Preface
Designing Safer Chemicals Downloaded from pubs.acs.org by 185.223.164.51 on 09/15/18. For personal use only.
WHEN
C O N G R E S S P A S S E D T H E P O L L U T I O N P R E V E N T I O N A C T of
1990,
a new era in the philosophy and policy of controlling the risks of toxic chemicals was born. Experience of the previous two decades clearly demonstrated that exposure-based solutions to the problems of toxic chemicals are both limited in their effectiveness and increasingly expensive for private industry and society as a whole. The Pollution Prevention Act is nonregulatory in nature but serves as guidance by providing a hierarchical series of approaches to pollution prevention. A t the top of this series is "source prevention". In other words, the ultimate approach to preventing problems with toxic chemical substances is not to produce such substances in the first place. The U.S Environmental Protection Agency's (EPA's) principal initiative to carry out the congressional mandate of source prevention has been the establishment of the Green Chemistry Program. The initial concept developed and implemented under Green Chemistry was the "Alternative Synthetic Pathways" concept presented in symposia at the 1993 and 1994 national meetings of the American Chemical Society (ACS). This concept has evolved into a highly successful program that will undoubtedly lead to the replacement of many of the time-honored, yet polluting, chemical synthesis methodologies employed by academia and private industry today. The sister concept under the Green Chemistry Program is that of "Designing Safer Chemicals". This concept relates to the systematic design or redesign of industrial and commercial chemicals with the specific intent of making them safe or safer for humans and the environment without substantial changes in their efficacy. The concept also encompasses the means by which molecular manipulation for both safety and efficacy can be integrated into every facet of the development, manufacture, and use of industrial-type chemicals. It is this concept, designing safer chemicals, that is the subject of this book. To many, designing safer industrial chemicals as a fundamental approach in preventing pollution at its source may appear to be somewhat naive or idealistic. There exists an underlying assumption that most chemicals are inherently toxic and that the risks associated with their production and use are inevitable. However, on closer examination, the idea of producing nontoxic or less toxic chemicals does not only seem reasonable, we believe it is achievable. Our belief is rooted in the roles of the medicinal chemist and the pesticide chemist who strive to develop safe vii
drug products and pesticides, respectively. Through careful forethought and strategic molecular manipulation, these chemists minimize unwanted toxicity while maintaining desired efficacy. Our belief is further supported by the fact that commercially viable, nontoxic or less toxic industrial chemicals have already been developed by private industry. Although the idea of designing safer chemicals is not new, the conceptual framework of how this idea can be developed and implemented was first initiated by us in 1992 and culminated with its presentation in the day-long session "Designing Safer Chemicals" at the 208th A C S National Meeting in Washington, D C , in August 1994. This publication presents virtually all of the important information presented at that session and includes additional information that is highly relevant to the concept of designing safer chemicals. This book is intended primarily for synthetic chemists in industry, academia, and government. These individuals represent the principal architects in the design, redesign, or evaluation of chemicals that ultimately fulfill the needs of an ever-advancing technological society. This group and their expertise represent the nucleus of the multidisciplinary team and knowledge base that will be required to implement the concept of designing safer chemicals. The book is intended also for a broader audience of other scientists and technical managers in private industry and academia; in the fields of chemistry, biochemistry, pharmacology, and toxicology; as well as those in organizations that fund research in these areas. The implementation of the concept will require a concerted effort on the part of all of these individuals, organizations, and institutions. Turning the concept of designing safer chemicals into a reality will also require the introduction of new paradigms and significant changes in many existing paradigms. These will include changes in our approach to chemical education, new emphasis on mechanistic research in toxicology, and the introduction of greater multidisciplinary collaboration in the research and development of industrial chemicals. As a part of the paradigm changes, we envision the evolution of a new hybrid chemist who acquires not only the knowledge and experience of the industrial chemist in terms of structure-efficacy relationships, but also the expertise of the medicinal and pesticide chemists with respect to structure-biologicalactivity relationships at the molecular level. This new multidisciplinary scientist, or more specifically, this "toxicological chemist", will serve as a new professional whose role is to design safer chemicals, a new subspecialty in the field of synthetic chemistry. The goals of this publication are to create an awareness of and an interest in the concept of designing safer industrial chemicals for all those
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engaged in the research, development, and manufacture of industrial chemicals. To accomplish these goals we have attempted to explain the concept, present a framework of important methodologies associated therewith, and provide examples of the technical and commercial feasibility of the concept when applied to large-volume industrial chemicals. Our efforts really begin with an illustration on the front cover. Here the structure of benzidine is shown in red. Although this substance contains chemical properties that are highly desirable for use in dyestuffs, its commercial usefulness is greatly limited because it is highly carcinogenic. On the other hand, 2,2'-diethylbenzidine, the structure shown in green, represents an analog of benzidine that retains the properties that make it useful in dyestuffs, but it is considerably less carcinogenic. The design of the latter substance was based on an understanding of the mechanism of carcinogenicity of benzidene at the molecular level and knowledge of the chemistry required for commercial usefulness. We have also attempted to provide insight into the major steps that must be taken to fully implement the concept and establish the design of safer chemicals as an essential new paradigm for the future development or modification of industrial chemicals. To our knowledge, this is the first book of its kind. The future of the Green Chemistry Program and, more specifically, the concept of designing safer chemicals, looks promising. In March 1995, President Clinton announced the creation of the Green Chemistry Challenge Program. This new national agenda initiated an ongoing partnership among the E P A , private industry, and academia to recognize and promote fundamental breakthroughs in chemistry that achieve the goals of pollution prevention. The president specifically mentioned the design of safer chemicals as one of the major components of the Green Chemistry Challenge Program. Further, this initiative established a grants program for academic institutions to pursue fundamental research in Green Chemistry, including the design of safer chemicals. The E P A and the National Science Foundation have recently announced the availability of funds for research in this area, and further funding by these and other federal institutions is expected to continue and indeed grow. As we move into the 21st century, it is clear that we have the tools and the resources to further unlock the secrets of molecular toxicology and to integrate this knowledge with our understanding of the relationships between chemical structure and industrial application. What is needed now is the collective resolve of individuals and organizations in both the public and private sectors to build the proper infrastructure and make the necessary changes to effectively implement the concept of designing safer chemicals. It is hoped that this book will jump-start the process of understanding and acceptance and will serve as the initial catalyst for its implementation.
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Acknowledgments We are particularly pleased with ACS's interest in publishing a book on the subject of designing safer chemicals. We greatly appreciate their support in promoting the concept to chemists and relevant scientists and technical managers in other fields of study. The editors express their sincerest gratitude to the authors for careful preparation of their chapters, to Carol A . Farris for her encouragement and willingness to assist us with this undertaking, and to Barbara Pralle and Vanessa Johnson-Evans of A C S Books for their patience and assistance. Disclaimer This book was edited by Stephen C. DeVito and Roger L . Garrett in their private capacities. No official support or endorsement of or from the U.S. E P A is intended or should be inferred. S T E P H E N C. D E V I T O R O G E R L. G A R R E T T
Office of Pollution Prevention and Toxics U.S. Environmental Protection Agency Mail Code 7403 401 M Street, SW Washington, DC 20460 May 3, 1996
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