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Background A scientific framework on exposure science will boost the multiuse of exposure knowledge across EU chemicals-related policies and improve risk assessment, risk management and communication across EU safety, security and sustainability domains. Objective To stimulate public and private actors to align and strengthen the cross-policy adoption of exposure assessment data, methods and tools across EU legislation. Methods By mapping and analysing the EU regulatory landscape making use of exposure information, policy and research challenges and key areas of action are identified and translated into opportunities enhancing policy and scientific efficiency. Results Identified key areas of actions are to develop a common scientific exposure assessment framework, supported by baseline acceptance criteria and a shared knowledge base enhancing exchangeability and acceptability of exposure knowledge within and across EU chemicals-related policies. Furthermore, such framework will improve communication and management across EU chemical safety, security and sustainability policies comprising sourcing, manufacturing and global trade of goods and waste management. In support of building such a common framework and its effective use in policy and industry, exposure science innovation needs to be better embedded along the whole policymaking cycle, and be integrated into companies' safety and sustainability management systems. This will help to systemically improve regulatory risk management practices. Significance This paper constitutes an important step towards the implementation of the EU Green Deal and its underlying policy strategies, such as the Chemicals Strategy for Sustainability.

The fields of toxicology and chemical risk assessment seek to reduce, and eventually replace, the use of animals for the prediction of toxicity in humans. In this context, physiologically based kinetic (PBK) modelling based on in vitro and in silico kinetic data has the potential to a play significant role in reducing animal testing, by providing a methodology capable of incorporating in vitro human data to facilitate the development of in vitro to in vivo extrapolation of hazard information. In the present article, we discuss the challenges in: 1) applying PBK modelling to support regulatory decision making under the toxicology and risk-assessment paradigm shift towards animal replacement; 2) constructing PBK models without in vivo animal kinetic data, while relying solely on in vitro or in silico methods for model parameterization; and 3) assessing the validity and credibility of PBK models built largely using non-animal data. The strengths, uncertainties, and limitations of PBK models developed using in vitro or in silico data are discussed in an effort to establish a higher degree of confidence in the application of such models in a regulatory context. The article summarises the outcome of an expert workshop hosted by the European Commission Joint Research Centre (EC-JRC) – European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), on "Physiologically-Based Kinetic modelling in risk assessment – reaching a whole new level in regulatory decision-making" held in Ispra, Italy, in November 2016, along with results from an international survey conducted in 2017 and recently reported activities occurring within the PBK modelling field. The discussions presented herein highlight the potential applications of next generation (NG)-PBK modelling, based on new data streams.

The default approach in the risk assessment (RA) of chemicals is to assess external exposure by combining different sources and routes of exposure. This kind of approach contains various uncertainties and may overestimate exposure, since conservative estimates are needed due to the limited data on, for example, the absorption of the chemical and interspecies and intraspecies differences. Human biomonitoring (HBM) can help improve RA by providing measured data on combined exposures. In some cases, biomonitoring data can even provide a direct link to health effects. In some cases, biomonitoring allows to link exposure to specific contexts such as occupational settings. Although recent years have seen good examples of the use of biomonitoring in the risk assessment of chemicals, much work is still needed to improve its use in regulatory RA and human impact assessment (HIA). The European Human Biomonitoring Initiative (HBM4EU) was recently launched for fulfilling the gap between the exposure to hazardous chemical agents and their impact on human health. One of the aims of the HBM4EU project is to enhance the use of HBM data in RA and HIA of chemicals in different regulatory contexts including legislation on chemicals, plant protection products, and biocides, as well as legislation on cosmetics, food safety, and occupational safety. RA models for mixtures are also considered. Firstly, current RA practices are evaluated: is the use of biomonitoring integrated with the available RA guidance, and do give RA schemes have good examples of the advanced use of biomonitoring? A survey is also conducted to gather information from national regulatory risk assessors (in the EU, but also in non-EU countries) on their risk assessment practices, the use of HBM, and the obstacles and challenges related to its use. The challenges of the use of HBM data in RA may include a lack of guidance in the use of biomonitoring, a lack of knowledge regarding the interpretation of biomonitoring results, or the inability to link biomonitoring ...

The 7th amendment to the EU Cosmetics Directive prohibits to put animal-tested cosmetics on the market in Europe after 2013. In that context, the European Commission invited stakeholder bodies (industry, non-governmental organisations, EU Member States, and the Commission's Scientific Committee on Consumer Safety) to identify scientific experts in five toxicological areas, i.e. toxicokinetics, repeated dose toxicity, carcinogenicity, skin sensitisation, and reproductive toxicity for which the Directive foresees that the 2013 deadline could be further extended in case alternative and validated methods would not be available in time. The selected experts were asked to analyse the status and prospects of alternative methods and to provide a scientifically sound estimate of the time necessary to achieve full replacement of animal testing. In summary, the experts confirmed that it will take at least another 7-9 years for the replacement of the current in vivo animal tests used for the safety assessment of cosmetic ingredients for skin sensitisation. However, the experts were also of the opinion that alternative methods may be able to give hazard information, i.e. to differentiate between sensitisers and non-sensitisers, ahead of 2017. This would, however, not provide the complete picture of what is a safe exposure because the relative potency of a sensitiser would not be known. For toxicokinetics, the timeframe was 5-7 years to develop the models still lacking to predict lung absorption and renal/biliary excretion, and even longer to integrate the methods to fully replace the animal toxicokinetic models. For the systemic toxicological endpoints of repeated dose toxicity, carcinogenicity and reproductive toxicity, the time horizon for full replacement could not be estimated.