ASSESSING PESTICIDE TOXICITY IN MAN AND CORRELATIONS WITH LABORATORY ANIMAL STUDIES

Abstract

Our knowledge about the adverse effects of pesticide exposure in humans derives from two main sources. The first source is primarily epidemiologic and consists of the observations made on individuals exposed to pesticides acutely or chronically as a result of their occupation (formulators, applicators, pickers and other agricultural workers, etc.) or from accidental or intentional (suicide and homicide) exposure. The second source is toxicologic and is obtained by evaluating the toxicity data base for the pesticide and predicting the type and severity of adverse effects that will be produced in man. Each source has limitations and problems which constrain the extent of our knowledge of pesticide effects in humans. The data from poison control centers involved in the treatment of acute pesticide poisoning, for example, provides documentation of the type of adverse effects produced in man by pesticide exposure but rarely provides the type of dose information that is needed to fully characterize pesticide toxicity in a single species. Epidemiologic studies of workers in various pesticide related occupations are also frequently lacking in exposure-dose information and are further confounded by multiple factors which complicate interpretation (concomitant exposure to other agents, current and previous medical history, previous occupational exposures, etc.). With regard to the toxicity data base in animals, there are always uncertainties associated with predicting results in the target species (humans) on the basis of data obtained in the test species (animal toxicity tests). Differences in metabolism, absorption, distribution, excretion and even in the receptor response to the pesticide can invalidate such predictions even when they are made on the basis of a toxicity data base that has met all of the required test protocols. It is evident that our continued ability to benefit from the use of pesticides while avoiding their potential adverse effects depends on the knowledge that we obtain both from observations made in man and predictions that we can make from our tests in animals. It is also evident that we need to strengthen the linkage between the observations obtained from man and those provided by the animal tests. Two examples of how we might accomplish this are: to utilize sophisticated monitoring of body fluids in occupational exposed pesticide wrokers (during the experimental use permit period, for example) to provide better dosage information, and to focus our animal test protocols on some of the more clinically relevant aspects of pesticide poisoning, such as antidote and treatment regimes. Much of the uncertainty which is associated with the prediction of human effects on the basis of tests in animals could be eliminated, for example, if we develop procedures that can be safely used to characterize the kinetics of a pesticide in man. With such information ye could base our prediction on the most predictive species rather than on the most sensitive species, as we currently often do.