Detailed Review Paper on the State of the Science on Novel In Vitro and In Vivo Screening and Testing Methods and Endpoints for Evaluating Endocrine Disruptors

Abstract

The Organisation for Economic Co-operation and Development (OECD) is an intergovernmental organisation in which representatives of 34 industrialised countries in North and South America, Europe and the Asia and Pacific region, as well as the European Commission, meet to co-ordinate and harmonise policies, discuss issues of mutual concern, and work together to respond to international problems. Most of the OECD's work is carried out by more than 200 specialised committees and working groups composed of member country delegates. Observers from several countries with special status at the OECD, and from interested international organisations, attend many of the OECD's workshops and other meetings. Committees and working groups are served by the OECD Secretariat, located in Paris, France, which is organised into directorates and divisions. The Environment, Health and Safety Division publishes free-of-charge documents in ten different series: Testing and Assessment; Good Laboratory Practice and Compliance Monitoring; Pesticides and Biocides; Risk Management; Harmonisation of Regulatory Oversight in Biotechnology; Safety of Novel Foods and Feeds; Chemical Accidents; Pollutant Release and Transfer Registers; Emission Scenario Documents; and Safety of Manufactured Nanomaterials. More information about the Environment, Health and Safety Programme and EHS publications is available on the OECD's World Wide Web site (www.oecd.org/ehs/). This publication was developed in the IOMC context. The contents do not necessarily reflect the views or stated policies of individual IOMC Participating Organisations.The Inter-Organisation Programme for the Sound Management of Chemicals (IOMC) was established in 1995 following recommendations made by the 1992 UN Conference on Environment and Development to strengthen co-operation and increase international co-ordination in the field of chemical safety. The Participating Organisations are FAO, ILO, UNEP, UNIDO, UNITAR, WHO, World Bank and OECD. UNDP is an observer. The purpose of the IOMC is to promote co-ordination of the policies and activities pursued by the Participating Organisations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment.

Endocrine disruption in teleosts and amphibians is mediated by anthropogenic and natural environmental factors: implications for risk assessment

“…B 379: 20220505 Authority) developed a guidance document [24] explaining how to assess EATS modalities for regulatory purposes. From an endocrinological point of view, it is obvious that EDs in vertebrates are not restricted only to EATS; they also impact reproduction, metamorphosis and development, but might affect further endocrine systems as well [24][25][26] by non-EATS modalities. In addition, the OECD compiled the recent knowledge about endocrine disruption in freshwater [27], providing hints for a conceptual framework to address this issue for regulatory purposes.…”

“…However, further endocrine pathways are present and resemble potential targets for ED. The potential for non-EATS modalities to also become a subject for ED research was mentioned quite early on [20,25], and has recently been reviewed [26], there including endocrine pathways such as retinoic acid, peroxisome proliferator-activated receptors (PPARs), insulin receptor signalling, gastrointestinal hormones and cardiovascular-related hormones. It is suggested that even further endocrine systems are impacted by as-yet only partly identified ED [20,22,25] that work on stress axes regulating catecholamines or gluco-and mineralo-corticosteroids, (anti)gestagenic MOA and growth axis, acting via growth hormone and insulin-like growth factors.…”

Contribution of the Endocrine Perspective in the Evaluation of Endocrine Disrupting Chemical Effects: The Case Study of Pubertal Timing

“…As already mentioned, the non-sensitive endpoints (in rodents) recommended by the US EPA and OECD are primarily body and organ weight (pituitary gland, uterus, prostate, etc.). The OECD recently proposed amended guidelines [51]. Regarding tissue level responses to (anti)estrogenic EDCs, the proposal is microarray analysis using estrogen-responsive tissues derived from in vivo exposures (could be applied to any in vivo exposure assays) and/or microarray analysis using estrogen-responsive cultured cells.…”

“…Moreover, the response could be heterogeneous in a given tissue, meaning that a response in a specific cell type might be missed. Regarding organ-level and whole-organism responses, the OECD's proposal is to analyze GnRH neuron development in the brains of chronically exposed fish (fish life cycle toxicity test) with emphasis on the extension of the critical window of exposure to prenatal life using such a testing procedure [51]. This has the merit of studying a neuroendocrine endpoint and involves prenatal exposure.…”

AOP Key Event Relationship report: Linking decreased retinoic acid levels with disrupted meiosis in developing oocytes

“…Because atRA synthesis is a known target for certain environmental chemicals, for instance the thiocarbamate herbicides pebulate, vernolate, butylate and tri-allate ( Quistad et al, 1994 ), cyanamide ( Nagasawa et al, 1990 , Shirota et al, 1987 ) and the isoflavone daidzin ( Lowe et al, 2008 ), the retinoid signaling pathway should be considered in chemical safety assessment and regulation. Indeed, this notion was proposed by the OECD almost a decade ago in a Detailed Review Paper ( OECD, 2012 ). A recently published ‘Detailed Review Paper on the Retinoid Signaling Pathway’ (supported by the European Commission and OECD) included an annex focusing on both male and female reproduction ( OECD, 2021 ).…”