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

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).

Effects of the Gestagen Levonorgestrel in a Life Cycle Test with Zebrafish (Danio rerio).

The amount of pharmaceuticals transferred to the aquatic environment via municipal and hospital waste water is steadily increasing. The progress in medical research has resulted in the manufacture of active substances of increased stability, specificity, and potency, which can trigger adverse effects in aquatic organisms. Moreover, advanced analytical methods allow the detection of pharmaceuticals in environmental matrices at very low concentrations, which increases the number of substances to be assessed.

A tiered high-throughput screening approach for evaluation of estrogen and androgen receptor modulation by environmentally relevant bisphenol A substitutes.

Bisphenol A (BPA) is a high production volume chemical with a broad application spectrum. As an endocrine disrupting chemical, mainly by modulation of nuclear receptors (NRs), BPA has an adverse impact on organisms and is identified as a substance of very high concern under the European REACH regulation. Various BPA substitution candidates have been developed in recent years, however, information concerning the endocrine disrupting potential of these substances is still incomplete or missing.

A combined FSTRA-shotgun proteomics approach to identify molecular changes in zebrafish upon chemical exposure.

The fish short-term reproduction assay (FSTRA) is a common in vivo screening assay for assessing endocrine effects of chemicals on reproduction in fish. However, the current reliance on measures such as egg number, plasma vitellogenin concentration and morphological changes to determine endocrine effects can lead to false labelling of chemicals with non-endocrine modes- of-action. Here, we integrated quantitative liver and gonad shotgun proteomics into the FSTRA in order to investigate the causal link between an endocrine mode-of-action and adverse effects assigned to the endocrine axis.

Fast Multiplex real time PCR method for sex-identification of medaka () by non-invasive sampling.

Medaka fish () has been widely used in fish screening and multi-generation tests to provide relevant data to assess impacts of endocrine disrupting chemicals (EDCs) in fish populations. The genotypic differentiation of Medaka sex allows diagnosing the sex reversal, and is required in current test guidelines (e.g.

Knotting nets: Molecular junctions of interconnecting endocrine axes identified by application of the adverse outcome pathway concept.

To be defined as an endocrine disruptor, a substance has to meet several criteria, including the induction of specific adverse effects, a specific endocrine mode of action, and a plausible link between both. The latter criterion in particular might not always be unequivocally determined, especially because the endocrine system consists of diverse endocrine axes. The axes closely interact with each other, and manipulation of one triggers effects on the other.

Validation of the OECD reproduction test guideline with the New Zealand mudsnail Potamopyrgus antipodarum using trenbolone and prochloraz.

The Organisation for Economic Cooperation and Development (OECD) provides several standard test methods for the environmental hazard assessment of chemicals, mainly based on primary producers, arthropods, and fish. In April 2016, two new test guidelines with two mollusc species representing different reproductive strategies were approved by OECD member countries. One test guideline describes a 28-day reproduction test with the parthenogenetic New Zealand mudsnail Potamopyrgus antipodarum.

Optimizing the design of a reproduction toxicity test with the pond snail Lymnaea stagnalis.

This paper presents the results from two ring-tests addressing the feasibility, robustness and reproducibility of a reproduction toxicity test with the freshwater gastropod Lymnaea stagnalis (RENILYS strain). Sixteen laboratories (from inexperienced to expert laboratories in mollusc testing) from nine countries participated in these ring-tests. Survival and reproduction were evaluated in L.

Linking the response of endocrine regulated genes to adverse effects on sex differentiation improves comprehension of aromatase inhibition in a Fish Sexual Development Test.

The Fish Sexual Development Test (FSDT) is a non-reproductive test to assess adverse effects of endocrine disrupting chemicals. With the present study it was intended to evaluate whether gene expression endpoints would serve as predictive markers of endocrine disruption in a FSDT. For proof-of-concept, a FSDT according to the OECD TG 234 was conducted with the non-steroidal aromatase inhibitor fadrozole (test concentrations: 10μg/L, 32μg/L, 100μg/L) using zebrafish (Danio rerio).

Environmental effect assessment for sexual endocrine-disrupting chemicals: Fish testing strategy.

Current standard testing and assessment tools are not designed to identify specific and biologically highly sensitive modes of action of chemicals, such as endocrine disruption. This information, however, can be important to define the relevant endpoints for an assessment and to characterize thresholds of their sublethal, population-relevant effects. Starting a decade ago, compound-specific risk assessment procedures were amended by specifically addressing endocrine-disrupting properties of substances.

Background pathology of the ovary in a laboratory population of zebrafish Danio rerio.

Adult zebrafish Danio rerio originating from one stock used as control animals in a toxicological study were examined histopathologically for the occurrence of spontaneous lesions in the gonads. While no histopathological changes were seen in the testes, the ovaries showed lesions consisting mainly of acute granulomatous inflammation with increased atresia and the presence of egg debris in the ovarian parenchyma and in the oviduct. Since infectious agents could not be detected and the fish were not exposed to toxicants, we consider these lesions as spontaneous alterations of the ovaries.