R H S Westerink


Affiliation: Utrecht University
Country: The Netherlands


  1. Zwartsen A, Litjens C, Hondebrink L, van den Heuvel J, Greupink R, Russel F, et al. Differential effects of psychoactive substances on human wildtype and polymorphic T356M dopamine transporters (DAT). Toxicology. 2019;: pubmed publisher
    ..As such, the presence of this polymorphism could affect treatment efficiency with these substances as well as susceptibly for toxicity and addiction for individuals carrying this polymorphism. ..
  2. Meijer M, Hamers T, Westerink R. Acute disturbance of calcium homeostasis in PC12 cells as a novel mechanism of action for (sub)micromolar concentrations of organophosphate insecticides. Neurotoxicology. 2014;43:110-116 pubmed publisher
    ..These data demonstrate that concentration-dependent inhibition of depolarization-evoked [Ca(2+)]i is a novel mechanism of action of (sub)micromolar concentrations of OPs that could partly underlie OP-induced neurotoxicity. ..
  3. de Groot M, Westerink R. Chemically-induced oxidative stress increases the vulnerability of PC12 cells to rotenone-induced toxicity. Neurotoxicology. 2014;43:102-109 pubmed publisher
    ..These chemically-stressed cell models may therefore prove valuable to investigate how increased cellular stress influences neurotoxic outcome, for example in case of mixture toxicity. ..
  4. Tukker A, Wijnolts F, de Groot A, Westerink R. Human iPSC-derived neuronal models for in vitro neurotoxicity assessment. Neurotoxicology. 2018;67:215-225 pubmed publisher
    ..Our results thus indicate that hiPSC-derived neuronal models must be carefully designed and characterized prior to large-scale use in neurotoxicity screening. ..
  5. Zwartsen A, Hondebrink L, Westerink R. Neurotoxicity screening of new psychoactive substances (NPS): Effects on neuronal activity in rat cortical cultures using microelectrode arrays (MEA). Neurotoxicology. 2018;66:87-97 pubmed publisher
  6. Meijer M, Hendriks H, Heusinkveld H, Langeveld W, Westerink R. Comparison of plate reader-based methods with fluorescence microscopy for measurements of intracellular calcium levels for the assessment of in vitro neurotoxicity. Neurotoxicology. 2014;45:31-7 pubmed publisher
    ..We therefore conclude that standard plate reader-based methods are not sufficiently sensitive and reliable to measure the highly dynamic and transient changes in [Ca(2+)]i that occur during chemical exposure. ..
  7. Hendriks H, Koolen L, Dingemans M, Viberg H, Lee I, Leonards P, et al. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice. Arch Toxicol. 2015;89:2345-54 pubmed publisher
    ..Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment. ..
  8. Westerink R, Ewing A. The PC12 cell as model for neurosecretion. Acta Physiol (Oxf). 2008;192:273-85 pubmed
    ..As PC12 cells have some advantages over other models for neurosecretion, including chromaffin cells, it is more than likely that in the following decade PC12 cells will continue to serve as a model to study exocytosis. ..
  9. Hendriks H, Westerink R. Neurotoxicity and risk assessment of brominated and alternative flame retardants. Neurotoxicol Teratol. 2015;52:248-69 pubmed publisher
    ..Until these data gaps in environmental behavioral and toxicological profiles are filled, large scale use of these chemicals should be cautioned. ..

