Applying a modified systematic review and integrated assessment framework (SYRINA) - a case study on triphenyl phosphate.

This work presents a case study in applying a systematic review framework (SYRINA) to the identification of chemicals as endocrine disruptors. The suitability and performance of the framework is tested with regard to the widely accepted World Health Organization definition of an endocrine disruptor (ED). The endocrine disrupting potential of triphenyl phosphate (TPP), a well-studied flame retardant reported to exhibit various endocrine related effects was assessed. We followed the 7 steps of the SYRINA framework, articulating the research objective via Populations, Exposures, Comparators, Outcomes (PECO) statements, performed literature search and screening, conducted study evaluation, performed data extraction and summarized and integrated the evidence. Overall, 66 studies, consisting of in vivo, in vitro and epidemiological data, were included. We concluded that triphenyl phosphate could be identified as an ED based on metabolic disruption and reproductive function. We found that the tools used in this case study and the optimizations performed on the framework were suitable to assess properties of EDs. A number of challenges and areas for methodological development in systematic appraisal of evidence relating to endocrine disrupting potential were identified; significant time and effort were needed for the analysis of in vitro mechanistic data in this case study, thus increasing the workload and time needed to perform the systematic review process. Further research and development of this framework with regards to grey literature (non-peer-reviewed literature) search, harmonization of study evaluation methods, more consistent evidence integration approaches and a pre-defined method to assess links between adverse effect and endocrine activity are recommended. It would also be advantageous to conduct more case studies for a chemical with less data than TPP.

Conflicts of Interest in the Assessment of Chemicals, Waste, and Pollution.

Pollution by chemicals and waste impacts human and ecosystem health on regional, national, and global scales, resulting, together with climate change and biodiversity loss, in a triple planetary crisis. Consequently, in 2022, countries agreed to establish an intergovernmental science-policy panel (SPP) on chemicals, waste, and pollution prevention, complementary to the existing intergovernmental science-policy bodies on climate change and biodiversity. To ensure the SPP's success, it is imperative to protect it from conflicts of interest (COI). Here, we (i) define and review the implications of COI, and its relevance for the management of chemicals, waste, and pollution; (ii) summarize established tactics to manufacture doubt in favor of vested interests, i.e., to counter scientific evidence and/or to promote misleading narratives favorable to financial interests; and (iii) illustrate these with selected examples. This analysis leads to a review of arguments for and against chemical industry representation in the SPP's work. We further (iv) rebut an assertion voiced by some that the chemical industry should be directly involved in the panel's work because it possesses data on chemicals essential for the panel's activities. Finally, (v) we present steps that should be taken to prevent the detrimental impacts of COI in the work of the SPP. In particular, we propose to include an independent auditor's role in the SPP to ensure that participation and processes follow clear COI rules. Among others, the auditor should evaluate the content of the assessments produced to ensure unbiased representation of information that underpins the SPP's activities.

Addressing chemical pollution in biodiversity research.

Climate change, biodiversity loss, and chemical pollution are planetary-scale emergencies requiring urgent mitigation actions. As these "triple crises" are deeply interlinked, they need to be tackled in an integrative manner. However, while climate change and biodiversity are often studied together, chemical pollution as a global change factor contributing to worldwide biodiversity loss has received much less attention in biodiversity research so far. Here, we review evidence showing that the multifaceted effects of anthropogenic chemicals in the environment are posing a growing threat to biodiversity and ecosystems. Therefore, failure to account for pollution effects may significantly undermine the success of biodiversity protection efforts. We argue that progress in understanding and counteracting the negative impact of chemical pollution on biodiversity requires collective efforts of scientists from different disciplines, including but not limited to ecology, ecotoxicology, and environmental chemistry. Importantly, recent developments in these fields have now enabled comprehensive studies that could efficiently address the manifold interactions between chemicals and ecosystems. Based on their experience with intricate studies of biodiversity, ecologists are well equipped to embrace the additional challenge of chemical complexity through interdisciplinary collaborations. This offers a unique opportunity to jointly advance a seminal frontier in pollution ecology and facilitate the development of innovative solutions for environmental protection.

Opportunities to tackle antibiotic resistance development in the aquatic environment through the Water Framework Directive.

