document

A physiologically-based kinetic (PBK) model for work-related diisocyanate exposure: Relevance for the design and reporting of biomonitoring studies

Scholten, B. (author), Westerhout, J. (author), Pronk, A. (author), Stierum, R. (author), Vlaanderen, J. (author), Vermeulen, R. (author), Jones, K. (author), Santonen, T. (author), Portengen, L. (author)

Diisocyanates are highly reactive substances and known causes of occupational asthma. Exposure occurs mainly in the occupational setting and can be assessed through biomonitoring which accounts for inhalation and dermal exposure and potential effects of protective equipment. However the interpretation of biomonitoring data can be challenging for...

article 2023

document

The 50th percentile of the general population single eating occasion intake of food is optimal for the calculation of action levels for precautionary allergen labelling

Blom, W.M. (author), Westerhout, J. (author), Houben, G.F. (author)

Lack of guidance regarding selection of food intake values for allergen risk assessment can lead to different outcomes for similar levels of allergens in food products. Several food consumption survey databases (United States, North-West Europe, and Netherlands) were analyzed to identify optimal food intake percentiles using a sensitivity...

article 2023

document

Sesame eliciting and safe doses in a large sesame allergic population

Nachshon, L. (author), Westerhout, J. (author), Remington, B. Blom, W.M. (author), Levy, M.B. (author), Goldberg, M.R. (author), Epstein-Rigbi, N. (author), Katz, Y. (author), Elizur, A. (author)

Background: Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited. Methods: All sesame oral food challenges (OFCs),...

article 2023

document

Coupling food compounds data from FooDB and Phenol‐Explorer to the Dutch food coding system NEVO: towards a novel approach to studying the role of food in health and disease

Meima, M.Y. (author), Westerhout, J (author), Bijlsma, S. (author), Meijerink, M. (author), Houben, G.F. (author)

he relationship between diet and disease has been widely studied. The majority of studies have focused on the role and effects of food groups, nutrients or specific compounds, neglecting the wide range of compounds that make up our food. Each compound possesses unique characteristics and exerts distinct effects in the body. Analyzing...

article 2023

document

Reviewing the Chinese-Specific Reference Amounts Study Conducted by Sun et al., 2022

Blom, W.M. (author), Westerhout, J. (author), Houben, G.F. (author)

The need for region-specific food intake values to accurately estimate food allergen risk is underscored by the recent Ad Hoc Joint Food and Agriculture Organization/World Health Organization (FAO/WHO) Expert Consultation on Risk Assessment of Food Allergens (1). A recent study published by Sun et al. in China CDC Weekly 2022, titled A Chinese...

article 2023

document

Intestinal explant barrier chip: long-term intestinal absorption screening in a novel microphysiological system using tissue explants

Eslami Amirabadi, H. (author), Donkers, J.M. (author), Wieringa, E. (author), Ingenhut, B. (author), Pieters, L. (author), Stevens, L. (author), Donkers, T. (author), Westerhout, J. (author), Masereeuw, R. (author), Bobeldijk-Pastorova, I. (author), Nooijen, I. (author), van de Steeg, E. (author)

The majority of intestinal in vitro screening models use cell lines that do not reflect the complexity of the human intestinal tract and hence often fail to accurately predict intestinal drug absorption. Tissue explants have intact intestinal architecture and cell type diversity, but show short viability in static conditions. Here, we present a...

article 2022

document

Towards best use and regulatory acceptance of generic physiologically based kinetic (PBK) models for in vitro-to-in vivo extrapolation (IVIVE) in chemical risk assessment

Najjar, A. (author), Punt, A. (author), Wambaugh, J. (author), Paini, A. (author), Ellison, C. (author), Fragki, S. (author), Bianchi, E. (author), Zhang, F. (author), Westerhout, J. (author), Mueller, D. (author), Li, H. (author), Shi, Q. (author), Gant, T.W. (author), Botham, P. (author), Bars, R. (author), Piersma, A. (author), van Ravenzwaay, B. (author), Kramer, N.I. (author)

With an increasing need to incorporate new approach methodologies (NAMs) in chemical risk assessment and the concomitant need to phase out animal testing, the interpretation of in vitro assay readouts for quantitative hazard characterisation becomes more important. Physiologically based kinetic (PBK) models, which simulate the fate of chemicals...

