Packaging Of Substances Research Articles

Monocytes and macrophages transmit inflammatory signals to each other via extracellular vesicles

Monocytes and macrophages play an important role in the development of inflammatory diseases, including sepsis, etc. In addition to their role as “scavengers,” macrophages secrete various substances (mainly cytokines and chemokines), which have a systemic effect and modulate the microenvironment of the inflammatory focus. Disruption of their normal function can cause various immune pathologies and changes in tissue homeostasis. Macrophages are able to transmit signals to other cells in the area of inflammation, including various cytokines and other compounds. Usually, they are secreted directly into the extracellular space. However, the lifetime and range of action of these substances may be limited. An alternative method of intercellular communication is the packaging of substances into extracellular vesicles, which can help in signal propagation. Extracellular vesicles are small particles with a bilayer lipid membrane that transport various biologically active substances. There are different types of extracellular vesicles, each of which can have its own specific effect on other cells. Due to the presence of specific receptors on the surface of the vesicles, they can make selective delivery of biological molecules to certain cells. Vesicles can contain various components, such as nucleic acids, proteins, lipids, and even individual cell organelles. Therefore, it is not surprising that vesicles are able to modulate physiological processes in the body and be involved in the pathogenesis of various diseases. Establishing the mechanisms of vesicle participation in the development of inflammatory diseases, including chronic ones, is extremely important. The aim of the present study was to determine whether extracellular vesicles are capable of modulating the immune response. To do this, we assessed cytokine secretion by macrophages treated with vesicles from LPS-stimulated monocytes and macrophages. It was found that cells that received vesicles from LPS-activated monocytes and macrophages secrete more pro-inflammatory signaling molecules: the cytokine IL-6 and the chemokine IL-8. The results demonstrate that intercellular interaction and transmission of the inflammatory signal of monocytic cells also occurs through extracellular vesicles. In the future, additional research is needed to understand the full picture of what substances in the extracellular vesicles of monocytes and macrophages allow them to have an immunomodulatory effect not only on each other, but also on other types of cells.

A battery of in silico models application for pesticides exerting reproductive health effects: Assessment of performance and prioritization of mechanistic studies

Given the high attention to endocrine disrupting chemicals (EDC), there is an urgent need for the development of rapid and reliable approaches for the screening of large numbers of chemicals with respect to their endocrine disruption potential. This study aimed at the assessment of the correlation between the predicted results of a battery of in silico tools and the reported observed adverse effects from in vivo reproductive toxicity studies. We used VirtualToxLab (VTL) software and the EndocrineDisruptome (ED) online tool to evaluate the binding affinities to nuclear receptors of 17 pesticides, 7 of which were classified as reprotoxic substances under Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP). Then, we aligned the results of the in silico modelling with data from ToxCast assays and in vivo reproductive toxicity studies. We combined results from different in silico tools in two different ways to improve the characteristics of their predictive performance. Reproductive toxicity can be caused by various mechanisms; however, in this study, we demonstrated that the use of a battery of in silico tools for assessing the binding to nuclear receptors can be useful for identifying hazardous compounds and for prioritizing further studies.

Initial evaluation of USP apparatus 4 for measuring dissolution profile of man-made vitreous fibers

We report the successful evaluation of a US Pharmacopeia Apparatus 4 (USP-4) system in measuring the dissolution profiles of man-made vitreous fibers (MMVF)11Man-made vitreous fibers (MMVF) is the terminology commonly used in the European Union to refer to mineral wool fibers, it is also the terminology used in the classification entries for these materials in Regulation (EC) No 1272/2008 classification, labelling and packaging of substances and mixtures as the term synthetic vitreous fibers (SVF) is also used in literature and other jurisdictions to refer to mineral wool fibers.. Glass and stone wool fibers with different (high- and low-) solubility profiles were tested in closed-loop configuration using a sodium/potassium phosphate buffer solution or an acetate buffer, respectively. Results confirm a need to operate in diluted conditions to avoid silicon saturation in the simulant solution and suppression of fiber dissolution. A clear fiber-to-fiber differentiation with good cell-to-cell reproducibility was achieved. These findings support the continued development of a USP-4 protocol for MMVF in vitro acellular testing.

