Effect-based methods including cell-based bioassays, reporter gene assays and whole-organism assays have been applied for decades in water quality monitoring and testing of enriched solid-phase ...extracts. There is no common EU-wide agreement on what level of bioassay response in water extracts is acceptable. At present, bioassay results are only benchmarked against each other but not against a consented measure of chemical water quality. The EU environmental quality standards (EQS) differentiate between acceptable and unacceptable surface water concentrations for individual chemicals but cannot capture the thousands of chemicals in water and their biological action as mixtures. We developed a method that reads across from existing EQS and includes additional mixture considerations with the goal that the derived effect-based trigger values (EBT) indicate acceptable risk for complex mixtures as they occur in surface water. Advantages and limitations of various approaches to read across from EQS are discussed and distilled to an algorithm that translates EQS into their corresponding bioanalytical equivalent concentrations (BEQ). The proposed EBT derivation method was applied to 48 in vitro bioassays with 32 of them having sufficient information to yield preliminary EBTs. To assess the practicability and robustness of the proposed approach, we compared the tentative EBTs with observed environmental effects. The proposed method only gives guidance on how to derive EBTs but does not propose final EBTs for implementation. The EBTs for some bioassays such as those for estrogenicity are already mature and could be implemented into regulation in the near future, while for others it will still take a few iterations until we can be confident of the power of the proposed EBTs to differentiate good from poor water quality with respect to chemical contamination.
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•Effect-based triggers (EBTs) for bioassays discriminate good from poor water quality.•EBTs can be derived by read across from existing water quality guideline values.•Mixture factor warranted for bioassays responding to many different chemicals.•EBT derivation method applicable to every bioassay subject to data availability•Here we derived preliminary EBTs for 32 bioassays and discuss many more.
This study reports the use of the recently developed EASZY assay that uses transgenic cyp19a1b-GFP zebrafish (Danio rerio) embryos to assess in vivo estrogenic activity of 33 surface (SW) and waste ...water (WW) samples collected across Europe that were previously well-characterized for estrogen hormones and in vitro estrogenic activity. We showed that 18 out of the 33 SW and WW samples induced estrogenic responses in the EASZY assay leading to a significant and concentration-dependent up-regulation of the ER-regulated cyp19a1b gene expression in the developing brain. The in vivo 17β-estradiol-equivalents (EEQs) were highly correlated with, both, the chemical analytical risk quotient (RQ) based on steroidal estrogen concentrations and EEQs reported from five different in vitro reporter gene assays. Regression analyses between the vitro and in vivo effect concentrations allowed us to determine an optimal cut-off value for each in vitro assay, above which in vivo responses were observed. These in vitro assay-specific effect-based trigger values (EBTs), ranging from 0.28 to 0.58 ng EEQ/L define the sensitivity and specificity of the individual in vitro assays for predicting a risk associated with substances acting through the same mode of action in water samples. Altogether, this study demonstrates the toxicological relevance of in vitro-based assessment of estrogenic activity and recommends the use of such in vitro/in vivo comparative approach to refine and validate EBTs for mechanism-based bioassays.
•Estrogenic activity of 33 water samples was assessed in a transgenic zebrafish assay.•In vivo EEQs were correlated with EEQs from 5 in vitro assays.•In vivo EEQs were correlated with risk quotient based on E1, E2, EE2 concentrations.•In vitro Assay-specific effect-based triggers values were defined.•Improvement of sensitivity and sensitivity for risk prediction of estrogens
Background
The regulatory evaluation of ecotoxicity studies for environmental risk and/or hazard assessment of chemicals is often performed using the method established by Klimisch and colleagues in ...1997. The method was, at that time, an important step toward improved evaluation of study reliability, but lately it has been criticized for lack of detail and guidance, and for not ensuring sufficient consistency among risk assessors.
Results
A new evaluation method was thus developed: Criteria for Reporting and Evaluating ecotoxicity Data (CRED). The CRED evaluation method aims at strengthening consistency and transparency of hazard and risk assessment of chemicals by providing criteria and guidance for reliability and relevance evaluation of aquatic ecotoxicity studies. A two-phased ring test was conducted to compare and characterize the differences between the CRED and Klimisch evaluation methods. A total of 75 risk assessors from 12 countries participated. Results show that the CRED evaluation method provides a more detailed and transparent evaluation of reliability and relevance than the Klimisch method. Ring test participants perceived it to be less dependent on expert judgement, more accurate and consistent, and practical regarding the use of criteria and time needed for performing an evaluation.
Conclusions
We conclude that the CRED evaluation method is a suitable replacement for the Klimisch method, and that its use may contribute to an improved harmonization of hazard and risk assessments of chemicals across different regulatory frameworks.
