Complex Mixtures

In the laboratory, testing the toxic effects for a single compound is a straightforward process. However, many common harmful substances occur naturally as mixtures and can interact to exhibit greater toxic effects as a mixture than the individual components exhibit separately. Complex Mixtures addresses the problem of identifying and classifying complex mixtures, investigating the effect of exposure, and the research problems inherent in testing their toxicity to human beings. A complete series of case studies is presented, including one that examines the cofactors of alcohol consumption and cigarette smoke.

Contained in this volume are the proceedings of the international conference on the "Genetic Toxicology of Complex Mixtures," held from July 4-7, 1989, in Washington, DC. This meeting was a satellite of the "Fifth International Conference on Environmental Mutagens" and the seventh in a biennial series of conferences on "Short-term Bioassays in the Analysis of Complex Environmental Mixtures. " Our central objective in calling together key researchers from around the world was to extend our knowledge of the application of the methods of genetic toxicology and analytical chemistry in the evaluation of chemical mixtures as they exist in the environment. This conference emphasized the study of genotoxicants in air and water, and the assessment of human exposure and cancer risk. The latest strategies and methodologies for biomonitoring of genotoxicants (including transformation products) were described in the context of the ambient environment. Source character ization and source apportionment were discussed as an aid to understand ing the origin and relative contribution of various kinds of complex mix tures to the ambient environment. Similarly, investigations of genotoxi cants found in the indoor environment (sidestream cigarette smoke) and in drinking water (chlorohydroxyfuranones) were given special attention in terms of their potential health impacts. New molecular techniques were described to enable more precise quantitation of internal dose and dose to-target tissues. The emphasis of presentations on exposures/effects assessment was on integrated quantitative evaluation of human exposure and potential health effects.

Drag Reduction of Complex Mixtures discusses the concept of drag reduction phenomena in complex mixtures in internal and external flows that are shown experimentally by dividing flow patterns into three categories. The book is intended to support further experiments or analysis in drag reduction. As accurately modeling flow behavior with drag reduction is always complex, and since drag reducing additives or solid particles are mixed in fluids, this book covers these complex phenomena in a concise, but comprehensive manner. Comprehensively addresses a range of drag reduction themes involving different kinds of complex mixtures Provides data to support further experimentation and computer modeling of drag in complex flow Includes an introduction to the nature and characteristics of different kinds of complex mixtures

With this proceedings of the fourth symposium on complex mixtures, we continue to revise and extend our knowledge of genetic methods for the evaluation of chemical mixtures in the environment. The early chapters of this volume are devoted to new bioassay techniques that are directly applicable to the monitoring of environments contaminated with genotoxic chemicals. Microbiological methods have been further refined to meet the special needs of atmospheric monitoring so that very small samples may now be efficiently tested. New in situ methods utilizing green plants actually avoid many of the usual difficulties of sample collection and preparation and offer special advantages in monitoring wastewater, sludges, and hazardous wastes. Insects also are being employed very effectively in the evaluation of gaseous air pollutants in controlled laboratory investigations. Increased emphasis has been placed on a comprehensive assessment of the potential of complex mixtures t9 cause various kinds of genetic damage. New assays for chromosome structural and numerical aberrations in mammalian cells in vitro have been developed and are being applied in laboratory studies. Efforts to link tests for gene mutation and cell transformation in vitro with assays for tumorigenesis in vivo are contributing to the validation of the short-term testing approach. Studies comparing in vitro and in vivo data on a coal conversion by-product, on polycyclic aromatic hydrocarbons, and on mineral fibers are reported in separate papers. Later chapters are devoted to investigations on the fractionation and biological evaluation of specific chemical components within complex mixtures.

In the four years since the 1978 Symposium on the Application of Short-Term Bioassays in the Fractionation and Analysis of Complex Environmental Mixtures the use of short-term bioassays to evaluate potential health hazards of complex environmental mixtures has substantially increased. Increased research activity has been particularly noticeable in mobile source emissions, where initial observations on the mutagenic activity of diesel particulate extracts reported at the 1978 symposium stimulated the development of major research programs in government and industry. In the absence of appropriate reference materials, the U.S. Environmental Protection Agency initiated comparative genotoxicity studies to determine the relative mutagenic and carcinogenic activity and, ultimately, the potential human health risk due to exposure to various complex emission products. Among the materials investigated were those of known health risk, such as coke oven and roofing tar emissions and cigarette smoke condensates, and those of unknown hazard, such as exhaust from diesel-and gasoline-powered vehicles. Studies on diesel emission products proved useful in short term bioassay development, as the diesel exhaust extracts were genetically active with low cellular toxicity and could be obtained in relatively large quantities. Availability of such samples aided chemical characterization, and it was eventually determined that the nitro-polynuclear aromatic hydrocarbons were among the mutagenic components of diesel exhaust particulate.

In this book, both basic and advanced concepts are discussed for considering mixtures from initial exposure characterization through evaluation of risk associated with combined exposures. This book will provide an introduction to key issues and multiple options for evaluating both the toxicity of mixtures as well as the risk associated with exposure to mixtures. Additionally, promising tools adapted from other disciplines will be discussed in the context of mixtures toxicology and risk assessment. Finally, the discussion will move beyond chemical mixtures to address incorporating non-chemical stressors into toxicity studies and cumulative risk assessments. Although exposure to multiple chemical and non-chemical stressors is the rule, not the exception, consideration of mixtures in toxicology and risk assessment continues to be a significant challenge. This book will be an essential resource for researchers and professionals in the fields of toxicology, epidemiology, exposure science, risk assessment, and statistics.