - \ 2017
University. Promotor(en): Ivonne Rietjens, co-promotor(en): Ans Punt; Sebas Wesseling; Jochem Louisse. - Wageningen : Wageningen University - ISBN 9789463430807 - 207
animal testing alternatives - in vitro - toxicity - models - risk assessment - toxins - carboxylic acids - alternatieven voor dierproeven - toxiciteit - modellen - risicoschatting - toxinen - carbonzuren

This PhD thesis aimed to provide additional evidence to demonstrate the potential of an integrated testing strategy using in vitro assays with physiologically based kinetic (PBK) modeling based-reverse dosimetry to predict in vivo toxicity without animal testing. Kidney toxicity was chosen as the toxicity endpoint and aristolochic acids (AAs) were selected as model chemicals. AAs are natural nephrotoxic, genotoxic and carcinogenic chemicals present in Aristolochia species. PBK models for rat, mouse and human were developed for aristolochic acid I (AAI) based on kinetic parameter values derived from in vitro incubations using relevant tissue fractions. Then, in vitro concentration-response curves for cytotoxicity of AAI were obtained in kidney cell lines and translated to in vivo dose-response curves for kidney toxicity using PBK modeling-based reverse dosimetry. The points of departure (PODs) obtained from these predicted in vivo dose-response curves generally fell within the range of PODs derived from in vivo literature data on kidney toxicity of AAI. The same PBK models were subsequently used to translate the in vitro concentration-response curves for AAI-DNA adduct formation to in vivo dose-response curves for kidney AAI-DNA adduct formation. The predicted in vivo AAI-DNA adduct formation in the rat, mouse and human kidney varied within an order of magnitude compared to the in vivo values reported in the literature. The PBK models were also used to predict the dose level that would be required in humans to obtain the level of DNA adducts in rats at the BMD10 (the benchmark dose causing a 10% extra risk above background level) value for AAI-induced tumor formation in the rat kidney. This analysis revealed that the dose level required to induce the level of DNA adduct formation that equals the DNA adduct level at the BMD10 were similar to AA doses estimated to be taken in Belgian patients that developed urinary tract cancer. Given that the exposure to AAI is often accompanied by the presence of AAII, in a next study the relative formation of DNA adducts by these two major AA congeners was investigated. The results revealed that the relative higher formation of AAI-DNA adducts as compared to AAII-DNA adducts observed in vitro was not reflected in vivo where the levels formed upon exposure to equal dose levels were relatively similar. PBK model based translation of the in vitro data to the in vivo situation revealed that PBK model based prediction of in vivo DNA adduct formation is feasible. However, predicted AAI-DNA adduct levels were higher than predicted AAII-DNA adduct levels, indicating that the difference between the in vitro and in vivo AAI-/AAII-DNA adduct ratios could only in part be explained by differences in in vivo kinetics of AAI compared to AAII. The discrepancy between the difference in DNA adduct formation of AAI and AAII in the in vitro and the in vivo situation is an issue that needs further investigation to also adequately predict the relative differences between the two AAs. In a final chapter this thesis aimed to investigate the possible risks associated with exposure to AAs based on AA levels measured in plant food supplements (PFS) and herbal products. This is of interest given the restrictions on the presence of AAs in food, installed in various countries including The Netherlands, after the incidences with induction of Aristolochic Acid Nephropathy upon use of herbal weight loss preparations that accidentally contained AAs. The risk assessment of PFS and herbal products containing AAs purchased via online markets revealed that consumers can still be exposed to AA-containing PFS and herbal products and that the corresponding levels of exposure raise concern especially for people who frequently use the products. Altogether, this thesis presented further support for the use of combined in vitro-PBK modeling based alternative tools for risk assessment and revealed the continued risks posed by AAs present in PFS and herbal products.

Bodemhydrofysische gegevens in BRO en BIS : update 2016
Bakker, G. ; Heinen, M. ; Wesseling, J.G. ; Groot, W.J.M. de; Assinck, F.B.T. ; Hummelink, E.W.J. - \ 2017
Wageningen : Wageningen Environmental Research (Wageningen Environmental Research rapport 2789) - 77
bodemfysica - hydrologie - water - bodem - soil physics - hydrology - soil
Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in basil-containing sauce of pesto
Al-Malahmeh, Amer J. ; Al-Ajlouni, Abdalmajeed M. ; Wesseling, Sebas ; Vervoort, Jacques ; Rietjens, Ivonne M.C.M. - \ 2017
Toxicology Reports 4 (2017). - ISSN 2214-7500 - p. 1 - 8.
Basil-based pesto - Combined risk assessment - Margin of exposure (MOE) - Toxic equivalency factors (TEFs)

