The codification of hazard and its impact on the hazard versus risk controversy.

The long running controversy about the relative merits of hazard-based versus risk-based approaches has been investigated. There are three levels of hazard codification: level 1 divides chemicals into dichotomous bands of hazardous and non-hazardous; level 2 divides chemicals into bands of hazard based on severity and/or potency; and level 3 places each chemical on a continuum of hazard based on severity and/or potency. Any system which imposes compartments onto a continuum will give rise to issues at the boundaries, especially with only two compartments. Level 1 schemes are only justifiable if there is no variation in severity, or potency or if there is no threshold. This is the assumption implicit in GHS/EU classification for carcinogenicity, reproductive toxicity and mutagenicity. However, this assumption has been challenged. Codification level 2 hazard assessments offer a range of choices and reduce the built-in conflict inherent in the level 1 process. Level 3 assessments allow a full range of choices between the extremes and reduce the built-in conflict even more. The underlying reason for the controversy between hazard and risk is the use of level 1 hazard codification schemes in situations where there are ranges of severity and potency which require the use of level 2 or level 3 hazard codification. There is not a major difference between level 2 and level 3 codification, and they can both be used to select appropriate risk management options. Existing level 1 codification schemes should be reviewed and developed into level 2 schemes where appropriate.

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.

Weight-of-Evidence Approach for Assessing Removal of Metals from the Water Column for Chronic Environmental Hazard Classification.

The United Nations and the European Union have developed guidelines for the assessment of long-term (chronic) chemical environmental hazards. This approach recognizes that these hazards are often related to spillage of chemicals into freshwater environments. The goal of the present study was to examine the concept of metal ion removal from the water column in the context of hazard assessment and classification. We propose a weight-of-evidence approach that assesses several aspects of metals including the intrinsic properties of metals, the rate at which metals bind to particles in the water column and settle, the transformation of metals to nonavailable and nontoxic forms, and the potential for remobilization of metals from sediment. We developed a test method to quantify metal removal in aqueous systems: the extended transformation/dissolution protocol (T/DP-E). The method is based on that of the Organisation for Economic Co-operation and Development (OECD). The key element of the protocol extension is the addition of substrate particles (as found in nature), allowing the removal processes to occur. The present study focused on extending this test to support the assessment of metal removal from aqueous systems, equivalent to the concept of "degradability" for organic chemicals. Although the technical aspects of our proposed method are different from the OECD method for organics, its use for hazard classification is equivalent. Models were developed providing mechanistic insight into processes occurring during the T/DP-E method. Some metals, such as copper, rapidly decreased (within 96 h) under the 70% threshold criterion, whereas others, such as strontium, did not. A variety of method variables were evaluated and optimized to allow for a reproducible, realistic hazard classification method that mimics reasonable worst-case scenarios. We propose that this method be standardized for OECD hazard classification via round robin (ring) testing to ascertain its intra- and interlaboratory variability. Environ Toxicol Chem 2019;38:1839-1849. © 2019 SETAC.

Grouping of nanomaterials to read-across hazard endpoints: from data collection to assessment of the grouping hypothesis by application of chemoinformatic techniques.

BACKGROUND: An increasing number of manufactured nanomaterials (NMs) are being used in industrial products and need to be registered under the REACH legislation. The hazard characterisation of all these forms is not only technically challenging but resource and time demanding. The use of non-testing strategies like read-across is deemed essential to assure the assessment of all NMs in due time and at lower cost. The fact that read-across is based on the structural similarity of substances represents an additional difficulty for NMs as in general their structure is not unequivocally defined. In such a scenario, the identification of physicochemical properties affecting the hazard potential of NMs is crucial to define a grouping hypothesis and predict the toxicological hazards of similar NMs. In order to promote the read-across of NMs, ECHA has recently published "Recommendations for nanomaterials applicable to the guidance on QSARs and Grouping", but no practical examples were provided in the document. Due to the lack of publicly available data and the inherent difficulties of reading-across NMs, only a few examples of read-across of NMs can be found in the literature. This manuscript presents the first case study of the practical process of grouping and read-across of NMs following the workflow proposed by ECHA. METHODS: The workflow proposed by ECHA was used and slightly modified to present the read-across case study. The Read-Across Assessment Framework (RAAF) was used to evaluate the uncertainties of a read-across within NMs. Chemoinformatic techniques were used to support the grouping hypothesis and identify key physicochemical properties. RESULTS: A dataset of 6 nanoforms of TiO2 with more than 100 physicochemical properties each was collected. In vitro comet assay result was selected as the endpoint to read-across due to data availability. A correlation between the presence of coating or large amounts of impurities and negative comet assay results was observed. CONCLUSION: The workflow proposed by ECHA to read-across NMs was applied successfully. Chemoinformatic techniques were shown to provide key evidence for the assessment of the grouping hypothesis and the definition of similar NMs. The RAAF was found to be applicable to NMs.

