An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials

Additional file 1: Table S1. Comparison of significant in vitro LOAECs (significant as compared to the negative benchmark material corundum) to NOAECs and LOAECs recorded in rat STISs. Table S2. Bioactivity of four types of CeO2 NMs in rat STISs as compared to cellular effects recorded in the in vitro NR8383 AM assay

Hazard Identification of Inhaled Nanomaterials: Making use of Short-term Inhalation Studies

A major health concern for nanomaterials is their potential toxic effect after inhalation of dusts. Correspondingly, the core element of tier 1 in the currently proposed Integrated Testing Strategy (ITS) is a short-term rat inhalation study (STIS) for this route of exposure. STIS comprises a comprehensive scheme of biological effects and marker determination in order to generate appropriate information on early key elements of pathogenesis, such as inflammatory reactions in the lung and indications of effects in other organs. Within the STIS information on the persistence, progression and/or regression of effects is obtained. The STIS also addresses organ burden in the lung and potential translocation to other tissues. Up to now STIS was performed in research projects and routine testing of nanomaterials. Meanwhile rat STIS results for more than 20 nanomaterials are available including the representative nanomaterials listed by the Organization for Economic Cooperation and Development (OECD) Working Party on Manufactured Nanomaterials (WPMN), which has endorsed a list of representative Manufactured Nanomaterials (MN) as well as a set of relevant endpoints to be addressed. Here, results of STIS carried out with different nanomaterials are discussed as case studies. The ranking of different nanomaterials potential to induce adverse effects and the ranking of the respective NOAEC is the same among the STIS and the corresponding sub-chronic and chronic studies. In another case study, a translocation of a coated silica nanomaterial was judged critical for its safety assessment. Thus, STIS enables application of the proposed ITS, as long as reliable and relevant in vitro methods for the tier 1 testing are still missing. Compared to traditional subacute and subchronic inhalation testing (according to OECD test guidelines (TG) 412 and 413), STIS uses less animals and resources and offers additional information on organ burden and pro-/regression of potential effects.JRC.D-Institute for Reference Materials and Measurements (Geel

Methacrylsäure : MAK Value Documentation in German language, 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of methacrylic acid of 5 ml/m3, considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effects of methacrylic acid are goblet cell hyperplasia/hypertrophy in the respiratory epithelia and reduced body weight gain in rats, which is probably a secondary effect of the irritation at 350 ml/m3 in a 90‐day study. Since 2014 the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the NOAEC of 100 ml/m3 corresponds to a work place air concentration of 33 ml/m3. As the goblet cell hyperplasia is judged to be adaptive and its incidence is not significantly increased, the MAK value is elevated to 50 ml/m3. Since local effects are critical, the assignment to Peak Limitation Category I and the excursion factor 2 are confirmed. Studies with the read‐across methyl methacrylate which is cleaved to methacrylic acid show that damage to the embryo or foetus is unlikely when the MAK value for methacrylic acid is observed, and the assignment to Pregnancy Risk Group C is confirmed. Methacrylic acid and methyl methacrylate are not genotoxic. Carcinogenicity studies with methacrylic acid are lacking but methyl methacrylate is not carcinogenic. Skin contact does not contribute significantly to systemic toxicity and sensitization is not expected

A critical appraisal of existing concepts for the grouping of nanomaterials

AbstractThe grouping of substances serves to streamline testing for regulatory purposes. General grouping approaches for chemicals have been implemented in, e.g., the EU chemicals regulation. While specific regulatory frameworks for the grouping of nanomaterials are unavailable, this topic is addressed in different publications, and preliminary guidance is provided in the context of substance-related legislation or the occupational setting. The European Centre for Ecotoxicology and Toxicology of Chemicals Task Force on the Grouping of Nanomaterials reviewed available concepts for the grouping of nanomaterials for human health risk assessment. In their broad conceptual design, the evaluated approaches are consistent or complement each other. All go beyond the determination of mere structure–activity relationships and are founded on different aspects of the nanomaterial life cycle. These include the NM’s material properties and biophysical interactions, specific types of use and exposure, uptake and kinetics, and possible early and apical biological effects. None of the evaluated grouping concepts fully take into account all of these aspects. Subsequent work of the Task Force will aim at combining the available concepts into a comprehensive ‘multiple perspective’ framework for the grouping of nanomaterials that will address all of the mentioned aspects of their life cycles

Grouping and read-across approaches for risk assessment of nanomaterials

Physicochemical properties of chemicals affect their exposure, toxicokinetics/fate and hazard, and for nanomaterials, the variation of these properties results in a wide variety of materials with potentially different risks. To limit the amount of testing for risk assessment, the information gathering process for nanomaterials needs to be efficient. At the same time, sufficient information to assess the safety of human health and the environment should be available for each nanomaterial. Grouping and read-across approaches can be utilised to meet these goals. This article presents different possible applications of grouping and read-across for nanomaterials within the broader perspective of the MARINA Risk Assessment Strategy (RAS), as developed in the EU FP7 project MARINA. Firstly, nanomaterials can be grouped based on limited variation in physicochemical properties to subsequently design an efficient testing strategy that covers the entire group. Secondly, knowledge about exposure, toxicokinetics/fate or hazard, for example via properties such as dissolution rate, aspect ratio, chemical (non-)activity, can be used to organise similar materials in generic groups to frame issues that need further attention, or potentially to read-across. Thirdly, when data related to specific endpoints is required, read-across can be considered, using data from a source material for the target nanomaterial. Read-across could be based on a scientifically sound justification that exposure, distribution to the target (fate/toxicokinetics) and hazard of the target material are similar to, or less than, the source material. These grouping and read-across approaches pave the way for better use of available information on nanomaterials and are flexible enough to allow future adaptations related to scientific developments