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Adult dose-dependent behavioral and cognitive disturbances after a single neonatal PFHxS dose
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
2013 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 303, 185-191 p.Article in journal (Refereed) Published
Abstract [en]

Perfluoroalkyl acids, including perfluorohexane sulfonate (PFHxS), are fluorinated organic compounds used as surfactants and water and stain repellents in carpets, paper, and textiles, with characteristics to bioaccumulate and biomagnify in the food chain. PFHxS is found in umbilical cord blood, human milk and child serum from all over the world. We have recently reported that neonatal exposure to certain perfluoroalkyl acids, PFOS and PFOA, can induce persistent aberrations in spontaneous behavior and also affect learning and memory functions in the adult animal. The present study indicates that a single exposure to PFHxS on postnatal day 10, during a vulnerable period of brain development can alter adult spontaneous behavior and cognitive function in both male and female mice, effects that are both dose-response related and long-lasting/irreversible. PFHxS affected the cholinergic system, manifested as altered nicotine-induced behavior in adult animals. This is also in agreement with earlier studies on neonatal exposure to PFOS and PFOA. The present findings show that PFHxS, a member of the perfluoroalkyl acid group, can act as a developmental neurotoxicant and affect the cholinergic system and cognitive function and the effects show similarities with effects earlier reported after neonatal exposure to other POPs, such as bisphenol A, PBDEs and PCBs.

Place, publisher, year, edition, pages
2013. Vol. 303, 185-191 p.
Keyword [en]
Perfluorohexane sulfonate (PFHxS), Neonatal, Developmental neurotoxicity, Behavior
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-199010DOI: 10.1016/j.tox.2012.12.013ISI: 000316522300020OAI: oai:DiVA.org:uu-199010DiVA: diva2:619244
Available from: 2013-05-02 Created: 2013-05-02 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Developmental neurotoxicity of persistent and non-persistent pollutants: Behavioral and neurochemical assessments of a perfluorinated compound, pesticides and interaction effects
Open this publication in new window or tab >>Developmental neurotoxicity of persistent and non-persistent pollutants: Behavioral and neurochemical assessments of a perfluorinated compound, pesticides and interaction effects
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The focus of this thesis was to investigate developmental neurotoxic effects of different persistent and non-persistent environmental pollutants, alone or in binary mixtures, when exposure occurs during a critical period of brain development, in mice. The compounds investigated included a perfluorinated compound, perfluorohexane sulphonate (PFHxS), and four different pesticides, endosulfan, cypermethrin, chlorpyrifos and carbaryl.

Both persistent and non-persistent pollutants are detected in the environment and in humans, which shows that exposure to these compounds is occurring in real life. Humans can therefore be exposed to various pollutants during their whole lifetime, starting from the gestational period to adulthood. Furthermore, exposure to environmental pollutants is rarely exclusive to a single compound, but rather occurs through combinations of various pollutants present in the environment. Exposure to environmental pollutants during human brain development have been suggested to be a possible cause for neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Previous studies have shown that chemicals can induce irreversible disorders in brain function when exposure to these chemicals occurs during a critical defined period of the brain development known as the brain growth spurt (BGS). The BGS is characterized by a rapid growth and development of the immature brain. In humans, and mice, this period also overlaps the lactation period indicating that newborns and toddlers can be exposed via mothers’ milk as well.

This thesis has shown that a single oral exposure to PFHxS, endosulfan, cypermethrin, chlorpyrifos or carbaryl can induce developmental neurotoxic effects in mice, when exposure occurs during a critical period of brain development. These effects are manifested as persistent altered adult spontaneous behavior in a novel home environment, modified habituation, altered susceptibility of the cholinergic system and changed levels of neuroproteins in the mouse brain. Furthermore, a single neonatal co-exposure to a binary mixture of carbaryl/chlorpyrifos or PFHxS/endosulfan can interact and exacerbate the adult behavioral effects. These effects were seen at dosages were the single compound did not elicit a response or induced a much weaker behavioral effect. This indicates that risk assessments conducted on single compounds might underestimate interaction effects of mixtures when co-exposed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1283
Keyword
Brain, Neonatal, Mixtures, Cholinergic system, Organochlorines, Pyrethroids, Organophosphates, Carbamates, Insecticides, PFCs, PFAAs, PFHxS, Endosulfan, Cypermethrin, Chlorpyrifos, Carbaryl
National Category
Natural Sciences
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-261742 (URN)978-91-554-9326-4 (ISBN)
Public defence
2015-10-23, Zootissalen, EBC, Villavägen 9, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2015-10-02 Created: 2015-09-03 Last updated: 2015-10-05

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Viberg, HenrikLee, IwaEriksson, Per

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