Developmental neurotoxicity of propylthiouracil in rats

Marta Axelstad Petersen, Pernille Reimer Hansen, Sofie Christiansen, Christine Lydia Nellemann, Karin Sørig Hougaard, S.P. Lund, Ulla Hass

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Abstract

It has been known for a long time that markedly lowered thyroid hormone levels during development can have severe consequences for the intellectual, behavioural and auditory development of the child. However, recent studies indicate that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups.

The overall aim was to provide detailed knowledge on the relationship between effects on thyroid hormone levels and long-lasting developmental neurotoxicity effects. Groups of 16–18 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/(kg day)) from gestation day 7 to postnatal day (PND) 16 and the development and behaviour of the offspring was assessed. Measurements of thyroid hormone levels during the dosing period showed that both dams and pups in the higher dose groups had markedly lowered T4 levels, but these levels normalized shortly after dosing had stopped. The tested endpoints all showed statistically significant changes in the high dose group. Pup motor activity levels were lowered on PND 14, while they were elevated on PND 23 and in adulthood, and auditory function in adult animals was impaired.

Generally the results showed that PTU exposure and the resulting hypothyroxinemia influenced behaviour and hearing function. This supports that exposure to TDC's in general may cause long-lasting developmental neurotoxicity.
Original languageEnglish
JournalToxicology Letters
Volume172
Issue numberSuppl. 1
Pages (from-to)S177-S177
ISSN0378-4274
DOIs
Publication statusPublished - 7 Oct 2007
Event44th Congress of the European Societies of Toxicology - Amsterdam, Netherlands
Duration: 7 Oct 200710 Oct 2007
Conference number: 44
http://www.eurotox2007.org/

Conference

Conference44th Congress of the European Societies of Toxicology
Number44
CountryNetherlands
CityAmsterdam
Period07/10/200710/10/2007
Internet address

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