A Weight of Evidence approach to classify nanomaterials according to the EU Classification, Labelling and Packaging Regulation criteria

In the context of the European Union (EU) Horizon 2020 GRACIOUS project (Grouping, Read-Across, Characterisation and classification framework for regulatory risk assessment of manufactured nanomaterials and Safer design of nano-enabled products), we proposed a quantitative Weight of Evidence (WoE) approach for hazard classification of nanomaterials (NMs). This approach is based on the requirements of the European Regulation on Classification, Labelling and Packaging of Substances and Mixtures (the CLP regulation), which implements the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS) in the European Union. The goal of this WoE methodology is to facilitate classification of NMs according to CLP criteria, following the decision trees defined in ECHA's CLP regulatory guidance. In the WoE, results from heterogeneous studies are weighted according to data quality and completeness criteria, integrated, and then evaluated by expert judgment to obtain a hazard classification, resulting in a coherent and justifiable methodology. Moreover, the probabilistic nature of the proposed approach enables highlighting the uncertainty in the analysis. The proposed methodology involves the following stages: (1) collection of data for different NMs related to the endpoint of interest: each study related to each NM is referred as a Line of Evidence (LoE); (2) computation of weighted scores for each LoE: each LoE is weighted by a score calculated based on data quality and completeness criteria defined in the GRACIOUS project; (3) comparison and integration of the weighed LoEs for each NM: A Monte Carlo resampling approach is adopted to quantitatively and probabilistically integrate the weighted evidence; and (4) assignment of each NM to a hazard class: according to the results, each NM is assigned to one of the classes defined by the CLP regulation. Furthermore, to facilitate the integration and the classification of the weighted LoEs, an online R tool was developed. Finally, the approach was tested against an endpoint relevant to CLP (Aquatic Toxicity) using data retrieved from the eNanoMapper database, results obtained were consistent to results in REACH registration dossiers and in recent literature.

The Necessity of Recycling of Waste Li-Ion Batteries Used in Electric Vehicles as Objects Posing a Threat to Human Health and the Environment

The automotive industry is one of the fastest-growing sectors of the modern economy. Growing customer expectations, implementing solutions related to electromobility, and increasingly stringent legal restrictions in the field of environmental protection, determine the development and introduction of innovative technologies in the field of car production. To power the most modern vehicles that include electric and hybrid cars, packages of various types of lithium-ion cells are used, the number of which is constantly growing. After use, these batteries, due to their complex chemical composition, constitute hazardous waste that is difficult to manage and must be recycled in modern technological lines. The article presents the morphological characteristics of the currently used types of Li-ion cells, and the threats to the safety of people and the environment that may occur in the event of improper use of Li-ion batteries and accumulators have been identified and described on the basis of the Regulation of the European Parliament and Council (EC) No. 1272/2008 of 16 December 2008 and No. 1907/2006 of 18 December 2006 on the classification, labeling and packaging of substances and mixtures and the registration, evaluation, authorization and restriction of chemicals (REACH), establishing the European Chemicals Agency.

Updating the European Union's regulation on classification, labelling and packaging of substances and mixtures (CLP): A key opportunity for consumers, workers and stakeholders with interests in the legislation and toxicology of hazardous chemicals.

Recent advancements in toxicology and the European Union's Green Deal, with its Chemicals Strategy for Sustainability, have paved the way for major changes in EU legislation on the control of environmental chemicals for a cleaner and safer environment. Another substantial legislative advancement underway is the update of the "Regulation on Classification, Labelling and Packaging of Substances and Mixtures (CLP)," an ambitious piece of EU legislation with exceptional scientific toxicological background in identifying a hazard, aiming at better protecting its citizens and the environment from the risk of chemical substances and products, the occupational settings included. Update of CLP legislation additionally aims at facilitating the free exchange of chemicals in the European Internal Market, provided that proper labelling and packaging processes are implemented. Participation in the ongoing online public consultation on these issues, ending on November 15, 2021, is of key relevance to ensure a transparent and effective definition of such an important piece of legislation, fully compliant with current EU priorities in terms of human and environmental protection and animal welfare.

