Interference with endogenous developmental processes that are regulated by the aryl hydrocarbon receptor (AHR), through sustained exogenous activation, causes molecular, structural, and functional cardiac abnormalities in avian, mammalian and piscine...

Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The...

The thyroid hormones (TH) are essential for brain development, maturation, and function as they regulate the early key developmental processes. Normal human brain development and cognitive function relays on sufficient production of TH during the...

This AOP describes one adverse outcome that may result from the inhibition of thyroperoxidase (TPO) during mammalian development. Chemical inhibition of TPO results in decreased thyroid hormone (TH) synthesis, and subsequent reduction in circulating...

This AOP details the linkage between activation of the aryl hydrocarbon receptor (AhR) and early life stage mortality in oviparous vertebrates. It can be initiated mostly by dioxin-like compounds, which are able to bind to the AhR causing...

This AOP begins with the interaction of chemicals to the picrotoxin binding site of the ionotropic GABA receptor complex causing blockage of the ion channel. As a result, decrease in inward chloride conductance occurs, followed by a reduction in...

The present AOP describes antagonistic chemical binding to the peroxisome proliferator-activated receptor α (PPARα), resulting in preferential binding a co-repressor to the overall PPARα signalling complex causing a chain of events that includes:...

This AOP details the linkage between binding and activation of androgen receptor (AR) in females and reductions in cumulative fecundity and spawning. AR-mediated activities are among the major concerns in endocrine disruptor screening programs....

This AOP links chronic NMDA receptors inhibition during brain development to neurodegeneration in hippocampus and cortex with amyloid plaque deposition and tau hyperphosphorylation, and impairment of learning and memory, which are considered as...

This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that...

Under physiological conditions activation of glutamate ionotropic receptors such as N-methyl-D-aspartate (NMDARs), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPARs) and kainate (KARs) is responsible for basal excitatory synaptic...

It is well documented and accepted that learning and memory processes rely on physiological functioning of the glutamate receptor N-methyl-D-aspartate (NMDAR). Both animal and human studies investigating NMDA itself, experiments with NMDAR...

This adverse outcome pathway details the linkage between inhibition of gonadal aromatase activity in females and reproductive dysfunction, as measured through the adverse effect of reduced cumulative fecundity and spawning. Initial development of...

Germ cell/heritable mutations are important regulatory endpoints for international agencies interested in protecting the health of future generations. However, germ cell mutation analysis has been hampered by a lack of efficient tools. The motivation...

Liver fibrosis is an important human health issue associated with chemical exposure. It is a typical result of chronic toxic injury and one of the considered endpoints for regulatory purposes. This AOP describes the linkage between hepatic injury...

This document is a supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways (AOPs). It provides focused and practical instructions for both AOP developers and reviewers and is intended to assist in identifying,...