Rebecca J. Brown, Grace H. Panter, Natalie Burden, Lennart Weltje, James R. Wheeler, Edward R. Salinas, Yvonne Wolf, Laurent Lagadic
<p>The egg-yolk precursor protein vitellogenin (VTG) is a biomarker for the determination of in vivo endocrine activity of chemicals in animals. Measurements of VTG in fish and amphibians are included in Organisation for Economic Co-operation and Development (OECD) test guidelines to provide support for identifying potential endocrine-active substances acting on the estrogen, androgen, and steroidogenesis (EAS) pathways. Induction of VTG in male fish is often associated with estrogenic activity, whereas inhibition in female fish may be related to substances that inhibit estrogen synthesis. The VTG protein or mRNA is measured in the plasma, liver, or whole body of fish, depending on the species and developmental stage, and on the specific test guideline requirements. Concerns have been raised regarding the variability of VTG measurements in fish, which could challenge the reliability and acceptability of VTG results for use in regulatory assessment of chemicals (Brown et al., <span>2023</span>). Hence, it is important to correctly measure and interpret VTG results, because ambiguous effects could trigger additional, potentially unnecessary, higher tier testing (i.e., animal-intensive life-cycle studies) to confirm or refute the VTG result. A literature review of VTG data from standard fish species exposed to 106 substances showed high intra- and interlaboratory variability in VTG concentrations, as well as discrepancies in the interpretation of results based on large differences between fish held in dilution water versus solvent controls, or due to the presence of outlier measurements (Brown et al., <span>2023</span>). For instance, the coefficient of variation of VTG concentrations in control adult fathead minnows (<i>Pimephales promelas</i>) was 543.2% for males and 206.1% for females. The same review also found evidence for false-positive/negative responses and situations in which the VTG results were difficult to interpret.</p><p>Findings from a laboratory survey to help understand the sources of variability in VTG protein and mRNA measurements identified three areas for improvement and harmonization: (1) sampling and storage, (2) quantification, and (3) data handling and statistical analysis (Burden et al., <span>2023</span>).</p><p>The survey also highlighted a need for the development of a decision logic to assist in the acceptability, determination, and interpretation of VTG measurements. This would support the development of new OECD guidance detailing best practice for VTG methodology, applicable across relevant test guideline studies but also applicable to studies published in the open literature. In the proposed decision logic (Figure 1), the reliability of the VTG results is assessed separately from the overall study reliability, because a reliable study (as evaluated against, for example, the Klimisch criteria [Klimisch et al., <span>1997</span>] or the Criteria for Reporting and Evaluating Ecotoxicity Data [Moermond et al., <span>20
{"title":"A Decision Logic for the Reliability Assessment and Interpretation of Vitellogenin Measurements","authors":"Rebecca J. Brown, Grace H. Panter, Natalie Burden, Lennart Weltje, James R. Wheeler, Edward R. Salinas, Yvonne Wolf, Laurent Lagadic","doi":"10.1002/etc.5946","DOIUrl":"10.1002/etc.5946","url":null,"abstract":"<p>The egg-yolk precursor protein vitellogenin (VTG) is a biomarker for the determination of in vivo endocrine activity of chemicals in animals. Measurements of VTG in fish and amphibians are included in Organisation for Economic Co-operation and Development (OECD) test guidelines to provide support for identifying potential endocrine-active substances acting on the estrogen, androgen, and steroidogenesis (EAS) pathways. Induction of VTG in male fish is often associated with estrogenic activity, whereas inhibition in female fish may be related to substances that inhibit estrogen synthesis. The VTG protein or mRNA is measured in the plasma, liver, or whole body of fish, depending on the species and developmental stage, and on the specific test guideline requirements. Concerns have been raised regarding the variability of VTG measurements in fish, which could challenge the reliability and acceptability of VTG results for use in regulatory assessment of chemicals (Brown et al., <span>2023</span>). Hence, it is important to correctly measure and interpret VTG results, because ambiguous effects could trigger additional, potentially unnecessary, higher tier testing (i.e., animal-intensive life-cycle studies) to confirm or refute the VTG result. A literature review of VTG data from standard fish species exposed to 106 substances showed high intra- and interlaboratory variability in VTG concentrations, as well as discrepancies in the interpretation of results based on large differences between fish held in dilution water versus solvent controls, or due to the presence of outlier measurements (Brown et al., <span>2023</span>). For instance, the coefficient of variation of VTG concentrations in control adult fathead minnows (<i>Pimephales promelas</i>) was 543.2% for males and 206.1% for females. The same review also found evidence for false-positive/negative responses and situations in which the VTG results were difficult to interpret.</p><p>Findings from a laboratory survey to help understand the sources of variability in VTG protein and mRNA measurements identified three areas for improvement and harmonization: (1) sampling and storage, (2) quantification, and (3) data handling and statistical analysis (Burden et al., <span>2023</span>).</p><p>The survey also highlighted a need for the development of a decision logic to assist in the acceptability, determination, and interpretation of VTG measurements. This would support the development of new OECD guidance detailing best practice for VTG methodology, applicable across relevant test guideline studies but also applicable to studies published in the open literature. In the proposed decision logic (Figure 1), the reliability of the VTG results is assessed separately from the overall study reliability, because a reliable study (as evaluated against, for example, the Klimisch criteria [Klimisch et al., <span>1997</span>] or the Criteria for Reporting and Evaluating Ecotoxicity Data [Moermond et al., <span>20","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":"43 9","pages":"1933-1935"},"PeriodicalIF":3.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/etc.5946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian J. Tornabene, Kelly L. Smalling, Blake R. Hossack
