Next generation risk assessment for occupational chemical safety - A real world example with sodium-2-hydroxyethane sulfonate.

Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g. under EU REACH. By contrast, a large proportion of regulatory worker safety assessments are underpinned by toxicological studies using experimental animals. Consequently, occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Here, a workflow for conducting NGRA under an occupational safety context was developed, which is illustrated with a case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were estimated using a standard occupational exposure model following a comprehensive life cycle assessment of SI and considering factory-specific data. Outputs of this model were then used to estimate internal exposures using a Physiologically Based Kinetic (PBK) model, which was constructed with SI specific Absorption, Distribution, Metabolism and Excretion (ADME) data. PBK modelling indicated a worst-case plasma maximum concentration (Cmax) of 0.8 µM across the SI life cycle. SI bioactivity was assessed in a battery of NAMs relevant to systemic, reproductive, and developmental toxicity; a cell stress panel, high throughput transcriptomics in three cell lines (HepG2, HepaRG and MCF-7 cells), pharmacological profiling and specific assays relating to developmental toxicity (Reprotracker and devTOX quickPredict). Points of Departure (PoDs) for SI ranged from 104 to 5044 µM. Cmax values obtained from PBK modelling of occupational exposures to SI were compared with PoDs from the bioactivity assays to derive Bioactivity Exposure Ratios (BERs) which demonstrated the safety for workers exposed to SI under current levels of factory specific risk management. In summary, the tiered and iterative workflow developed here represents an opportunity for integrating non animal approaches for a large subset of substances for which systemic worker safety assessment is required. Such an approach could be followed to ensure that animal testing is only conducted as a "last resort" e.g. under EU REACH.

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.

The use of Bayesian methodology in the development and validation of a tiered assessment approach towards prediction of rat acute oral toxicity.

There exists consensus that the traditional means by which safety of chemicals is assessed-namely through reliance upon apical outcomes obtained following in vivo testing-is increasingly unfit for purpose. Whilst efforts in development of suitable alternatives continue, few have achieved levels of robustness required for regulatory acceptance. An array of "new approach methodologies" (NAM) for determining toxic effect, spanning in vitro and in silico spheres, have by now emerged. It has been suggested, intuitively, that combining data obtained from across these sources might serve to enhance overall confidence in derived judgment. This concept may be formalised in the "tiered assessment" approach, whereby evidence gathered through a sequential NAM testing strategy is exploited so to infer the properties of a compound of interest. Our intention has been to provide an illustration of how such a scheme might be developed and applied within a practical setting-adopting for this purpose the endpoint of rat acute oral lethality. Bayesian statistical inference is drawn upon to enable quantification of degree of confidence that a substance might ultimately belong to one of five LD50-associated toxicity categories. Informing this is evidence acquired both from existing in silico and in vitro resources, alongside a purposely-constructed random forest model and structural alert set. Results indicate that the combination of in silico methodologies provides moderately conservative estimations of hazard, conducive for application in safety assessment, and for which levels of certainty are defined. Accordingly, scope for potential extension of approach to further toxicological endpoints is demonstrated.

Inherent Safety Assessment of Industrial-Scale Production of Chitosan Microbeads Modified with TiO2 Nanoparticles.

In this study, the inherent safety analysis of large-scale production of chitosan microbeads modified with TiO2 nanoparticles was developed using the Inherent Safety Index (ISI) methodology. This topology was structured based on two main stages: (i) Green-based synthesis of TiO2 nanoparticles based on lemongrass oil extraction and titanium isopropoxide (TTIP) hydrolysis, and (ii) Chitosan gelation and modification with nanoparticles. Stage (i) is divided into two subprocesses for accomplishing TiO2 synthesis, lemongrass oil extraction and TiO2 production. The plant was designed to produce 2033 t/year of chitosan microbeads, taking crude chitosan, lemongrass, and TTIP as the primary raw materials. The process was evaluated through the ISI methodology to identify improvement opportunity areas based on a diagnosis of process risks. This work used industrial-scale process inventory data of the analyzed production process from mass and energy balances and the process operating conditions. The ISI method comprises the Chemical Inherent Safety Index (CSI) and Process Inherent Safety Index (PSI) to assess a whole chemical process from a holistic perspective, and for this process, it reflected a global score of 28. Specifically, CSI and PSI delivered scores of 16 and 12, respectively. The analysis showed that the most significant risks are related to TTIP handling and its physical-chemical properties due to its toxicity and flammability. Insights about this process's safety performance were obtained, indicating higher risks than those from recommended standards.

