ES/RP 531 Fundamentals of Environmental Toxicology Fall 2005 ESRP531 Lect_1 Overview.doc Page 1 of 17 August 22, 2005 Lecture 1: Introduction to Environmental Toxicology; History; Overview of Concepts I. Environmental Toxicology vs. Toxicology A. Toxicology is popularly known as the “science of poisons”, but such a simplistic definition defies what toxicology has evolved into today. 1. In the classic 1975 text, “The Science of Poisons” by L. J. Casarett and J. Doull, the authors started by posing the question “What Is Toxicology”, and concluded that there was no simple answer. 2. Toxicology has evolved from a diversity of fields, and definitions often reflect the area of study from which the definition originates. a. In other words, pharmacologists, chemists, and ecologist might be interested in the principles of toxicology as applied to their particular area of interest, but they might define toxicology from their perspective. b. The following graphic illustrates that toxicology itself relies on the principles and practices of all disciplines; thus it can best be described as a multidisciplinary study of the nature of adverse effects associated with exposure to natural and synthetic chemicals. 1. Note that all chemicals, their adverse effects, and magnitude of exposure are key elements of toxicology. 2. Toxicology is not limited to just defining the magnitude of toxicity of synthetic compounds, like drugs or classical poisons, but it seeks also to predict health (human or environmental) effects (Casarett and Doull 1975). 3. In volume 1 of the second edition of the three volume tome, “General and Applied Toxicology (edited by B. Ballantyne, T. Marrs, and T. Syversen; published by Grove’s Dictionaries, Inc., NY in 1999), toxicology was defined as: a. “Toxicology is a study of the interaction between chemicals and biological systems in order to quantitatively determine the potential for chemical(s)ES/RP 531 Fundamentals of Environmental Toxicology Fall 2005 ESRP531 Lect_1 Overview.doc Page 2 of 17 to produce injury which results in adverse effects in living organisms, and to investigate the nature, incidence, mechanism of production, factors influencing their development, and reversibility of such effects”. (p. 4) b. The key issues in toxicology include: 1. The potential to cause injury is predicated on chemicals and/or their conversion products coming into close structural and/or functional contact with tissues(s) or organ(s). 2. The observed toxicity should be related quantitatively to the degree of exposure to the chemical. a. The influence of differing exposure doses on the magnitude and/or incidence of the toxic effects should be investigated. b. Dose-response relationships are of prime importance in confirming a causal relationship between chemical exposure and toxic effect, in assessing relevance of the observed toxicity to practical exposure conditions, and to allow hazard evaluations and risk assessment. c. The primary aim of most toxicology studies is to determine the potential for harmful effects in the intact living organism. 1. Results with non-human organisms, for example rodents or wildlife, have a tendency to always be extrapolated to humans. d. Toxicological investigations ideally allow evaluation of the following characteristics of toxicity; 1. The basic structural, functional, or biochemical injury produced; 2. Dose response relationships; 3. The mechanisms of toxicity (a.k.a. mode of action) (a) Defined as the fundamental chemical and biological interactions and resultant aberrations that are responsible for the genesis and longevity of the toxic response; 4. Factors that influence toxic response, including: (a) Route of exposure (b) Species (c) Sex (d) Formulation of test chemical (e) Environmental (or ambient) conditions 5. Development of approaches for recognition of specific toxic responses (i.e., diagnosis of symptomology) 6. The reversibility of effects, either spontaneously or with antidotal treatment B. Toxicology is considered a comparatively recent science, but over the last 30 years it has greatly developed and expanded in its scope. The reasons listed by Ballantyne et al. 1999 include: 1. Exponential increase in the number of synthetically produced industrial chemicals 2. Major increase in the number and nature of new drugs, pharmaceutical preparation, tissue-implantable materials and medical devices;ES/RP 531 Fundamentals of Environmental Toxicology Fall 2005 ESRP531 Lect_1 Overview.doc Page 3 of 17 3. Increase in the number rand types of pesticides and other substances used in agriculture and the food industry; 4. Mandatory testing and regulation of chemicals used commercially, domestically and medically; 5. Enhanced public awareness of potential adverse effects from xenobiotics (i.e., non-naturally occurring substances) to man, animals and the environment; 6. Litigation, principally as a consequence of occupational-related illness, unrecognized or poorly documented product safety concerns (including drugs) and environmental harm. C. Environmental Toxicology itself is one of many subspecialties of toxicology 1. The subspecialties are listed by Ballantyne et al (1999): a. Clinical 1. Causation, diagnosis and management of established poisoning in humans b. Veterinary 1. Causation, diagnosis and management of established poisoning in domestic and wild animals c. Forensic 1. Establishing the cause of death or intoxication in humans, by analytical procedures, and with particular reference to legal processes d. Occupational 1. Assessing the potential of adverse effects from chemicals in the occupational environment and the recommendation of appropriate protective and precautionary measures e. Pharmacological 1. Assessing the toxicity of therapeutic agents f. Toxinology 1. Assessing the toxicity of substances of plant and animal origin and produced by pathogenic bacteria 2. The study of naturally occurring toxins in food usually fall under the rubric of “food toxicology” g. Regulatory 1. Administrative function concerned with the development and interpretations of mandatory toxicology testing programs, and with particular reference to controlling the use, distribution, handling and availability of chemicals used commercially, domestically, and therapeutically h. Laboratory 1. Design and conduct of in vivo and in vitro toxicology testing programs i.