A retrospective study on EU harmonised classifications for carcinogenicity to guide future research

Under European Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP), chemicals can be classified as carcinogenic if they are considered to induce tumours, increase tumour incidence and/or malignancy, or shorten the time to tumour occurrence. Cancer classifications are divided into different hazard categories: Carc. 1A (known human carcinogen), Carc. 1B (presumed human carcinogen), Carc. 2 (suspected human carcinogen), and chemicals not classified for carcinogenicity. Selecting which classification is appropriate can be challenging, as judgements need to be made both on the existing hazard data and on its relevance to humans. One aspect to be considered in defining human relevance is a chemical's mode of action (MoA); the series of necessary key events that lead from an exposure to the adverse effect (in this case, tumours). This work aims to identify and discuss some of the features that have led ECHA's Committee for Risk Assessment (RAC) to decide upon harmonised cancer classifications for chemicals, and to prioritise future research on MoA and/or human relevance. RAC bases its decisions on cancer classification on both the weight-of-evidence (WoE) and strength-of-evidence (SoE) of this particular activity. Multiple factors contribute, including the species in which tumours are seen, and the relevance of the MoA to human health.

Environmental Risk Assessment of Nanomaterials in the Light of New Obligations Under the REACH Regulation: Which Challenges Remain and How to Approach Them?

ABSTRACTWithin the European regulation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH, EC No 1907/2006) specific provisions for nanomaterials were included, which have become effective on 1 January 2020. Although knowledge on the peculiarities of testing and assessing fate and effects of nanomaterials in the environment strongly increased in the last years, uncertainties about how to perform a reliable and robust environmental risk assessment for nanomaterials still remain. These uncertainties are of special relevance in a regulatory context, challenging both industry and regulators. The present paper presents current challenges in regulatory hazard and exposure assessment under REACH, as well as classification of nanomaterials, and makes proposals to address them. Still, the nanospecific considerations made here are expected to also be valid for environmental risk assessment approaches in other regulations of chemical safety. Inter alia, these proposals include a way forward to account for exposure concentrations in aquatic toxicity test systems, a discussion of how to account for availability of dissolving nanomaterials in aquatic test systems, and a pragmatic proposal to deduce effect data for soil organisms. Furthermore, it specifies how to potentially deal with nanoforms under the European regulation on Classification, Labelling and Packaging of substances and mixtures (CLP) and outlines the needs for proper exposure assessments of nanomaterials from a regulatory perspective. Integr Environ Assess Manag 2020;16:706–717. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Skin Surface Film Liquid as New Migration Medium for the Determination of PAHs Released from Rubber Containing Consumer Goods

ABSTRACTExposure of consumers, in particular children, to polycyclic aromatic hydrocarbons (PAHs) via contact with consumer products has been the subject of considerable public attention over the last years. Eight PAHs with a harmonized classification as carcinogen 1B, according to the Regulation EC No 1272/2008 on classification, labeling and packaging of substances and mixtures, have been identified in plastic and rubber contained in some consumer articles, such as toys, bicycle grips or sporting goods. These constitute a potential source for dermal, or even oral, exposure. Concerning the former, it is desirable to develop easy and reliable methods for migration determination using simulated environments that mimic as realistically as possible the hydro-lipidic film on human skin composed of aqueous sweat and sebum.This work proposes a protocol for the determination of PAH release from rubber using a migration simulant that mimics real skin conditions. Various compositions of skin surface film liquid (SSFL), a mixture of aqueous sweat and sebum, were tested for their stability and suitability for the measurements. The results indicated that SSFL containing 0.2% sebum showed good agreement with relative migration rates obtained using 20% ethanol, which in past studies has proved to be a valid migration medium for this purpose. The aqueous SSFL has the advantage that it does not interact with the elastomer sample matrix.The SSFL described in this work may serve as a migration simulant for future product-to-skin migration studies, in which the simulant's properties need to realistically reflect the conditions on human skin.

Transformation/dissolution characterization of tungsten and tungsten compounds for aquatic hazard classification.

