EU-ToxRisk is working with the Predictive Toxicology Exploratory Programme at Syngenta, a leading crop protection products company. This case study focuses on a number of early research phase Syngenta proprietary chemicals designed for plant disease prevention and weed control. These compounds were, however, found to induce some unexpected and unacceptable toxicity in animals, the exact underlying mechanisms of which could not be identified, leaving the compounds to be discontinued. To aid the design of safe and effective plant protection products in the future, it is important to understand the underlying mechanisms of toxicity of these compounds. The goal of this case study is to use a panel of EU-ToxRisk test systems to closely examine the biological mechanisms underlying the toxicity observed by Syngenta. Furthermore, together with EU-ToxRisk experts, Syngenta wants to explore whether new approach methodologies (NAMs) deployed in this case study could be used in a regulatory submission.
Since the start of the project, EU-ToxRisk has been closely working with the Joint Research Centre (JRC) – the European Commission's science and knowledge service. The JRC has been a member of the steering team and contributed to several work packages. In addition, the JRC has had a key role in supporting the ongoing work of the case studies by acting as the central facility to store and distribute the case study chemicals. This close collaboration was further formalised in May 2018 through the signing of a collaboration agreement between EU-ToxRisk and the JRC. Going forward, an ab initio case study under the joint leadership of EU-ToxRisk, the JRC, and Unilever has been taking shape since early 2019 and testing is expected to start late 2019.
The cosmetics industry in Europe has been at the cutting edge of developing and implementing New Approach Methodologies (NAMs) for safety assessment. Cosmetics Europe is a European trade association for the cosmetics and personal care industry and a key industry partner in EU-ToxRisk. A collaborative case study was launched in June 2017, to determine if it is possible to carry out a read-across assessment on different length parabens using NAMs. Cosmetics Europe has a wealth of expertise on kinetic assessments of compounds and EU-ToxRisk contributes expertise on the analysis of compound dynamics.
The Tox21 program is a collaboration between four US government agencies to develop new ways to rapidly test whether substances can have an adverse effect on human health. The approaches taken in Tox21 are complementary to efforts in EU-ToxRisk in that they also employ new technologies such as high-throughput transcriptomics and in vitro and in silico based tests. Representatives of the Tox21 program are members of the EU-ToxRisk Scientific Advisory Board as well as Regulatory Advisory Board (SAB/RAB). To ensure knowledge exchange and optimal communication between Tox21 and EU-ToxRisk, several face-to-face meetings between representatives of the two projects have been held (Sep 2016, Mar 2017, Mar 2018, Mar 2019), as well as a number of working groups. These working groups are dedicated to particular topics of interest to both projects and serve to exchange knowledge and approaches in a series of web-based calls.