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Developmental neurotoxicity evaluation of acrylamide based on in vitro to in vivo extrapolation by pregnancy PBTK modelling
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. (Anna Forsby)ORCID iD: 0000-0002-4886-9042
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. (Anna Forsby)ORCID iD: 0000-0001-9296-4007
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.ORCID iD: 0000-0001-6298-201x
(English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185Article in journal (Other academic) Submitted
Abstract [en]

Acrylamide (ACR) is a known neurotoxicant that can pass the placenta and has been detected in breast milk. Some in vivo and in vitro studies indicate that ACR exposure might lead to developmental neurotoxicity (DNT). Here, we have developed a physiologically-based toxicokinetic model for a pregnant human population using PK-Sim. We performed an in vitro to in vivo extrapolation (IVIVE) of data collected from human neuroblastoma SH-SY5Y cells exposed during differentiation to ACR. The developed PBTK model was successfully evaluated and predicted fetal plasma concentrations in the low nM range after exposing the model to an estimated average daily intake for pregnant women. The IVIVE showed that low concentrations of ACR (fM-nM) that induced attenuated differentiation of the SH-SY5Y neuronal cell model, were relevant for human exposure to ACR from oral intake. However, doses estimated in the IVIVE from concentrations in the µM range, were found to be unrealistic by exposure through food intake for an average daily intake. However, in case of exposure due to environmental pollution or occupational exposure, these concentrations may be reached in fetal plasma. The findings in this study raise the concern regarding ACR exposure during pregnancy as well as the relevance of testing concentrations in vitro that are several orders of magnitude higher than the predicted fetal plasma concentrations.

Keywords [en]
Acrylamide, developmental neurotoxicity, physiologically based toxicokinetic modelling, in vitro to in vivo extrapolation
National Category
Pharmacology and Toxicology
Research subject
Neurochemistry and Neurotoxicology
Identifiers
URN: urn:nbn:se:su:diva-233136OAI: oai:DiVA.org:su-233136DiVA, id: diva2:1894205
Available from: 2024-09-02 Created: 2024-09-02 Last updated: 2024-09-03

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Johansson, YlvaForsby, Anna

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