A risk assessment of basil-based pesto sauces containing methyleugenol and related alkenylbenzenes was performed based on their levels detected in a series of pesto sauces available on the Dutch market. The estimated daily intake (EDI) values of alkenylbenzenes as a result of consumption of the different pesto sauces amounted to 1.2–44.3 μg/kg bw for individual alkenylbenzenes, 14.3–43.5 μg/kg bw when adding up the alkenylbenzene levels assuming equal potency, and 17.3–62.9 μg/kg bw when expressed in methyleugenol equivalents using alkenylbenzenes defined toxic equivalency factors (TEF). The margin of exposure approach (MOE), used to evaluate the potential risks, resulted in MOE values that were generally lower than 10000 indicating a priority for risk management when assuming daily consumption. The levels of methyleugenol detected in the pesto sauces would allow consumption of 1.1–29.8, 7.5–208, 15.1–416.5, and 32.4–892.5 g of pesto sauce on a daily basis, once a week, once every two weeks, and once a month, respectively, to achieve MOE values above the 10000 limit indicating low priority for risk management. It is concluded that consumption of pesto sauces would only be of concern if consumed on a daily basis over longer periods of time.

Protein oleogels from heat-set whey protein aggregates
Vries, Auke de; Wesseling, Anne ; Linden, Erik van der; Scholten, Elke - \ 2017
Journal of Colloid and Interface Science 486 (2017). - ISSN 0021-9797 - p. 75 - 83.
Microstructure - Oil structuring - Oleogels - Organogels - Protein functionality - Rheology

In this research we use heat-set whey protein aggregates (diameter ∼ 200 nm) as novel building blocks for structure formation in liquid oil to form oleogels. To transfer the aggregates to the oil phase, a solvent exchange procedure to sunflower oil was applied using acetone as an intermediate solvent. We found that agglomeration of the aggregates was prevented and the particle size in oil did not change from that in the initial aqueous phase. The small protein aggregates assemble into a space-spanning network, thereby providing solid-like properties to liquid oil. From oscillatory rheology we conclude that the aggregates are highly effective in forming a network. Already at ∼3% we found that G′ > G″ and G′ scales with protein concentration as G′ ∼ cp 5.3. Applying a fractal gel network theory to the rheological data we deduce that the gels are in the strong link regime with a fractal dimension of 2.2. The results show that protein aggregates, besides their well-known functionality in aqueous solvents, are capable of forming a network in liquid oil. This provides a novel and promising way to design oleogels with tuneable rheological properties, applicable to e.g. foods, pharmaceuticals and/or cosmetics.

Physiologically based kinetic modeling of the bioactivation of myristicin
Al-Malahmeh, Amer J. ; Al-Ajlouni, Abdelmajeed ; Wesseling, Sebastiaan ; Soffers, Ans E.M.F. ; Al-Subeihi, A. ; Kiwamoto, Reiko ; Vervoort, Jacques ; Rietjens, Ivonne M.C.M. - \ 2017
Archives of Toxicology 91 (2017). - ISSN 0340-5761 - 22 p.
Alkenylbenzenes - Myristicin - Physiologically based kinetic (PBK) modeling - Read-across-based risk assessment - Safrole

The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene myristicin that were developed by extension of the PBK models for the structurally related alkenylbenzene safrole in rat and human. The newly developed myristicin models revealed that the formation of the proximate carcinogenic metabolite 1′-hydroxymyristicin in liver is at most 1.8 fold higher in rat than in human and limited for the ultimate carcinogenic metabolite 1′-sulfoxymyristicin to (2.8–4.0)-fold higher in human. In addition, a comparison was made between the relative importance of bioactivation for myristicin and safrole. Model predictions indicate that for these related compounds, the formation of the 1′-sulfoxy metabolites in rat and human liver is comparable with a difference of 10 derived for safrole of 1.9–5.1 mg/kg bw per day. Using an estimated daily intake of myristicin of 0.0019 mg/kg bw per day resulting from the use of herbs and spices, this results in MOE values for myristicin that amount to 1000–2700, indicating a priority for risk management. The results obtained illustrate that PBK modeling provides insight into possible species differences in the metabolic activation of myristicin. Moreover, they provide an example of how PBK modeling can facilitate a read-across in risk assessment from a compound for which in vivo toxicity studies are available to a related compound for which tumor data are not reported, thus contributing to alternatives in animal testing.

Vluchtende vissen en dove dolfijnen als gevolg van bommen
Aarts, Geert - \ 2016

De stilte van de zee? Vergeet het maar. Allerlei geluiden - oude bommen, seismische proeven, schepen - beïnvloeden de dieren die erin leven. Promovendi in Leiden wierpen zich op de negatieve effecten.

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