PRINCIPLES OF TOXICOLOGY - Biology East Borneo

1.3 THE IMPORTANCE OF DOSE AND THE DOSE–RESPONSE RELATIONSHIP 13TABLE 1.4 ContinuedAdvantagesDisadvantagese. Animal Toxicity TestsEasily manipulated and controlledTest species response is of uncertain human relevance;thus, the predictive value is lower than that ofhuman studiesBest ability to measure subtle responsesSpecies responses may vary significantly bothqualitatively and quantitatively; thus, a number ofdifferent species should be testedWidest range of potential toxicities to studyExposures levels may not be relevant to (they may farexceed) the human exposure levelChance to identify and elucidate mechanisms of Selecting the best animal species to study, i.e., thetoxicity that allow for more accurate riskspecies with the most accurate surrogate responses,extrapolations to be made using all five categories is always unknown and is difficult to determine aof toxicity test datapriori (without a certain amount of human test data);thus, animal data poses somewhat of a catch-22situation, i.e., you are testing animals to predicthuman responses to the chemical but must know thehuman response to that chemical to accurately selectthe proper animal test speciesCheaper to perform than full-scale epidemiologystudiesNo risk of producing adverse human health effectsduring the studySource: Adapted from Beck et al. (1989).May be a poor measure of the variability inherent tohuman exposures because animal studies are so wellcontrolled for genetics, doses, observation periods,etc.The reproducibility of the animal response may createa false sense of precision when attempting humanextrapolationsf. Alternatives to Traditional Animal TestingType of Toxicity Test Advantages DisadvantagesStructure–activityrelationships (SARs)In vitro testingAlternative animal testing(nonmammalian andnonavian species)Does not require the use of anyexperimental animalsQuick to performReduces the number of experimentalanimals neededAllows for better control of the toxicantconcentration at the target siteAllows for the study of isolatedfunctions such as nerve-muscleinteraction and release ofneurotransmitterEasier to control for host factors such asage dependency, nutritional status,and concurrent diseasePossible to use human tissueLess expensive and quicker (due toshorter lifespans) than using higheranimalsSince a whole organisms is used allowsfor absorption, distribution,biotransformation, and elimination ofthe toxicantMany toxicants with very similarchemical properties have verydifferent toxicitiesCannot fully approximate thecomplexities that take place in wholeorganisms (i.e., absorption,distribution, biotransformation, andelimination)Since the animal is far removed fromhumans, the effect of a toxicant canbe very different from that found withhigher animals