The transformation/dissolution protocol (T/DP) for metals and sparingly soluble metal compounds was applied to determine the transformation/dissolution (T/D) characteristics of yellow tungsten trioxide, WO3 ; blue tungsten oxide, WOx, x taken as 2.9; tungsten disulphide, WS2 ; tungsten metal, W; 3 samples of tungsten carbide, WC; sodium tungstate, Na2 WO4 · 2H2 O; ammonium paratungstate (APT), (NH4 )10 (H2 W12 O42 ) · 4H2 O; and ammonium metatungstate (AMT) (NH4 )6 (H2 W12 O40 ) · 3H2 O. The T/D data were used to derive aquatic hazard classification outcomes under the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS) and European Union Classification, Labelling and Packaging of Substances and Mixtures (EU CLP) schemes by comparing the data with selected acute and chronic ecotoxicity reference values (ERVs) of 31 and 3.37 mg W/L, respectively. In addition to the concentration of total dissolved tungsten (W), the T/D solutions were analyzed for the concentration of the tungstate anion, because speciation can be an important factor in establishing the ecotoxicity of dissolved metals. Results show that the tungstate anion was the predominant W-bearing species in solution for all substances examined at pH 6 and 8.5. It was found that the 100 mg/L loadings of both the yellow WO3 and the blue WOx exceeded the 31 mg/L acute ERV, so they would classify as Acute 3-Chronic 3 under the UN GHS scheme but they would not classify under the EU CLP. An effect of pH on the reactivity of the W metal was observed with 3% and 16% W dissolution at pH 6 and 8.5, respectively. Tungsten metal would not classify under either the UN GHS or EU CLP schemes nor would the WS2 . The WCs were the least reactive in terms of the 1% or less dissolution of the contained W at pH 6. A critical surface area for WC was calculated. The sodium tungstate, APT and the AMT all yielded, at pH 8.5, total dissolved W concentrations that would result in UN GHS Acute 3-Chronic 3 classifications. Integr Environ Assess Manag 2018;14:498-508. © 2018 Her Majesty the Queen in Right of Canada. Integrated Environmental Assessment and Management © 2018 SETAC.

Environmental risk assessment of biocidal products: identification of relevant components and reliability of a component-based mixture assessment

BackgroundBiocidal products are mixtures of one or more active substances (a.s.) and a broad range of formulation additives. There is regulatory guidance currently under development that will specify how the combined effects of the a.s. and any relevant formulation additives shall be considered in the environmental risk assessment of biocidal products. The default option is a component-based approach (CBA) by which the toxicity of the product is predicted from the toxicity of ‘relevant’ components using concentration addition. Hence, unequivocal and practicable criteria are required for identifying the ‘relevant’ components to ensure protectiveness of the CBA, while avoiding unnecessary workload resulting from including by default components that do not significantly contribute to the product toxicity. The present study evaluated a set of different criteria for identifying ‘relevant’ components using confidential information on the composition of 21 wood preservative products. Theoretical approaches were complemented by experimentally testing the aquatic toxicity of seven selected products.ResultsFor three of the seven tested products, the toxicity was underestimated for the most sensitive endpoint (green algae) by more than factor 2 if only the a.s. were considered in the CBA. This illustrated the necessity of including at least some additives along with the a.s. Considering additives that were deemed ‘relevant’ by the tentatively established criteria reduced the underestimation of toxicity for two of the three products. A lack of data for one specific additive was identified as the most likely reason for the remaining toxicity underestimation of the third product. In three other products, toxicity was overestimated by more than factor 2, while prediction and observation fitted well for the seventh product. Considering all additives in the prediction increased only the degree of overestimation.ConclusionsSupported by theoretical calculations and experimental verifications, the present study developed criteria for the identification of CBA-relevant components in a biocidal product. These criteria are based on existing criteria stated in the regulation for classification, labelling and packaging of substances. The CBA was found sufficiently protective and reliable for the tested products when applying the here recommended criteria. The lack of available aquatic toxicity data for some of the identified relevant components was the main reason for underestimation of product toxicity.