More Information


  1. Hondebrink L, Hermans E, Schmeink S, van Kleef R, Meulenbelt J, Westerink R. Structure-dependent inhibition of the human α1β2γ2 GABAA receptor by piperazine derivatives: A novel mode of action. Neurotoxicology. 2015;51:1-9 pubmed publisher
    ..g., adverse effects during overdoses. Therefore, this important mode of action is not only relevant for therapeutic psychiatric interventions, but could also proof valuable for therapeutic interventions in intoxications. ..
  2. Meijer M, Brandsema J, Nieuwenhuis D, Wijnolts F, Dingemans M, Westerink R. Inhibition of Voltage-Gated Calcium Channels After Subchronic and Repeated Exposure of PC12 Cells to Different Classes of Insecticides. Toxicol Sci. 2015;147:607-17 pubmed publisher
    ..The data suggest that an acute exposure paradigm is sufficient for screening chemicals for effects on VGCCs and that PC12 cells are a sensitive model for detection of effects on VGCCs. ..
  3. de Ree H, van den Berg M, Brand T, Mulder G, Simons R, Veldhuijzen van Zanten B, et al. Health risk assessment of exposure to TriCresyl Phosphates (TCPs) in aircraft: a commentary. Neurotoxicology. 2014;45:209-15 pubmed publisher
    ..Additional research is thus required to unravel the underlying causes for the reported health complaints. ..
  4. de Groot M, Kock M, Westerink R. Assessment of the neurotoxic potential of exposure to 50Hz extremely low frequency electromagnetic fields (ELF-EMF) in naïve and chemically stressed PC12 cells. Neurotoxicology. 2014;44:358-64 pubmed publisher
    ..Though our data require confirmation, e.g. in developing neuronal cells in vitro or (developing) animals, it appears that the neurotoxic risk of ELF-EMF exposure is limited. ..
  5. de Groot M, van Kleef R, de Groot A, Westerink R. In Vitro Developmental Neurotoxicity Following Chronic Exposure to 50 Hz Extremely Low-Frequency Electromagnetic Fields in Primary Rat Cortical Cultures. Toxicol Sci. 2016;149:433-40 pubmed publisher
    ..Our combined data therefore indicate that chronic ELF-EMF exposure has only limited (developmental) neurotoxic potential in vitro. ..
  6. Duarte D, Rutten J, van den Berg M, Westerink R. In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures. Neurotoxicology. 2017;59:222-230 pubmed publisher
    ..Moreover, prolonged and/or repeated exposure to TCPs may exacerbate the observed neurotoxic effects, which argues for additional research. ..
  7. Dingemans M, Schütte M, Wiersma D, de Groot A, van Kleef R, Wijnolts F, et al. Chronic 14-day exposure to insecticides or methylmercury modulates neuronal activity in primary rat cortical cultures. Neurotoxicology. 2016;57:194-202 pubmed publisher
    ..These data indicate that the effects of chronic 14-day exposures to methylmercury and insecticides at low concentrations on spontaneous neuronal activity in vitro can be predicted in rapid acute screening studies using mwMEAs. ..
  8. Hondebrink L, Kasteel E, Tukker A, Wijnolts F, Verboven A, Westerink R. Neuropharmacological characterization of the new psychoactive substance methoxetamine. Neuropharmacology. 2017;123:1-9 pubmed publisher
    ..Rapid in vitro screening methods as those presented here, could be of utmost importance for gaining a first mechanistic insight to aid the risk assessment of emerging NPS. ..
  9. Heusinkveld H, Westerink R. Comparison of different in vitro cell models for the assessment of pesticide-induced dopaminergic neurotoxicity. Toxicol In Vitro. 2017;45:81-88 pubmed publisher
    ..This clearly indicates that care should be taken when interpreting (neuro)toxicity data as the chosen cell model may greatly influence the outcome. ..
  10. Hondebrink L, Zwartsen A, Westerink R. Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?. Pharmacol Ther. 2018;182:193-224 pubmed publisher
    ..These fingerprints can be implemented in the risk assessments of NPS that are necessary for eventual control measures to reduce Public Health risks. ..
  11. Westerink R, Beekwilder J, Wadman W. Differential alterations of synaptic plasticity in dentate gyrus and CA1 hippocampal area of Calbindin-D28K knockout mice. Brain Res. 2012;1450:1-10 pubmed publisher
    ..It is hypothesized that CB functions as a postsynaptic Ca(2+) buffer as well as a presynaptic Ca(2+) sensor. ..
  12. Kasteel E, Westerink R. Comparison of the acute inhibitory effects of Tetrodotoxin (TTX) in rat and human neuronal networks for risk assessment purposes. Toxicol Lett. 2017;270:12-16 pubmed publisher
    ..Consequently, we used experimental animal data to derive a human acute reference dose of 1.33?g/kg body weight, which corresponds to maximum concentration of TTX in shellfish of 200?g/kg. ..