Best practices for developmental toxicity assessment for classification and labeling.

Many chemicals are going through a hazard-based classification and labeling process in Europe. Because of the significant public health implications, the best science must be applied in assessing developmental toxicity data. The European Teratology Society and Health and Environmental Sciences Institute co-organized a workshop to consider best practices, including data quality and consistency, interpretation of developmental effects in the presence of maternal toxicity, human relevance of animal data, and limits of chemical classes. Recommendations included larger historical control databases, more pharmacokinetic studies in pregnant animals for dose setting and study interpretation, generation of mechanistic data to resolve questions about whether maternal toxicity is causative of developmental toxicity, and more rigorous specifications for what constitutes a chemical class. It is our hope that these recommendations will form the basis for subsequent consensus workshops and other scientific activities designed to improve the scientific robustness of data interpretation for classification and labeling.

An Assessment of the Robustness of the COSHH-Essentials (C-E) Target Airborne Concentration Ranges 15 Years on, and Their Usefulness for Determining Control Measures.

The Health and Safety Executive (HSE) in Great Britain (GB), in association with its stakeholders, developed the Control of Substances Hazardous to Health (COSHH)-Essentials (C-E) control banding tool in 1998. The objective was to provide a simple tool for employers, particularly small and medium-sized enterprises (SMEs), to help select and apply appropriate measures for the adequate control of exposure to hazardous substances. The tool used hazard classification information (R-phrases) to assign substances to one of five health hazard groups, each with its respective 'target airborne concentration range'. The validity of the allocation of substances to a target airborne concentration range was demonstrated at the time using 111 substances that had a current health-based Occupational Exposure Limit (OEL) in GB. The C-E control banding approach remains an important tool to complement exposure assessment/monitoring and the selection and use of suitable control measures for hazardous substances. These include engineering controls and personal protective equipment (PPE). The C-E based control banding approach has been adopted around the world. This paper extends the original validation exercise, using a greater number of chemical substances, to establish whether the target airborne concentration ranges remain appropriate. This is of particular interest in light of the introduction of the Globally Harmonized System (GHS) for classification, in which R-phrases have now been replaced by hazard-statements (H-statements). The validation exercise includes substances with OELs published by nine bodies internationally; and the Derived No-Effect Levels (DNELs) assigned by registrants under the European Union-Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulations. When compared against 8-hour TWA OELs for 850 substances drawn from nine bodies and a limited number of DNELS, the C-E target airborne concentration ranges remain valid. This comparative work also informs a wider consideration around the practicality and the applicability of the C-E generic approach to facilitate the implementation of good practice control for a wide range of substances (more than 95%) which do not have any recognized OEL.

A Framework for Hazard Banding.

Exposure limits are absent for thousands of chemicals, creating a need for guidance that occupational exposure banding can help to fill, according to the authors of a new guidance document.

Use of a modified GreenScreen tool to conduct a screening-level comparative hazard assessment of conventional silver and two forms of nanosilver.