ECOLOGICAL DETERMINANTS IN THE FORMATION OF THE POPULATION'S ATTITUDE TO THE DEVELOPMENT OF NUCLEAR ENERGY. / EKOLOGIChNI DETERMINANTY U FORMUVANNI STAVLENNIa NASELENNIa DO ROZVYTKU ATOMNOÏ ENERGETYKY.

OBJECTIVE: Evaluation of the key environmental determinants that shape the response of the social environment tothe activities of nuclear power plants. MATERIALS AND METHODS: The poll was conducted in the observation zone (OZ) of the South-Ukrainian NPP (SUNPP).A repetition-free probabilistic selection was used in the population survey. The sample of respondents from the population of the SUNPP OZ was 322 people with the sampling error of 5.4 % and confidence interval of 95.0%. An ordinal 5-point measurement scale was used to assess the quality of life and anxiety, and nominal measurement scaleswere used for other issues. All the age groups of population from 20 to 65 years were taken into account. The sociohygienic, sociological, statistical and mathematical research methods were applied in the process of work (relativevalues, averages, reliability of paired differences according to Student's t test). RESULTS: The level of perception of radiation risk by the population of the NPP OZ was the lowest among respondentsof satellite cities of Rivne NPP (RNPP) and SUNPP compared to the population of rural settlements and cities of theOZ. Storage and shipment of radioactive waste are the determinant among the factors that form an environmentalthreat to the population of OZ as a result of NPP activities. Social factors that determine the assessment of environmental safety of NPP activities are employment at the NPP, place of residence, gender, age, level of education of thepopulation, etc. The «Ch-image¼ of the ecological catastrophe formed in the population of Ukraine as a result of theChNPP accident , regardless of the place of residence on the territory of Ukraine, influences behavior, formation ofplans and assessments, especially in population living near the ionizing radiation sources. CONCLUSION: The current legislation governing the relationship between functioning NPPs and the communities inwhich they are located needs to be improved, guided by the basic principle of environmental public health - socialjustice, i.e. the human right to a healthy environment. It means that the settlements of the OZ (communities)receive funds to compensate for risk living in compliance with certain safety rules to maintain health. Legal regulation and constant awareness of population are the main directions for the formation of adequate assessments.

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.

Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures.

Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.

The implementation of RAAF in the OECD QSAR Toolbox.

The Read-Across Assessment Framework (RAAF) was developed by the European Chemicals Agency (ECHA) as an internal tool providing a framework for a consistent, structured and transparent assessment of grouping of chemicals and read-across. Following a RAAF-based evaluation, also developers and users of read-across predictions outside ECHA can judge whether their read-across rationale is sufficiently robust from a regulatory perspective. The aim of this paper is to describe the implementation of RAAF functionalities in the OECD QSAR Toolbox report. These can be activated in the prediction report after performing a readacross prediction. Once the user manually selects the appropriate scenario, the RAAF assessment elements appear and are automatically aligned with the suitable category elements of the Toolbox report. Subsequently, these are evaluated as part of the category consistency assessment functionality. The implementation of the RAAF functionality is illustrated in practice with two examples.

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.

Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff.