article 2022

document

Reproducibility of food challenge to cow's milk: Systematic review with individual participant data meta-analysis

Turner, P.J. (author), Patel, N. (author), Campbell, D.E. (author), Sampson, H.A. (author), Maeda, M. (author), Katsunuma, T. (author), Westerhout, J. (author), Blom, W.M. (author), Baumert, J.L. (author), Houben, G.F. (author), Remington, B.C. (author)

Background: Cow's milk (CM) is an increasingly common cause of severe allergic reactions, but there is uncertainty with respect to severity of reactions at low-level CM exposure, as well as the reproducibility of reaction thresholds. Objective: We undertook an individual participant data (IPD) meta-analysis of studies reporting double-blind,...

article 2022

document

Applicability of generic PBK modelling in chemical hazard assessment: A case study with IndusChemFate

Fragki, S. (author), Piersma, A.H. (author), Westerhout, J. (author), Kienhuis, A. (author), Kramer, N.I. (author), Zeilmaker, M.J. (author)

Toxicology is moving away from animal testing towards in vitro tools to assess chemical safety. This new testing framework requires a quantitative method, i.e. kinetic modelling, which extrapolates effective concentrations in vitro to a bioequivalent human dose in vivo and which can be applied on “high throughput screening” of a wide variety of...

article 2022

document

Updated full range of Eliciting Dose values for Cow's milk for use in food allergen risk assessment

Blom, W.M. (author), Westerhout, J. (author), Baumert, J.L. (author), Meima, M.Y. (author), Turner, P.J. (author), Ebisawa, M. (author), Yanagida, N. (author), Remington, B.C. (author), Houben, G.F. (author)

Access to Eliciting Doses (ED) for allergens enables advanced food allergen risk assessment. Previously, the full ED range for 14 allergenic foods, including milk, and recommendations for their use were provided (Houben et al., 2020). Additional food challenge studies with cow's milk-allergic patients added 247 data points to the original...

article 2022

document

Health Risk Assessment of Ortho-Toluidine Utilising Human Biomonitoring Data of Workers and the General Population

Huuskonen, P. (author), Karakitsios, S. (author), Scholten, B. (author), Westerhout, J. (author), Sarigiannis, D.A. (author), Santonen, T. (author)

The aim of this work was to demonstrate how human biomonitoring (HBM) data can be used to assess cancer risks for workers and the general population. Ortho-toluidine, OT (CAS 95-53-4) is an aniline derivative which is an animal and human carcinogen and may cause methemoglobinemia. OT is used as a curing agent in epoxy resins and as intermediate...

article 2022

document

Assessment of dermal absorption of aluminium from a representative antiperspirant formulation using a ( 26 Al)Al microtracer approach: a follow-up study in humans

de Ligt, R. (author), Westerhout, J. (author), Grossouw, D. (author), Buters, T.P. (author), Rissman, R. (author), Burggraaf, J. (author), Windhorst, A.D. (author), Tozer, S. (author), Pappa, G. (author), Wal, B. (author), Bury, D. (author), Mason, D.R. (author), Vaes, W.H.J. (author)

A follow-up study was performed in 12 healthy women to evaluate systemic exposure to aluminium following topical application of a representative antiperspirant formulation under real-life use conditions (part A) and to assess the local fate of topically applied aluminium by taking additional tape strips and skin biopsies (Part B). A simple roll...

article 2022

document

A systematic comparison of food intake data of the United States and the Netherlands for food allergen risk assessment

Meima, M.Y. (author), Blom, W.M. (author), Westerhout, J. (author), Kruizinga, A.G. (author), Remington, B.C. (author), Wheeler, M.W. (author), Houben, G.F. (author)

article 2021

document

Suitability of low-dose open food challenge data to supplement double-blind placebo-controlled data in generation of food allergen threshold dose distributions

Remington, B.C. (author), Westerhout, J. (author), Dubois, A.E.J. (author), Blom, W.M. (author), Kruizinga, A.G. (author), Taylor, S.L. (author), Houben, G.F. (author), Baumert, J.L. (author)

Food allergen threshold dose distributions are used in food allergen risk assessment to determine the level of risk within a food-allergic population to a defined exposure amount of allergenic food protein and to help inform allergen risk management decisions. There has been a long-standing interest in determining threshold dose distributions...

article 2021

document

The population threshold for soy as an allergenic food – Why did the Reference Dose decrease in VITAL 3.0?