BACKGROUND: Increased concern for potential health and environmental impacts of chemicals, including nanomaterials, in consumer products is driving demand for greater transparency regarding potential risks. Chemical hazard assessment is a powerful tool to inform product design, development and procurement and has been integrated into alternative assessment frameworks. The extent to which assessment methods originally designed for conventionally-sized materials can be used for nanomaterials, which have size-dependent physical and chemical properties, have not been well established. We contracted with a certified GreenScreen profiler to conduct three GreenScreen hazard assessments, for conventional silver and two forms of nanosilver. The contractor summarized publicly available literature, and used defined GreenScreen hazard criteria and expert judgment to assign and report hazard classification levels, along with indications of confidence in those assignments. Where data were not available, a data gap (DG) was assigned. Using the individual endpoint scores, an aggregated benchmark score (BM) was applied. RESULTS: Conventional silver and low-soluble nanosilver were assigned the highest possible hazard score and a silica-silver nanocomposite called AGS-20 could not be scored due to data gaps. AGS-20 is approved for use as antimicrobials by the US Environmental Protection Agency. CONCLUSIONS: An existing method for chemical hazard assessment and communication can be used - with minor adaptations- to compare hazards across conventional and nano forms of a substance. The differences in data gaps and in hazard profiles support the argument that each silver form should be considered unique and subjected to hazard assessment to inform regulatory decisions and decisions about product design and development. A critical limitation of hazard assessments for nanomaterials is the lack of nano-specific hazard data - where data are available, we demonstrate that existing hazard assessment systems can work. The work is relevant for risk assessors and regulators. We recommend that regulatory agencies and others require more robust data sets on each novel nanomaterial before granting market approval.

A quantitative weight of evidence methodology for the assessment of reproductive and developmental toxicity and its application for classification and labeling of chemicals.

Hazard assessment of chemicals usually applies narrative assessments with a number of weaknesses. Therefore, application of weight of evidence (WoE) approaches are often mandated but guidance to perform a WoE assessment is lacking. This manuscript describes a quantitative WoE (QWoE) assessment for reproductive toxicity data and its application for classification and labeling (C&L). Because C&L criteria are based on animal studies, the scope is restricted to animal toxicity data. The QWoE methodology utilizes numerical scoring sheets to assess reliability of a publication and the toxicological relevance of reported effects. Scores are given for fourteen quality aspects, best practice receives the highest score. The relevance/effects scores (0 to four) are adjusted to the key elements of the toxic response for the endpoint and include weighting factors for effects on different levels of the biological organization. The relevance/effects scores are then assessed against the criteria dose-response, magnitude and persistence of effects, consistency of observations with the hypothesis, and relation of effects to human disease. The quality/reliability scores and the relevance/effect scores are then multiplied to give a numerical strength of evidence for adverse effects. This total score is then used to assign the chemical to the different classes employed in classification.

On the Strength and Validity of Hazard Banding.

Hazard Banding (HB) is a process of allocating chemical substances in bands of increasing health hazard based on their hazard classifications. Recent Control Banding (CB) tools use the classifications of the United Nations Global Harmonized System (UN GHS) or the European Union Classifications, Labelling and Packaging (EU CLP) which are grouped over 5 HBs. The use of CB is growing worldwide for the risk control of substances without an Occupational Exposure Limit Value (OELV). Well-known CB-tools like HSE-COSHH Essentials, BAuA-Einfaches Maßnahmenkonzept Gefahrstoffe (EMKG), and DGUV-IFA-Spaltenmodell (IFA) use however different GHS/CLP groupings which may lead to dissimilar HBs and control regimes for individual substances. And as the choice for a CB tool seems to be determined by geography and/or local status these differences may hamper a global, aligned HSE approach. Therefore, the HB-engines of the three public CBs and an in-company (Solvay) CB called 'Occupational Exposure Banding' (S-OEB) were compared mutually and ranked in their relation with the OELV as the 'de facto' standard. This was investigated graphically and using a 5 strength indicator, statistical method. A data set of 229 substances with high-quality GHS/CLP classifications and OELVs was used. HB concentration ranges, as linked to S-OEB and COSHH, were validated against the corresponding OELV distributions. The four HB-engines allocate between 23 and 64% of the 229 substances in the same bands. The remaining substances differ at least one band, with IFA placing more substances in a higher hazard band, EMKG doing the opposite and COSHH and S-OEB in between. The overall strength scores of S-OEB, IFA, and EMGK HB-engines are higher than COSHH, with S-OEB having the highest overall strength score. The lower ends of the concentration ranges defined for the 3 'highest' hazard bands of S-OEB were in good agreement with the 10th percentiles of the corresponding OELV distributions obtained from the substance data set. The lower ends of the COSHH concentration ranges comply with the 10th percentiles of the COSHH OELV distributions for dust/aerosol but not for vapour/gas substances. Both the S-OEB and COSHH concentration ranges underestimate the overall width of the OELV distributions that can span 2-3 orders of magnitude. As the performance of the S-OEB HB-engine meets our criteria of being at least as good as the public engines, it will be used as a standard within Solvay's global operations. In addition, the method described here to evaluate the strength of HB-engines and the validity of their corresponding concentration ranges is a useful tool enabling further developments and worldwide alignment of HB.

