Three-tiered approach for standard information requirements for polymers requiring registration under REACH

Polymers are a very large class of chemicals comprising often complex molecules with multiple functions used in everyday products. The EU Commission is seeking to develop environmental and human health standard information requirements (SIRs) for man-made polymers requiring registration (PRR) under a revised Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation. Conventional risk assessment approaches currently used for small molecules may not apply to most polymers. Therefore, we propose a conceptual three-tiered regulatory approach for data generation to assess individual and groups of polymers requiring registration (PRR). A key element is the grouping of polymers according to chemistry, physico-chemical properties and hazard similarity. The limited bioavailability of many polymers is a prominent difference to many small molecules and is a key consideration of the proposed approach. Methods assessing potential for systemic bioavailability are integral to Tier 1. Decisions for further studies are based on considerations of properties and effects, combined with systemic bioavailability and use and exposure considerations. For many PRRs, Tier 1 data on hazard, use and exposure will likely be sufficient for achieving the protection goals of REACH. Vertebrate animal studies in Tiers 2 and 3 can be limited to targeted testing. The outlined approach aims to make use of current best scientific evidence and to reduce animal testing whilst providing data for an adequate level of protection

Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their revaluation

The threshold of toxicological concern (TTC) approach is a resource-effective de minimismethod for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies. It is being increasingly used to screen and prioritise substances with low exposure for which there is little or no toxicological information. The first step in the approach is the identification of substances that may be DNA-reactive mutagens, to which the lowest TTC value is applied. This TTC value was based on analysis of the cancer potency database and involved a number of assumptions that no longer reflect the state-of-the-science and some of which were not as transparent as they could have been. Hence, review and updating of the database is proposed, using inclusion and exclusion criteria reflecting current knowledge. A strategy for the selection of appropriate substances for TTC determination, based on consideration of weight of evidence for genotoxicity and carcinogenicity is outlined. Identification of substances that are carcinogenic by a DNA-reactive mutagenicmode of action and those that clearly act by a non-genotoxic mode of action will enable the protectiveness to be determined of both the TTC for DNA-reactive mutagenicityand that applied by default to substances that may be carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class I-III compounds). Critical to the application of the TTC approach to substances that are likely to be DNA-reactive mutagens is the reliability of the software tools used to identify such compounds. Current methods for this task are reviewed and recommendations made for their application

The way forward for assessing the human health safety of cosmetics in the EU - Workshop proceedings

Although the need for non-animal alternatives has been well recognised for the human health hazard assessment of chemicals in general, it has become especially pressing for cosmetic ingredients due to the full implementation of testing and marketing bans on animal testing under the European Cosmetics Regulation. This means that for the safety assessment of cosmetics, the necessary safety data for both the ingredients and the finished product can be drawn from validated (or scientifically-valid), so-called "Replacement methods". In view of the challenges for safety assessment without recourse to animal test data, the Methodology Working Group of the Scientific Committee on Consumer Safety organised a workshop in February 2019 to discuss the key issues in regard to the use of animal-free alternative methods for the safety evaluation of cosmetic ingredients. This perspective article summarises the outcomes of this workshop and reflects on the state-of-the-art and possible way forward for the safety assessment of cosmetic ingredients for which no experimental animal data exist. The use and optimisation of "New Approach Methodology" that could be useful tools in the context of the "Next Generation Risk Assessment" and the strategic framework for safety assessment of cosmetics were discussed in depth