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Relationship: 1743

Title

A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream). More help

Decrease, Cuticular chitin content leads to Increase, Premature molting

Upstream event

The causing Key Event (KE) in a Key Event Relationship (KER). More help

Decrease, Cuticular chitin content

Downstream event

The responding Key Event (KE) in a Key Event Relationship (KER). More help

Increase, Premature molting

Key Event Relationship Overview

The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE. More help

AOPs Referencing Relationship

AOP Name	Adjacency	Weight of Evidence	Quantitative Understanding	Point of Contact	Author Status	OECD Status
S-adenosylmethionine depletion leading to population decline (2)	adjacent			Allie Always (send email)	Under development: Not open for comment. Do not cite
S-adenosylmethionine depletion leading to population decline (1)	adjacent			Agnes Aggy (send email)	Under development: Not open for comment. Do not cite
Chitin synthase 1 inhibition leading to mortality	adjacent	Moderate	Low	Brendan Ferreri-Hanberry (send email)	Open for citation & comment	WPHA/WNT Endorsed
Sulfonylureareceptor binding leading to mortality	adjacent	Moderate	Moderate	Arthur Author (send email)	Under development: Not open for comment. Do not cite	Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER. More help

Term	Scientific Term	Evidence	Link
crustaceans	Daphnia magna	Moderate	NCBI
insects	insects	Moderate	NCBI

Sex Applicability

An indication of the the relevant sex for this KER. More help

Sex	Evidence
Unspecific	Moderate

Life Stage Applicability

An indication of the the relevant life stage(s) for this KER. More help

Term	Evidence
Larvae	High
Juvenile	High
Adult	Moderate

Key Event Relationship Description

Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves. More help

As the arthropod cuticle is a central part in the molting process, its proper composition is indispensable for a proper molt. The ecdysis motor program, the behavioral part of ecdysis, constitutes a distinct motor pattern to split and shed the old cuticle (Ayali 2009). As the cuticle supports muscular function (Vincent and Wegst 2004), it needs to possess a certain integrity in order to successfully molt. The integrity of the cuticle is also important after ecdysis as arthropods, such as insects and crustaceans, expand the new cuticle by swallowing air or water in order to build up pressure to split the old and expand the new exoskeleton and provide stability to the soft new cuticle (Clarke 1957; Lee 1961; Dall et al. 1978; deFur et al. 1985). The arthropod cuticle mostly consists of chitin embedded in and crosslinked with a matrix of proteins (Muthukrishnan et al. 2012). If the chitin content is too low, the cuticle may not possess enough integrity to support muscular function or withstand the beforementioned stresses of ecdysis, which leads to the organism being stuck in the old cuticle or the rupture of the new cuticle.

Evidence Collection Strategy

Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings. Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible. More help

Evidence Map 2.0

ID	Experimental Design	Species	Upstream Observation	Downstream Observation	Citation (first author, year)	Notes

Evidence Map

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help

Title	First Author	Biological Plausibility	Dose Concordance	Temporal Concordance	Incidence Concordance

Biological Plausibility

Dose Concordance Evidence

Temporal Concordance Evidence

Incidence Concordance Evidence

Uncertainties and Inconsistencies

Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance. More help

The absence of studies (quantitatively) assessing premature molting constitutes a major data gap. A further data gap is the absence of studies which assess both, the decrease in cuticular chitin content and the increase in premature molting.

Known modulating factors

This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references. More help

Quantitative Understanding of the Linkage

Captures information that helps to define how much change in the upstream KE, and/or for how long, is needed to elicit a detectable and defined change in the downstream KE. More help

Response-response Relationship

Provides sources of data that define the response-response relationships between the KEs. More help

Due to the lack of studies linking the decrease in cuticular chitin content with the increase in premature molting, it is not possible to describe the nature of the response-response relationship.

Time-scale

Information regarding the approximate time-scale of the changes in KEdownstream relative to changes in KEupstream (i.e., do effects on KEdownstream lag those on KEupstream by seconds, minutes, hours, or days?). More help

Due to the nature of the process, premature molting onsets at the time of ecdysis after the decrease in cuticular chitin content.

Known Feedforward/Feedback loops influencing this KER

Define whether there are known positive or negative feedback mechanisms involved and what is understood about their time-course and homeostatic limits. More help

Domain of Applicability

A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms. More help

Taxonomic: In all likelihood, this KER is applicable to the whole phylum of arthropods as they all depend on the synthesis of chitin and molting in order to develop.

Life stage: This KER is applicable for organisms synthesizing chitin and molting in order to grow and develop, namely larval stages of insects and all life stages of crustaceans and arachnids.

Sex: This KER is applicable to all sexes.

Chemical: Occurrence of a decrease in cticular chitin content as well as premature molting was observed after treatment with the pyrimidine nucleosides polyoxin D, polyoxin B and nikkomycin Z (Gijswijt et al. 1979; Turnbull and Howells 1982; Calcott and Fatig 1984; Gelman and Borkovec 1986; Tellam et al. 2000; Arakawa et al. 2008; Zhuo et al. 2014). However, studies causally linking both endpoints are lacking.