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Relationship: 2686

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

Smaller and morphologically distorted facial cartilage structures leads to Increase, Early Life Stage Mortality

Upstream event
The causing Key Event (KE) in a Key Event Relationship (KER). More help
Downstream event
The responding Key Event (KE) in a Key Event Relationship (KER). More help

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
Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development adjacent Low Low Prarthana Shankar (send email) Under development: Not open for comment. Do not cite Under Review

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
fish fish Low 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
Embryo Moderate
Development 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
  • This KER describes evidence for craniofacial malformations (including smaller and morphologically distorted facial cartilage structure) leading to early life stage mortality.
  • Most of the evidence comes from biological plausibility, with some supporting evidence from the mammalian literature.
  • The occurrence of craniofacial malformations in fish and wildlife is still regarded as an adverse outcome in several regulatory contexts. For example, animal craniofacial deformities, specifically in birds and fish, are a commonly cited Beneficial Use Impairment (BUI) at Great Lakes Areas of Concern (AOCs) (IJC 1991). Significant reductions in the occurrence and prevalence of deformities at these sites is a criterion for delisting. Consequently, craniofacial malformation is an important phenotype for risk assessment of Ahr activating chemicals, even if it does not directly lead to reduced survival.

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 Supporting this KER

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help
Biological Plausibility
Addresses the biological rationale for a connection between KEupstream and KEdownstream.  This field can also incorporate additional mechanistic details that help inform the relationship between KEs, this is useful when it is not practical/pragmatic to represent these details as separate KEs due to the difficulty or relative infrequency with which it is likely to be measured.   More help
  • It is reasonable to infer that malformed jaw structure of animals in the wild could impact their feeding success, leading to reduced growth and possible early mortality. Impacts on animals to capture prey can also lead to population-wide changes to both the predators and prey (Weis et al. 2001), constraining foraging patterns and thus recruitment success.
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
  • Few studies have demonstrated the relationships between jaw malformations, reduced feeding, and mortality in fish (Noble et al. 2012).
  • Specifically, studies in developing zebrafish and mummichog (Fundulus heteroclitus) have found that low concentrations of TCDD or PCB126 exposure can lead to subtle malformations in the lower jaw, in addition to reduced feeding capabilities of the fish (Couillard et al. 2011; King Heiden et al. 2009). However, both studies observed a reduction in feeding even in the fish that did not display jaw malformations, consequently, reduced feeding was not directly linked to an inability to capture prey due to the craniofacial deformity. Overall, it is likely that a combination of different malformations (ex: effects on both the heart and jaw) contribute to Ahr activation-induced mortality.
  • The above results are corroborated by an evaluation of TCDD toxicity in seven fish species, where despite the observation of craniofacial malformations in all species, TCDD toxicity, including mortality, decreased once exogenous feeding began suggesting the lack of a strong causal link between craniofacial malformations and poor survival (Elonen et al. 1998).
  • An important caveat to the conclusions based on laboratory studies is that the relative abundance of food in an experimental test system relative to the natural environment may hide minor impacts on feeding efficiency that could be more impactful in nature. However, field-based investigations of the effect of craniofacial malformations on prey capture, feeding, and overall ecological fitness are difficult to address due to inherent complexities of the ecosystem.

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

References

List of the literature that was cited for this KER description. More help
  • Couillard CM, Légaré B, Bernier A, Dionne Z. 2011. Embryonic exposure to environmentally relevant concentrations of pcb126 affect prey capture ability of fundulus heteroclitus larvae. Mar Environ Res. 71(4):257-265.
  • Elonen GE, Spehar RL, Holcombe GW, Johnson RD, Fernandez JD, Erickson RJ, Tietge JE, Cook PM. 1998. Comparative toxicity of 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin to seven freshwater fish species during early life‐stage development. Environmental Toxicology and Chemistry: An International Journal. 17(3):472-483.
  • IJC. 1991. Commission approves list/delist criteria for great lakes areas of concern. Focus Int Comm Act. 16:2019-2003.
  • King Heiden TC, Spitsbergen J, Heideman W, Peterson RE. 2009. Persistent adverse effects on health and reproduction caused by exposure of zebrafish to 2,3,7,8-tetrachlorodibenzo-p-dioxin during early development and gonad differentiation. Toxicol Sci. 109(1):75-87.
  • Noble C, Jones HA, Damsgard B, Flood MJ, Midling KO, Roque A, Saether BS, Cottee SY. 2012. Injuries and deformities in fish: Their potential impacts upon aquacultural production and welfare. Fish Physiol Biochem. 38(1):61-83.
  • Weis JS, Smith G, Zhou T, Santiago-Bass C, Weis P. 2001. Effects of contaminants on behavior: Biochemical mechanisms and ecological consequences: Killifish from a contaminated site are slow to capture prey and escape predators; altered neurotransmitters and thyroid may be responsible for this behavior, which may produce population changes in the fish and their major prey, the grass shrimp. BioScience. 51(3):209-217.