Peripherally administered persistent organic pollutants distribute to the brain of developing chicken embryo in concentrations relevant for human exposure

Ajay Yadav; Steven Verhaegen; Mussie Ghezu Hadera; Hanne Friis Berntsen; Vidar Berg; Jan Ludvig Lyche; Azemira Sabaredzovic; Line Småstuen Haug; Oddvar Myhre; Karin Elisabeth Zimmer; Ragnhild Elisabeth Paulsen; Erik Ropstad; Fernando Boix

doi:10.1016/j.neuro.2021.10.013

Peripherally administered persistent organic pollutants distribute to the brain of developing chicken embryo in concentrations relevant for human exposure

Neurotoxicology. 2022 Jan:88:79-87. doi: 10.1016/j.neuro.2021.10.013. Epub 2021 Oct 29.

Affiliations

¹ Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, NO-0316, Oslo, Norway. Electronic address: ajay.yadav@nmbu.no.
² Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: steven.verhaegen@nmbu.no.
³ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, NO-0316, Oslo, Norway. Electronic address: mughezu@gmail.com.
⁴ Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway; National Institute of Occupational Health, P.O. Box 5330 Majorstuen, NO-0304, Oslo, Norway. Electronic address: Hanne.Berntsen@stami.no.
⁵ Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: vidar.berg@nmbu.no.
⁶ Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: jan.l.lyche@nmbu.no.
⁷ Department of Environmental Health, Norwegian Institute of Public Health, PO Box 222 Skøyen, N-0213, Oslo, Norway. Electronic address: Azemira.Sabaredzovic@fhi.no.
⁸ Department of Environmental Health, Norwegian Institute of Public Health, PO Box 222 Skøyen, N-0213, Oslo, Norway. Electronic address: LineSmastuen.Haug@fhi.no.
⁹ Department of Environmental Health, Norwegian Institute of Public Health, PO Box 222 Skøyen, N-0213, Oslo, Norway. Electronic address: oddvar.Myhre@fhi.no.
¹⁰ Department of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: karin.zimmer@nmbu.no.
¹¹ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, NO-0316, Oslo, Norway. Electronic address: r.e.paulsen@farmasi.uio.no.
¹² Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: erik.ropstad@nmbu.no.
¹³ Section for Drug Abuse Research, Dept. of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, PO Box 4404, Nydalen, 0403, Oslo, Norway. Electronic address: fernando.boix@ous-hf.no.

PMID: 34757084
DOI: 10.1016/j.neuro.2021.10.013

Abstract

Persistent organic pollutants (POPs) can reach the fetal brain and contribute to developmental neurotoxicity. To explore the distribution of POPs to the fetal brain, we exposed chicken embryos to a POP mixture, containing 29 different compounds with concentrations based on blood levels measured in the Scandinavian human population. The mixture was injected into the allantois at embryonic day 13 (E13), aiming at a theoretical concentration of 10 times human blood levels. POPs concentrations in the brain were measured at 0.5, 1, 2, 4, 6, 24, 48, and 72 h after administration. Twenty-seven of the individual compounds were detected during at least one of the time-points analyzed. Generally, the concentrations of most of the measured compounds were within the order of magnitude of those reported in human brain samples. Differences in the speed of distribution to the brain were observed between the per- and polyfluoroalkyl substances (PFASs), which have protein binding potential, and the lipophilic polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and brominated flame retardants (BFRs). Based on pharmacokinetic modeling, PFASs were best described by a one compartment model. PFASs displayed relatively slow elimination (Kel) and persisted at high levels in the brain. Lipophilic OCPs and PCBs could be fitted to a 2-compartment model. These showed high levels in the brain relative to the dose administrated as calculated by area under the curve (AUC)/Dose. Altogether, our study showed that chicken is a suitable model to explore the distribution of POPs into the developing brain at concentrations which are relevant for humans.

Keywords: Allantois; Brain concentration; Chicken embryo; POP mixture; Pharmacokinetic model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / drug effects*
Brain / embryology
Brain / growth & development
Chick Embryo
Dose-Response Relationship, Drug
Embryonic Development / drug effects
Persistent Organic Pollutants / adverse effects*