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Physiology-informed...
Physiology-informed toxicokinetic model for the zebrafish embryo test developed for bisphenols
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- Chelcea, Ioana C., 1994- (author)
- Umeå universitet,Kemiska institutionen
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- Vogs, Carolina (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Karolinska Institutet,Institutionen för biomedicin och veterinär folkhälsovetenskap (BVF),Department of Biomedical Science and Veterinary Public Health,Karolinska Institute
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- Hamers, Timo (author)
- Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, HV Amsterdam, Netherlands
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- Koekkoek, Jacco (author)
- Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, HV Amsterdam, Netherlands
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- Legradi, Jessica (author)
- Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, HV Amsterdam, Netherlands
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- Sapounidou, Maria (author)
- Umeå universitet,Kemiska institutionen
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- Örn, Stefan (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för biomedicin och veterinär folkhälsovetenskap (BVF),Department of Biomedical Science and Veterinary Public Health
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- Andersson, Patrik L. (author)
- Umeå universitet,Kemiska institutionen
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(creator_code:org_t)
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- Elsevier, 2023
- 2023
- English.
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In: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 345
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Abstract
Subject headings
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- Zebrafish embryos (ZFE) is a widely used model organism, employed in various research fields including toxicology to assess e.g., developmental toxicity and endocrine disruption. Variation in effects between chemicals are difficult to compare using nominal dose as toxicokinetic properties may vary. Toxicokinetic (TK) modeling is a means to estimate internal exposure concentration or dose at target and to enable extrapolation between experimental conditions and species, thereby improving hazard assessment of potential pollutants. In this study we advance currently existing TK models for ZFE with physiological ZFE parameters and novel experimental bisphenol data, a class of chemicals with suspected endocrine activity. We developed a five-compartment model consisting of water, plastic, chorion, yolk sack and embryo in which surface area and volume changes as well as the processes of biotransformation and blood circulation influence mass fluxes. For model training and validation, we measured internal concentrations in ZFE exposed individually to BPA, bisphenol AF (BPAF) and Z (BPZ). Bayesian inference was applied for parameter calibration based on the training data set of BPZ. The calibrated TK model predicted internal ZFE concentrations of the majority of external test data within a 5-fold error and half of the data within a 2-fold error for bisphenols A, AF, F, and tetrabromo bisphenol A (TBBPA). We used the developed model to rank the hazard of seven bisphenols based on predicted internal concentrations and measured in vitro estrogenicity. This ranking indicated a higher hazard for BPAF, BPZ, bisphenol B and C (BPB, BPC) than for BPA.
Subject headings
- NATURVETENSKAP -- Geovetenskap och miljövetenskap -- Miljövetenskap (hsv//swe)
- NATURAL SCIENCES -- Earth and Related Environmental Sciences -- Environmental Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Medicinsk biovetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Medical Bioscience (hsv//eng)
Keyword
- Bisphenols
- Embryo
- Endocrine disruptors
- PBTK
- Zebrafish
Publication and Content Type
- ref (subject category)
- art (subject category)
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