This AOP is licensed under the BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

AOP: 321


A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE.  More help

Reduced environmental pH leading to thinner shells in Mytilus edulis

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
Thinner shells in Mytilus Edulis due to ocean acidifcation
The current version of the Developer's Handbook will be automatically populated into the Handbook Version field when a new AOP page is created.Authors have the option to switch to a newer (but not older) Handbook version any time thereafter. More help
Handbook Version v2.0

Graphical Representation

A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs. More help
Click to download graphical representation template Explore AOP in a Third Party Tool


The names and affiliations of the individual(s)/organisation(s) that created/developed the AOP. More help

Submitted by James Ducker, PhD student in Marine Biology at the Chinese University of Hong Kong (CUHK), Hong Kong SAR. 

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section.   More help
James Ducker   (email point of contact)


Users with write access to the AOP page.  Entries in this field are controlled by the Point of Contact. More help
  • James Ducker


This field is used to identify coaches who supported the development of the AOP.Each coach selected must be a registered author. More help

OECD Information Table

Provides users with information concerning how actively the AOP page is being developed and whether it is part of the OECD Workplan and has been reviewed and/or endorsed. OECD Project: Assigned upon acceptance onto OECD workplan. This project ID is managed and updated (if needed) by the OECD. OECD Status: For AOPs included on the OECD workplan, ‘OECD status’ tracks the level of review/endorsement of the AOP . This designation is managed and updated by the OECD. Journal-format Article: The OECD is developing co-operation with Scientific Journals for the review and publication of AOPs, via the signature of a Memorandum of Understanding. When the scientific review of an AOP is conducted by these Journals, the journal review panel will review the content of the Wiki. In addition, the Journal may ask the AOP authors to develop a separate manuscript (i.e. Journal Format Article) using a format determined by the Journal for Journal publication. In that case, the journal review panel will be required to review both the Wiki content and the Journal Format Article. The Journal will publish the AOP reviewed through the Journal Format Article. OECD iLibrary published version: OECD iLibrary is the online library of the OECD. The version of the AOP that is published there has been endorsed by the OECD. The purpose of publication on iLibrary is to provide a stable version over time, i.e. the version which has been reviewed and revised based on the outcome of the review. AOPs are viewed as living documents and may continue to evolve on the AOP-Wiki after their OECD endorsement and publication.   More help
OECD Project # OECD Status Reviewer's Reports Journal-format Article OECD iLibrary Published Version
This AOP was last modified on April 29, 2023 16:03

Revision dates for related pages

Page Revision Date/Time


A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance. More help

Despite contemporary scientific efforts focusing on better understanding the consequences of ocean acidification, the overwhelming abundance of novel findings may be undermining the applications of studies. Climate research may benefit from the development of a conceptual framework synthesizing the sequential cascade of responses initiated by environmental stressors, termed Adverse Outcome Pathways (AOP) (Ankley et al., 2010).

Preliminary AOP for Mytilus edulis indicates that OA has a myriad of repercussions across biological levels, with multiple potential adverse outcomes to consider. The impacts are interconnected and demonstrate how molecular processes may affect whole-organism processes. The studies considering M. edulis provide a comprehensive AOP as it is a well-studied species, with most impacts at individual (whole-organism) level. 

Based on the evidence gathered to design this AOP, the following pathway was developed from the MIE of reduced environmental pH leading to alterations in genes encoding calcification and metabolic pathways. Following such alterations, signifcant changes were documented at cellular and organ level, including an imbalance in acid-base status, which led to the deregulation of growth and development at the individual level. Ultimately, such impacts resulted in the decline of populations. However, it is essential to note that these outcomes were not observed unilaterally. 

Indeed, frequent variation in outcomes was observed across studies. In particular, variations in the pathway was documented between sexes, life stages and temporal scales. Despite such variation the application of the AOP framework offers a unique perspective synthesizing our current understanding. Moreover, future research progressing our understanding on synergistic effects would further improve the efficacy of AOPs in climate research (Falkenberg et al., 2013).