A comparison of control banding tools for nanomaterials.

Control banding (CB) is a useful approach to evaluate and control the risk of exposure to nanomaterials (NM) due to uncertainty surrounding their toxicity and challenges associated with their measurement. Four CB tools specifically developed for NMs (NanoSafer, Stoffenmanager-Nano, NanoTool, and the Precautionary matrix) have been evaluated for their changes to differences in hazard and exposure input data. The hazard and exposure classification were also compared with experimental data. The tools provided different hazard and emission/exposure outputs when compared with each other and with experimental data. For some of the tools the information required to estimate the hazard is not always available in the Safety Data Sheet and it requires expert judgement. The tools have the potential to be valuable starting points to assess areas of high priority, although outputs should be interpreted with care. Further work should be done to improve their estimates, especially the inclusion of modifiers that account for the effectiveness of the ventilation and the effect of high temperatures during the process.

Hazard banding in compliance with the new Globally Harmonised System (GHS) for use in control banding tools.

Many control banding tools use hazard banding in risk assessments for the occupational handling of hazardous substances. The outcome of these assessments can be combined with advice for the required risk management measures (RMMs). The Globally Harmonised System of Classification and Labelling of Chemicals (GHS) has resulted in a change in the hazard communication elements, i.e. Hazard (H) statements instead of Risk-phrases. Hazard banding schemes that depend on the old form of safety information have to be adapted to the new rules. The purpose of this publication is to outline the rationales for the assignment of hazard bands to H statements under the GHS. Based on this, this publication proposes a hazard banding scheme that uses the information from the safety data sheets as the basis for assignment. The assignment of hazard bands tiered according to the severity of the underlying hazards supports the important principle of substitution. Additionally, the set of assignment rules permits an exposure-route-specific assignment of hazard bands, which is necessary for the proposed route-specific RMMs. Ideally, all control banding tools should apply the same assignment rules. This GHS-compliant hazard banding scheme can hopefully help to establish a unified hazard banding strategy in the various control banding tools.

[APPLICATION OF BIOMONITORING METHODOLOGY FOR THE ASSESSMENT OF EXPOSURE TO ENVIRONMENTAL POLLUTANTS].

In this article there are presented the current views on the technology for the assessment of the exposure to chemical pollutants with the use of the methodology of human biomonitoring and the main advantages of the latter are highlighted. There are presented main problems of the implementation of biomonitoring studies in Russia such as: beginning with the lack of the national system of the biomonitoring, and accomplishing with the inconsistency in the data within the country, the inability to assess the trend according to levels of exposure in the regional or national context. Due to the inconvenience of the Russian regulatory basis on human biomonitoring, there is persisted technological backwardness in terms of the delivery of the design, presentation and evaluation of research results, which results in the decline of the significance of biomonitoring for public health in the country. There is preserved a need for standardization and harmonization of methods and procedures of human biomonitoring (HBM) in Russia with international requirements. A serious concern is the lack of Russian programs on standardization of procedures and interlaboratcy comparison of results according to biomarkers of the exposure, the insufficient involvement of national laboratories in international programs of the comparison, the difficulties with the acquisition of standard samples of the compositionfor different environmental pollutants in biological tissues. The restraint ofthe development of HBM in the Russian Federation is caused by a complex of reasons. The most urgent task is the development of the national concept of the system with subsequent formation of technological, institutional and organizational framework of biomonitoring, as well as the improvement of Russian normative-methodical base.