「화학물질관리법」과 「산업안전보건법」의 영업비밀 사전 허가 제도 도입과 관련한 쟁점 분석

Objectives: The major objectives of this study are to review the issues surrounding trade secret claims in the Chemicals Control Act and Amendment on Occupational Safety and Health Act(1917-227) and to propose a way of improving the reliability of chemical information in MSDSs, labels and National Chemical Survey results. Materials: To review the issues on trade secret claims, we made an analysis frame which was divided into three steps: Value and Problem Recognition; New Regulation Design; and Enforcement and Amendment. We then compared Korean issues with issues from the United States’ Hazard Communication Standard and Emergency Planning & Community Right-to-Know Act, Canada’s Workplace Hazardous Materials Information System and Hazardous Materials Information Review Act and the European Union’s Regulation on Classification, Labelling and Packaging of substances and Mixtures. Results: The stage of right-to-know development in Korea has passed the Value and Problem Recognition phase, so efforts are needed to elaborately design new regulation. Conclusions: We recommend two ways to improve right-to-know in Korea. First, strict examination of the quality of documents for trade secret claims is very important. Second, trade secrets should be limited to less-hazardous substances.

Classification of dermal sensitizers in pharmaceutical manufacturing

Workers in development and manufacturing of pharmaceuticals are at risk for occupational contact dermatitis (OCD) of irritative (ICD) or allergic (ACD) origin, due to contacts with reactive intermediates (IM) and drug substances (DS). We examined, if alternative methods could replace presently used animal tests for identification of ACD in pharmaceutical development and manufacturing, without apparent loss of worker health, in line with regulations. The status of alternative methods for regulatory toxicology for consumer products has recently been reviewed by the Organisation for Economic Co-operation and Development (OECD) and the European Commission’s Joint Research Center (JRC) for the European Chemicals Agency (ECHA). They concluded that prediction of skin sensitization potential, extent and quality by in vitro methods, for regulatory assessments, will depend on the regulatory purpose and level of confidence required. Some alternative methods are currently in validation. Current Globally Harmonized System (GHS) regulations on classification, labeling and packaging of substances and mixtures depend on human and animal data, whereas alternative methods may provide supportive evidence. Since the levels of workplace skin exposure to DS and IM in manufacturing of pharmaceuticals are usually not known, it is not possible to conduct quantitative risk assessments based on threshold calculations for contact sensitizers.

Comprehension of hazard pictograms of chemical products among cleaning workers

To assess the comprehension among cleaning workers of the hazard pictograms as defined by the Globally Harmonized System (GHS) of the United Nations, concerning the classification, labeling and packaging of substances and mixtures. A sample of 118 workers was surveyed on their perception of the GHS hazard pictograms. Comprehensibility was measured by the percentage of correct answers and the degree to which they reflected International Organization for Standardization and American National Standards Institute standards for minimum level of comprehension. The influence of different variables to predict comprehension capacity was assessed using a logistic regression model. Three groups of pictograms could be distinguished which were statistically differentiated by their comprehensibility. Pictograms reflecting "acute toxicity" and "flammable", were described correctly by 94% and 95% of the surveyed population, respectively. For pictograms reflecting "systemic toxicity", "corrosive", "warning", "environment" and "explosive" the frequency of correct answers ranged from 48% to 64%, whereas those for pictograms "oxidizing" and "compressed gas" were interpreted correctly by only 7% of respondents. Prognostic factors for poor comprehension included: not being familiar with the pictograms, not having received training on safe use of chemical products, being an immigrant and being 54 years of age or older. Only two pictograms exceeded minimum standards for comprehension. Training, a tool proven to be effective to improve the correct interpretation of danger symbols, should be encouraged, especially in those groups with greater comprehension difficulties.

SWeRF—A Method for Estimating the Relevant Fine Particle Fraction in Bulk Materials for Classification and Labelling Purposes

In accordance with the European regulation for classification, labelling and packaging of substances and mixtures (CLP) as well as the criteria as set out in the Globally Harmonized System (GHS), fine fraction of crystalline silica (CS) has been classified as a specific target organ toxicity, the specific organ in this case being the lung. Generic cut-off values for products containing a fine fraction of CS trigger the need for a method for the quantification of the fine fraction of CS in bulk materials. This article describes the so-called SWeRF method, the size-weighted relevant fine fraction. The SWeRF method combines the particle size distribution of a powder with probability factors from the EN 481 standard and allows the relevant fine fraction of a material to be calculated. The SWeRF method has been validated with a number of industrial minerals. This will enable manufacturers and blenders to apply the CLP and GHS criteria for the classification of mineral products containing RCS a fine fraction of CS.

