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. The main endpoint of the test is reproduction, reflected by the embryo number in the brood pouch per female. The development of a new OECD test guideline involves several phases including inter-laboratory validation studies to demonstrate the robustness of the proposed test design and the reproducibility of the test results. Therefore, a ring test of the reproduction test with P. antipodarum was conducted including eight laboratories with the test substances trenbolone and prochloraz and results are presented here. Most laboratories could meet test validity criteria, thus demonstrating the robustness of the proposed test protocol. Trenbolone did not have an effect on the reproduction of the snails at the tested concentration range (nominal: 10-1000 ng/L). For prochloraz, laboratories produced similar EC10 and NOEC values, showing the inter-laboratory reproducibility of results. The average EC10 and NOEC values for reproduction (with coefficient of variation) were 26.2 µg/L (61.7%) and 29.7 µg/L (32.9%), respectively. This ring test shows that the mudsnail reproduction test is a well-suited tool for use in the chronic aquatic hazard and risk assessment of chemicals

The effect of gaze camouflage and social anxiety on social attention in naturalistic situations

This study investigated how trait social anxiety and gaze camouflage influence gaze behavior, place preference, and autonomic responses (heart rate and skin conductance) using a naturalistic field-like experimental design

Electrocortical responses in anticipation of avoidable and inevitable threats: a multisite study

When faced with danger, human beings respond with a repertoire of defensive behaviors, including freezing and active avoidance. Previous research has revealed a pattern of physiological responses, characterized by heart rate bradycardia, reduced visual exploration, and heightened sympathetic arousal in reaction to avoidable threats, suggesting a state of attentive immobility in humans. However, the electrocortical underpinnings of these behaviors remain largely unexplored. To investigate the visuocortical components of attentive immobility, we recorded occipital alpha activity, along with eye-movements and autonomic responses, while participants awaited either an avoidable, inevitable, or no threat. To test the robustness and generalizability of our findings, we collected data from a total of 101 participants at two laboratories. Across sites, we observed an enhanced suppression of occipital alpha activity during avoidable threats, in contrast to inevitable or no threat trials, particularly towards the end of the trial that prompted avoidance responses. This response pattern coincided with heart rate bradycardia, centralization of gaze and increased sympathetic arousal. Furthermore, our findings expand on previous research by revealing that the amount of alpha suppression, along with centralization of gaze, and heart rate changes, predict the speed of motor response times. Collectively, these findings indicate that when individuals encounter avoidable threats, they enter a state of attentive immobility, which enhances perceptual processing and facilitates action preparation. This state appears to reflect freezing-like behavior in humans

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

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

In order to be defined as endocrine disruptor, a substance has to meet several criteria, including the induction of specific adverse effects, specific endocrine mode-of-action and a plausible link between both. Especially the latter criterion might not always be unequivocally determined, particularly as the endocrine system consists of diverse endocrine axes. The axes closely interact with each other, and manipulation of one triggers effects on the other. This review aimed at identifying some of the many interconnections between these axes. This study focusses on fish, but also considers data obtained in studies on amphibians and mammals if these assist in closing data gaps, as most of the endocrine mechanisms are evolutionary conserved. The review comprises data of ecotoxicological studies, as well as data on physiological processes. The gathered information delivers data on hormone/hormone receptor interactions or gene transcription regulation. The identified key events (KE) and KE relationships (KER) provide explanations for unexpected effects on one axis, exerted by substances suspected to act specifically on another axis. Based on these data, several adverse outcome pathway (AOP) segments were identified, describing connections between the HPG- and HPT-axes, the HPG- and HPA/I-axes, and the HPT- and HPA/I-axes. Central KEs identified across axes were altered aromatase activity, and altered expression and function of the proteins 11beta-hydroxysteroid dehydrogenase (11beta-HSD) and steroidogenic acute regulatory (StAR) protein. Substance classes, which act on more than one endocrine axis were for example goitrogens or aromatase inhibitors. Despite the wealth of gathered information, it only provides a small insight into the molecular nets of endocrine axes, demonstrating the complexity of the interconnections between endocrine axes

Bewertung des endokrinen Potenzials von Bisphenol Alternativstoffen in umweltrelevanten Verwendungen. Abschlussbericht

Bisphenol A (BPA) is mainly used as raw material in the production of plastic products. Due to its hormone-like effects in humans and other organisms, the use of BPA is closely connected to human health and environmental risks. Thus, there is high interest in substances with similar properties to BPA regarding its use in plastic products, however do not negatively influence the endocrine system of any organism. There are substantial data gaps regarding the molecular mode of action of many substitution candidates, which impede the assessment of their influence on the environment. A literature research was performed in order to identify environmentally relevant BPA substitution candidates. Furthermore, the interaction of these substances with a set of nuclear receptors was investigated, which might be responsible for the endocrine effects of BPA. The application of a number of biochemical and cell-based screening assays, the influence of these substances on the estrogen receptors α and β, as well as of the androgen receptor was determined

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. In this study, we intended to investigate the endocrine potential of BPA substitution candidates used in environmentally relevant applications such as thermal paper or epoxy resins. Based on an extensive literature and patent search, 33 environmentally relevant BPA substitution candidates were identified. In order to evaluate the endocrine potential of the BPA replacements, a screening cascade consisting of biochemical and cell-based assays was employed to investigate substance binding to the NRs estrogen receptor α and β, as well as androgen receptor, co-activator recruitment and NR-mediated reporter gene activation. In addition, a computational docking approach for retrospective prediction of receptor binding was carried out. Our results show that some BPA substitution candidates, for which so far no or only very few data were available, possess a substantial endocrine disrupting potential (TDP, BPZ), while several substances (BPS, D-8, DD70, DMP-OH, TBSA, D4, CBDO, ISO, VITC, DPA, and DOPO) did not reveal any NR binding