Risk Assessment in the 21st Century: The Contributions of HESI’s RISK21 Project

Introduction
Many chemicals in the environment and the workplace have undergone toxicological and exposure data development to understand their safety. However, these data are resource intensive in animal usage and cost. Many other chemicals have little or no data, and the option of extensive data development is unrealistic. A new paradigm for safety evaluation must be designed that takes advantage of new thinking, new technology and new science. Two US National Research Council reports: “Toxicology Testing in the 21st Century” and “Science and Decisions: Advancing Risk Assessment” articulate shortcomings and challenges to the way toxicology, exposure evaluation, and risk assessment are currently done. Although the reports offer general scientific approaches and concepts to move ahead, a concerted effort is needed to coalesce current thinking.

Methods
Given the global implications of these challenges, a multi-sector, international team was assembled (“RISK21”). This team of experts from academia, government, non-governmental organizations, and the private sector was organized under the auspices of the ILSI Health and Environmental Sciences Institute with the vision to bring applicable, accurate, and resource appropriate approaches to the evolving world of human health risk assessment.

Results
The RISK21 Project has developed an integrated evaluation strategy that: 1) identifies data needs for the specific condition to be addressed (“problem formulation”), 2) identifies methods to estimate likely exposure ranges, 3) describes fit-for-purpose in vitro and in vivo toxicological data acquisition, and 4) provides alternative methods to address human health risk assessments, including cumulative risk. The latter will include not only mixtures of chemicals but also consideration of non-chemical stressors and conditions.

Discussion
The project will describe both the challenges of utilizing new toxicity testing paradigms and how best to apply our advancing knowledge to understand and manage potential environmental and occupational risks to human health more accurately, efficiently, and effectively.