Antibiotics are critical components of modern health care. Protecting their efficacy through managing the rise in antibiotic resistance is therefore a global concern. It is not known to what extent environmental pollution from antibiotics contributes to the development of resistance, but encountered concentrations are frequently above concentrations predicted to select for resistance. Hence, measures are needed to manage risks. Here, we analyse if the indirect health risks from antibiotics in the aquatic environment can be considered in the context of the EU Water Framework Directive and the setting of environmental quality standards (EQS). By scrutinising current legislation, we conclude that it is possible to take the indirect health risks from antimicrobial resistance into account when deriving EQS for substances with antibiotic activity. We base this on the following conclusions: (1) human health concerns can be the main driver when setting an EQS, (2) an EQS can be based on data not specified in the guidance document, and (3) there are no restrictions against establishing EQS using data on antimicrobial resistance properties. In addition, since antimicrobial resistance travel across borders, we see strong reasons to prioritise setting these EQS on the EU level over the national level. Even though there is no agreed-upon method for how to develop EQS protective against resistance selection, there are several suggestions available in the literature and a couple of examples of regulatory initiatives. Also, addressing antimicrobial resistance through the Water Framework Directive can act as a driving force for other applicable legislation where such risks are not considered. We end by providing a set of recommendations for the European Commission and the Members States' future work on addressing aquatic pollution and antimicrobial resistance.

The Role of Behavioral Ecotoxicology in Environmental Protection.

For decades, we have known that chemicals affect human and wildlife behavior. Moreover, due to recent technological and computational advances, scientists are now increasingly aware that a wide variety of contaminants and other environmental stressors adversely affect organismal behavior and subsequent ecological outcomes in terrestrial and aquatic ecosystems. There is also a groundswell of concern that regulatory ecotoxicology does not adequately consider behavior, primarily due to a lack of standardized toxicity methods. This has, in turn, led to the exclusion of many behavioral ecotoxicology studies from chemical risk assessments. To improve understanding of the challenges and opportunities for behavioral ecotoxicology within regulatory toxicology/risk assessment, a unique workshop with international representatives from the fields of behavioral ecology, ecotoxicology, regulatory (eco)toxicology, neurotoxicology, test standardization, and risk assessment resulted in the formation of consensus perspectives and recommendations, which promise to serve as a roadmap to advance interfaces among the basic and translational sciences, and regulatory practices.

Pharmaceuticals and Environment: a web-based decision support for considering environmental aspects of medicines in use.

PURPOSE: The database Pharmaceuticals and Environment is a non-commercial, freely available web-based decision support presenting compiled environmental information for pharmaceutical substances. It was developed by Region Stockholm and launched in 2016 at janusinfo.se. The purpose of this paper is to present the database, report on its current use, and reflect on lessons learned from developing and managing the database. METHODS: A standard operating procedure describes the work and content of the database, e.g., how information is retrieved, processed, and presented. Google Analytics was used for metrics. Issues related to the database have been discussed and handled by a reference group. The experiences from this work are presented. RESULTS: The database contains environmental hazard and risk information, primarily gathered from regulatory authorities and pharmaceutical companies. There are also assessments comparing substances within some groups of pharmaceuticals. The database is used by the Swedish Drug and Therapeutics Committees to include environmental aspects when recommending pharmaceuticals for health care providers. Page views show that users primarily look for information on commonly used substances, e.g., diclofenac and paracetamol/acetaminophen. Major problems for the development of the database are lack of data, lack of transparency, and discrepancies in the available environmental information. CONCLUSION: In the absence of an adequate decision support produced by the regulatory authorities, we find the database Pharmaceuticals and Environment to be useful for Swedish Drug and Therapeutics Committees and health care providers, and it is our belief that the information can be valuable also in other settings.

Emerging investigator series: use of behavioural endpoints in the regulation of chemicals.

Interest in behavioural ecotoxicology is growing, partly due to technological and computational advances in recording behaviours but also because of improvements of detection capacity facilitating reporting effects at environmentally relevant concentrations. The peer-reviewed literature now contains studies investigating the effects of chemicals, including pesticides and pharmaceuticals, on migration, dispersal, aggression, sociability, reproduction, feeding and anti-predator behaviours in vertebrates and invertebrates. To understand how behavioural studies could be used in regulatory decision-making we: (1) assessed the legal obstacles to using behavioural endpoints in EU chemicals regulation; (2) analysed the known cases of use of behavioural endpoints in EU chemicals regulation; and (3) provided examples of behavioural endpoints of relevance for population level effects. We conclude that the only legal obstacle to the use of behavioural endpoints in EU chemicals regulation is whether an endpoint is considered to be relevant at the population level or not. We also conclude that ecotoxicity studies investigating behavioural endpoints are occasionally used in the EU chemicals regulation, and underscore that behavioural endpoints can be relevant at the population level. To improve the current use of behavioural studies in regulatory decision-making contribution from all relevant stakeholders is required. We have the following recommendations: (1) researchers should conduct robust, well-designed and transparent studies that emphasize the relevance of the study for regulation of chemicals; (2) editors and scientific journals should promote detailed, reliable and clearly reported studies; (3) regulatory agencies and the chemical industry need to embrace new behavioural endpoints of relevance at the population level.