BACKGROUND: Occupational exposure to hazardous drugs can decrease fertility and result in miscarriages, stillbirths, and cancers in healthcare staff. Several recommended practices aim to reduce this exposure, including protective clothing, gloves, and biological safety cabinets ('safe handling'). There is significant uncertainty as to whether using closed-system drug-transfer devices (CSTD) in addition to safe handling decreases the contamination and risk of staff exposure to infusional hazardous drugs compared to safe handling alone. OBJECTIVES: To assess the effects of closed-system drug-transfer of infusional hazardous drugs plus safe handling versus safe handling alone for reducing staff exposure to infusional hazardous drugs and risk of staff contamination. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, OSH-UPDATE, CINAHL, Science Citation Index Expanded, economic evaluation databases, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to October 2017. SELECTION CRITERIA: We included comparative studies of any study design (irrespective of language, blinding, or publication status) that compared CSTD plus safe handling versus safe handling alone for infusional hazardous drugs. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and extracted data. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models. We assessed risk of bias according to the risk of bias in non-randomised studies of interventions (ROBINS-I) tool, used an intracluster correlation coefficient of 0.10, and we assessed the quality of the evidence using GRADE. MAIN RESULTS: We included 23 observational cluster studies (358 hospitals) in this review. We did not find any randomised controlled trials or formal economic evaluations. In 21 studies, the people who used the intervention (CSTD plus safe handling) and control (safe handling alone) were pharmacists or pharmacy technicians; in the other two studies, the people who used the intervention and control were nurses, pharmacists, or pharmacy technicians. The CSTD used in the studies were PhaSeal (13 studies), Tevadaptor (1 study), SpikeSwan (1 study), PhaSeal and Tevadaptor (1 study), varied (5 studies), and not stated (2 studies). The studies' descriptions of the control groups were varied. Twenty-one studies provide data on one or more outcomes for this systematic review. All the studies are at serious risk of bias. The quality of evidence is very low for all the outcomes.There is no evidence of differences in the proportion of people with positive urine tests for exposure between the CSTD and control groups for cyclophosphamide alone (RR 0.83, 95% CI 0.46 to 1.52; I² = 12%; 2 studies; 2 hospitals; 20 participants; CSTD: 76.1% versus control: 91.7%); cyclophosphamide or ifosfamide (RR 0.09, 95% CI 0.00 to 2.79; 1 study; 1 hospital; 14 participants; CSTD: 6.4% versus control: 71.4%); and cyclophosphamide, ifosfamide, or gemcitabine (RR not estimable; 1 study; 1 hospital; 36 participants; 0% in both groups).There is no evidence of a difference in the proportion of surface samples contaminated in the pharmacy areas or patient-care areas for any of the drugs except 5-fluorouracil, which was lower in the CSTD group than in the control (RR 0.65, 95% CI 0.43 to 0.97; 3 studies, 106 hospitals, 1008 samples; CSTD: 9% versus control: 13.9%).The amount of cyclophosphamide was lower in pharmacy areas in the CSTD group than in the control group (MD -49.34 pg/cm², 95% CI -84.11 to -14.56, I² = 0%, 7 studies; 282 hospitals, 1793 surface samples). Additionally, one interrupted time-series study (3 hospitals; 342 samples) demonstrated a change in the slope between pre-CSTD and CSTD (3.9439 pg/cm², 95% CI 1.2303 to 6.6576; P = 0.010), but not between CSTD and post-CSTD withdrawal (-1.9331 pg/cm², 95% CI -5.1260 to 1.2598; P = 0.20). There is no evidence of difference in the amount of the other drugs between CSTD and control groups in the pharmacy areas or patient-care areas.None of the studies report on atmospheric contamination, blood tests, or other measures of exposure to infusional hazardous drugs such as urine mutagenicity, chromosomal aberrations, sister chromatid exchanges, or micronuclei induction.None of the studies report short-term health benefits such as reduction in skin rashes, medium-term reproductive health benefits such as fertility and parity, or long-term health benefits related to the development of any type of cancer or adverse events.Five studies (six hospitals) report the potential cost savings through the use of CSTD. The studies used different methods of calculating the costs, and the results were not reported in a format that could be pooled via meta-analysis. There is significant variability between the studies in terms of whether CSTD resulted in cost savings (the point estimates of the average potential cost savings ranged from (2017) USD -642,656 to (2017) USD 221,818). AUTHORS' CONCLUSIONS: There is currently no evidence to support or refute the routine use of closed-system drug transfer devices in addition to safe handling of infusional hazardous drugs, as there is no evidence of differences in exposure or financial benefits between CSTD plus safe handling versus safe handling alone (very low-quality evidence). None of the studies report health benefits.Well-designed multicentre randomised controlled trials may be feasible depending upon the proportion of people with exposure. The next best study design is interrupted time-series. This design is likely to provide a better estimate than uncontrolled before-after studies or cross-sectional studies. Future studies may involve other alternate ways of reducing exposure in addition to safe handling as one intervention group in a multi-arm parallel design or factorial design trial. Future studies should have designs that decrease the risk of bias and enable measurement of direct health benefits in addition to exposure. Studies using exposure should be tested for a relevant selection of hazardous drugs used in the hospital to provide an estimate of the exposure and health benefits of using CSTD. Steps should be undertaken to ensure that there are no other differences between CSTD and control groups, so that one can obtain a reasonable estimate of the health benefits of using CSTD.

