This workshop, supported by the Division of Chemistry, aims to identify knowledge gaps and develop an action plan to fill these gaps in order to address one of the grand challenges in chemical sustainability: design of chemical products with minimal unintended biological activity. As such, the workshop will define the required advances and synergistic collaborations to meet this challenge starting from existing tools, knowledge, data and infrastructure. Furthermore, the workshop will help identify specific areas where incentives for innovation are necessary to address the goals of safer chemical design.
The workshop will explore interdisciplinary approaches and articulate a systems-level view of design of chemical products with minimal unintended biological activity. This will require collaborative efforts from representatives in chemistry, chemical and environmental engineering, toxicology, public health, environmental health sciences and public policy. A structured approach to the complex and multidisciplinary nature of the underlying science will provide educational benefits to the community, enabling the development of unique curriculum and outreach materials. A peer-reviewed consensus publication written by workshop participants will raise awareness of the current state of the science and future needs to achieve the goal of designing safer chemicals from first principles.
The planned workshop was conducted from June 27-28, 2013 in Washington, DC, with more than 20 participants representing government (US EPA, National Science Foundation); academia (6 US institutions and 1 Canadian institution); and the private sector (small business and large corporate entities in the chemical enterprise). The June meeting resulted in a draft report discussing the state of the art of in silico approaches to safer chemical design and making recommendations for future action specific to each of the stakeholder groups. The workshop participants reached consensus around goals for future development of the safer chemical design concept. These were aimed at improving efficiency of toxicity testing, improving upon one-chemical-at-a-time approaches, incorporating data from both conventional and innovative sources, and prioritizing chemicals for further research and substitution. Among the recommendations were: 1) Further advance research that links chemical properties (e.g. spectroscopic parameters) to toxicity endpoints, using iterative validation to evaluate and strengthen the relationships between molecular features and health outcomes. 2) Promote the development of large databases to support the use of algorithms derived from in silico models, with the goal of filling knowledge gaps and expanding the number of toxicity endpoints that can be usefully predicted in silico. 3) Strengthen data collection and curation protocols in the scientific community, for example via establishment of publicly accessible databases that integrate information related to biochemical as well as toxicological data, toxicokinetics, adverse outcome pathways, chemical structure and property information, and chemical use information. Data quality indicators and data quality tracking would encourage flexibility and adaptibility to other data systems. 4) Ensure that tool development remains current with advances in technology, particularly with respect to improved understanding of the relationships between genetic and epigenetic expression, proteomic, genomic, and metabolomic sciencie, the role of human microbiomes, and inter-cellular transport and signaling. 5) Encourage tool developers to be transparent about applicability domains and technological limitations of various approaches. This would raise confidence in the underlying science, provide a better basis for decisionmaking, and help education efforts across stakeholder groups. 6) Engage a wider cross-section of the general public, students (elementary through graduate level), and professional practitioners to ensure awareness and understanding of the fundamental science and its implications for technology and daily life. The workshop and follow-up activities brought together scientists from a range of stakeholder groups and areas of technical expertise to help bring clarity to the complex, trans-disciplinary challenges facing future design of safer chemicals. Outputs of the project included a series of actionable proposals and recommendations to advance the state of the science. Broadly, these are focused on 1) improving knowledge of chemical-biological interactions and adverse outcome pathways; 2) systematic data curation and validation; 3) expanding and clarifying the applicability of computational models; and 4) supporting the development of infrastructure for long-term research needs and cooperation among stakeholders. Further, the project helped to establish a community of interest among chemists, toxicologists, and researchers from allied fields. Outputs of the project will facilitate future design of educational activities, scientific meetings, and research collaboration
