A framework for chemical safety assessment incorporating new approach methodologies within REACH.

The long-term investment in new approach methodologies (NAMs) within the EU and other parts of the world is beginning to result in an emerging consensus of how to use information from in silico, in vitro and targeted in vivo sources to assess the safety of chemicals. However, this methodology is being adopted very slowly for regulatory purposes. Here, we have developed a framework incorporating in silico, in vitro and in vivo methods designed to meet the requirements of REACH in which both hazard and exposure can be assessed using a tiered approach. The outputs from each tier are classification categories, safe doses, and risk assessments, and progress through the tiers depends on the output from previous tiers. We have exemplified the use of the framework with three examples. The outputs were the same or more conservative than parallel assessments based on conventional studies. The framework allows a transparent and phased introduction of NAMs in chemical safety assessment and enables science-based safety decisions which provide the same level of public health protection using fewer animals, taking less time, and using less financial and expert resource. Furthermore, it would also allow new methods to be incorporated as they develop through continuous selective evolution rather than periodic revolution.

Optimising testing strategies for classification of human health and environmental hazards - A proof-of-concept study.

This paper outlines a new concept to optimise testing strategies for improving the efficiency of chemical testing for hazard-based risk management. While chemical classification based on standard checklists of information triggers risk management measures, the link is not one-to-one. Toxicity testing may be performed with no impact on the safe use of chemicals . Each hazard class and category is not assigned a unique pictogram and for the purpose of this proof-of-concept study, the level of concern for a chemical for the population and the environment is simplistically considered to be reflected by the hazard pictograms. Using active substances in biocides and plant protection products as a dataset, three testing strategies were built with the boundary condition that an optimal approach must indicate a given level of concern while requiring less testing (strategy B), prioritising new approach methodologies (strategy C) or combining the two considerations (strategy D). The implementation of the strategies B and D reduced the number of tests performed by 6.0% and 8.8%, respectively, while strategy C relied the least on in vivo methods. The intentionally simplistic approach to optimised testing strategies presented here could be used beyond the assessment of biocides and plant protection products to gain efficiencies in the safety assessment of other chemical groups, saving animals and making regulatory testing more time- and cost-efficient.

The ChemSM-Hub project in the light of a new paradigm for chemical safety management.

OBJECTIVES: The work is aimed to present and promote the Chemical Safety Management Training Hub for Chemicals Users (ChemSM-Hub) project implemented by the Nofer Institute of Occupational Medicine in cooperation with the Lodz University of Technology, Poland, and other partners from Germany (Oekopol GmbH), Greece (Prolipsis) and Romania (Romtens). The project is co-funded by the European Commission under the Erasmus+ program, whose aim is to support downstream users (DUs) and distributors (Ds) of chemicals in complying with the REACH and CLP Regulations by developing an innovative training program in chemical safety management (CSM), available via the online project platform, adapted to the real needs of the target groups. MATERIAL AND METHODS: The methodology for implementing the ChemSM-Hub project includes: 1) conducting survey research among the target groups, 2) conducting a state-of-the-art review of literature and websites, 3) developing the Dissemination and Promotion Plan, 4) developing the Monitoring and Evaluation Procedure, 5) developing the CSM training curriculum, 6) designing the project e-learning platform and mobile app, 7) developing the "Training pattern for trainers" guidance, and 8) organizing training events. RESULTS: The project is being implemented in response to the changing EU legislation on chemicals. As a result of the project, a CSM training program has been established consisting of 3 modules (introductory, basic and advanced) with varying degrees of complexity. In addition, a pocket guide has been developed that contains basic information for DUs and Ds regarding the REACH and CLP Regulations, as well as the "Training pattern for trainers" guidance containing a CSM training session plan for trainers. All these materials will be available via the project platform, and their selected elements also via a mobile app. CONCLUSIONS: The publication is aimed to familiarize the potential users of the ChemSM-Hub training program with its thematic scope, the structure of the training and the expected results. It is also a way to promote online training adapted to the needs of its target groups. Int J Occup Med Environ Health. 2020;33(3):247-61.

Population susceptibility: A vital consideration in chemical risk evaluation under the Lautenberg Toxic Substances Control Act.

The 2016 Frank Lautenberg Chemical Safety for the 21st Century Act (Lautenberg TSCA) amended the 1976 Toxic Substances Control Act (TSCA) to mandate protection of susceptible and highly exposed populations. Program implementation entails a myriad of choices that can lead to different degrees of public health protections. Well-documented exposures to multiple industrial chemicals occur from air, soil, water, food, and products in our workplaces, schools, and homes. Many hazardous chemicals are associated with or known to cause health risks; for other industrial chemicals, no data exist to confirm their safety because of flaws in 1976 TSCA. Under the 2016 Lautenberg amendments, the United States Environmental Protection Agency (EPA) must evaluate chemicals against risk-based safety standards under enforceable deadlines, with an explicit mandate to identify and assess risks to susceptible and highly exposed populations. Effective public health protection requires EPA to implement the Lautenberg TSCA requirements by incorporating intrinsic and extrinsic factors that affect susceptibility, adequately assessing exposure among vulnerable groups, and accurately identifying highly exposed groups. We recommend key scientific and risk assessment principles to inform health-protective chemical policy such as consideration of aggregate exposures from all pathways and, when data are lacking, the use of health-protective defaults.

