Abstract: Science and expert judgment are the foundation for safety assessments of chemicals added to food to ensure their use is safe. Hazard characterization is the first step in a safety assessment. Advances in science and technology pose challenges to the regulatory system and raise questions about whether the current hazard identification and characterization process is able to systematically and transparently encompass such advances while remaining defensible. An April 2011 workshop sponsored by The Pew Charitable Trusts, the Institute of Food Technologists, and the journal Nature brought together over 80 experts in science and food policy from government, industry, academia, and public interest organizations to examine the principles underlying the development and use of scientific evidence needed for chemical hazard characterization. Participants discussed challenges of identifying adverse health effects, advances in science, uses of new screening technologies and human biomonitoring data, updating of study designs, and development and review of toxicity test guidelines. Brainstorming sessions allowed participants to propose alternatives to enhance FDA's evaluation of science for safety assessment. Although there was no intention to reach a consensus, several themes emerged including the need for clear procedures to develop validated toxicity tests; importance of regularly updating guidance documents relied upon by regulators and industry; benefits of transparency and public access to information; potential for greater interagency collaboration; opportunities to improve hypothesis-based research to make it more useful to regulatory decision making; and importance of staying abreast of scientific developments to ensure that safety assessments are made using sensitive and relevant methods.