TY  - GEN
AU  - Rinderknecht, Maximilian
AU  - Koegst, Johannes
AU  - Ehrlich, Tomke
AU  - Gölz, Lisa
AU  - Raskovic, Bozidar
AU  - Braunbeck, Thomas
AU  - Baumann, Lisa Annie
PY  - 2022
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/6934
AB  - Currently, both for human health and environmental safety evaluation, endocrine disruptor (ED) testing requires multiple studies across different species. The EU H2020 project “ERGO” is focused on the optimisation of existing test guidelines (TGs) relevant to endocrine activity and adversity for human and environmental health. New TGs would be beneficial to the 3R (replace, reduce, refine) principles and would also reduce time and costs for ED testing. The Hypothalamus-Pituitary-Thyroid axis (HPT) is highly conserved and plays important roles in both early development and homeostasis across vertebrate classes. Except for thyroid hormone system disruption (THSD), zebrafish (Danio rerio) is already commonly used as a model species in ED assessment. In order to expand existing TGs to allow for a comprehensive assessment using a single species only, new thyroid-related endpoints have to be evaluated in different developmental stages. Given that eye development is directly regulated by thyroid hormones (THs), possible endpoints include eye malformations. For this purpose, a fish early life-stage toxicity test (FELS, OECD TG 210) with iopanoic acid (IOP) and potassium perchlorate (PCL) was conducted. These substances were selected for their known effects on the HPT axis with different modes of action. In addition to the 34-d exposure phase, a recovery phase of 30 d was added to
determine the potential to recover from adverse effects on eye development. We assessed the eye-to-body-ratio, the thickness of the inner plexiform layer (IPL), the retinal pigment epithelium (RPE) and the photoreceptor layer (PL) as well as the ratio of the outer segment (OS of the PRL to the total PRL thickness). These endpoints have previously been shown to be sensitive to
disruption of the HPT in zebrafish embryos. Results show that eye malformations also manifest in later life-stages but tend to be reversible after recovery in clean water. Significant differences were observed for the RPE and the IPL at both time points with the OS/PRL ratio showing significant effects at 64 d. These results support the inclusion of the eye development, especially the thickness of the RPE, as a thyroid-sensitive endpoint into TG 210, thus allowing for a comprehensive assessment of ED effects in a single species. This would help reduce the number of amphibian studies required. TH level measurements are ongoing and will provide mechanistic data for our understanding of effects observed at apical level.
PB  - Society of Environmental Toxicology and Chemistry Europe
T2  - SETAC Europe 32nd Annual Meeting “Towards a reduced pollution society”
T1  - Implementation of Thyroid-Sensitive Endpoints Into the Fish Early Life-Stage Test (FELS, OECD TG 210) With Zebrafish (Danio rerio) - Part 2: Eye Development and Thyroid Hormones
EP  - 61
SP  - 61
UR  - https://hdl.handle.net/21.15107/rcub_agrospace_6934
ER  - 

@misc{
author = "Rinderknecht, Maximilian and Koegst, Johannes and Ehrlich, Tomke and Gölz, Lisa and Raskovic, Bozidar and Braunbeck, Thomas and Baumann, Lisa Annie",
year = "2022",
abstract = "Currently, both for human health and environmental safety evaluation, endocrine disruptor (ED) testing requires multiple studies across different species. The EU H2020 project “ERGO” is focused on the optimisation of existing test guidelines (TGs) relevant to endocrine activity and adversity for human and environmental health. New TGs would be beneficial to the 3R (replace, reduce, refine) principles and would also reduce time and costs for ED testing. The Hypothalamus-Pituitary-Thyroid axis (HPT) is highly conserved and plays important roles in both early development and homeostasis across vertebrate classes. Except for thyroid hormone system disruption (THSD), zebrafish (Danio rerio) is already commonly used as a model species in ED assessment. In order to expand existing TGs to allow for a comprehensive assessment using a single species only, new thyroid-related endpoints have to be evaluated in different developmental stages. Given that eye development is directly regulated by thyroid hormones (THs), possible endpoints include eye malformations. For this purpose, a fish early life-stage toxicity test (FELS, OECD TG 210) with iopanoic acid (IOP) and potassium perchlorate (PCL) was conducted. These substances were selected for their known effects on the HPT axis with different modes of action. In addition to the 34-d exposure phase, a recovery phase of 30 d was added to
determine the potential to recover from adverse effects on eye development. We assessed the eye-to-body-ratio, the thickness of the inner plexiform layer (IPL), the retinal pigment epithelium (RPE) and the photoreceptor layer (PL) as well as the ratio of the outer segment (OS of the PRL to the total PRL thickness). These endpoints have previously been shown to be sensitive to
disruption of the HPT in zebrafish embryos. Results show that eye malformations also manifest in later life-stages but tend to be reversible after recovery in clean water. Significant differences were observed for the RPE and the IPL at both time points with the OS/PRL ratio showing significant effects at 64 d. These results support the inclusion of the eye development, especially the thickness of the RPE, as a thyroid-sensitive endpoint into TG 210, thus allowing for a comprehensive assessment of ED effects in a single species. This would help reduce the number of amphibian studies required. TH level measurements are ongoing and will provide mechanistic data for our understanding of effects observed at apical level.",
publisher = "Society of Environmental Toxicology and Chemistry Europe",
journal = "SETAC Europe 32nd Annual Meeting “Towards a reduced pollution society”",
title = "Implementation of Thyroid-Sensitive Endpoints Into the Fish Early Life-Stage Test (FELS, OECD TG 210) With Zebrafish (Danio rerio) - Part 2: Eye Development and Thyroid Hormones",
pages = "61-61",
url = "https://hdl.handle.net/21.15107/rcub_agrospace_6934"
}

Rinderknecht, M., Koegst, J., Ehrlich, T., Gölz, L., Raskovic, B., Braunbeck, T.,& Baumann, L. A.. (2022). Implementation of Thyroid-Sensitive Endpoints Into the Fish Early Life-Stage Test (FELS, OECD TG 210) With Zebrafish (Danio rerio) - Part 2: Eye Development and Thyroid Hormones. in SETAC Europe 32nd Annual Meeting “Towards a reduced pollution society”
Society of Environmental Toxicology and Chemistry Europe., 61-61.
https://hdl.handle.net/21.15107/rcub_agrospace_6934

Rinderknecht M, Koegst J, Ehrlich T, Gölz L, Raskovic B, Braunbeck T, Baumann LA. Implementation of Thyroid-Sensitive Endpoints Into the Fish Early Life-Stage Test (FELS, OECD TG 210) With Zebrafish (Danio rerio) - Part 2: Eye Development and Thyroid Hormones. in SETAC Europe 32nd Annual Meeting “Towards a reduced pollution society”. 2022;:61-61.
https://hdl.handle.net/21.15107/rcub_agrospace_6934 .

Rinderknecht, Maximilian, Koegst, Johannes, Ehrlich, Tomke, Gölz, Lisa, Raskovic, Bozidar, Braunbeck, Thomas, Baumann, Lisa Annie, "Implementation of Thyroid-Sensitive Endpoints Into the Fish Early Life-Stage Test (FELS, OECD TG 210) With Zebrafish (Danio rerio) - Part 2: Eye Development and Thyroid Hormones" in SETAC Europe 32nd Annual Meeting “Towards a reduced pollution society” (2022):61-61,
https://hdl.handle.net/21.15107/rcub_agrospace_6934 .