AOP Development Strategy


Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. More help

Over the past two decades, it is estimated that over half of global carbon dioxide emissions has been absorbed by the oceans (Sabine et al., 2004), resulting in the average oceanic pH declining by 0.1 units compared to pre-industrial levels in a process termed ocean acidification (OA) (Caldeira et al., 2005).

Predictions have mainly focused on surface ocean waters resulting in weak representation for coastal ecosystems and taxonomic groups within them (Fabri et al., 2008) despite their socioeconomic value (Falkenberg and Tubb 2017). One such group are the molluscs, which are used as valuable ecological models and represent a taxon of widespread aqua cultural importance in coastal systems (Costanza et al., 1997). Additionally, molluscs are comparatively well studied in terms of climate related impacts and therefore provide extensive information useful to be used in novel frameworks (e.g. see review by Gazeau et al 2013).

Ocean acidification is recognised to impact the physiology, behaviour and evolution of molluscs (Kroeker et al. 2010; Gazeau et al. 2013). Organisms with calcium carbonate-based shells may be particularly susceptible due to the dependence of shell formation on pH and carbon chemistry (Beniash et al. 2010; Tomanek et al. 2011; Parker et al. 2012). However, the severity of impacts is unclear as calcifying organisms may be resilient to highly variable coastal environments (Duarte et al. 2013) and are also known to exhibit varying sensitivities depending on biological context including factors such as life stage, community composition and nutritional status (Kroeker et al., 2013). Moreover, the effects of acidification are known to synergistically interact with other anthropogenic stressors, such as toxicants (Cao et al., 2018, 2019) and climatic stressors, particularly ocean warming (Kroeker et al., 2013).

Climate research may benefit from the development of a conceptual framework synthesizing the sequential cascade of responses initiated by environmental stressors, termed Adverse Outcome Pathways (AOP) (Ankley et al., 2010). AOPs were first developed in 1992 and have been used primarily for toxicology purposes in order to collect key information on the sequential consequences of toxicants across biological processes (see Figure 1). Since being implemented, the adoption of AOPs has gained momentum leading to the design of online databases gathering information on a myriad of stressors and their impacts around the globe ( AOPs are used to synthesize information for actions plans, establishing risk assessments supported by empirical data on biological context and spatiotemporal trends aiming to improve risk characterization of targeted species to particular stressors (Ankley et al., 2010). To date, the AOP framework has yet to be used to address ocean acidification, with few examples applied to climate science even if AOPs can incorporate vital biological pathways impacted by climatic stressors (Hooper et al., 2013). Indeed, the effects of anthropogenic climate change (e.g. increased temperatures, hypoxia or acidification) are akin to human derived toxicants as they represent a potentially lethal threat to organisms that have yet to experience such severe and frequent alterations in environmental conditions. Thus, AOPs would provide a unique and comprehensive tool using a risk assessment approach to climate related impacts on ecosystems and the species within them (Falkenberg et al., 2018; Hooper et al., 2013). 


Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components.  Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used). More help

Summary of the AOP

This section is for information that describes the overall AOP.The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed. More help


Molecular Initiating Events (MIE)
An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP. More help
Key Events (KE)
A measurable event within a specific biological level of organisation. More help
Adverse Outcomes (AO)
An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

Relationships Between Two Key Events (Including MIEs and AOs)

This table summarizes all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP.Each table entry acts as a link to the individual KER description page. More help

Network View

This network graphic is automatically generated based on the information provided in the MIE(s), KEs, AO(s), KERs and Weight of Evidence (WoE) summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs. More help

Prototypical Stressors

A structured data field that can be used to identify one or more “prototypical” stressors that act through this AOP. Prototypical stressors are stressors for which responses at multiple key events have been well documented. More help

Life Stage Applicability

The life stage for which the AOP is known to be applicable. More help

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available. More help

Sex Applicability

The sex for which the AOP is known to be applicable. More help

Overall Assessment of the AOP

Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). More help

Domain of Applicability

Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context. More help

Life stages

Acidification is recognised to impact Mytilus edulis across life stages from larval form through to adult stages. However, sensitivity varies considerably in response to acidification. In particular, embryonic and larval stages are known to be most susceptible to acidifcation, with considerable reductions in size and development resulting in higher mortality (Gazeau et al., 2013; Thomsen et al., 2015).