Harmful algal blooms (HABs) are a persistent and increasing problem globally, yet we still have limited knowledge about how they affect wildlife. Although semi-aquatic and aquatic amphibians and reptiles have experienced large declines and occupy environments where HABs are increasingly problematic, their vulnerability to HABs remains unclear. To inform monitoring, management, and future research, we conducted a literature review, synthesized the studies, and report on the mortality events describing effects of cyanotoxins from HABs on freshwater herpetofauna. Our review identified 37 unique studies and 71 endpoints (no-observed-effect and lowest-observed-effect concentrations) involving 11 amphibian and 3 reptile species worldwide. Responses varied widely among studies, species, and exposure concentrations used in experiments. Concentrations causing lethal and sublethal effects in laboratory experiments were generally 1 to 100 µg/L, which contains the mean value of reported HAB events but is 70 times less than the maximum cyanotoxin concentrations reported in the environment. However, one species of amphibian was tolerant to concentrations of 10,000 µg/L, demonstrating potentially immense differences in sensitivities. Most studies focused on microcystin-LR (MC-LR), which can increase systemic inflammation and harm the digestive system, reproductive organs, liver, kidneys, and development. The few studies on other cyanotoxins illustrated that effects resembled those of MC-LR at similar concentrations, but more research is needed to describe effects of other cyanotoxins and mixtures of cyanotoxins that commonly occur in the environment. All experimental studies were on larval and adult amphibians; there were no such studies on reptiles. Experimental work with reptiles and adult amphibians is needed to clarify thresholds of tolerance. Only nine mortality events were reported, mostly for reptiles. Given that amphibians likely decay faster than reptiles, which have tissues that resist decomposition, mass amphibian mortality events from HABs have likely been under-reported. We propose that future efforts should be focused on seven major areas, to enhance our understanding of effects and monitoring of HABs on herpetofauna that fill important roles in freshwater and terrestrial environments. Environ Toxicol Chem 2024;43:1936–1949. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
{"title":"Effects of Harmful Algal Blooms on Amphibians and Reptiles are Under-Reported and Under-Represented","authors":"Brian J. Tornabene, Kelly L. Smalling, Blake R. Hossack","doi":"10.1002/etc.5941","DOIUrl":"10.1002/etc.5941","url":null,"abstract":"<p>Harmful algal blooms (HABs) are a persistent and increasing problem globally, yet we still have limited knowledge about how they affect wildlife. Although semi-aquatic and aquatic amphibians and reptiles have experienced large declines and occupy environments where HABs are increasingly problematic, their vulnerability to HABs remains unclear. To inform monitoring, management, and future research, we conducted a literature review, synthesized the studies, and report on the mortality events describing effects of cyanotoxins from HABs on freshwater herpetofauna. Our review identified 37 unique studies and 71 endpoints (no-observed-effect and lowest-observed-effect concentrations) involving 11 amphibian and 3 reptile species worldwide. Responses varied widely among studies, species, and exposure concentrations used in experiments. Concentrations causing lethal and sublethal effects in laboratory experiments were generally 1 to 100 µg/L, which contains the mean value of reported HAB events but is 70 times less than the maximum cyanotoxin concentrations reported in the environment. However, one species of amphibian was tolerant to concentrations of 10,000 µg/L, demonstrating potentially immense differences in sensitivities. Most studies focused on microcystin-LR (MC-LR), which can increase systemic inflammation and harm the digestive system, reproductive organs, liver, kidneys, and development. The few studies on other cyanotoxins illustrated that effects resembled those of MC-LR at similar concentrations, but more research is needed to describe effects of other cyanotoxins and mixtures of cyanotoxins that commonly occur in the environment. All experimental studies were on larval and adult amphibians; there were no such studies on reptiles. Experimental work with reptiles and adult amphibians is needed to clarify thresholds of tolerance. Only nine mortality events were reported, mostly for reptiles. Given that amphibians likely decay faster than reptiles, which have tissues that resist decomposition, mass amphibian mortality events from HABs have likely been under-reported. We propose that future efforts should be focused on seven major areas, to enhance our understanding of effects and monitoring of HABs on herpetofauna that fill important roles in freshwater and terrestrial environments. <i>Environ Toxicol Chem</i> 2024;43:1936–1949. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. <i>Environmental Toxicology and Chemistry</i> published by Wiley Periodicals LLC on behalf of SETAC.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":"43 9","pages":"1936-1949"},"PeriodicalIF":3.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/etc.5941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelvin J Santana Rodriguez, Daniel L Villeneuve, Jenna E Cavallin, Brett R Blackwell, John Hoang, Rachel N Hofer, Kathleen M Jensen, Michael D Kahl, Robin N Kutsi, Emma Stacy, Mackenzie L Morshead, Gerald T Ankley