[The development of a comprehensive assessment of occupational risk by taking into account the total hazard of working conditions].

In the paper the methodological problems of establishing a general class of working conditions on the results of certification of workplaces are analyzed There is proposed the use of an additional parameter - the index of harm, characterizing the degree of correspondence of the general level of harmful occupational factors to applicable health standards with taking into account the nonequivalence of their display. The recommendations for the use of hazard index as the main criterion for a priori evaluation ofthe category ofsuspected occupational risk and the tool to establish by the correlation methods cause-and-effect relations between indices of health status and the impact ofoccupational factors are presented. As exemplified by real working conditions the possibilities of the use the index of harm as an indicator describing the hazard probability are considered with comprehensive assessment of occupational risk of health problems on the basis of the matrix method with the use of the table of vectors and nomograms "probability of harm - the severity of the consequences". The use of index of harm will permit to increase the objectivity of the assessment and the efficacy of management of occupational hazards in the workplaces.

A decision analytic approach to exposure-based chemical prioritization.

The manufacture of novel synthetic chemicals has increased in volume and variety, but often the environmental and health risks are not fully understood in terms of toxicity and, in particular, exposure. While efforts to assess risks have generally been effective when sufficient data are available, the hazard and exposure data necessary to assess risks adequately are unavailable for the vast majority of chemicals in commerce. The US Environmental Protection Agency has initiated the ExpoCast Program to develop tools for rapid chemical evaluation based on potential for exposure. In this context, a model is presented in which chemicals are evaluated based on inherent chemical properties and behaviorally-based usage characteristics over the chemical's life cycle. These criteria are assessed and integrated within a decision analytic framework, facilitating rapid assessment and prioritization for future targeted testing and systems modeling. A case study outlines the prioritization process using 51 chemicals. The results show a preliminary relative ranking of chemicals based on exposure potential. The strength of this approach is the ability to integrate relevant statistical and mechanistic data with expert judgment, allowing for an initial tier assessment that can further inform targeted testing and risk management strategies.

Chemical hazards in the organisation.

The use of hazardous chemicals in organisations represents a substantial risk to occupational health, safety and the environment (OHSE). Organisational directors and managers have a responsibility to provide and maintain organisational management systems that manage these risks. The risk management approach of establishing organisational considerations, identifying chemical hazards (health and environmental), assessing and controlling risks and evaluating management activities has become the de facto means of managing organisational hazards in general and may be satisfactorily applied to the management of chemicals in the organisation. The Globally Harmonized System for the Classification and Labelling of Chemicals (GHS) is now at the forefront of major regulatory issues facing the chemicals manufacturing industry and downstream users of chemicals. The GHS offers one system for the classification of all dangerous, toxic and environmental (ecotoxic) effects of chemicals. Organisations should develop occupational health, safety and environment (OHSE) management systems which contain programs and procedures that contain systems for inventory control, hazard communication, competency training, risk assessment and control, transport and storage, monitoring and health surveillance, chemical emergencies (including accident investigation), waste minimisation and disposal, record keeping and management system review.

Control banding approaches for nanomaterials.

Control banding (CB) has been developed as a pragmatic tool to manage the risk resulting from exposure to a wide variety of potentially hazardous substances in the absence of firm toxicological and exposure information. Currently, the CB approach is applied for emerging risks such as nanoparticles, by the development of various CB-based tools. Six of these are compared. Despite their similarity, i.e. combining hazard and exposure into control or risk bands, the structure, the applicability domains, and the assignment of the hazard and exposure bands, show differences that may affect the consistency of the resulting outcome amongst the various CB tools. The value of the currently available CB tools for nanomaterials can be enhanced by transparently elucidating these differences for user consideration during the selection of a tool for a specific scenario of application.

