Molecular Basis of Risk Assessment

An important problem facing environmental health scientists is understanding the role environmental agents play in the etiology of human disease. Assessing and predicting the actions of environmental contaminants on human health is a difficult and controversial problem. The current risk assessment paradigm is a four step process that involves identification of hazards, defining a dose response in animals, a mathematical assessment of risk and exposure assessment and some means of managing the risk. This paradigm has come under criticism recently because of shortcomings that relate to the lack of consideration of human biology in the risk assessment process. The criticisms, in part, relate to inaccurate exposure assessment, lack of biological markers, unresolved molecular mechanisms, and animal to human extrapolation. Developing sound, quantitative methods for predicting human risks requires developing accurate methods and models for assessing exposure, understanding molecular mechanisms of toxicity, and developing risk assessment models that incorporate information on mechanisms of toxicity.

The study of chemically induced human disease is usually undertaken in the various disciplines of industrial hygiene, toxicology, epidemiology, and risk assessment. Scientists in these fields rarely communicate with one another, let alone with the risk assessment community. They rarely read the same journals, they usually attend different conferences, and are often unaware of research outside their narrow field. Health professionals must deal with information from these fields to assess whether an illness is chemically induced. Because of the lack of communication between basic scientists and regulators, risk assessors are usually uninformed about the latest diagnostic strategies to determine whether diseases they observe are related to chemical exposures. There is a need for doctoral level scientists with experience and education in exposure assessment, epidemiology, molecular toxicology and policy formation who can transcend the process of assessing risk from exposure to environmental agents.

We propose to address this need through a Ph.D. training program in the Molecular Basis of Risk Assessment, which will give students the transdisciplinary training in exposure, modern toxicology, epidemiology, and environmental policy required to develop sound health risk assessment approaches.

Currently, the faculty in the Division engages in the study of the interaction between humans and the harmful aspects of their environment. It combines the disciplines of exposure assessment (air, water, and food), toxicology, epidemiology and health policy and management to reduce the adverse effects of toxicants, infectious agents and physical hazards. The subdisciplines within the Division are environmental toxicology, environmental chemistry, environmental epidemiology, environmental policy, microbiology, industrial hygiene and occupational health. Although not all faculty members of the Division directly participate in the Molecular Basis of Risk Assessment Training Program, they are a valuable resource to the program.

A specialty in toxicology was established in the mid-1980's that emphasized training in classical regulatory toxicology and risk assessment. Until recently, toxicology training in the Division of Environmental and Occupational Health remained a single-person area of research. In 1995, the need for a strong research-oriented program in toxicology was recognized, and space and resources within the Division were committed to the development of graduate training in toxicology. Since 1995, the toxicology faculty expanded to three full time members, with complementary research interests. Together with colleagues in pharmacology and medicinal chemistry, a total of six faculty members will participate in the toxicology portion of the training program. Research in toxicology within the Division currently focuses on molecular toxicology, with emphasis on receptor-mediated toxicity, cellular signaling, and physiological fate of xenobiotics.

Research in occupational and environmental epidemiology was introduced into the Division in the early 1980s. The focus of research in this group is on understanding the causal impact of environment and occupation on human health. This group develops studies to identify environmental factors that cause diseases and injuries. The study of environmental and occupational epidemiology requires knowledge of both subject matter and methods. The research comprises epidemiologic methods, biostatistics, basic sciences, toxicology, and environmental health. Students may focus in one of three components: exposures related to cancer, molecular epidemiology, and epidemiologic methods.

Research in exposure assessment grew out of research in environmental chemistry and industrial hygiene. This area of research is new to the Division and is expanding because of addition of new faculty members in the past three years. Even though its roots are in traditional areas of environmental health, exposure assessment is an emerging scientific discipline with its own vocabulary and conceptual focus. Investigators are working to integrate analytical chemistry, physics, statistics, toxicology and other diverse knowledge bases in studies that are both laboratory and field-based. The overall goal is to integrate both measurement and prediction of how, when, where, and why environmental exposures occur, enter an individual, and are dispersed throughout the body. Computer models are also used to predict how contaminants are distributed throughout the large populations. These capabilities lead to studies that provide the scientific basis for making public health policy decisions.

The focus of our education efforts is on sampling strategies, methods of measuring inhalation, ingestion and dermal exposure, development of time-concentration profiles of individuals for epidemiological investigations, characterization of sources and concentrations of pollutants, mathematical models that elucidate personal exposure, dose, or source-receptor relationships, and chemical biological markers within the general population as well as sensitive sub-groups.

Because of their broad research interests in the environmental health sciences faculty of the are uniquely qualified to provide the requisite training for a transdisciplinary training program in the Molecular Basis of Risk Assessment.