Transcriptomic Point of Departure (tPOD) of androstenedione in zebrafish embryos as a potential surrogate for chronic endpoints.

Autor: Essfeld F; Department Ecotoxicogenomics, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany., Ayobahan SU; Department Ecotoxicogenomics, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany., Strompen J; Department Ecotoxicogenomics, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany., Alvincz J; Department Ecotoxicogenomics, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany., Schmidt-Posthaus H; Institute for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, 3012 Bern, Switzerland., Woelz J; Bayer AG Pharmaceuticals, Muellerstr. 170-178, 13353 Berlin, Germany., Mueller T; Bayer AG, REACH Management, Kaiser-Wilhelm-Allee 10, 51373 Leverkusen, Germany., Ringbeck B; Department Trace Analysis and Environmental Monitoring, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany., Teigeler M; Department Ecotoxicology, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany., Eilebrecht E; Department Ecotoxicology, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany., Eilebrecht S; Department Ecotoxicogenomics, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany. Electronic address: sebastian.eilebrecht@ime.fraunhofer.de.
Jazyk: angličtina
Zdroj: The Science of the total environment [Sci Total Environ] 2024 Nov 25; Vol. 953, pp. 176026. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1016/j.scitotenv.2024.176026
Abstrakt: The transcriptomic Point of Departure (tPOD) is increasingly used in ecotoxicology to derive quantitative endpoints from RNA sequencing studies. Utilizing transcriptomic data in zebrafish embryos as a New Approach Methodology (NAM) is beneficial due to its acknowledgment as an alternative to animal testing under EU Directive 2010/63/EU. Transcriptomic profiles are available in zebrafish for various modes of action (MoA). The limited literature available suggest that tPOD values from Fish Embryo Toxicity (FET) tests align with, but are generally lower than, No Observed Effect Concentrations (NOEC) from long-term chronic fish toxicity tests. In studies with the androgenic hormone androstenedione in a Fish Sexual Development Test (FSDT), a significant shift in the sex ratio towards males was noted at all test concentrations, making it impossible to determine a NOEC (NOEC <4.34 μg/L). To avoid additional animal testing in a repetition of the FSDT and adhere to the 3Rs principle (replacement, reduction, and refinement), a modified zebrafish FET (zFET) was conducted aiming to determine a regulatory acceptable effect threshold. This involved lower concentration ranges (20 to 6105 ng/L), overlapping with the masculinization-observed concentrations in the FSDT. The tPOD analysis in zFET showed consistent results with previous FSDT findings, observing strong expression changes in androgen-dependent genes at higher concentrations but not at lower ones, demonstrating a concentration-response relationship. The tPOD values for androstenedione were determined as 24 ng/L (10th percentile), 60 ng/L (20th gene), and 69 ng/L (1st peak). The 10th percentile tPOD value in zFET was 200 times lower than the lowest concentration in the FSDT. Comparing the tPOD values to literature suggests their potential to inform on the NOEC range in FSDT tests.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The study was financed by Bayer AG. The study was conducted and analyzed under the quality assurance system good laboratory practice (FSDT) or according to good scientific practice (tPOD) at Fraunhofer IME. Bayer AG had no influence on the conduction or evaluation of the study.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: