Publications & Documents

This adverse outcome pathway links inhibition of aromatase activity in teleost fish during gonadogenesis to increased differentiation to testis resulting in a male-biased sex ratio in the population, and ultimately, reduced population sustainability. Most gonochoristic fish species develop either as males or females and do not change sex throughout their life span. However, in species where sexual differentiation is controlled at least to some degree by environmental factors, there can be a window of development during gonadal differentiation that is sensitive to a variety of exogenous conditions. During this window, endocrine active chemicals, aromatase inhibitors in particular, have the potential to alter gonad development and sex differentiation. This AOP is referred to as AOP 346 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This adverse outcome pathway links androgen receptor agonism in teleost fish during gonadogenesis to male-biased sexual differentiation and consequently, reduced population growth rate. Sex determination in teleost fishes is highly plastic; it can be genetically or environmentally influenced. Species with environmentally-based sex determination in particular can be very sensitive to exogenous chemicals during the period of differentiation. Exogenous hormones are of ecological concern because they have the potential to alter gonad development and sex differentiation. This AOP is referred to as AOP 376 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

Stressors that exhibit immunosuppression might act by different mechanisms, i.e. alter the number of cells involved in the immune response, the ability of the cells to produce cytokines, chemokines, antibodies or growth factors, the composition of the subpopulations of cells present at the site of the response, or the function of the cells. This Adverse Outcome Pathway (AOP) describes how impairment of the signaling receptor IL-1R1 in T cells can lead to impaired T cell activation and antibody production, leading to increased susceptibility to infection. The AOP focuses on the blocking of binding of IL-1 to IL-1R1, leading to the Inhibition of Nuclear factor kappa B (NF-kB). This AOP is referred to as AOP 277 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

The present Adverse Outcome Pathway (AOP) describes the linkage between lung cancer initiated from the Deposition of Energy (DoE) into a cell by a prototypic stressor such as radon gas. The multiple ionization events from DoE can directly break DNA double strands and initiate the activation of repair machinery through non-homologous end joining, an efficient, but error-prone process. When double strand breaks occur in DNA regions that transcribe critical genes, mutations generated by faulty repair may alter the function of these genes or cause chromosomal aberrations. These events alter the functions of many gene products and affect cell growth, cycling, and apoptosis. Cell proliferation is then promoted by escaping the regulatory control and forming hyperplasia in lung epithelial cells, leading eventually to lung cancer. Although the weight of evidence for this AOP is strong, uncertainties remain on dose-effect relationships across KEs, particularly for DoE delivered at low doses and dose-rates.

The cardiovascular system is the first functional organ system to develop in the vertebrate embryo, reflecting its critical role during normal development and pregnancy. This Adverse Outcome Pathway focuses on the regulation and disruption of vasculogenesis-angiogenesis during embryonic development via disruption of the Vascular Endothelial Growth Factor (VEGF) signaling pathway. This pathway is a critical regulatory system for assembly of embryonic blood vessels. Genetic studies have shown that perturbing the VEGF signaling system can invoke varying degrees of adverse consequences, ranging from congenital angiodysplasia to fetal malformations and embryolethality. This AOP is referred to as AOP 43 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

Endocrine disrupting chemicals (EDCs) are contaminants of emerging environmental and health concern that have been detected in freshwater, wastewater and drinking water. They interfere with the endocrine system in humans and wildlife, and produce adverse effects such as developmental, reproductive, neurological and immune effects. Their presence in water raises concerns for the integrity of ecosystems and biodiversity. Addressing the challenges of EDCs in water is particularly complex due to their ability to trigger adverse effects at very low concentrations, their potency in mixtures with other chemicals, and the vast range of sources and entryways of this group of chemicals into the environment. This report presents new water quality monitoring methods, such as bioassays and non-targeted analysis, that are well equipped to capture the impacts of EDCs in water. These new methods supplement the traditional substance-by-substance chemical analysis of water quality. The report also outlines policy instruments to manage the chemicals’ lifecycle from source to end-of-pipe. It proposes tools and regulations that respond to the negative effects of endocrine disruption, even if the culprit chemical is still unknown. The analysis draws on case studies from OECD countries to provide practical examples and concrete policy actions.

Volume 10 of the Series contains the consensus document on the 'Environmental Considerations for Risk/Safety Assessment for the Release of Transgenic Plants' developed by the OECD Working Party on the Harmonisation of Regulatory Oversight in Biotechnology. Transgenic plant varieties are subject to official risk/safety assessment, science-based and case-by-case, before their potential release into the environment. The document contains general information on environmental risk/safety assessment, its key concepts, structure and planning. Annexes describe seven examples of environmental considerations routinely examined by assessors and taken from experience gained during such assessment: Invasiveness and weediness; Vertical gene flow; Organisms (animals); Soil functions; Plant health; Crop management practices; and Biodiversity (protected species and habitats/ecosystems). The purpose of this document is not to elaborate new terminology or to describe how to undertake an actual risk/safety assessment, but rather to outline an approach and provide illustrative examples for helping assessors in planning and structuring an environmental risk/safety assessment. This document should be of interest to regulators and safety assessors, as well as to plant breeders and the wider scientific community. More information, including other tools for environmental risk/safety assessment such as OECD consensus documents on the biology of crop species, are found at BioTrack Online.

This Adverse Outcome Pathway (AOP) describes the linkage between oxidative DNA damage and irreversible genomic damage (chromosomal aberrations and mutations). DNA damage is considered an important contributor to the adverse health effects of many environmental toxicants and this AOP may thus be of widespread use to the regulatory community. Although increase in oxidative DNA damage is the molecular initiating event for this AOP, there are numerous upstream key events that can also lead to DNA oxidation. Thus, this AOP may be expanded upstream, and could be incorporated into a variety of AOP networks. Furthermore, the AOP points to critical research gaps required to establish the quantitative associations and modulating factors that connect KEs across the AOP, and highlights the utility of novel test methods in understanding and evaluating the implications of oxidative DNA damage. This AOP is referred to as AOP 296 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This method provides information on health hazard likely to arise from exposure to test substance (liquids, solids and aerosols) by application on the eye. This Test Guideline is intended preferably for use with albino rabbit. The test substance is applied in a single dose in the conjunctival sac of one eye of each animal. The other eye, which remains untreated, serves as a control. The initial test uses an animal; the dose level depends on the test substance nature. A confirmatory test should be made if a corrosive effect is not observed in the initial test, the irritant or negative response should be confirmed using up to two additional animals. It is recommended that it be conducted in a sequential manner in one animal at a time, rather than exposing the two additional animals simultaneously. The duration of the observation period should be sufficient to evaluate fully the magnitude and reversibility of the effects observed. The eyes should be examined at 1, 24, 48, and 72 hours after test substance application. The ocular irritation scores should be evaluated in conjunction with the nature and severity of lesions, and their reversibility or lack of reversibility. Use of topical anesthetics and systemic analgesics to avoid or minimize pain and distress in ocular safety testing procedures is described.