[Ten years of the application of REACH and CLP - assessing the knowledge and implementation of these regulations by Polish users of chemicals]. / Dziesiec lat obowiazywania REACH i CLP ­ ocena znajomosci i wdrazania przepisów przez polskich uzytkowników chemikaliów.

BACKGROUND: The aim of this work was to assess the awareness among both downstream users and distributors of chemicals in Poland, as regards legal regulations applicable to chemicals (i.e., the Regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals - REACH, and the Registration on classification, labelling and packaging - CLP), and to identify on this basis the needs for training and information campaigns addressed to these professional groups, by means of a questionnaire survey. MATERIAL AND METHODS: The SurveyMonkey Internet survey software was selected for this purpose. Two groups of respondents were surveyed - downstream users (DU) and distributors (D) of chemicals, and consumers. RESULTS: Responses were obtained from 65 downstream users and distributors of chemicals, and from 98 consumers. As many as 23% of the respondents did not know the obligations imposed on their company by REACH and CLP. Over 59% of the DU/D respondents did not have the opportunity to participate in chemical safety management (CSM) training in the last 5 years. Eighty percent of the respondents were interested in participating in free courses that would enable them to broaden their knowledge of the classification, labeling and marketing of chemicals. CONCLUSIONS: Despite the 10 years of the application of REACH and CLP, many people working for chemical enterprises still do not know their company's obligations set out in these regulations. The percentage of people positively assessing their competences increases with the size of the enterprise. The results of the survey indicate the need to organize continuous training for people using chemicals in their professional activity and for distributors. It is very important to ensure training at the basic level of chemical distributors. Such training should provide them with elementary knowledge on the hazards posed by chemicals, which could then be passed to consumers in an understandable manner. Med Pr. 2019;70(4):435-44.

In vitro to in vivo extrapolation for high throughput prioritization and decision making.

In vitro chemical safety testing methods offer the potential for efficient and economical tools to provide relevant assessments of human health risk. To realize this potential, methods are needed to relate in vitro effects to in vivo responses, i.e., in vitro to in vivo extrapolation (IVIVE). Currently available IVIVE approaches need to be refined before they can be utilized for regulatory decision-making. To explore the capabilities and limitations of IVIVE within this context, the U.S. Environmental Protection Agency Office of Research and Development and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods co-organized a workshop and webinar series. Here, we integrate content from the webinars and workshop to discuss activities and resources that would promote inclusion of IVIVE in regulatory decision-making. We discuss properties of models that successfully generate predictions of in vivo doses from effective in vitro concentration, including the experimental systems that provide input parameters for these models, areas of success, and areas for improvement to reduce model uncertainty. Finally, we provide case studies on the uses of IVIVE in safety assessments, which highlight the respective differences, information requirements, and outcomes across various approaches when applied for decision-making.

The unsteady state and inertia of chemical regulation under the US Toxic Substances Control Act.

After 40 years, the 1976 US Toxic Substances Control Act (TSCA) was revised under the Frank R. Lautenberg Chemical Safety for the 21st Century Act. Its original goals of protecting the public from hazardous chemicals were hindered by complex and cumbersome administrative burdens, data limitations, vulnerabilities in risk assessments, and recurring corporate lawsuits. As a result, countless chemicals were entered into commercial use without toxicological information. Few chemicals of the many identified as potential public health threats were regulated or banned. This paper explores the factors that have worked against a comprehensive and rational policy for regulating toxic chemicals and discusses whether the TSCA revisions offer greater public protection against existing and new chemicals.

Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance.

The application of chemical-specific toxicokinetic or toxicodynamic data to address interspecies differences and human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default or categorically-based uncertainty factors. The present review summarizes the state-of-the-science since the introduction of the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) guidance on chemical-specific adjustment factors (CSAF) in 2005 and the availability of recent applicable guidance including the WHO/IPCS guidance on physiologically-based pharmacokinetic (PBPK) modeling in 2010 as well as the U.S. EPA guidance on data-derived extrapolation factors in 2014. A summary of lessons learned from an analysis of more than 100 case studies from global regulators or published literature illustrates the utility and evolution of CSAF in regulatory decisions. Challenges in CSAF development related to the adequacy of, or confidence in, the supporting data, including verification or validation of PBPK models. The analysis also identified issues related to adequacy of CSAF documentation, such as inconsistent terminology and often limited and/or inconsistent reporting, of both supporting data and/or risk assessment context. Based on this analysis, recommendations for standardized terminology, documentation and relevant interdisciplinary research and engagement are included to facilitate the continuing evolution of CSAF development and guidance.

Comparing REACH Chemical Safety Assessment information with practice-a case-study of polymethylmethacrylate (PMMA) in floor coating in The Netherlands.

