At the moment, over 350.000 chemicals are registered worldwide for production and use. Their application, however, may harm human health and the environment. To manage the safety of chemicals,... Show moreAt the moment, over 350.000 chemicals are registered worldwide for production and use. Their application, however, may harm human health and the environment. To manage the safety of chemicals, particular chemical legislations are in place, which make use of risk and hazard assessments. However, there are several challenges for current risk and hazard assessments, including i) a lack of (reliable) data, and ii) a relative slow and inefficient evaluation and regulation process. In this thesis, I investigate specifically whether more extensive and targeted use of chemical similarity within risk and hazard assessment has the potential to improve these aspects. Chemical similarity could be a valuable factor as similarities between two chemicals could be a sign of similar physicochemical and/or toxic properties. The separate sections within this thesis specifically focus on chemical similarity in relation to screening, data generation and evaluation of substances. The results of this thesis indicate that chemical similarity could be used to identify and evaluate hazardous properties of single and groups of chemicals. Accordingly, I promote more extensive use of chemical similarity within risk and hazard assessment as it has the ability to circumvent several issues related to a lack of data and evaluation efficiency. Show less
The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum on repeated dose toxicity (RDT) testing to identify synergies between industrial sectors and... Show moreThe European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum on repeated dose toxicity (RDT) testing to identify synergies between industrial sectors and stakeholders along with opportunities to progress these in existing research frameworks. Although RTD testing is not performed across all industrial sectors, the OECD accepted tests can provide a rich source of information and play a pivotal role for safety decisions relating to the use of chemicals. Currently there are no validated alternatives to repeated dose testing and a direct one-to-one replacement is not appropriate. However, there are many projects and initiatives at the international level which aim to implement various aspects of replacement, reduction and refinement (the 3Rs) in RDT testing. Improved definition of use, through better problem formulation, aligned to harmonisation of regulations is a key area, as is the more rapid implementation of alternatives into the legislative framework. Existing test designs can be optimised to reduce animal use and increase information content. Greater use of exposure-led decisions and improvements in dose selection will be beneficial. In addition, EPAA facilitates sharing of case studies demonstrating the use of Next Generation Risk Assessment applying various New Approach Methodologies to assess RDT. Show less
Roelofs, E.; Persoon, L.; Qamhiyeh, S.; Verhaegen, F.; Ruysscher, D. de; Scholz, M.; ... ; Lambin, P. 2010
This report introduces a framework for comparing radiotherapy treatment planning in multicentric in silico clinical trials. Quality assurance, data incompatibility, transfer and storage issues, and... Show moreThis report introduces a framework for comparing radiotherapy treatment planning in multicentric in silico clinical trials. Quality assurance, data incompatibility, transfer and storage issues, and uniform analysis of results are discussed. The solutions that are given provide a useful guide for the set-up of future multicentric planning studies or public repositories of high quality data. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 97 (2010) 567-571 Show less
