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This article discusses the measurement and interpretation of vitellogenin (VTG) in fish and amphibians as a biomarker for endocrine activity. The reliability and acceptability of VTG results are important for regulatory assessments of chemicals. The article highlights the variability in VTG measurements and the need for improvement in sampling, quantification, and data handling. It proposes a decision logic to assist in the interpretation of VTG measurements and calls for the development of OECD guidance on best practices for VTG assessment. The article emphasizes the importance of considering other factors and endpoints in conjunction with VTG results to determine endocrine activity. [Extracted from the article]

The presence of endocrine‐active chemicals (EACs) in the environment continues to cause concern for wildlife given their potential for adverse effects on organisms. However, there is a significant lack of understanding about the potential effects of EACs on populations. This has real‐world limitations for EAC management and regulation, where the aim in environmental risk assessment is to protect populations. We propose a methodological approach for the application of modeling in addressing the population relevance of EAC exposure in fish. We provide a case study with the fungicide prochloraz to illustrate how this approach could be applied. We used two population models, one for brown trout (Salmo trutta; inSTREAM) and the other for three‐spined stickleback (Gasterosteus aculeatus) that met regulatory requirements for development and validation. Effects data extracted from the literature were combined with environmentally realistic exposure profiles generated with the FOCUS SW software. Population‐level effects for prochloraz were observed in some modeling scenarios (hazard‐threshold [HT]) but not others (dose–response), demonstrating the repercussions of making different decisions on implementation of exposure and effects. The population responses, defined through changes in abundance and biomass, of both trout and stickleback exposed to prochloraz were similar, indicating that the use of conservative effects/exposure decisions in model parameterization may be of greater significance in determining population‐level adverse effects to EAC exposure than life‐history characteristics. Our study supports the use of models as an effective approach to evaluate the adverse effects of EACs on fish populations. In particular, our HT parameterization is proposed for the use of population modeling in a regulatory context in accordance with Commission Regulation (EU) 2018/605. Environ Toxicol Chem 2023;42:1624–1640. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

The amphibian metamorphosis assay (AMA; US Environmental Protection Agency [USEPA] test guideline 890.1100 and Organisation for Economic Co‐Operation and Development test guideline 231) has been used for more than a decade to assess the potential thyroid‐mediated endocrine activity of chemicals. In 2013, in the context of the Endocrine Disruptor Screening Program of the USEPA, a Scientific Advisory Panel reviewed the results from 18 studies and recommended changes to the AMA test guideline, including a modification to a fixed‐stage design rather than a fixed‐time (i.e., 21‐d) design. We describe an extended test design for the AMA (or EAMA) that includes thyroid histopathology and time to metamorphosis (Nieuwkoop–Faber [NF] stage 62), to address both the issues with the fixed‐time design and the specific question of thyroid‐mediated adversity in a shorter assay than the larval amphibian growth and development assay (LAGDA; Organisation for Economic Co‐Operation and Development test guideline 241), using fewer animals and resources. A demonstration study was conducted with the EAMA (up to NF stage 58) using sodium perchlorate. Data analyses and interpretation of the fixed‐stage design of the EAMA are more straightforward than the fixed‐time design because the fixed‐stage design avoids confounded morphometric measurements and thyroid histopathology caused by varying developmental stages at test termination. It also results in greater statistical power to detect metamorphic delays than the fixed‐time design. By preferentially extending the AMA to NF stage 62, suitable data can be produced to evaluate thyroid‐mediated adversity and preclude the need to perform a LAGDA for thyroid mode of action analysis. The LAGDA remains of further interest should investigations of longer term effects related to sexual development modulated though the hypothalamus–pituitary–gonadal axis be necessary. However, reproduction assessment or life cycle testing is currently not addressed in the LAGDA study design. This is better addressed by higher tier studies in fish, which should then include specific thyroid‐related endpoints. Environ Toxicol Chem 2021;40:2135–2144. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Recent regulatory testing programs have been designed to evaluate whether a chemical has the potential to interact with the endocrine system and could cause adverse effects. Some endocrine pathways are highly conserved among vertebrates, providing a potential to extrapolate data generated for one vertebrate taxonomic group to others (i.e., biological read‐across). To assess the potential for biological read‐across, we reviewed tools and approaches that support species extrapolation for fish, amphibians, birds, and reptiles. For each of the estrogen, androgen, thyroid, and steroidogenesis (EATS) pathways, we considered the pathway conservation across species and the responses of endocrine‐sensitive endpoints. The available data show a high degree of confidence in the conservation of the hypothalamus–pituitary–gonadal axis between fish and mammals and the hypothalamus–pituitary–thyroid axis between amphibians and mammals. Comparatively, there is less empirical evidence for the conservation of other EATS pathways between other taxonomic groups, but this may be due to limited data. Although more information on sensitive pathways and endpoints would be useful, current developments in the use of molecular target sequencing similarity tools and thoughtful application of the adverse outcome pathway concept show promise for further advancement of read‐across approaches for testing EATS pathways in vertebrate ecological receptors. Environ Toxicol Chem 2020;39:739–753. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Abstract: Environmental risk assessment of chemical mixtures is challenging because of the multitude of possible combinations that may occur. Aquatic risk from chemical mixtures in an agricultural landscape was evaluated prospectively in 2 exposure scenario case studies: at field scale for a program of 13 plant‐protection products applied annually for 20 yr and at a watershed scale for a mixed land‐use scenario over 30 yr with 12 plant‐protection products and 2 veterinary pharmaceuticals used for beef cattle. Risk quotients were calculated from regulatory exposure models with typical real‐world use patterns and regulatory acceptable concentrations for individual chemicals. The results could differentiate situations when there was concern associated with single chemicals from those when concern was associated with a mixture (based on concentration addition) with no single chemical triggering concern. Potential mixture risk was identified on 0.02 to 7.07% of the total days modeled, depending on the scenario, the taxa, and whether considering acute or chronic risk. Taxa at risk were influenced by receiving water body characteristics along with chemical use profiles and associated properties. The present study demonstrates that a scenario‐based approach can be used to determine whether mixtures of chemicals pose risks over and above any identified using existing approaches for single chemicals, how often and to what magnitude, and ultimately which mixtures (and dominant chemicals) cause greatest concern. Environ Toxicol Chem 2018;37:674–689. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. [ABSTRACT FROM AUTHOR]