For the majority of bivalve species and some gastropods that are more primitive, fertilization occurs in the surrounding water; for example, eggs and sperm of bivalves are shed into the suprabranchial cavity where they are released into the water column with the exhalant current (Barnes 1974).

Our knowledge of the impacts of ocean acidification on the fertilization on broadcast spawning shelled molluscs is based on a limited number of studies (9), covering only seven species (Table 2). CO2-induced hypercapnia is believed to have a narcotic effect on sperm, reducing its speed and motility, thereby reducing fertilization success (Havenhand et al. 2008; Byrne 2011; Reuter et al. 2011).

Thus, the present AOP provides an insight into a mechanistic process capable of affecting mussels across life stages. Nonetheless, the variations described above is indicative of the consideration required to extract the exact consequences expected from acidifcation.

Other species

The effects of ocean acidification on the growth and shell production by juvenile and adult shelled molluscs are variable among species and even within the same species, precluding the drawing of a general picture (see Gazeau et al., 2013). This is, however, not the case for pteropods, with all species tested so far, being negatively impacted by ocean acidification. 

Ubiquitous elements? Cellular changes, genes and reactions in other bivalves – similar? Spatiotemporal differences in populations?

The present AOP may be applicable to other bivalve species as the process of calcification is similar across taxa (REFs). 

Physiology and behavioural changes for other taxa or groups

In the mussel M. edulis, for example, exposure to elevated CO2 of 1,120 latm (-0.3 pH unit) for 60 days led to a significant increase in SMR (Thomsen and Melzner 2010). In juveniles of the oyster C. virginica, exposure to elevated CO2 of *3,300 latm (-0.7 pH unit) for 20 weeks, a level much higher than that used in the previous study (and therefore not shown in Fig. 4), caused an increase in SMR which was accompanied by a decrease in both shell and somatic growth and survival (Beniash et al. 2010). A number of other shelled mollusc species have also suffered reduced survival following chronic exposure to elevated CO2 (snail S. lubuanus, Shirayama and Thornton 2005; mussel M. edulis, Berge et al. 2006; clam M. mercenaria, Green et al. 2009; oyster C. virginica, Dickinson et al. 2012; clam T. squamosa, Watson et al. 2012b).

In the limpet Patella vulgata (Marchant et al. 2010), mussels Perna viridis (Liu and He 2012) and M. galloprovincialis (Fernandez-Reiriz et al. 2012) and oyster Pinctada fucata (Liu and He 2012), there was no observable change in SMR during exposure to elevated CO2 (see Fig. 4). Trade-offs in energy allocation may still exist, however, such that metabolic stimulation occurs in one tissue whereas metabolic depression occurs in another (Lannig et al. 2010).

Other stressors

The data suggest for several shelled molluscan species that ocean acidification combined with ocean warming may have even greater impacts than those documented for ocean acidification alone. This is the case, for instance, for the fluted giant clam (Tridacna squamosa) which showed much lower survival when low pH was combined with higher temperature (Watson et al. 2012b).

Essentiality of the Key Events

The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs. More help
  • Biological plausibility: Is there a mechanistic (i.e. structural or functional) relationship between KEup and KE down consistent with established biological knowledge?

YES – known physiological processes

  • Empirical support: Does the empirical evidence support that a change in the KEup leads to an appropriate change in the KE down? Does KEup occur at lower doses and earlier time points than KE down and is the incidence of KEup higher than that for KE down?

Type of studies?

Variation in results?

