Developmental neurotoxicity evaluation of acrylamide based on in vitro to in vivo extrapolation by pregnancy PBTK modelling DOI Creative Commons
Ylva Johansson,

Roseline Awoga,

Anna Forsby

и другие.

Toxicology, Год журнала: 2024, Номер unknown, С. 153950 - 153950

Опубликована: Сен. 1, 2024

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

Язык: Английский

Developmental neurotoxicity evaluation of acrylamide based on in vitro to in vivo extrapolation by pregnancy PBTK modelling DOI Creative Commons
Ylva Johansson,

Roseline Awoga,

Anna Forsby

и другие.

Toxicology, Год журнала: 2024, Номер unknown, С. 153950 - 153950

Опубликована: Сен. 1, 2024

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

Язык: Английский

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