The Impact of Novel Assessment Methodologies in Toxicology on Green Chemistry and Chemical Alternatives.

The field of experimental toxicology is rapidly advancing by incorporating novel techniques and methods that provide a much more granular view into the mechanisms of potential adverse effects of chemical exposures on human health. The data from various in vitro assays and computational models are useful not only for increasing confidence in hazard and risk decisions, but also are enabling better, faster and cheaper assessment of a greater number of compounds, mixtures, and complex products. This is of special value to the field of green chemistry where design of new materials or alternative uses of existing ones is driven, at least in part, by considerations of safety. This article reviews the state of the science and decision-making in scenarios when little to no data may be available to draw conclusions about which choice in green chemistry is "safer." It is clear that there is no "one size fits all" solution and multiple data streams need to be weighed in making a decision. Moreover, the overall level of familiarity of the decision-makers and scientists alike with new assessment methodologies, their validity, value and limitations is evolving. Thus, while the "impact" of the new developments in toxicology on the field of green chemistry is great already, it is premature to conclude that the data from new assessment methodologies have been widely accepted yet.

Use and limitations of offsite consequence analysis tools from South Korea and the United States in hydrogen fluoride accidental release.

We investigated the characteristics and limitations in the event of hydrofluoric acid (HF) leakage by comparing and analyzing the offsite consequence analysis (OCA) tools based on the chemical plant operating conditions. We reviewed the tools Korea Offsite Risk Assessment (KORA) from South Korea and Risk Management Plan*Comp (RMP*Comp™) and Areal Location of Hazardous Atmospheres (ALOHA) from the United States. The scenario studied was based on a leak event from a 50% HF aqueous solution storage tank, and the operating conditions taken into consideration were the operating temperature and dike installation conditions. The results from the OCA differed; KORA presented a smaller range of offsite impact than did ALOHA. The offsite impact ranges of KORA and ALOHA increased as the operating temperature and dike installation area increased. However, RMP*Comp differed greatly in its offsite impact range results in the operating temperature range of 25 °C to 30 °C. Moreover, in the alternative scenario, a limitation existed in that the offsite impact range was not changed by the dike installation conditions. The offsite impact range analyzed via KORA and ALOHA reflected the reality of an HF leak accident better than that analyzed via RMP*Comp. Therefore, it is more reasonable to use KORA and ALOHA instead of RMP*Comp in OCA. Moreover, users should realize that ALOHA has a somewhat wider range of offsite impact than KORA does in OCA. The separation distance from the storage tank when installing a dike is effective between 1 and 1.5 m in consideration of securing the minimum workspace for workers. Integr Environ Assess Manag 2018;14:205-211. © 2017 SETAC.

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.

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.

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.

Workshop: use of "read-across" for chemical safety assessment under REACH.

Read-across has generated much attention, since it may be used as an alternative approach for addressing the information requirements under REACH. Experience in the application of "read-across" has undoubtedly been gained within the context of the 2010 registrations (>1000 tonnes/annum). Industry, European Chemicals Agency (ECHA) and EU Member States all conceptually accept read-across approaches but difficulties still remain in applying them consistently in practice. A workshop on the 'Use of Read-Across for Chemical Safety Assessment under REACH', organised by ECHA with the active support of Cefic LRI was held on the 3rd October 2012 to gain insight on how ECHA evaluates read-across justifications, to share Industry experiences with read-across approaches and to discuss practical strategies to help develop scientifically valid read-across for future submissions.

Specific environmental release categories--A tool for improving chemical safety assessment in the EC--report of a multi-stakeholder workshop.

In April 2011, experts from industry and authorities met for a workshop to discuss experience and future developments regarding the use of specific environmental release categories (SPERCs) in chemicals safety assessment (CSA) under the European Chemicals Regulation Registration, Evaluation and Authorization of Chemicals (REACH). This article provides a summary of the workshop. It briefly explains what a SPERC is, why SPERCs are needed, where the challenges of the concept are, and what improvements are needed to make SPERCs a useful tool for assessments under REACH.