Hydraulic fracturing: a toxicological threat for groundwater and drinking-water?

This paper deals with the possible impact of hydraulic fracturing (fracking), employed in the exploitation of unconventional shale gas and tight gas reservoirs, on groundwater, which is the most important source of drinking-water in Germany and many other European countries. This assessment, which is part of an interdisciplinary study by a panel of neutral experts on the risks and environmental impact of hydraulic fracturing, is based mainly on data obtained from three ExxonMobil drilling sites in northern Germany. First, the basic technical aspects of fracking and its relevant water fluxes are explained. The type, purpose and fate of the constituents of the fracking fluids are discussed. The chemicals used in the fracking fluids are assessed with regard to their hazardous properties according to the Regulation (EC) No. 1272/2008 of the European Parliament and of the Council on the classification, labelling and packaging of substances and mixtures (CLP regulation) and the German “Water Hazard Classes”. Contamination of groundwater by ingredients of fracking fluids may occur from under ground or may result from above-ground accidents associated with the transport, storage and handling of hazardous substances used as additives in fracking fluids. The degree of groundwater contamination cannot be predicted in a general way. Therefore, different dilutions of the fracking fluid in groundwater are considered. It is shown that the concentrations of most ingredients resulting from a 1:10,000 up to 1:100,000 dilution of the fracking fluid in groundwater are below health-based reference values such as the limit values of the European Drinking Water Directive, the WHO Guideline Values for Drinking-water Quality, and other health-based guide values for drinking-water. Regarding the salinity of fracking fluids, a dilution of 1:1,000 is sufficient to reach concentrations which are acceptable for drinking-water. From the human-toxicological point of view, the constituents of flowback water are more problematic with respect to drinking-water produced from groundwater than those of the fracking fluids. The few reliable data which have become available, as well as hydrogeological considerations, point in the direction of considerable salt concentrations and toxic constituents, e.g., Hg, As, Pb, Zn, Cd, BTX, PAHs, or even radioactive elements. The identification and assessment of reaction products and metabolites, which are produced as a result of the fracking operation and the metabolic activity of microorganisms, are important topics for further research. The recommendations include the need for a better understanding of the environmental impact of fracking operations, especially with regard to the development of sustainable rules for planning, permission, performance and management of fracking, and for the monitoring of groundwater quality around fracked drilling sites.

In the shadow of the Cosmetic Directive — Inconsistencies in EU environmental hazard classification requirements for UV-filters

UV-filters are chemicals with potentially environmental hazardous properties. In the European Union (EU), UV-filters contained in sunscreen products are currently regulated by the Cosmetic Directive (from July 2013 by the Cosmetic Products Regulation). Environmental hazard classifications according to the regulation on classification, labelling and packaging of substances and mixtures (CLP) must be determined for UV-filters contained in industrial chemical products, whereas UV-filters contained in sunscreens are exempted from CLP. In this study we determined the potential environmental hazard classifications of UV-filters and sunscreen products if the CLP regulation was to be required for cosmetic products. Two sunscreen products were evaluated in accordance with the aquatic environmental hazard criteria for mixtures. The results highlight that the inconsistencies in the current EU regulation of UV filters hamper the risk management of environmental hazards of UV filters used in cosmetic products. Almost 50% of the investigated UV-filters approved for use in cosmetic products on the European market according to the current Cosmetic Directive were identified to meet the CLP classification as being hazardous to the aquatic environment. Assuming a worst-case scenario, the two examined sunscreens could both be classified as hazardous to the aquatic environment with long-lasting effects according to CLP classification criteria. Hence, if the CLP regulation was applicable to sunscreen products, both brands could potentially be labelled with the environmental hazard pictogram and associated hazard and precautionary statements. Including cosmetic products, and thereby sunscreens, in the CLP regulation would contribute to a more harmonized and transparent regulation of potentially hazardous substances on the EU market.