•Reliable effect biomarkers are available for most of the relevant MoAs.•Increasing AOP knowledge fosters the use of effect biomarkers in regulatory context.•PBK/D models allow interpretation and ...simulation of biomarkers of effect.•An inter-regulatory setting of effect-based trigger values is demanded.•Effect-biomarkers have in many cases reached a level of maturity ensuring use in mixture assessments.
Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring.
Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as ‘omics data will aid this process.
Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.
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•EU-wide diclofenac and steroidal estrogen monitoring was performed with LC-MS/MS and biotests.•Low estrogenicity and partly high COX-inhibition were found in the sampled surface ...waters.•Bioassays showed good screening function and applicability for investigative monitoring.•LC-MS/MS detection of EE2 remains challenging at its predicted no-effect level of 35 pg/L.•Standard addition tackled LC-MS/MS detection challenges.
Three steroidal estrogens, 17α-ethinylestradiol (EE2), 17β-estradiol (E2), estrone (E1), and the non-steroidal anti-inflammatory drug (NSAID), diclofenac have been included in the first Watch List of the Water Framework Directive (WFD, EU Directive 2000/60/EC, EU Implementing Decision 2015/495). This triggered the need for more EU-wide surface water monitoring data on these micropollutants, before they can be considered for inclusion in the list of priority substances regularly monitored in aquatic ecosystems. The revision of the priority substance list of the WFD offers the opportunity to incorporate more holistic bioanalytical approaches, such as effect-based monitoring, alongside single substance chemical monitoring. Effect-based methods (EBMs) are able to measure total biological activities (e.g., estrogenic activity or cyxlooxygenase COX-inhibition) of specific group of substances (such as estrogens and NSAIDs) in the aquatic environment at low concentrations (pg/L). This makes them potential tools for a cost-effective and ecotoxicologically comprehensive water quality assessment. In parallel, the use of such methods could build a bridge from chemical status assessments towards ecological status assessments by adressing mixture effects for relevant modes of action. Our study aimed to assess the suitability of implementing EBMs in the WFD, by conducting a large-scale sampling and analysis campaign of more than 70 surface waters across Europe. This resulted in the generation of high-quality chemical and effect-based monitoring data for the selected Watch List substances. Overall, water samples contained low estrogenicity (0.01–1.3 ng E2-Equivalent/L) and a range of COX-inhibition activity similar to previously reported levels (12–1600 ng Diclofenac-Equivalent/L). Comparison between effect-based and conventional analytical chemical methods showed that the chemical analytical approach for steroidal estrogens resulted in more (76%) non-quantifiable data, i.e., concentrations were below detection limits, compared to the EBMs (28%). These results demonstrate the excellent and sensitive screening capability of EBMs.
Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission’s Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical ...policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures.
In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders.
HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.
In this paper, we critically examine the assumption that most employees, and especially those not identified as talents, find exclusive talent management less fair than inclusive talent management. ...Across two factorial survey studies—one of which manipulates talent status experimentally (N = 300), the other using field data on meta‐perceived talent ratings (N = 209)—we examine the extent to which the perceived fairness of talent management is predicted by self‐interest (i.e., the extent to which you yourself are seen as talented) versus principle (i.e., a dispositional preference for equality‐vs. merit‐based allocations). We found a clear effect of talent status, indicating that perceived fairness is at least partly determined by self‐interest (i.e., whether one personally stands to gain or lose from exclusive talent management). We also found an effect for preferred allocation norm—implying that fairness perceptions are influenced by matters of principle, independently from self‐interest—but only on the boundary condition that organizations provide a transparent justification for their chosen (inclusive or exclusive) talent philosophy. Two major gaps are addressed: the lack of data on how employees perceive and experience talent management practices, and the inability of common study designs to make causal claims.
In high customer-contact services, employees are an imperative part of a company's service quality. While the effect of employee commitment on brand-supportive behaviors has already been studied, it ...remains unclear what drives employees’ brand commitment. This study explores the brand-oriented leadership of top management as an important driver of internal branding process and an indirect predictor of employees’ commitment. Moreover, three mediators are examined in relation to how brand-oriented leadership affects brand commitment. Using a sample of 226 hospitality employees working in a European hotel chain, our results indicate that employee brand knowledge, employee-brand fit, and psychological contract fulfillment fully mediate the relationship between brand-oriented leadership and brand commitment. The results support the importance of top management's leadership in internal branding and its role in achieving employees’ emotional attachment to the brand. We also suggest that, for leadership to enhance commitment, leaders must compel employees to possess brand-relevant knowledge, share similar brand values, and perceive their psychological contract as being fulfilled.
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