Significance of adverse outcome pathways in biomarker-based environmental risk assessment in aquatic organisms

In environmental risk assessments（ERA）, biomarkers have been widely used as an early warning signal of environmental contamination. However, biomarker responses have limitation due to its low relevance to adverse outcomes（e.g., fluctuations in community structure, decreases in population size, and other similar ecobiologically relevant indicators of community structure and function）. To mitigate these limitations, the concept of adverse outcome pathways（AOPs） was developed. An AOP is an analytical, sequentially progressive pathway that links a molecular initiating event（MIE） to an adverse outcome. Recently, AOPs have been recognized as a potential informational tool by which the implications of molecular biomarkers in ERA can be better understood. To demonstrate the utility of AOPs in biomarker-based ERA, here we discuss a series of three different biological repercussions caused by exposure to benzo（a）pyrene（Ba P）, silver nanoparticles（Ag NPs）, and selenium（Se）. Using mainly aquatic invertebrates and selected vertebrates as model species, we focus on the development of the AOP concept. Aquatic organisms are suitable bioindicator species whose entire lifespans can be observed over a short period; moreover, these species can be studied on the molecular and population levels.Also, interspecific differences between aquatic organisms are important to consider in an AOP framework, since these differences are an integral part of the natural environment.The development of an environmental pollutant-mediated AOP may enable a better understanding of the effects of environmental pollutants in different scenarios in the diverse community of an ecosystem.

An Overview of Adverse Outcome Pathway Links between PM_(2.5)Exposure and Cardiac Developmental Toxicity

Fine particulate matter(PM_(2.5))is a significant risk factor for birth defects.As the first and most important organ to develop during embryogenesis,the heart’s potential susceptibility to PM_(2.5)has attracted growing concern.Despite several studies supporting the cardiac developmental toxicity of PM_(2.5),the diverse study types,models,and end points have prevented the integration of mechanisms.In this Review,we present an adverse outcome pathway framework to elucidate the association between PM_(2.5)-induced molecular initiating events and adverse cardiac developmental outcomes.Activation of the aryl hydrocarbon receptor(AhR)and excessive generation of reactive oxygen species(ROS)were considered as molecular initiating events.The excessive production of ROS induced oxidative stress,endoplasmic reticulum stress,DNA damage,and inflammation,resulting in apoptosis.The activation of the AhR inhibited the Wnt/β-catenin pathway and then suppressed cardiomyocyte differentiation.Impaired cardiomyocyte differentiation and persistent apoptosis resulted in abnormalities in the cardiac structure and function.All of the aforementioned events have been identified as key events(KEs).The culmination of these KEs ultimately led to the adverse outcome,an increased morbidity of congenital heart defects(CHDs).This work contributes to understanding the causes of CHDs and promotes the safety evaluation of PM_(2.5).

A perspective on molecular and cellular biology-based developmental toxicology biomarkers

The process of development is intricate and couple-dependent phenomenon.Accordingly,the study of molecular and cellular biology-based developmental toxicology biomarkers increasingly is becoming an important part of risk assessment and management of chemicals for detection of health outcomes and/or biological endpoint like cytotoxicity,cell death,etc.Since,the evolution of developmental toxicology field a number of tools/markers have been developed or addressed to deal with developmental outcomes,which can ultimately be used for the development of adverse outcome pathways(AOPs)of developmental toxicants.As a result,this paper provides an overview of the current state of developmental toxicology biomarkers and describes the strategies used in the selection and evaluation of such biomarkers in the context of developmental toxicity studies.Here,we discuss about the biological markers that are directly linked to developmental toxicity with respect to future revolutionary perspectives.Additionally,this chapter will address different associated outcomes of developmental exposure by intriguing advance techniques.The discussion focuses on the challenges associated with the development of biomarkers for developmental toxicity and highlights some of the recent advances in this area.Finally,the chapter concludes with a brief discussion of the future prospects for the use of molecular and cellular biology-based developmental toxicity biomarkers.Hope the present state of the art will provide a succinct summary of recent developments of biomarkers of developmental toxicology.

Toxicity mechanisms and bioavailability of copper to fish based on an adverse outcome pathway analysis

Copper(Cu)exists in a variety of forms in different aquatic environments,and affects their bioavailability.In this study we provide a systematic review on toxicity of Cu which focuses on identifying evidence in the mechanisms of Cu toxicity,and apply an adverse outcome pathway(AOP)analysis to identify multiple potential mechanisms and their interactions of Cu toxicity to fish.This analysis process included the mechanisms of behavior toxicant,oxidative toxicant,ion regulation disruption toxicity,as well as endocrine disruption toxicity.It was found that at low levels of Cu exposure,swimming,avoid predators,locating prey and other sensory functions will be impaired,and the organism will suffer from metabolic alkalosis and respiratory acidosis following the inhibition of the carbonic anhydrase active.The main pathway of acute toxicity of Cu to fish is the inhibition of the Na^(+)/K^(+)-ATPase enzyme,and lead to reduced intracellular sodium absorption,as well as Cu-induced increased cell permeability,in turn resulting in increased sodium ion loss,leading to cardiovascular collapse and respiratory insufficiency.The endocrine disruption toxicity of Cu to fish caused growth inhibition and reproductive reduction.In addition,there are several key pathways of Cu toxicity that are affected by hardness(e.g.,Ca^(2+))and intracellular DOC concentrations,including inhibiting Cu-induction,improving branchial gas exchange,altering membrane transport functions,decreasing Na+loss,and increasing Na+uptake.The results of the AOP analysis will provide a robust framework for future directed research on the mechanisms of Cu toxicity.