On the development of QSPR models for regulatory frameworks: The heat of decomposition of nitroaromatics as a test case

Many regulatory frameworks, e.g. related to the Transport of Dangerous Goods, the Registration, Evaluation, Authorisation and restriction of chemicals (REACH) or the Classification, Labelling and Packaging of substances and mixtures (CLP), require the characterization of the hazards of chemicals, which could be complex. In particular, the REACH regulation involves an extensive quantity of works, to gather toxicological, eco-toxicological and physico-chemical properties for a large number of compounds. So, the full characterization by experimental way is time-consuming and cost-expensive. Alternative methods are therefore encouraged to complement experimental tests. The Quantitative Structure–Property Relationships (QSPR) approach is one of the recommended methods, provided that they are developed within the rigorous guidelines proposed by the Organization for Economic Co-operation and Development (OECD). In this context, a series of nitroaromatic compounds has been analyzed to achieve new QSPR models for the prediction of their heat of decomposition respecting the requirements for application in regulatory frameworks.Three multilinear models were obtained upon the set of descriptors considered for their development (constitutional, topological or both) that do not need any preliminary time expensive quantum chemical calculations. They were tested by internal and external validation tests. Good performances for the two ones including constitutional descriptors were obtained in particular in terms of predictive power in a well defined applicability domain (RIN2 = 0.81–0.87). They are easier to apply than our previous quantum chemical based model, since they do not need any preliminary calculations.

Risk assessment of nanomaterials in cosmetics: a European union perspective

In Europe, the data requirements for the hazard and exposure characterisation of chemicals are defined according to the REACH regulation and its guidance on information requirements and chemical safety assessment (Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), and its guidance documents; available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:396:0001:0849:EN:PDF; and at: http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm). This is the basis for any related risk assessment. The standard reference for the testing of cosmetic ingredients is the SCCP’s ‘Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation’ (The SCCP’s Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (2006); available at: http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_03j.pdf), which refers to the OECD guidelines for the testing of chemicals (The OECD Guidelines for the Testing of Chemicals as a collection of the most relevant internationally agreed testing methods used by government, industry and independent laboratories to assess the safety of chemical products; available at: http://www.oecd.org/topic/0,2686,en_2649_34377_1_1_1_1_37407,00.html). According to the cosmetics directive [76/768/EEC], compounds that are classified as mutagenic, carcinogenic or toxic to reproduction are banned for the use in cosmetic products. Since December 2010, the respective labelling is based on the rules of regulation (EC) No. 1272/2008 (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006, Official Journal L 353, 31/12/2008, pages 1–1355; available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:353:0001:1355:en:PDF) on classification, labelling and packaging of substances and mixtures (CLP). There is no further impact from the CLP regulation on cosmetic products, because regulation (EC) No. 1223/2009 on cosmetic products defines its own labelling rules (Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products; available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:342:0059:0209:en:PDF). Special notification procedures are mandatory for preservatives, colourants and UV-filters where a safety approval from the European ‘Scientific Committee on Consumer Safety’ (SCCS) is needed prior to marketing. The risk assessment of nanomaterials in consumer products still poses a significant challenge as highlighted by the example of UV-filters in sunscreens since nanomaterials cannot be classified as a homogenous group of chemicals but still need to be addressed in risk characterisation on a case by case basis.

The Italian Helpdesk under the Regulation (EC) No. 1272/2008 (CLP): three-year activity and experience (2009-2011)

The Regulation (EC) No. 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) sets further obligations for manufacturers, importers, distributors, downstream users of substances either on their own or in mixtures. According to the European mandate, each Member State has constituted its National Helpdesk to provide advice to the interested parties on their duties under this Regulation. In Italy, the contact point for questions has been established at the National Centre for Chemical Substances of the Istituto Superiore di Sanità. The responders of the Italian CLP Helpdesk process the requests that have been submitted by the dedicated website. Applicants are asked to complete the form with all the required information. The Helpdesk staff also take part in the European network of CLP, REACH and ECHA Helpdesks together with the European Commission and other parties, that is the HelpNet. The present paper describes the results of the three-year activity of the Italian CLP Helpdesk (2009-2011).