On June 1st, 2007 the European regulation on Registration, Evaluation and Restriction of Chemical substances (REACH) came into force. Aim of the regulation is safe use of chemicals for humans and for the environment. The core element of REACH is chemical safety assessment of chemicals and communication of health and safety hazards and risk management measures throughout the supply chain. Extended Safety Data Sheets (Ext-SDS) are the primary carriers of health and safety information. The aim of our project was to find out whether the actual exposure to methyl methacrylate (MMA) during the application of polymethylmethacrylate (PMMA) in floor coatings as assessed in the chemical safety assessment, reflect the exposure situations as observed in the Dutch building practice. Use of PMMA flooring and typical exposure situations during application were discussed with twelve representatives of floor laying companies. Representative situations for exposure measurements were designated on the basis of this inventory. Exposure to MMA was measured in the breathing zone of the workers at four construction sites, 14 full shift samples and 14 task based samples were taken by personal air sampling. The task-based samples were compared with estimates from the Targeted Risk Assessment Tool (v3.1) of the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC-TRA) as supplied in the safety assessment from the manufacturer. For task-based measurements, in 12 out of 14 (86%) air samples measured exposure was higher than estimated exposure. Recalculation with a lower ventilation rate (50% instead of 80%) together with a higher temperature during mixing (40°C instead of 20°C) in comparison with the CSR, reduced the number of underestimated exposures to 10 (71%) samples. Estimation with the EMKG-EXPO-Tool resulted in unsafe exposure situations for all scenarios, which is in accordance with the measurement outcomes. In indoor situations, 5 out of 8 full shift exposures (62%) to MMA were higher than the Dutch occupational exposure limit of 205mg/m3 (8h TWA), which equals the DNEL. For semi-enclosed situations this was 1 out of 6 (17%). Exposures varied from 31 to 367mg/m3. The results emphasize that ECETOC-TRA exposure estimates in poorly controlled situations need better underpinning.

Recomendaciones sobre la prevención de intoxicaciones / Recommendations for the prevention of poisoning

Las intoxicaciones constituyen la quinta causa de muerte por una lesión no intencionada en la región europea de la OMS, si bien España se encuentra en el grupo con una menor tasa. La mayoría de las intoxicaciones no voluntarias se dan en niños pequeños, en su casa, por la ingesta de medicamentos o productos del hogar. De estos últimos un porcentaje importante se almacena en recipientes no originales o al alcance de los niños. En el presente artículo, el Comité de Seguridad y Prevención de Lesiones No Intencionadas en la Infancia de la Asociación Española de Pediatría proporciona una serie de recomendaciones tanto educativas como legales para prevenir este tipo de lesiones

Poisoning is the fifth leading cause of death from unintentional injury in the WHO European region, while Spain is in the group with a lower rate. Most involuntary poisonings occur in young children while they are at the home, due to unintentional ingestion of therapeutic drugs or household products. Of these, a large percentage is stored in non-original containers and/or within reach of children. In this article, the Committee on Safety and Non-Intentional Injury Prevention in Childhood of the Spanish Association of Pediatrics provides a series of recommendations, educational as well as legal, to prevent such cases

Optimizing the aquatic toxicity assessment under REACH through an integrated testing strategy (ITS).

To satisfy REACH requirements a high number of data on chemical of interest should be supplied to the European Chemicals Agency. To organize the various kinds of information and help the registrants to choose the best strategy to obtain the needed information limiting at the minimum the use of animal testing, integrated testing strategies (ITSs) schemes can be used. The present work deals with regulatory data requirements for assessing the hazards of chemicals to the aquatic pelagic environment. We present an ITS scheme for organizing and using the complex existing data available for aquatic toxicity assessment. An ITS to optimize the choice of the correct prediction strategy for aquatic pelagic toxicity is described. All existing information (like physico-chemical information), and all the alternative methods (like in silico, in vitro or the acute-to-chronic ratio) are considered. Moreover the weight of evidence approach to combine the available data is included.

[Justifying expedience connected with development of Federal Law "On chemical safety"].

Based on analysis of present legal acts and regulations concerning chemicals handling in Russia, the authors necessitate development of Federal Law "On chemical safety".

Chemical safety, health care costs and the Affordable Care Act.

On May 22, 2013, the late Senator Frank Lautenberg (D-NJ), Senator David Vitter (R-LA) and 19 of their colleagues introduced bipartisan chemical safety legislation in the US Senate, "The Chemical Safety Improvement Act of 2013." The bill's purpose is to protect human health and the environment against the hazards of toxic chemicals, by requiring the US Environmental Protection Agency (EPA) to examine the safety of all chemicals in consumer products. The bill is currently before the Senate Committee on Environment and Public Works, chaired by Senator Barbara Boxer (D-CA). This legislation is critically important for physicians and healthcare organizations because it creates significant new opportunities to prevent disease and cut healthcare costs.

[Problems in the system of state regulation of chemical safety].

In the paper the analysis of the problems of chemical safety abroad and in Russian Federation is presented, possible ways for their solutions, including the need for legal and scientific-methodical support for population health risk assessment are considered.