Maybe a non linear relationship between OA amount and thinning of shells

  • Uncertainties and Inconsistencies: conditions for KE to be fulfilled or not, what might interfere with outcomes e.g. dose responses, individual variations, adaptation & acclimation potential

Spatiotemporal variations – biological context etc.

Evidence Assessment

Addressess the biological plausibility, empirical support, and quantitative understanding from each KER in an AOP. More help

Increased abundance of studies in recent years. 

Ample reviews on the topic considering numerous perspectives. 

Finally, even identical species have shown differing responses of fertilization to ocean acidification. For example, gametes of the Pacific oyster, C. gigas, from populations in Japan (Kurihara et al. 2007) and Sweden (Havenhand and Schlegel 2009) experienced no reduction in percentage fertilization, sperm swimming speed and motility (sperm tested only in the Swedish population) when reared at elevated pCO2 of 1,000–2,300 latm (-0.3 to -0.8 pH unit).

This suggests that intraspecific variation may exist between populations due to both environmental and genetic differences that may lead to within-species differences in fertilization response to ocean acidification stress

The results of the studies to date suggest that for a number of shelled mollusc species, ocean acidification will cause a rise in the cost of maintenance and a shift in energy budgets, unless acclimation across life-history stages or evolutionary adaptation occurs. The tissue and mechanisms responsible for such cost increments have not been identified; however, comparative findings in fish gills indicate that elevated costs of ion and acid–base regulation in gill tissue may be involved (Deigweiher et al. 2009). Future studies would benefit from assessment of the effects of ocean acidification on the entire energy budget of shelled molluscs to identify whether altered partitioning of the energy budget is occurring and which critical fitness-sustaining processes will be most vulnerable.

Very few studies focusing on the effect of ocean acidification on shelled molluscs actually report on the level and on the variations in pH in the ecosystem the organisms were taken from (e.g. Thomsen et al. 2010).

Known Modulating Factors

Modulating factors (MFs) may alter the shape of the response-response function that describes the quantitative relationship between two KES, thus having an impact on the progression of the pathway or the severity of the AO.The evidence supporting the influence of various modulating factors is assembled within the individual KERs. More help

Quantitative Understanding

Optional field to provide quantitative weight of evidence descriptors.  More help

Considerations for Potential Applications of the AOP (optional)

Addressess potential applications of an AOP to support regulatory decision-making.This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. More help

Despite being crucial physiological traits for ecological success, very little is known of the effects of ocean acidification on shelled mollusc health and the potential for shelled mollusc species to resist predators and/or disease. Bibby et al. (2008) showed an effect of acidification (-0.2 to -1.1 pH unit) on the immune response of the blue mussel (M. edulis).

Finally, differences in the accumulation of metals have also been documented in juveniles of the clam, Ruditapes philippinarum, where metal accumulation (Zn, Pb, Cu, Ni, Cr, Hg, As; but not Cd) was found to increase upon exposure to elevated pCO2 for 28 days (-1.0 pH unit; Lopez et al. 2010). This highlights the potential ecotoxicological consequences that may be associated with ocean acidification stress in addition to the developmental and physiological effects that have been documented.

Risk assessments

Ecosystem mangament 


In addition, shelled molluscs have a significant economic value as the global shellfish aquaculture industry reached a global value of US$ 13.1 billion in 2008 (FAO 2008). In recent decades, severe declines in shelled mollusc populations have been reported. Surveys conducted annually along the coast of British Columbia have shown a decline of up to 80 % in some populations since 1978 (Hankewich and Lessard 2006). Moreover, in hatcheries located on the northwest coast of the USA, there has been a year-by-year decline in the survival of oyster larvae since 2005, which appears to be connected to the upwelling of acidified deep waters shifting coastward and associated near-shore ocean acidification (Barton et al. 2012). Indeed, Feely et al. (2008) have noticed that even though seasonal upwelling of waters undersaturated with aragonite (one of the most soluble metastable forms of calcium carbonate) is a natural feature on the northern California shelf, the uptake of anthropogenic CO2 has increased the affected area over recent decades.


List of the literature that was cited for this AOP. More help