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reliability and relevance evaluations of REACH data.

Regulatory authorities rely on hazard and risk assessments performed under REACH for identifying chemicals of concern and to take action. Therefore, these assessments must be systematic and transparent. This study investigates how registrants evaluate and report data evaluations under REACH and the procedures established by the European Chemicals Agency (ECHA) to support these data evaluations. Data on the endpoint repeated dose toxicity were retrieved from the REACH registration database for 60 substances. An analysis of these data shows that the system for registrants to evaluate data and report these evaluations is neither systematic nor transparent. First, the current framework focuses on reliability, but overlooks the equally important aspect of relevance, as well as how reliability and relevance are combined for determining the adequacy of individual studies. Reliability and relevance aspects are also confused in the ECHA guidance for read-across. Second, justifications for reliability evaluations were mainly based on studies complying with GLP and test guidelines, following the Klimisch method. This may result in GLP and guideline studies being considered reliable by default and discounting non-GLP and non-test guideline data. Third, the reported rationales for reliability were frequently vague, confusing and lacking information necessary for transparency. Fourth, insufficient documentation of a study was sometimes used as a reason for judging data unreliable. Poor reporting merely affects the possibility to evaluate reliability and should be distinguished from methodological deficiencies. Consequently, ECHA is urged to improve the procedures and guidance for registrants to evaluate data under REACH to achieve systematic and transparent risk assessments.

Toxicity studies used in registration, evaluation, authorisation and restriction of chemicals (REACH): How accurately are they reported?

Toxicity studies on chemicals registered under the European Union's Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation are provided as summaries instead of as a full study report. Because the registration data are used by regulatory agencies to identify chemicals of concern, the study summaries must accurately reflect the information in studies. A "study summary" should include sufficient information on the objectives, methods, results, and conclusions in the full study report in order for the relevance of the study to be determined. Sometimes a "robust study summary" is required, which should contain more detailed information to enable an independent assessment of the study. The aim of the present investigation is to examine how well published toxicity papers were reflected in study summaries submitted by registrants under REACH. Summaries of 20 published studies (peer-reviewed studies, including 1 abstract) were examined and broad categories of various types of observed differences were derived. The extent to which information in the published studies was reported, as well as how accurately the information was reflected, varied. How accurately the information was reflected also varied. Differences between the published studies and the summaries included simple typing errors, unclear and incomplete reporting, as well as the omission of information on, for example, study design, results, or interpretation of the results, which in some cases could be considered relevant for the risk assessment. This raises concerns regarding the accuracy of study summaries and their use for decision making. Moreover, the possibility for third parties to independently assess and scrutinize the summaries is limited. Considering that we rely on REACH registration data for chemical safety, all data used for risk assessment should be accessible for thorough examination and fully independent assessment. Integr Environ Assess Manag 2019;00:000-000. © 2019 SETAC.

A call for action: Improve reporting of research studies to increase the scientific basis for regulatory decision-making.

This is a call for action to scientific journals to introduce reporting requirements for toxicity and ecotoxicity studies. Such reporting requirements will support the use of peer-reviewed research studies in regulatory decision-making. Moreover, this could improve the reliability and reproducibility of published studies in general and make better use of the resources spent in research.

The Essential Elements of a Risk Governance Framework for Current and Future Nanotechnologies.

Societies worldwide are investing considerable resources into the safe development and use of nanomaterials. Although each of these protective efforts is crucial for governing the risks of nanomaterials, they are insufficient in isolation. What is missing is a more integrative governance approach that goes beyond legislation. Development of this approach must be evidence based and involve key stakeholders to ensure acceptance by end users. The challenge is to develop a framework that coordinates the variety of actors involved in nanotechnology and civil society to facilitate consideration of the complex issues that occur in this rapidly evolving research and development area. Here, we propose three sets of essential elements required to generate an effective risk governance framework for nanomaterials. (1) Advanced tools to facilitate risk-based decision making, including an assessment of the needs of users regarding risk assessment, mitigation, and transfer. (2) An integrated model of predicted human behavior and decision making concerning nanomaterial risks. (3) Legal and other (nano-specific and general) regulatory requirements to ensure compliance and to stimulate proactive approaches to safety. The implementation of such an approach should facilitate and motivate good practice for the various stakeholders to allow the safe and sustainable future development of nanotechnology.