Taylor, S.L. (author), Houben, G.F. (author), Blom, W.M. (author), Westerhout, J. (author), Remington, B.C. (author), Crevel, R.W.R. (author), Brooke-Taylor, S. (author), Baumert, J.L. (author)

Background. Soy is globally recognized as a commonly allergenic food. The VITAL (Voluntary Incidental Trace Allergen Labeling) Scientific Expert Panel (VSEP) of the Allergen Bureau of Australia & New Zealand used data on minimal reactive doses in low-dose clinical challenges of soy-allergic individuals to elaborate and propose the first...

article 2021

document

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Fragki, S.S. (author), Dirven, H. (author), Fletcher, T. (author), Grasl-Kraupp, B. (author), Guetzkow, K.B. (author), Hoogenboom, R. (author), Kersten, S. (author), Lindeman, B. (author), Louisse, J. (author), Peijnenburg, A. (author), Aldert H., (author), Piersma, A.H. (author), Princen, H.M.G. (author), Uhl, M. (author), Westerhout, J. (author), Zeilmaker, M.J. (author), Luijten, M. (author)

Associations between per- and polyfluoroalkyl substances (PFASs) and increased blood lipids have been repeatedly observed in humans, but a causal relation has been debated. Rodent studies show reverse effects, i.e. decreased blood cholesterol and triglycerides, occurring however at PFAS serum levels at least 100-fold higher than those in humans....

article 2021

document

Updated population minimal eliciting dose distributions for use in risk assessment of 14 priority food allergens

Remington, B.C. (author), Westerhout, J. (author), Meima, M.Y. (author), Blom, W.M. (author), Kruizinga, A.G. (author), Wheeler, M.W. (author), Taylor, S.L. (author), Houben, G.F. (author), Baumert, J.L. (author)

Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset...

article 2020

document

Full range of population Eliciting Dose values for 14 priority allergenic foods and recommendations for use in risk characterization

Houben, G.F. (author), Baumert, J.L. (author), Blom, W.M. (author), Kruizinga, A.G. (author), Meima, M.Y. (author), Remington, B.C. (author), Wheeler, M.W. (author), Westerhout, J. (author), Taylor, S.L. (author)

Previously, we published selected Eliciting Dose (ED) values (i.e. ED01 and ED05 values) for 14 allergenic foods, predicted to elicit objective allergic symptoms in 1% and 5%, respectively, of the allergic population (Remington et al., 2020). These ED01 and ED05 values were specifically presented and discussed in the context of establishing...

article 2020

document

Deriving individual threshold doses from clinical food challenge data for population risk assessment of food allergens

Westerhout, J. (author), Baumert, J.L. (author), Blom, W.M. (author), Allen, K.J. (author), Ballmer-Weber, B. (author), Crevel, R.W.R. (author), Dubois, A.E.J. (author), Fernández-Rivas, M. (author), Greenhawt, M.J. (author), Hourihane, J.O. (author), Koplin, J.J. (author), Kruizinga, A.G. (author), Le, T.M. (author), Sampson, H.A. (author), Shreffler, W.G. (author), Turner, P.J. (author), Taylor, S.L. (author), Houben, G.F. (author), Remington, B.C. (author)

Background: Food allergies are a significant public health issue, and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility of limiting risks to zero, quantitative allergen risk assessment and management strategies are needed. Objective: We sought...

article 2019

document

Allergenicity prediction of novel and modified proteins: Not a mission impossible! Development of a Random Forest allergenicity prediction model

Westerhout, J. (author), Krone, T. (author), Snippe, A. (author), Babé, L. (author), McClain, S.U. (author), Ladics, G.S. (author), Houben, G.G. (author), Verhoeckx, K.C. (author)

Alternative and sustainable protein sources (e.g., algae, duckweed, insects) are required to produce (future) foods. However, introduction of new food sources to the market requires a thorough risk assessment of nutritional, microbial and toxicological risks and potential allergic responses. Yet, the risk assessment of allergenic potential of...

article 2019