title: Adverse outcome pathways during early fish development: a conceptual framework for identification of chemical screening and prioritization strategies.
abstract: The fish early life-stage (FELS) test guideline (OECD 210 or OCSPP 850.1400) is the most frequently used bioassay for predicting chronic fish toxicity and supporting aquatic ecological risk assessments around the world. For each chemical, the FELS test requires a minimum of 360 fish and 1 to 3 months from test initiation to termination. Although valuable for predicting fish full life-cycle toxicity, FELS tests are labor and resource intensive and, due to an emphasis on apical endpoints, provide little to no information about chemical mode of action. Therefore, the development and implementation of alternative testing strategies for screening and prioritizing chemicals has the potential to reduce the cost and number of animals required for estimating FELS toxicity and, at the same time, provides insights into mechanisms of toxicity. Using three reference chemicals with well-established yet distinct adverse outcome pathways (AOPs) in early life stages of fish, we proposed FELS-specific AOPs as conceptual frameworks for identifying useful chemical screening and prioritization strategies. The reference chemicals selected as case studies were a cardiotoxic aryl hydrocarbon receptor agonist (2,3,7,8-tetrachlorodibenzo-p-dioxin), neurotoxic acetylcholinesterase inhibitor (chlorpyrifos), and narcotic surfactant (linear alkylbenzene sulfonate). Using qualitative descriptions for each chemical during early fish development, we developed generalized AOPs and, based on these examples, proposed a three-tiered testing strategy for screening and prioritizing chemicals for FELS testing. Linked with biologically based concentration-response models, a tiered testing strategy may help reduce the reliance on long-term and costly FELS tests required for assessing the hazard of thousands of chemicals currently in commerce.
authors.affiliation: Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29208, USA. volz@mailbox.sc.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Volz
authors.forename: Scott
authors.initials: S
authors.lastname: Belanger
authors.forename: Michelle
authors.initials: M
authors.lastname: Embry
authors.forename: Stephanie
authors.initials: S
authors.lastname: Padilla
authors.forename: Hans
authors.initials: H
authors.lastname: Sanderson
authors.forename: Kristin
authors.initials: K
authors.lastname: Schirmer
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
authors.forename: Daniel
authors.initials: D
authors.lastname: Villeneuve
mesh_terms: D017738:Alkanesulfonic Acids / Q000145:classification / Q000493:pharmacokinetics / Q000633:toxicity; D000826:Animal Testing Alternatives; D000818:Animals; D004390:Chlorpyrifos / Q000145:classification / Q000493:pharmacokinetics / Q000633:toxicity; D004784:Environmental Monitoring / Q000379:methods*; D005399:Fishes / Q000502:physiology*; D015386:Hazardous Substances / Q000145:classification / Q000493:pharmacokinetics / Q000633:toxicity*; D006292:Health Priorities; D057166:High-Throughput Screening Assays / Q000379:methods*; D008018:Life Cycle Stages / Q000187:drug effects*; D008403:Mass Screening / Q000379:methods*; D000072317:Polychlorinated Dibenzodioxins / Q000145:classification / Q000493:pharmacokinetics / Q000633:toxicity; D012107:Research Design; D018570:Risk Assessment; D036401:Toxicity Tests, Chronic
chemical_list: D017738:Alkanesulfonic Acids; D015386:Hazardous Substances; D000072317:Polychlorinated Dibenzodioxins; C030641:alkylbenzyl sulfonic acid; D004390:Chlorpyrifos