In this article the author discusses role of adverse outcome pathway (AOP) framework in chemical safety assessment. Topics discussed include use of biomarkers in environmental monitoring, toxicity testing guidelines proposed by the Organization for Economic Co-operation and Development (OECD) and, need to understand internal dose for molecular initiating events.

The relative sensitivity of amphibians to chemicals in the environment, including plant protection product active substances, is the subject of ongoing scientific debate. The objective of this study was to compare systematically the relative sensitivity of amphibians and fish to chemicals. Acute and chronic toxicity data were obtained from the U.S. Environmental Protection Agency (U.S. EPA) ECOTOX database and were supplemented with data from the scientific and regulatory literature. The overall outcome is that fish and amphibian toxicity data are highly correlated and that fish are more sensitive (both acute and chronic) than amphibians. In terms of acute sensitivity, amphibians were between 10- and 100-fold more sensitive than fish for only four of 55 chemicals and more than 100-fold more sensitive for only two chemicals. However, a detailed inspection of these cases showed a similar acute sensitivity of fish and amphibians. Chronic toxicity data for fish were available for 52 chemicals. Amphibians were between 10- and 100-fold more sensitive than fish for only two substances (carbaryl and dexamethasone) and greater than 100-fold more sensitive for only a single chemical (sodium perchlorate). The comparison for carbaryl was subsequently determined to be unreliable and that for sodium perchlorate is a potential artifact of the exposure medium. Only a substance such as dexamethasone, which interferes with a specific aspect of amphibian metamorphosis, might not be detected using fish tests. However, several other compounds known to influence amphibian metamorphosis were included in the analysis, and these did not affect amphibians disproportionately. These analyses suggest that additional amphibian testing is not necessary during chemical risk assessment. Environ. Toxicol. Chem. 2013;32:984-994. © 2013 SETAC [ABSTRACT FROM AUTHOR]

Aquatic toxicity tests with substances that are poorly soluble in water have been conducted using different methods, and estimates of toxicity have varied accordingly. The present study illustrates differences in toxicity values resulting from variation in test designs and solution preparation methods, and offers guidance on the best way to conduct these tests. Consequences for environmental risk assessment and classification are also discussed. The present study mainly considers active ingredients of plant protection products, but is also considered relevant to other chemicals. It is recommended that toxicity tests be conducted only up to the saturation limit, dispersants avoided, and solvents used only if necessary to support handling and speed of dissolution. Analytical measurements of exposure concentrations should reflect what organisms are exposed to. If acute toxicity testing at the saturation limit yields no adverse effects, further testing should not normally be required; the toxicity value of the endpoints should be considered as the saturation limit and adverse classification should not be required. Chronic testing, if required, should then be conducted at the practical saturation limit as this is the most realistic worst-case exposure scenario. If no adverse effects occur, the risk should be acceptable because higher aqueous exposure cannot occur. This could be substantiated by testing additional species. Assessment factors on no observed effect concentration (NOEC) values at the saturation limit require careful consideration in the risk assessment to avoid unnecessarily low regulatory acceptable concentrations. Environ. Toxicol. Chem. 2012; 31: 1662-1669. © 2012 SETAC [ABSTRACT FROM AUTHOR]

Filtration of a solution may lower metal concentrations through adsorption of metal species to the filter. Processes such as filter-sterilizing nutrient solution and filtration of field water are sensitive to these sorption artifacts, yet basic data on the affinity of different filters for metals are lacking. This article describes the adsorption of five metals to eight types of 0.2-µm membrane filters used for sterilizing a plant (Lemna minor L.) culture medium. Filters of cellulose acetate, cellulose nitrate, mixed cellulose ester, nylon, polyamide, polycarbonate, polyester, and polyvinylidene fluoride were tested for their affinity toward mono- (K), di- (Mn, Cu, Zn), and trivalent (lanthanum [La]) metals. Metal concentrations were quantified using radioisotopes and speciation was calculated. Results showed that metals had the lowest affinity for polycarbonate and nylon filters and the highest affinity for cellulose- and polyester-type filters. Furthermore, it was shown that the metal load on cellulose filters correlated best with free ion concentrations (indicating electrostatic attraction), while loads on other filters correlated better with total metal concentrations. Filtering a 5-ml solution of pH 5 did not affect its metal concentrations, ranging from 10 nM (La) to 49 µM (K). To minimize filtration artifacts, we propose using polycarbonate or nylon filters, especially when dealing with low volumes of high pH and low metal species concentrations. [ABSTRACT FROM AUTHOR]

Describes the accumulation and elimination of lanthanum (La) by common duckweed. Use of speciation modeling to assure that solubility products were not exceeded; Amount of La adsorbed on the glass; Need for the monitoring of lanthanide emissions due to the high bioconcentration factor.