The evolution of skin notations for occupational risk assessment: a new NIOSH strategy.

This article presents an overview of a strategy for assignment of hazard-specific skin notations (SK), developed by the National Institute for Occupational Safety and Health (NIOSH). This health hazard characterization strategy relies on multiple SKs capable of delineating systemic (SYS), direct (DIR), and immune-mediated (SEN) adverse effects caused by dermal exposures to chemicals. One advantage of the NIOSH strategy is the ability to combine SKs when it is determined that a chemical may cause multiple adverse effects following dermal contact (e.g., SK: SYS-DIR-SEN). Assignment of the SKs is based on a weight-of-evidence (WOE) approach, which refers to the critical examination of all available data from diverse lines of evidence and the derivation of a scientific interpretation based on the collective body of data including its relevance, quality, and reported results. Numeric cutoff values, based on indices of toxic potency, serve as guidelines to aid in consistently determining a chemical's relative toxicity and hazard potential. The NIOSH strategy documents the scientific rationale for determination of the hazard potential of a chemical and the subsequent assignment of SKs. A case study of acrylamide is presented as an application of the NIOSH strategy.

Environmental and health hazard ranking and assessment of plastic polymers based on chemical composition.

Plastics constitute a large material group with a global annual production that has doubled in 15 years (245 million tonnes in 2008). Plastics are present everywhere in society and the environment, especially the marine environment, where large amounts of plastic waste accumulate. The knowledge of human and environmental hazards and risks from chemicals associated with the diversity of plastic products is very limited. Most chemicals used for producing plastic polymers are derived from non-renewable crude oil, and several are hazardous. These may be released during the production, use and disposal of the plastic product. In this study the environmental and health hazards of chemicals used in 55 thermoplastic and thermosetting polymers were identified and compiled. A hazard ranking model was developed for the hazard classes and categories in the EU classification and labelling (CLP) regulation which is based on the UN Globally Harmonized System. The polymers were ranked based on monomer hazard classifications, and initial assessments were made. The polymers that ranked as most hazardous are made of monomers classified as mutagenic and/or carcinogenic (category 1A or 1B). These belong to the polymer families of polyurethanes, polyacrylonitriles, polyvinyl chloride, epoxy resins, and styrenic copolymers. All have a large global annual production (1-37 million tonnes). A considerable number of polymers (31 out of 55) are made of monomers that belong to the two worst of the ranking model's five hazard levels, i.e. levels IV-V. The polymers that are made of level IV monomers and have a large global annual production (1-5 million tonnes) are phenol formaldehyde resins, unsaturated polyesters, polycarbonate, polymethyl methacrylate, and urea-formaldehyde resins. This study has identified hazardous substances used in polymer production for which the risks should be evaluated for decisions on the need for risk reduction measures, substitution, or even phase out.

Classification and labeling of industrial products with extreme pH by making use of in vitro methods for the assessment of skin and eye irritation and corrosion in a weight of evidence approach.

Classification and labeling of products with extreme pH values (≤ 2 or ≥ 11.5) is addressed in chemicals legislation. Following determination of pH and alkaline/acid reserve, additional in vitro tests are needed, especially to substantiate results less than corrosive. However, only limited experience with the practical application of in vitro methods to determine appropriate classifications for pH extreme products is available so far. Expert judgment and weight of evidence are given major roles under the globally harmonized system of classification and labeling of chemicals (GHS) and should be performed on a sound data basis. We have used a tiered testing strategy to assess 20 industrial products (cleaning and metal pretreatment) regarding their corrosive and irritating properties towards human skin models in vitro in the EpiDerm skin corrosion and/or skin irritation test. Nine dilutions of individual compounds were additionally tested. Non-corrosive samples were tested in the Hen's egg test chorioallantoic membrane (HET-CAM). We demonstrate how data is combined in a weight of evidence expert judgment, and give examples of classification decisions. To our knowledge this is the first comprehensive analysis of industrial products with extreme pH values to determine irritating and corrosive properties by making use of in vitro methods in a weight of evidence approach.